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Rheumatic feverIs there any disease group more ’deserving’ of a place at buy kamagra oral jelly online australia the neglected tropical disease table than the post streptococcal illnesses, glomerulonephritis and rheumatic kamagra for her fever?. These dropped off the radar of most high income countries in the second half of the 20th century but have continued to smoulder, largely unchecked, in low and middle income countries (LMICs). The burden buy kamagra oral jelly online australia is frightening.

300 000 incident cases per year and 30 million prevalent cases, the damage from chronic carditis resulting, in so many, in heart failure and stroke.There are a number of approaches. Primary prevention (vaccination) remains a work in progress. Secondary prevention (prompt treatment) is largely dependent on diagnosis which depends on a positive throat swab or serological evidence in buy kamagra oral jelly online australia the form of the ASOT and ADB titres and this is where the complexities begin.

Tertiary prevention, early diagnosis of heart disease by echo screening and prophylaxis has promise but is gestational. The range of population norms depends on exposure and threshold levels in one country might not be applicable elsewhere inevitably resulting in false buy kamagra oral jelly online australia positive and false negative results. Okello et al establishes a range of ASOT levels in urban Uganda and shows much higher mean titres than other comparable populations.

Joshua Osowicki and Andrew Steer discuss the implications of these findings in the context of a multipronged approach to rheumatic fever during the wait for the long yearned-for group A streptococcal treatment. See pages 825 and buy kamagra oral jelly online australia 813Febrile neutropaeniaOncological treatment is prolonged and draining for both a child and their family. A major contributor to the fatigue is the need for recurrent admissions for chemotherapy induced febrile neutropenia (FN).

Though evidence of benefit is scanty to non-existent, it is traditional to keep children in hospital on IV antibiotic treatment for several days irrespective of culture results buy kamagra oral jelly online australia and clinical appearance. Sereveratne and colleagues assess the safety of a more flexible approach in a tertiary oncology centre, allowing discharge at 48 hours, even if culture positive as long as ‘wellness’ and social criteria were metIn total, 179 episodes of FN were reviewed from 47 patients. In 70% (125/179) of episodes, patients were discharged safely once 48 hours microbiology results were available, with only 5.6% (7/125) resulting in readmission in the 48 hours following discharge.

There were no deaths from sepsis buy kamagra oral jelly online australia. This approach won’t work for all episodes of febrile neutropenia, but, probably applies to the majority and the differences to quality of life if adopted widely are hard to overstate. See page 881Infectious disease mortalityTrends in buy kamagra oral jelly online australia infectious disease mirror changes in vaccination programmes, society and the environment, diagnostics and microbiological epidemiology.

Ferreras-Antolin examines Public Health England data over two eras, 2003 to 2005 and 2013 to 2015. In the latter period, there were 5088 death registrations recorded in children aged 28 days to <15 years in England and Wales (17.6 deaths/100 000 children annually) and, in the first 6897 (23.9/100 000). The incidence rate ratio (IRR) of 0.74 (95% CI 0.71 to 0.77) fell significantly and the stories behind these buy kamagra oral jelly online australia data are revealing.

There is little doubt that PCV vaccination has played a role though, in this series, it is too early to assess the contribution of the (2015 launched) meningococcal B programme. The raw data also mask the rise of (the still non-treatment preventable) invasive group A streptococcal disease (one of the arguments for varicella vaccination) and the future role for Group B streptococcal immunisation. Influenza deaths were rare and, despite a reduction buy kamagra oral jelly online australia between the eras was not a major explanator.

See page 857Fibre and constipationOne of the more entrenched tenets of child nutrition folklore is that of the association between fibre and constipation. In a re-analysis of data from the latest NICE review, information from the ALSPAC cohort (in which stool consistency pre-weaning was established) and monozygotic twin studies, Tappin persuasively argues (through triangulation analysis) that fibre is the result of and confounded by parental response to hard stool and is neither a cause buy kamagra oral jelly online australia of constipation or a treatment. Laxation (as advocated) should be the first line and used early to prevent the all too familiar chronic issues with undertreatment.

Soiling. Loss of self esteem buy kamagra oral jelly online australia. Poor mood and loss of appetite.

See page 864Drowning and autismDrowning is a major cause buy kamagra oral jelly online australia of global child mortality, particularly in low and middle income country settings. Interventions such as fencing off access and swimming lessons have partially ameliorated the risk, but progress has been slow and awareness probably still the single best form of prophylaxis. Autistic children represent a high risk group due to their inherent communication and behavioural issues.

Peden assesses the association between buy kamagra oral jelly online australia autism and drowning in Australia from coronial certificates between 2002 and 2018. Of the 667 cases of drowning among 0–19 year olds (with known history), 27 (4%) had an ASD diagnosis, relative risk 2.85 (95% CI 0.61 to 13.24). Children and adolescents with ASD were significantly more likely to drown when compared buy kamagra oral jelly online australia with those without ASD.

If aged 5–9 years (44.4% of ASD cases. 13.3% of non ASD cases). In a lake or dam (25.9% vs 10.0%) buy kamagra oral jelly online australia and during winter (37.0% vs 13.1%).

These sobering figures are likely to be an underestimate as the diagnosis of ASD is often not made until the age of 5 years, past the highest drowning risk preschool group. See page 869.

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The Fairy Meadow community will soon receive its own ambulance station under the NSW Government’s $232 million Rural Ambulance Infrastructure Reconfiguration (RAIR) program.Minister for Health Brad Hazzard said Fairy Meadow was identified as the ideal location to super kamagra 100mg base a new station to provide the best ambulance coverage across the Illawarra region, now and in the future.“This is a first for Fairy Meadow, providing paramedics with a modern facility with state-of-the-art equipment to help them carry out their vital job of saving lives in the local Illawarra communities,” Mr Hazzard said.“The next step will be choosing the best site in Fairy Meadow to build the ambulance station click to read more. To do this we have expert help from tried and tested international software which maps Triple Zero calls.”NSW Ambulance Assistant Commissioner Clare Lorenzen said the announcement was another welcome NSW Government initiative for regional and rural communities.“Operating from a new base in Fairy Meadow, our local paramedics will be well positioned to continue to provide the best possible high-quality emergency medical care super kamagra 100mg to residents of local communities,” Ms Lorenzen said.“The additional ambulance service in Fairy Meadow will support the Bulli and Wollongong ambulance stations to strengthen the coverage of the Illawarra region.” The RAIR program is the single largest investment in regional NSW Ambulance’s 126-year history, with 24 new or upgraded ambulance stations already delivered or under construction as part of the $132 million Stage 1 program. The new station for the Illawarra community is part of the NSW Government’s additional $100 million investment in Stage 2 of the RAIR program.In 2020-21, the NSW Government is investing more than $1 billion in services and capital works for NSW Ambulance.This includes $27 million of funding for 180 new NSW Ambulance staff across NSW, as part of kamagra price comparison the third tranche of the June 2018 commitment to recruit 750 additional paramedic and control super kamagra 100mg centre staff over four years.Work has started on installing additional security fencing on the Sydney Trains network to prevent trespassing and reduce self-harm incidents in the rail corridor.Minister for Transport and Roads Andrew Constance said the $4.5 million of new fencing is being installed across 2.3 kilometres of the rail corridor by the end of 2021.“This new fencing will not only improve safety and stop people accessing the rail network illegally, it will also help save lives,” Mr Constance said.“Tragically, 16 people lost their lives on the NSW rail network last year. There were also 155 near misses and 54 people injured from trespassing or entering the Sydney Trains rail corridor.”Minister for Mental Health Bronnie Taylor said any death by suicide is a tragedy that has a profound impact on the whole community.“We know that when we erect physical barriers in identified suicide ‘hot spots’, it significantly reduces the immediate risk to that individual’s life,” Mrs Taylor said.“I encourage anyone who is having suicidal thoughts to seek help, or talk to a trusted friend about their feelings immediately.”Sydney Trains Acting Chief Executive Pete Church said while most of the Sydney Trains network is already fenced, there are a few locations where people have been able to access the rail corridor.“When people trespass in super kamagra 100mg the rail corridor, they not only risk their life, but their actions can have a long lasting impact for their friends and family, as well as our customers and staff,” Mr Church said.TrackSAFE Executive Director Heather Neil said they work closely with Sydney Trains to raise awareness of rail safety issues, and to reduce near misses on the rail network.“Reducing accessibility to train lines through the installation of fences and other physical barriers is known to be a successful method of reducing trespass and self-harm incidents,” Ms Neil said.There were more than 2,600 trespassing incidents on the network, including nine people caught train surfing, in the 2019-20 financial year.

The minimum fine for trespassing is $400 but can be as high as $5,500.Other Sydney Trains initiatives to prevent trespassing and self-harm incidents include:Training for frontline staff to help them recognise the warning signs for suicide.Emergency super kamagra 100mg help points on every platform, which are directly linked to trained security operators 24 hours a day.More than 12,000 CCTV cameras monitoring the network, including high-definition cameras with stronger capabilities to identify trespassers.If you, or someone you know, is thinking about suicide or experiencing a personal crisis or distress, please seek help immediately by calling 000 or one of these services:Lifeline 13 11 14Suicide Call Back Service 1300 659 467NSW Mental Health Line 1800 011 511.

The Fairy Meadow community will soon receive its own ambulance station under the NSW Government’s $232 million Rural Ambulance Infrastructure Reconfiguration (RAIR) program.Minister for Health Brad Hazzard said Fairy Meadow was identified as buy kamagra oral jelly online australia the ideal location to base a new station to provide the best ambulance coverage across the Illawarra region, now and in the future.“This is a first for Fairy Meadow, providing paramedics with a modern facility with state-of-the-art equipment to help them carry out their vital job of saving lives in the local Illawarra communities,” Mr Hazzard said.“The next step will be choosing the best site in Fairy Meadow to build the ambulance station. To do this we have expert help from tried and tested international software which maps Triple Zero calls.”NSW Ambulance Assistant Commissioner Clare Lorenzen said the announcement was another welcome NSW Government initiative for regional buy kamagra oral jelly online australia and rural communities.“Operating from a new base in Fairy Meadow, our local paramedics will be well positioned to continue to provide the best possible high-quality emergency medical care to residents of local communities,” Ms Lorenzen said.“The additional ambulance service in Fairy Meadow will support the Bulli and Wollongong ambulance stations to strengthen the coverage of the Illawarra region.” The RAIR program is the single largest investment in regional NSW Ambulance’s 126-year history, with 24 new or upgraded ambulance stations already delivered or under construction as part of the $132 million Stage 1 program. The new station for the Illawarra community is part of the NSW Government’s additional $100 million investment in Stage 2 of the RAIR program.In 2020-21, the NSW Government is investing more than $1 billion in services and capital works for NSW Ambulance.This includes $27 million of funding for 180 new NSW Ambulance staff across NSW, as part of the third tranche of the June 2018 commitment to recruit 750 additional paramedic and control centre staff over four years.Work has started on installing additional security fencing on the Sydney Trains network to prevent trespassing and reduce self-harm incidents in the rail corridor.Minister for Transport and Roads Andrew Constance said the $4.5 million of new fencing is being installed across 2.3 kilometres of the rail corridor by the end of 2021.“This new fencing will not only improve safety and stop people accessing the rail network illegally, it will also help save buy kamagra oral jelly online australia lives,” Mr Constance said.“Tragically, 16 people lost their lives on the NSW rail network last year.

There were also 155 near misses and 54 people injured from trespassing or entering the Sydney Trains rail corridor.”Minister for Mental Health Bronnie Taylor said any death by suicide is a tragedy that has a profound impact on the whole community.“We know that when we erect physical barriers in identified suicide ‘hot spots’, it significantly reduces the immediate risk to that individual’s life,” Mrs Taylor said.“I encourage anyone who is having suicidal thoughts to seek help, or talk to a trusted friend about their feelings immediately.”Sydney Trains Acting Chief Executive Pete Church said while most of the Sydney Trains network is already fenced, there are a few locations where people have been able to access the rail corridor.“When people trespass in the rail corridor, they not only risk their life, but their actions can have a long lasting impact for their friends and family, as well as our customers and staff,” Mr Church said.TrackSAFE Executive Director Heather Neil said they work closely with Sydney Trains to raise awareness of rail safety issues, and to reduce near misses on the rail network.“Reducing accessibility to train lines through the installation of fences and other physical barriers is known to be a successful method of reducing trespass and self-harm incidents,” Ms Neil said.There were more than 2,600 buy kamagra oral jelly online australia trespassing incidents on the network, including nine people caught train surfing, in the 2019-20 financial year. The minimum fine for trespassing is $400 but can be as high as $5,500.Other Sydney Trains initiatives to prevent trespassing and self-harm incidents include:Training for frontline staff to help them recognise the warning signs for suicide.Emergency help points on every platform, which are directly linked to trained buy kamagra oral jelly online australia security operators 24 hours a day.More than 12,000 CCTV cameras monitoring the network, including high-definition cameras with stronger capabilities to identify trespassers.If you, or someone you know, is thinking about suicide or experiencing a personal crisis or distress, please seek help immediately by calling 000 or one of these services:Lifeline 13 11 14Suicide Call Back Service 1300 659 467NSW Mental Health Line 1800 011 511.

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One of the most prominent kamagra uk delivery vacant commercial sites in Northern Westchester could be getting a multi-million dollar facelift to transform it into a massive mixed-use building.A proposal to transform Yorktown Green into a mixed-use development featuring 150 apartments, ground-level retail locations, and a new supermarket was introduced to the Town go to the website Board this week to much fanfare. According to Olster Properties, the 15-acre development in the heart of Yorktown Heights on Downing kamagra uk delivery Drive would include the demolition of the current 90,000-square-foot building that was the home of a defunct Kmart as part of the projectIn its place would be a four-story U-shaped building that includes 84 one-bedroom and six two-bedroom residences, a small surrounding park, ground floor retail, and underground parking.The idea is to make the development attractive to Millennials and empty-nesters, officials said. It is unclear what the going rate would be for the apartments.“The concept of this is to provide alternatives to empty-nesters or young millennials,” Oster’s attorney Darius Chafizadeh said in a statement. €œThis would allow them to stay in town, or young ones to come back into your town and live here and be able to afford it without having to pay high property taxes.”As part of the development, a new supermarket would kamagra uk delivery replace the defunct Food Emporium building that has been vacant for nearly a decade, The Kmart has been out of business for more than two years as the company shuttered the doors of hundreds of locations amid a financial crunch.“Throughout the retail world, there’s a rethinking of how retail spaces are designed to service the world,” Oster architect Matthew Jarmet stated.

€œThis Kmart is kamagra uk delivery empty because of e-commerce. What we see as planners is that many retail centers - and some very large shopping malls as well that we’re working on - are being repositioned to mixed use.” According to Oster representatives, a formal application for Yorktown Green is in the final stages and is on track to be formally submitted to the Planning Board for approval in the coming weeks.“This proposal recognizes the evolving economy that we are facing, especially e-commerce,” Yorktown Supervisor Matt Slater said. €œYorktown Green has languished for too long and I look forward to seeing more details about Oster’s proposal.“It is a key property in many ways, not the least of which is its prominent location in the heart of town,” Slater kamagra uk delivery added. €œThe commitment to a complete re-thinking kamagra uk delivery and renewal of the property.

This is very welcome news and yet another sign of the economic upswing we are working hard to see in our town.” Click here to sign up for Daily Voice's free daily emails and news alerts..

One of the most prominent buy kamagra oral jelly online australia vacant commercial sites in Northern Westchester could be getting a multi-million dollar facelift to transform it into a massive mixed-use building.A proposal to transform Yorktown Green into a mixed-use development featuring 150 apartments, ground-level retail locations, and a new supermarket was introduced to the Town Board this week to much fanfare. According to Olster Properties, the 15-acre development in the heart of Yorktown Heights on Downing Drive would include the demolition of the current 90,000-square-foot building that was the home of a defunct Kmart as part of the projectIn buy kamagra oral jelly online australia its place would be a four-story U-shaped building that includes 84 one-bedroom and six two-bedroom residences, a small surrounding park, ground floor retail, and underground parking.The idea is to make the development attractive to Millennials and empty-nesters, officials said. It is unclear what the going rate would be for the apartments.“The concept of this is to provide alternatives to empty-nesters or young millennials,” Oster’s attorney Darius Chafizadeh said in a statement. €œThis would buy kamagra oral jelly online australia allow them to stay in town, or young ones to come back into your town and live here and be able to afford it without having to pay high property taxes.”As part of the development, a new supermarket would replace the defunct Food Emporium building that has been vacant for nearly a decade, The Kmart has been out of business for more than two years as the company shuttered the doors of hundreds of locations amid a financial crunch.“Throughout the retail world, there’s a rethinking of how retail spaces are designed to service the world,” Oster architect Matthew Jarmet stated. €œThis Kmart buy kamagra oral jelly online australia is empty because of e-commerce.

What we see as planners is that many retail centers - and some very large shopping malls as well that we’re working on - are being repositioned to mixed use.” According to Oster representatives, a formal application for Yorktown Green is in the final stages and is on track to be formally submitted to the Planning Board for approval in the coming weeks.“This proposal recognizes the evolving economy that we are facing, especially e-commerce,” Yorktown Supervisor Matt Slater said. €œYorktown Green has languished for too long and I look forward to seeing more details about Oster’s proposal.“It is a key property in many ways, not the buy kamagra oral jelly online australia least of which is its prominent location in the heart of town,” Slater added. €œThe commitment to buy kamagra oral jelly online australia a complete re-thinking and renewal of the property. This is very welcome news and yet another sign of the economic upswing we are working hard to see in our town.” Click here to sign up for Daily Voice's free daily emails and news alerts..

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V-safe Surveillance kamagra online canada have a peek at this web-site. Local and Systemic Reactogenicity in Pregnant Persons Table 1. Table 1 kamagra online canada. Characteristics of Persons Who Identified as Pregnant in the V-safe Surveillance System and Received an mRNA erectile dysfunction treatment.

Table 2 kamagra online canada. Table 2. Frequency of Local and Systemic Reactions Reported on the Day after mRNA erectile dysfunction treatment Vaccination in Pregnant kamagra online canada Persons. From December 14, 2020, to February 28, 2021, a total of 35,691 v-safe participants identified as pregnant.

Age distributions were kamagra online canada similar among the participants who received the Pfizer–BioNTech treatment and those who received the Moderna treatment, with the majority of the participants being 25 to 34 years of age (61.9% and 60.6% for each treatment, respectively) and non-Hispanic White (76.2% and 75.4%, respectively). Most participants (85.8% and 87.4%, respectively) reported being pregnant at the time of vaccination (Table 1). Solicited reports of injection-site pain, fatigue, headache, and kamagra online canada myalgia were the most frequent local and systemic reactions after either dose for both treatments (Table 2) and were reported more frequently after dose 2 for both treatments. Participant-measured temperature at or above 38°C was reported by less than 1% of the participants on day 1 after dose 1 and by 8.0% after dose 2 for both treatments.

Figure 1 kamagra online canada. Figure 1. Most Frequent Local and Systemic Reactions Reported in the V-safe Surveillance System on the Day kamagra online canada after mRNA erectile dysfunction treatment Vaccination. Shown are solicited reactions in pregnant persons and nonpregnant women 16 to 54 years of age who received a messenger RNA (mRNA) erectile dysfunction disease 2019 (erectile dysfunction treatment) treatment — BNT162b2 (Pfizer–BioNTech) or mRNA-1273 (Moderna) — from December 14, 2020, to February 28, 2021.

The percentage of respondents was calculated among those who completed a day 1 survey, with the top events shown of injection-site pain (pain), fatigue or tiredness kamagra online canada (fatigue), headache, muscle or body aches (myalgia), chills, and fever or felt feverish (fever).These patterns of reporting, with respect to both most frequently reported solicited reactions and the higher reporting of reactogenicity after dose 2, were similar to patterns observed among nonpregnant women (Figure 1). Small differences in reporting frequency between pregnant persons and nonpregnant women were observed for specific reactions (injection-site pain was reported more frequently among pregnant persons, and other systemic reactions were reported more frequently among nonpregnant women), but the overall reactogenicity profile was similar. Pregnant persons did not report having severe reactions more frequently than nonpregnant women, except for nausea and vomiting, which were reported slightly more frequently only after kamagra online canada dose 2 (Table S3). V-safe Pregnancy Registry.

Pregnancy Outcomes kamagra online canada and Neonatal Outcomes Table 3. Table 3. Characteristics of V-safe Pregnancy kamagra online canada Registry Participants. As of March 30, 2021, the v-safe pregnancy registry call center attempted to contact 5230 persons who were vaccinated through February 28, 2021, and who identified during a v-safe survey as pregnant at or shortly after erectile dysfunction treatment vaccination.

Of these, 912 were unreachable, 86 declined to participate, and 274 did not meet inclusion criteria (e.g., were never pregnant, were pregnant but received vaccination more than 30 days before kamagra online canada the last menstrual period, or did not provide enough information to determine eligibility). The registry enrolled 3958 participants with vaccination from December 14, 2020, to February 28, 2021, of whom 3719 (94.0%) identified as health care personnel. Among enrolled participants, most were 25 to 44 years of age (98.8%), non-Hispanic White (79.0%), and, at the time of interview, did not kamagra online canada report a erectile dysfunction treatment diagnosis during pregnancy (97.6%) (Table 3). Receipt of a first dose of treatment meeting registry-eligibility criteria was reported by 92 participants (2.3%) during the periconception period, by 1132 (28.6%) in the first trimester of pregnancy, by 1714 (43.3%) in the second trimester, and by 1019 (25.7%) in the third trimester (1 participant was missing information to determine the timing of vaccination) (Table 3).

Among 1040 participants (91.9%) who received a treatment in the first trimester and 1700 (99.2%) who received a kamagra online canada treatment in the second trimester, initial data had been collected and follow-up scheduled at designated time points approximately 10 to 12 weeks apart. Limited follow-up calls had been made at the time of this analysis. Table 4 kamagra online canada. Table 4.

Pregnancy Loss and Neonatal Outcomes in Published Studies and kamagra online canada V-safe Pregnancy Registry Participants. Among 827 participants who had a completed pregnancy, the pregnancy resulted in a live birth in 712 (86.1%), in a spontaneous abortion in 104 (12.6%), in stillbirth in 1 (0.1%), and in other outcomes (induced abortion and ectopic pregnancy) in 10 (1.2%). A total of 96 of 104 spontaneous abortions (92.3%) occurred before 13 weeks of gestation (Table 4), and 700 of kamagra online canada 712 pregnancies that resulted in a live birth (98.3%) were among persons who received their first eligible treatment dose in the third trimester. Adverse outcomes among 724 live-born infants — including 12 sets of multiple gestation — were preterm birth (60 of 636 among those vaccinated before 37 weeks [9.4%]), small size for gestational age (23 of 724 [3.2%]), and major congenital anomalies (16 of 724 [2.2%]).

No neonatal deaths were reported at the kamagra online canada time of interview. Among the participants with completed pregnancies who reported congenital anomalies, none had received erectile dysfunction treatment in the first trimester or periconception period, and no specific pattern of congenital anomalies was observed. Calculated proportions of pregnancy kamagra online canada and neonatal outcomes appeared similar to incidences published in the peer-reviewed literature (Table 4). Adverse-Event Findings on the VAERS During the analysis period, the VAERS received and processed 221 reports involving erectile dysfunction treatment vaccination among pregnant persons.

155 (70.1%) involved nonpregnancy-specific adverse events, and 66 (29.9%) involved pregnancy- or neonatal-specific adverse events (Table S4) kamagra online canada. The most frequently reported pregnancy-related adverse events were spontaneous abortion (46 cases. 37 in the first trimester, 2 in the second trimester, and 7 in which the trimester was unknown or not reported), followed kamagra online canada by stillbirth, premature rupture of membranes, and vaginal bleeding, with 3 reports for each. No congenital anomalies were reported to the VAERS, a requirement under the EUAs.Participants Figure 1.

Figure 1 kamagra online canada. Enrollment and Randomization. The diagram represents all enrolled participants through kamagra online canada November 14, 2020. The safety subset (those with a median of 2 months of follow-up, in accordance with application requirements for Emergency Use Authorization) is based on an October 9, 2020, data cut-off date.

The further procedures that one participant in the placebo group declined kamagra online canada after dose 2 (lower right corner of the diagram) were those involving collection of blood and nasal swab samples.Table 1. Table 1. Demographic Characteristics kamagra online canada of the Participants in the Main Safety Population. Between July 27, 2020, and November 14, 2020, a total of 44,820 persons were screened, and 43,548 persons 16 years of age or older underwent randomization at 152 sites worldwide (United States, 130 sites.

Argentina, 1 kamagra online canada. Brazil, 2. South Africa, 4 kamagra online canada. Germany, 6.

And Turkey, 9) in the phase 2/3 portion of the kamagra online canada trial. A total of 43,448 participants received injections. 21,720 received BNT162b2 kamagra online canada and 21,728 received placebo (Figure 1). At the data cut-off date of October 9, a total of 37,706 participants had a median of at least 2 months of safety data available after the second dose and contributed to the main safety data set.

Among these 37,706 participants, 49% were female, 83% were White, 9% were Black or African American, 28% were Hispanic or Latinx, 35% were obese (body mass index [the weight in kilograms divided by the square of the height kamagra online canada in meters] of at least 30.0), and 21% had at least one coexisting condition. The median age was 52 years, and 42% of participants were older than 55 years of age (Table 1 and Table S2). Safety Local kamagra online canada Reactogenicity Figure 2. Figure 2.

Local and Systemic Reactions Reported within 7 Days after kamagra online canada Injection of BNT162b2 or Placebo, According to Age Group. Data on local and systemic reactions and use of medication were collected with electronic diaries from participants in the reactogenicity subset (8,183 participants) for 7 days after each vaccination. Solicited injection-site (local) reactions are kamagra online canada shown in Panel A. Pain at the injection site was assessed according to the following scale.

Mild, does kamagra online canada not interfere with activity. Moderate, interferes with activity. Severe, prevents daily kamagra online canada activity. And grade 4, emergency department visit or hospitalization.

Redness and swelling were measured kamagra online canada according to the following scale. Mild, 2.0 to 5.0 cm in diameter. Moderate, >5.0 to 10.0 cm in kamagra online canada diameter. Severe, >10.0 cm in diameter.

And grade 4, necrosis or kamagra online canada exfoliative dermatitis (for redness) and necrosis (for swelling). Systemic events and medication use are shown in Panel B. Fever categories are designated in kamagra online canada the key. Medication use was not graded.

Additional scales were as kamagra online canada follows. Fatigue, headache, chills, new or worsened muscle pain, new or worsened joint pain (mild. Does not interfere with kamagra online canada activity. Moderate.

Some interference kamagra online canada with activity. Or severe. Prevents daily activity), kamagra online canada vomiting (mild. 1 to 2 times in 24 hours.

Moderate. >2 times in 24 hours. Or severe. Requires intravenous hydration), and diarrhea (mild.

2 to 3 loose stools in 24 hours. Moderate. 4 to 5 loose stools in 24 hours. Or severe.

6 or more loose stools in 24 hours). Grade 4 for all events indicated an emergency department visit or hospitalization. Н™¸ bars represent 95% confidence intervals, and numbers above the 𝙸 bars are the percentage of participants who reported the specified reaction.The reactogenicity subset included 8183 participants. Overall, BNT162b2 recipients reported more local reactions than placebo recipients.

Among BNT162b2 recipients, mild-to-moderate pain at the injection site within 7 days after an injection was the most commonly reported local reaction, with less than 1% of participants across all age groups reporting severe pain (Figure 2). Pain was reported less frequently among participants older than 55 years of age (71% reported pain after the first dose. 66% after the second dose) than among younger participants (83% after the first dose. 78% after the second dose).

A noticeably lower percentage of participants reported injection-site redness or swelling. The proportion of participants reporting local reactions did not increase after the second dose (Figure 2A), and no participant reported a grade 4 local reaction. In general, local reactions were mostly mild-to-moderate in severity and resolved within 1 to 2 days. Systemic Reactogenicity Systemic events were reported more often by younger treatment recipients (16 to 55 years of age) than by older treatment recipients (more than 55 years of age) in the reactogenicity subset and more often after dose 2 than dose 1 (Figure 2B).

The most commonly reported systemic events were fatigue and headache (59% and 52%, respectively, after the second dose, among younger treatment recipients. 51% and 39% among older recipients), although fatigue and headache were also reported by many placebo recipients (23% and 24%, respectively, after the second dose, among younger treatment recipients. 17% and 14% among older recipients). The frequency of any severe systemic event after the first dose was 0.9% or less.

Severe systemic events were reported in less than 2% of treatment recipients after either dose, except for fatigue (in 3.8%) and headache (in 2.0%) after the second dose. Fever (temperature, ≥38°C) was reported after the second dose by 16% of younger treatment recipients and by 11% of older recipients. Only 0.2% of treatment recipients and 0.1% of placebo recipients reported fever (temperature, 38.9 to 40°C) after the first dose, as compared with 0.8% and 0.1%, respectively, after the second dose. Two participants each in the treatment and placebo groups reported temperatures above 40.0°C.

Younger treatment recipients were more likely to use antipyretic or pain medication (28% after dose 1. 45% after dose 2) than older treatment recipients (20% after dose 1. 38% after dose 2), and placebo recipients were less likely (10 to 14%) than treatment recipients to use the medications, regardless of age or dose. Systemic events including fever and chills were observed within the first 1 to 2 days after vaccination and resolved shortly thereafter.

Daily use of the electronic diary ranged from 90 to 93% for each day after the first dose and from 75 to 83% for each day after the second dose. No difference was noted between the BNT162b2 group and the placebo group. Adverse Events Adverse event analyses are provided for all enrolled 43,252 participants, with variable follow-up time after dose 1 (Table S3). More BNT162b2 recipients than placebo recipients reported any adverse event (27% and 12%, respectively) or a related adverse event (21% and 5%).

This distribution largely reflects the inclusion of transient reactogenicity events, which were reported as adverse events more commonly by treatment recipients than by placebo recipients. Sixty-four treatment recipients (0.3%) and 6 placebo recipients (<0.1%) reported lymphadenopathy. Few participants in either group had severe adverse events, serious adverse events, or adverse events leading to withdrawal from the trial. Four related serious adverse events were reported among BNT162b2 recipients (shoulder injury related to treatment administration, right axillary lymphadenopathy, paroxysmal ventricular arrhythmia, and right leg paresthesia).

Two BNT162b2 recipients died (one from arteriosclerosis, one from cardiac arrest), as did four placebo recipients (two from unknown causes, one from hemorrhagic stroke, and one from myocardial infarction). No deaths were considered by the investigators to be related to the treatment or placebo. No erectile dysfunction treatment–associated deaths were observed. No stopping rules were met during the reporting period.

Safety monitoring will continue for 2 years after administration of the second dose of treatment. Efficacy Table 2. Table 2. treatment Efficacy against erectile dysfunction treatment at Least 7 days after the Second Dose.

Table 3. Table 3. treatment Efficacy Overall and by Subgroup in Participants without Evidence of before 7 Days after Dose 2. Figure 3.

Figure 3. Efficacy of BNT162b2 against erectile dysfunction treatment after the First Dose. Shown is the cumulative incidence of erectile dysfunction treatment after the first dose (modified intention-to-treat population). Each symbol represents erectile dysfunction treatment cases starting on a given day.

Filled symbols represent severe erectile dysfunction treatment cases. Some symbols represent more than one case, owing to overlapping dates. The inset shows the same data on an enlarged y axis, through 21 days. Surveillance time is the total time in 1000 person-years for the given end point across all participants within each group at risk for the end point.

The time period for erectile dysfunction treatment case accrual is from the first dose to the end of the surveillance period. The confidence interval (CI) for treatment efficacy (VE) is derived according to the Clopper–Pearson method.Among 36,523 participants who had no evidence of existing or prior erectile dysfunction , 8 cases of erectile dysfunction treatment with onset at least 7 days after the second dose were observed among treatment recipients and 162 among placebo recipients. This case split corresponds to 95.0% treatment efficacy (95% confidence interval [CI], 90.3 to 97.6. Table 2).

Among participants with and those without evidence of prior SARS CoV-2 , 9 cases of erectile dysfunction treatment at least 7 days after the second dose were observed among treatment recipients and 169 among placebo recipients, corresponding to 94.6% treatment efficacy (95% CI, 89.9 to 97.3). Supplemental analyses indicated that treatment efficacy among subgroups defined by age, sex, race, ethnicity, obesity, and presence of a coexisting condition was generally consistent with that observed in the overall population (Table 3 and Table S4). treatment efficacy among participants with hypertension was analyzed separately but was consistent with the other subgroup analyses (treatment efficacy, 94.6%. 95% CI, 68.7 to 99.9.

Case split. BNT162b2, 2 cases. Placebo, 44 cases). Figure 3 shows cases of erectile dysfunction treatment or severe erectile dysfunction treatment with onset at any time after the first dose (mITT population) (additional data on severe erectile dysfunction treatment are available in Table S5).

Between the first dose and the second dose, 39 cases in the BNT162b2 group and 82 cases in the placebo group were observed, resulting in a treatment efficacy of 52% (95% CI, 29.5 to 68.4) during this interval and indicating early protection by the treatment, starting as soon as 12 days after the first dose.Trial Design and Oversight In the Study of Tofacitinib in Hospitalized Patients with erectile dysfunction treatment Pneumonia (STOP-erectile dysfunction treatment), we compared tofacitinib with placebo in patients with erectile dysfunction treatment pneumonia. The trial protocol (available with the full text of this article at NEJM.org) was approved by the institutional ethics board at participating sites. The trial was conducted in accordance with Good Clinical Practice guidelines and the principles of the Declaration of Helsinki. The trial was sponsored by Pfizer and was designed and led by a steering committee that included academic investigators and representatives from Pfizer.

The trial operations and statistical analyses were conducted by the Academic Research Organization of the Hospital Israelita Albert Einstein in São Paulo. An independent data and safety monitoring board reviewed unblinded patient-level data for safety on an ongoing basis during the trial. Pfizer provided the entire trial budget, which covered all trial-related expenses including but not limited to investigator fees, costs related to investigational product suppliers and importation, insurance, applicable taxes and fees, and funding to support the activities of the data and safety monitoring board. All the authors vouch for the accuracy and completeness of the data and for the fidelity of the trial to the protocol.

The trial committee members and participating investigators are listed in the Supplementary Appendix, available at NEJM.org. Trial Population The trial included patients 18 years of age or older who had laboratory-confirmed erectile dysfunction as determined on reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay before randomization, who had evidence of erectile dysfunction treatment pneumonia on radiographic imaging (computed tomography or radiography of the chest), and who had been hospitalized for less than 72 hours. Information regarding the timing of the qualifying RT-PCR assay in relation to symptom onset is provided in Section S3.1 in the Supplementary Appendix. High-flow devices constituted the maximum oxygen support that was allowed for trial inclusion.

The main exclusion criteria were the use of noninvasive or invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) on the day of randomization, a history of thrombosis or current thrombosis, known immunosuppression, and any current cancer for which the patient was receiving active treatment. Details of the eligibility criteria are provided in Section S3.2. Written informed consent was obtained from each patient or from the patient’s legally authorized representative if the patient was unable to provide informed consent. Randomization, Interventions, and Follow-up Eligible patients were randomly assigned in a 1:1 ratio to receive either tofacitinib or placebo.

Randomization, with stratification according to site, was performed with the use of a central concealed, Web-based, automated randomization system. Patients received either oral tofacitinib at a dose of 10 mg or placebo twice daily for up to 14 days or until hospital discharge, whichever was earlier. If a participant underwent intubation before the end of the 14-day treatment period (or before discharge), they continued to receive tofacitinib or placebo if it was considered to be clinically appropriate by the treating physicians. A reduced-dose regimen of 5 mg of tofacitinib (or matching placebo) twice daily was administered in patients with an estimated glomerular fiation rate of less than 50 ml per minute per 1.73 m2 of body-surface area, in those with moderate hepatic impairment, and in those with concomitant use of a strong CYP3A4 inhibitor or a combination of a moderate CYP3A4 inhibitor and a strong CYP2C19 inhibitor.

The rationale for the tofacitinib dosage is provided in Section S3.3. All the patients were treated according to local standards of care for erectile dysfunction treatment, which could have included glucocorticoids, antibiotic agents, anticoagulants, and antiviral agents. Concomitant use of other JAK inhibitors, biologic agents, potent immunosuppressants, interleukin-1 inhibitors, interleukin-6 inhibitors, or potent CYP450 inducers was prohibited. Patients were assessed daily (up to day 28) while hospitalized.

Follow-up visits occurred on day 14 and on day kamagra online pharmacy uk 28 for participants who were discharged before day 14 or 28. Prespecified reasons for permanent discontinuation of the trial intervention are described in Section S3.4. Outcomes The primary outcome was death or respiratory failure during the 28 days of follow-up. Death or respiratory failure was determined to occur if participants met the criteria for category 6 (status of being hospitalized while receiving noninvasive ventilation or ventilation through high-flow oxygen devices), 7 (status of being hospitalized while receiving invasive mechanical ventilation or ECMO), or 8 (death) on the eight-level National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity (on a scale from 1 to 8, with higher scores indicating a worse condition) (Table S1 in the Supplementary Appendix).

Patients who were enrolled in the trial while they were receiving oxygen through high-flow devices (category 6) were considered to have met the criteria for the primary outcome if they presented with clinical worsening to category 7 or 8. The occurrence of the primary outcome was adjudicated by an independent clinical-events classification committee, whose members were unaware of the group assignments. The protocol and statistical analysis plan used an inverted ordinal scale, which was reversed in this report to be consistent with previous studies. Secondary efficacy outcomes were the cumulative incidence of death through day 28, the scores on the NIAID ordinal scale of disease severity at day 14 and at day 28, the status of being alive and not using mechanical ventilation or ECMO at day 14 and day 28, the status of being alive and not hospitalized at day 14 and day 28, cure (defined as resolution of fever and cough and no use of ventilatory or oxygen support), the duration of stay in the hospital, and the duration of stay in the intensive care unit (ICU).

The occurrence and severity of adverse events were evaluated and coded according to the Medical Dictionary for Regulatory Activities, version 23.1. Details of adverse event reporting, including the reporting of prespecified adverse events of special interest, are described in Section S3.5. Statistical Analysis We estimated that the assignment of 260 patients, with randomization performed in a 1:1 ratio, would provide the trial with 80% power to detect a between-group difference of 15 percentage points in the incidence of the primary outcome, assuming that 15% of the participants in the tofacitinib group and 30% of those in the placebo group would have an event (death or respiratory failure through day 28). The hypothesis of superiority was tested at a two-tailed alpha level of 5%.

The efficacy analyses included all the participants who underwent randomization. Safety analyses included all the participants who underwent randomization and took at least one dose of tofacitinib or placebo. The results for the primary efficacy outcome were analyzed by means of binary regression with Firth correction, with trial group and antiviral therapy for erectile dysfunction treatment as covariates, and are expressed as a risk ratio. The antiviral treatments on day 1 were used in the statistical model.

Dichotomous secondary outcomes were analyzed in a manner similar to that used for the primary outcome. The effect of the intervention on death through day 28 is expressed as a hazard ratio derived from Cox regression. For ordinal data, a proportional-odds model with adjustment for baseline antiviral therapy was used. An odds ratio of less than 1.0 represents a clinical improvement as assessed on the ordinal scale.

Odds proportionality was assessed with the use of the method of Pulkstenis–Robinson.9 We created Kaplan–Meier survival curves to express the time until the occurrence of the primary outcome, both overall and stratified according to the use of supplemental oxygen at baseline, and the occurrence of death through 28 days. As a sensitivity analysis, results for the primary outcome were analyzed by means of binary regression with Firth correction, with use of glucocorticoids and antiviral agents at baseline as covariates. In addition, results for the primary outcome were analyzed by means of logistic regression with Firth correction, with adjustment for baseline antiviral therapy. Prespecified subgroup analyses were performed according to age, sex, concomitant use of antiviral therapy, concomitant use of glucocorticoids, and time from symptom onset to randomization.

For the primary outcome, a two-sided P value of less than 0.05 was considered to indicate statistical significance. The 95% confidence intervals were estimated for all effect measures. The widths of the 95% confidence intervals for the secondary outcomes were not adjusted for multiple comparisons, so the intervals should not be used to infer definitive treatment effects. All the analyses were performed with the use of SAS software, version 9.4 (SAS Institute), and R software, version 3.6.3 (R Foundation for Statistical Computing).

Additional details about the statistical analysis are provided in Section S3.6.From the Department of Clinical Sciences Lund, Sections of Cardiology (J. Dankiewicz, D.E.), Neurology (T. Cronberg, G.L.), and Anesthesiology and Intensive Care (H. Levin, O.B.), Skåne University Hospital Lund, Lund University and Clinical Studies Sweden — Forum South, Skåne University Hospital (S.U.), Lund.

The Department of Clinical Sciences Lund, Section of Anesthesia and Intensive Care, Skåne University Hospital Malmö, Malmö, (J. Düring, S.S., H.F.). The Department of Clinical Sciences Lund, Sections of Anesthesiology and Intensive Care (M.A., N.N.) and Clinical Sciences Helsingborg (N.N.), Helsingborg Hospital, Helsingborg. The Department of Clinical Sciences Lund, Section of Anesthesiology and Intensive Care Lund, Hallands Hospital, Halmstad (J.U.).

The Department of Anesthesiology and Intensive Care Medicine, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg (C.R., A. Lundin). The Department of Clinical Science and Education, Center for Resuscitation Science, Karolinska Institutet, Södersjukhuset, Stockholm (P.N., J. Hollenberg, A.A.).

And the Department of Anesthesiology, Intensive Care, and Acute Medicine, Linköping University, Linköping (M.S.C.) — all in Sweden. Copenhagen Trial Unit, Center for Clinical Intervention Research, Copenhagen University Hospital (J.C.J.), and the Section of Biostatistics, Faculty of Health and Medical Sciences (T.L.), University of Copenhagen, Copenhagen, the Department of Regional Health Research, the Faculty of Health Sciences, University of Southern Denmark, Odense (J.C.J.), the Research Center for Emergency Medicine, the Department of Clinical Medicine (H.K.), and the Department of Intensive Care (A.M.G., S.C.), Aarhus University Hospital, Aarhus — all in Denmark. Adult Critical Care, University Hospital of Wales, Cardiff (M.P.W., M.P.G.M., J.M.C.), the Department of Intensive Care, Bristol Royal Infirmary, Bristol (M.T., J. Bewley, K.S.), Essex Cardiothoracic Centre, Basildon (T.R.K., G.V.K.), Anglia Ruskin University School of Medicine, Chelmsford, Essex (T.R.K., G.V.K.), and the Department of Anesthesiology and Intensive Care, Royal Victoria Hospital, Belfast (P.M.) — all in the United Kingdom.

Neuroscience Critical Care Research Group and Adult Intensive Care Medicine Service, Centre Hospitalier Universitaire Vaudois–Lausanne University Hospital and University of Lausanne, Lausanne (M. Oddo, S.A.-M.), the Departments of Intensive Care Medicine (M.H.) and Anesthesiology and Pain Medicine, Inselspital (A. Levis), Bern University Hospital, University of Bern, Bern, the Intensive Care Department, Kantonsspital St. Gallen, St.

Gallen (C. Schrag, E.F.), the Institute of Intensive Care Medicine, University Hospital Zurich, Zurich (M.M., P.D.W.G.), and the Cardiac Anesthesia and Intensive Care Department, Instituto Cardiocentro Ticino, Lugano (T. Cassina) — all in Switzerland. Descartes University of Paris and Cochin University Hospital, Paris (A.C., P.J.), Medical-Surgical Intensive Care Unit, Dupuytren Teaching Hospital, Limoges (P.V.) — all in France.

The 2nd Department of Medicine (J. Bělohlávek, O.S.), and the Department of Anesthesiology and Intensive Care Medicine (M. Otáhal), General University Hospital and First Faculty of Medicine, Charles University, Prague, the 1st Department of Internal Medicine–Cardioangiology, University Hospital Hradec Králové, and Faculty of Medicine, Charles University, Hradec Králové (M. Solar) — all in the Czech Republic.

The Department of Anesthesiology, Division of Emergencies and Critical Care, Oslo University Hospital, Rikshospitalet, Oslo (J. Hovdenes), the Department of Anesthesiology, Sørlandet Hospital, Arendal (R.B.O.), the Department of Anesthesiology and Intensive Care Medicine, St. Olav’s University Hospital, and the Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim (H. Langeland) — all in Norway.

The Division of Critical Care and Trauma, George Institute for Global Health, and Bankstown–Lidcombe Hospital, South Western Sydney Local Health District, Sydney (M. Saxena), and the Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine (G.M.E., A.D.N.), and the Department of Intensive Care, Alfred Health (A.D.N.), Monash University, Melbourne — all in Australia. The Medical Research Institute of New Zealand, Intensive Care Unit, Wellington Hospital, Wellington (P.J.Y., L.N.). The Departments of Surgical Sciences and Integrated Diagnostics (P.P.) and Anesthesiology and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neuroscience (P.P., I.B.), University of Genoa, Genoa, Italy.

The Department of Nephrology and Medical Intensive Care (C. Storm), and Klinik und Hochschulambulanz für Neurologie (C.L.), Charité Universitätzmedizin, Berlin, Germany. The Department of Intensive Care, Erasme University Hospital, Université Libre de Bruxelles, Brussels (F.S.T.). The Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Innsbruck, Austria (M.J.).

The Department of Emergency Medicine, University of Pittsburgh, Pittsburgh (C.C.). And University College Dublin Clinical Research Centre at St. Vincent’s University Hospital, Dublin, Ireland (A.D.N.).Address reprint requests to Dr. Nielsen at the Department of Anesthesiology and Intensive Care, Intensive Care Unit, Helsingborg Hospital, S Vallgatan 5, 251 87, Helsingborg, Sweden, or at [email protected].Participants Table 1.

Table 1. Characteristics of the Trial Participants at Baseline (Full Analysis Set). The trial began enrollment on September 21, 2020, and the data-cutoff date for the present analysis was January 22, 2021. A total of 44,325 participants underwent randomization, of whom 43,783 received treatment or placebo.

The per-protocol population included 39,321 erectile dysfunction–negative participants, of whom 19,630 received Ad26.COV2.S and 19,691 received placebo (Fig. S3). The demographic characteristics and coexisting conditions of the participants at baseline were balanced across the two groups (Table 1 and S4). A total of 9.6% of the participants were erectile dysfunction–seropositive at baseline.

The median follow-up was 58 days (range, 1 to 124), and 55% of participants had at least 8 weeks of follow-up. Later and slower recruitment of participants 60 years of age or older with coexisting conditions resulted in a shorter duration of follow-up in this subgroup (Table S5). Safety Figure 1. Figure 1.

Solicited Local and Systemic Adverse Events Reported within 7 days after the Administration of treatment or Placebo (Safety Subpopulation). Most solicited local and systemic adverse events occurred within 1 to 2 days after the administration of treatment or placebo and had a median duration of 1 to 2 days. No grade 4 local or systemic adverse events were reported. There were no local or systemic reactogenicity differences between participants who were seronegative at baseline and those who were seropositive (data not shown).

Pain was categorized as grade 1 (mild. Does not interfere with activity), grade 2 (moderate. Requires modification of activity or involves discomfort with movement), grade 3 (severe. Inability to perform usual activities), or grade 4 (potentially life-threatening.

Hospitalization or inability to perform basic self-care). Erythema and swelling were categorized as grade 1 (mild. 25 to 50 mm), grade 2 (moderate. 51 to 100 mm), grade 3 (severe.

>100 mm), or grade 4 (potentially life-threatening. Necrosis or leading to hospitalization). Systemic events were categorized as grade 1 (mild. Minimal symptoms), grade 2 (moderate.

Notable symptoms not resulting in loss of work or school time), grade 3 (severe. Incapacitating symptoms resulting in loss of work or school time), or grade 4 (life-threatening. Hospitalization or inability to perform basic self-care). Fever was defined as grade 1 (mild.

‰¥38.0 to 38.4°C), grade 2 (moderate. ‰¥38.5 to 38.9°C), grade 3 (severe. ‰¥39.0 to 40.0°C), or grade 4 (potentially life-threatening. >40°C).The safety subpopulation included 3356 participants in the treatment group and 3380 in the placebo group.

During the 7-day period after the administration of treatment or placebo, more solicited adverse events were reported by Ad26.COV2.S recipients than by placebo recipients and by participants 18 to 59 years of age than by those 60 years of age or older (Figure 1). In the treatment group, injection-site pain was the most common local reaction (in 48.6% of the participants). The most common systemic reactions were headache (in 38.9%), fatigue (in 38.2%), myalgia (in 33.2%), and nausea (in 14.2%). The adverse events of at least grade 3 that were considered by the investigators to be possibly related to Ad26.COV2.S or placebo are listed in Table S6.

Serious adverse events, excluding those related to erectile dysfunction treatment, were reported by 83 of 21,895 treatment recipients (0.4%) and by 96 of 21,888 placebo recipients (0.4%). Seven serious adverse events were considered by the investigators to be related to vaccination in the Ad26.COV2.S group (Table S7). A numeric imbalance was observed for venous thromboembolic events (11 in the treatment group vs. 3 in the placebo group).

Most of these participants had underlying medical conditions and predisposing factors that might have contributed to these events (Table S8). Imbalances were also observed with regard to seizure (which occurred in 4 participants in the treatment group vs. 1 in the placebo group) and tinnitus (in 6 vs. 0).

A causal relationship between these events and Ad26.COV2.S cannot be determined. These events will be monitored in the post-marketing setting. Three deaths were reported in the treatment group and 16 in the placebo group, all of which were considered by the investigators to be unrelated to the trial intervention (Table S7). No deaths related to erectile dysfunction treatment were reported in the treatment group, whereas 5 deaths related to erectile dysfunction treatment were reported in the placebo group.

Transverse sinus thrombosis with cerebral hemorrhage and a case of the Guillain–Barré syndrome were each seen in 1 treatment recipient. Efficacy Table 2. Table 2. treatment Efficacy against erectile dysfunction treatment with Onset at Least 14 Days and at Least 28 Days after the Administration of treatment or Placebo (Per-Protocol at-Risk Population).

In the per-protocol at-risk population, 468 centrally confirmed cases of symptomatic erectile dysfunction treatment with an onset at least 14 days after administration were observed, of which 464 were moderate to severe–critical (116 cases in the treatment group vs. 348 in the placebo group), which indicated treatment efficacy of 66.9% (adjusted 95% confidence interval [CI], 59.0 to 73.4) (Table 2). In terms of the primary end point of disease onset at least 28 days after administration, 66 cases of moderate to severe–critical erectile dysfunction treatment in the treatment group and 193 cases in the placebo group were observed, which indicated treatment efficacy of 66.1% (adjusted 95% CI, 55.0 to 74.8) (Table 2). Figure 2.

Figure 2. Cumulative Incidence of erectile dysfunction treatment with Onset at Least 1 Day after Vaccination and treatment Efficacy over Time. Panel A shows the cumulative incidence of moderate to severe–critical cases of erectile dysfunction disease 2019 (erectile dysfunction treatment). Circles indicate severe–critical cases.

Panel B shows the cumulative incidence of severe–critical cases. Cases included in the analyses in Panels A and B were centrally confirmed cases in the full analysis set among participants who were seronegative at baseline. Panel C shows the cumulative incidence of severe–critical cases in South Africa among participants who were seronegative at baseline. These cases were those that were positive on reverse-transcriptase–polymerase-chain-reaction (RT-PCR) testing from all sources, whether centrally confirmed or not.Table 3.

Table 3. treatment Efficacy against erectile dysfunction treatment with Onset at Least 14 Days and at Least 28 Days after Administration of treatment or Placebo, According to Country (Per-Protocol at-Risk Population). The cumulative incidence of the first occurrence of moderate to severe–critical erectile dysfunction treatment diverged between the two trial groups at approximately 14 days after the administration of treatment or placebo, which indicates an early onset of protection with the treatment (Figure 2A). Fewer cases in the treatment group were observed after day 14 while cases continued to accrue in the placebo group, which led to increasing treatment efficacy over time (Fig.

S4A). Efficacy against disease with an onset at least 28 days after administration was similar across age groups, but efficacy against disease with an onset 14 days after administration was higher among older participants than among younger participants (Table 2). This discrepancy probably resulted from differences in follow-up duration or from smaller sample sizes in subgroups. The number of primary end-point cases was similar to the number of cases of symptomatic erectile dysfunction treatment as defined according to the FDA harmonized definition (Table 2).

Thus, the primary end-point analyses captured most of the cases of symptomatic erectile dysfunction treatment. Estimates of treatment efficacy in the analyses of the two primary end points and the secondary end points of centrally confirmed cases differed by less than 2 percentage points from the estimates in analyses of positive cases from all sources, and the confidence intervals were similar (Table 2 and Table 3). treatment-efficacy estimates in the full analysis set were generally lower than those in the per-protocol population because the estimates included cases that occurred at or after 1 day after administration, when immunity was building (Table S9). With regard to severe–critical erectile dysfunction treatment, treatment efficacy was 76.7% (adjusted 95% CI, 54.6 to 89.1) against disease with onset at least 14 days after administration and 85.4% (adjusted 95% CI, 54.2 to 96.9) against disease with onset at least 28 days after administration (Table 2).

The cumulative-incidence curves began to separate approximately 7 days after administration. treatment efficacy increased with longer follow-up and was 92.4% after day 42 (post hoc calculation) (Figures 2B and S4B). The analysis of treatment efficacy against asymptomatic included all the participants with a newly positive N-immunoassay result at day 71 (i.e., those who had been seronegative or had no result available at day 29 and who were seropositive at day 71). Only 2650 participants had an N-immunoassay result available at day 71, and therefore only a preliminary analysis could be performed.

A total of 18 asymptomatic s were identified in the treatment group and 50 in the placebo group (treatment efficacy, 65.5%. 95% CI, 39.9 to 81.1). treatment efficacy against erectile dysfunction treatment involving medical intervention ranged from 75.0 to 100.0% (Table S10). Two cases of erectile dysfunction treatment with onset at least 14 days after administration in the Ad26.COV2.S group and 29 such cases in the placebo group led to hospitalization (treatment efficacy, 93.1%.

95% CI, 72.7 to 99.2) (Fig. S5). No hospitalizations for cases with an onset at least 28 days after administration occurred in the treatment group, as compared with 16 hospitalizations in the placebo group (treatment efficacy, 100%. 95% CI, 74.3 to 100.0).

Participants with moderate erectile dysfunction treatment who had received Ad26.COV2.S most frequently reported 4 to 6 symptoms, as compared with 7 to 9 symptoms in participants who had received placebo (Fig. S6). The total mean symptom-severity score as reported on the Symptoms of with erectile dysfunction-19 questionnaire was 24% (95% CI, −1 to 46) lower among treatment recipients than among placebo recipients at day 1 after symptom onset, 47% (95% CI, 23 to 66) lower at day 7 after symptom onset, and 53% (95% CI, 0 to 81) lower at day 14 after symptom onset among participants with an onset of moderate illness at least 28 days after administration (Fig. S1).

The estimates of treatment efficacy against severe–critical disease were consistently high across countries that had sufficient cases for analysis (Table 3). On the basis of interim sequencing data from 512 unique RT-PCR–positive samples obtained from 714 participants (71.7%) with erectile dysfunction , the reference sequence (Wuhan-Hu-1 including the D614G mutation) was detected predominantly in the United States (190 of 197 sequences [96.4%]) and the 20H/501Y.V2 variant (also called B.1.351) was detected predominantly in South Africa (86 of 91 sequences [94.5%]), whereas in Brazil, the reference sequence was detected in 38 of 124 sequences (30.6%) and the reference sequence with the E484K mutation (P.2 lineage) was detected in 86 of 124 sequences (69.4%). Despite the high prevalence of the 20H/501Y.V2 variant in South Africa and in erectile dysfunction treatment cases in the trial, treatment efficacy was maintained (52.0% against moderate to severe–critical disease and 73.1% against severe–critical disease with onset ≥14 days after administration. 64.0% against moderate to severe–critical disease and 81.7% against severe–critical disease with onset at ≥28 days after administration) (Figure 2C and Table 3).

In South Africa, no hospitalizations of participants with an onset of erectile dysfunction treatment at least 28 days after administration occurred in the treatment group, as compared with 6 hospitalizations in the placebo group. All five erectile dysfunction treatment–related deaths in the trial occurred in the placebo group in South Africa. No meaningful differences in treatment efficacy were observed among subgroups defined according to sex, race, or ethnic group (Fig. S7 and Table S11).

A lower point estimate of treatment efficacy was observed among participants 60 years of age or older with coexisting conditions in the analysis of cases with onset at least 28 days after administration (15 cases of moderate to severe–critical erectile dysfunction treatment among treatment recipients vs. 26 cases among placebo recipients) but not in the analysis of cases with onset at least 14 days after administration (22 vs. 63 cases) (Fig. S7).

Estimates of efficacy over time that were based on Kaplan–Meier analysis were similar among participants 60 years of age or older with coexisting conditions and those without coexisting conditions (Figs. S4C and S8). Two participants 60 years of age or older with coexisting conditions in the treatment group were hospitalized, as compared with 11 such participants in the placebo group (treatment efficacy, 81.6%. 95% CI, 15.8 to 98.0)..

V-safe Surveillance buy kamagra oral jelly online australia look at here. Local and Systemic Reactogenicity in Pregnant Persons Table 1. Table 1 buy kamagra oral jelly online australia. Characteristics of Persons Who Identified as Pregnant in the V-safe Surveillance System and Received an mRNA erectile dysfunction treatment. Table 2 buy kamagra oral jelly online australia.

Table 2. Frequency of Local and Systemic Reactions Reported buy kamagra oral jelly online australia on the Day after mRNA erectile dysfunction treatment Vaccination in Pregnant Persons. From December 14, 2020, to February 28, 2021, a total of 35,691 v-safe participants identified as pregnant. Age distributions were similar among buy kamagra oral jelly online australia the participants who received the Pfizer–BioNTech treatment and those who received the Moderna treatment, with the majority of the participants being 25 to 34 years of age (61.9% and 60.6% for each treatment, respectively) and non-Hispanic White (76.2% and 75.4%, respectively). Most participants (85.8% and 87.4%, respectively) reported being pregnant at the time of vaccination (Table 1).

Solicited reports of injection-site pain, fatigue, buy kamagra oral jelly online australia headache, and myalgia were the most frequent local and systemic reactions after either dose for both treatments (Table 2) and were reported more frequently after dose 2 for both treatments. Participant-measured temperature at or above 38°C was reported by less than 1% of the participants on day 1 after dose 1 and by 8.0% after dose 2 for both treatments. Figure 1 buy kamagra oral jelly online australia. Figure 1. Most Frequent Local and Systemic Reactions Reported in buy kamagra oral jelly online australia the V-safe Surveillance System on the Day after mRNA erectile dysfunction treatment Vaccination.

Shown are solicited reactions in pregnant persons and nonpregnant women 16 to 54 years of age who received a messenger RNA (mRNA) erectile dysfunction disease 2019 (erectile dysfunction treatment) treatment — BNT162b2 (Pfizer–BioNTech) or mRNA-1273 (Moderna) — from December 14, 2020, to February 28, 2021. The percentage of respondents was buy kamagra oral jelly online australia calculated among those who completed a day 1 survey, with the top events shown of injection-site pain (pain), fatigue or tiredness (fatigue), headache, muscle or body aches (myalgia), chills, and fever or felt feverish (fever).These patterns of reporting, with respect to both most frequently reported solicited reactions and the higher reporting of reactogenicity after dose 2, were similar to patterns observed among nonpregnant women (Figure 1). Small differences in reporting frequency between pregnant persons and nonpregnant women were observed for specific reactions (injection-site pain was reported more frequently among pregnant persons, and other systemic reactions were reported more frequently among nonpregnant women), but the overall reactogenicity profile was similar. Pregnant persons did not report having severe buy kamagra oral jelly online australia reactions more frequently than nonpregnant women, except for nausea and vomiting, which were reported slightly more frequently only after dose 2 (Table S3). V-safe Pregnancy Registry.

Pregnancy Outcomes buy kamagra oral jelly online australia and Neonatal Outcomes Table 3. Table 3. Characteristics of V-safe Pregnancy Registry buy kamagra oral jelly online australia Participants. As of March 30, 2021, the v-safe pregnancy registry call center attempted to contact 5230 persons who were vaccinated through February 28, 2021, and who identified during a v-safe survey as pregnant at or shortly after erectile dysfunction treatment vaccination. Of these, buy kamagra oral jelly online australia 912 were unreachable, 86 declined to participate, and 274 did not meet inclusion criteria (e.g., were never pregnant, were pregnant but received vaccination more than 30 days before the last menstrual period, or did not provide enough information to determine eligibility).

The registry enrolled 3958 participants with vaccination from December 14, 2020, to February 28, 2021, of whom 3719 (94.0%) identified as health care personnel. Among enrolled participants, most were 25 to 44 buy kamagra oral jelly online australia years of age (98.8%), non-Hispanic White (79.0%), and, at the time of interview, did not report a erectile dysfunction treatment diagnosis during pregnancy (97.6%) (Table 3). Receipt of a first dose of treatment meeting registry-eligibility criteria was reported by 92 participants (2.3%) during the periconception period, by 1132 (28.6%) in the first trimester of pregnancy, by 1714 (43.3%) in the second trimester, and by 1019 (25.7%) in the third trimester (1 participant was missing information to determine the timing of vaccination) (Table 3). Among 1040 participants (91.9%) who received a treatment in the first trimester and 1700 (99.2%) who received a treatment in the second trimester, initial data had been collected and follow-up buy kamagra oral jelly online australia scheduled at designated time points approximately 10 to 12 weeks apart. Limited follow-up calls had been made at the time of this analysis.

Table 4 buy kamagra oral jelly online australia. Table 4. Pregnancy Loss buy kamagra oral jelly online australia and Neonatal Outcomes in Published Studies and V-safe Pregnancy Registry Participants. Among 827 participants who had a completed pregnancy, the pregnancy resulted in a live birth in 712 (86.1%), in a spontaneous abortion in 104 (12.6%), in stillbirth in 1 (0.1%), and in other outcomes (induced abortion and ectopic pregnancy) in 10 (1.2%). A total of 96 of 104 buy kamagra oral jelly online australia spontaneous abortions (92.3%) occurred before 13 weeks of gestation (Table 4), and 700 of 712 pregnancies that resulted in a live birth (98.3%) were among persons who received their first eligible treatment dose in the third trimester.

Adverse outcomes among 724 live-born infants — including 12 sets of multiple gestation — were preterm birth (60 of 636 among those vaccinated before 37 weeks [9.4%]), small size for gestational age (23 of 724 [3.2%]), and major congenital anomalies (16 of 724 [2.2%]). No neonatal deaths were reported at buy kamagra oral jelly online australia the time of interview. Among the participants with completed pregnancies who reported congenital anomalies, none had received erectile dysfunction treatment in the first trimester or periconception period, and no specific pattern of congenital anomalies was observed. Calculated proportions of pregnancy and neonatal outcomes appeared buy kamagra oral jelly online australia similar to incidences published in the peer-reviewed literature (Table 4). Adverse-Event Findings on the VAERS During the analysis period, the VAERS received and processed 221 reports involving erectile dysfunction treatment vaccination among pregnant persons.

155 (70.1%) buy kamagra oral jelly online australia involved nonpregnancy-specific adverse events, and 66 (29.9%) involved pregnancy- or neonatal-specific adverse events (Table S4). The most frequently reported pregnancy-related adverse events were spontaneous abortion (46 cases. 37 in the first trimester, 2 in the second trimester, and 7 in which the trimester was unknown or not reported), buy kamagra oral jelly online australia followed by stillbirth, premature rupture of membranes, and vaginal bleeding, with 3 reports for each. No congenital anomalies were reported to the VAERS, a requirement under the EUAs.Participants Figure 1. Figure 1 buy kamagra oral jelly online australia.

Enrollment and Randomization. The diagram represents all enrolled participants buy kamagra oral jelly online australia through November 14, 2020. The safety subset (those with a median of 2 months of follow-up, in accordance with application requirements for Emergency Use Authorization) is based on an October 9, 2020, data cut-off date. The further procedures that one participant in the placebo group declined after dose 2 (lower right corner of the diagram) were those involving collection of blood and buy kamagra oral jelly online australia nasal swab samples.Table 1. Table 1.

Demographic Characteristics of the Participants in buy kamagra oral jelly online australia the Main Safety Population. Between July 27, 2020, and November 14, 2020, a total of 44,820 persons were screened, and 43,548 persons 16 years of age or older underwent randomization at 152 sites worldwide (United States, 130 sites. Argentina, 1 buy kamagra oral jelly online australia. Brazil, 2. South Africa, 4 buy kamagra oral jelly online australia.

Germany, 6. And Turkey, 9) in the phase buy kamagra oral jelly online australia 2/3 portion of the trial. A total of 43,448 participants received injections. 21,720 received BNT162b2 and buy kamagra oral jelly online australia 21,728 received placebo (Figure 1). At the data cut-off date of October 9, a total of 37,706 participants had a median of at least 2 months of safety data available after the second dose and contributed to the main safety data set.

Among these 37,706 participants, 49% were female, 83% were White, 9% were Black or African American, 28% were Hispanic or Latinx, 35% were obese (body mass index [the weight in buy kamagra oral jelly online australia kilograms divided by the square of the height in meters] of at least 30.0), and 21% had at least one coexisting condition. The median age was 52 years, and 42% of participants were older than 55 years of age (Table 1 and Table S2). Safety Local Reactogenicity Figure 2 buy kamagra oral jelly online australia. Figure 2. Local and Systemic Reactions Reported within buy kamagra oral jelly online australia 7 Days after Injection of BNT162b2 or Placebo, According to Age Group.

Data on local and systemic reactions and use of medication were collected with electronic diaries from participants in the reactogenicity subset (8,183 participants) for 7 days after each vaccination. Solicited injection-site (local) reactions are shown buy kamagra oral jelly online australia in Panel A. Pain at the injection site was assessed according to the following scale. Mild, does buy kamagra oral jelly online australia not interfere with activity. Moderate, interferes with activity.

Severe, prevents buy kamagra oral jelly online australia daily activity. And grade 4, emergency department visit or hospitalization. Redness and swelling were measured according to buy kamagra oral jelly online australia the following scale. Mild, 2.0 to 5.0 cm in diameter. Moderate, >5.0 to 10.0 buy kamagra oral jelly online australia cm in diameter.

Severe, >10.0 cm in diameter. And grade 4, necrosis or exfoliative dermatitis buy kamagra oral jelly online australia (for redness) and necrosis (for swelling). Systemic events and medication use are shown in Panel B. Fever categories are designated in buy kamagra oral jelly online australia the key. Medication use was not graded.

Additional scales were as follows buy kamagra oral jelly online australia. Fatigue, headache, chills, new or worsened muscle pain, new or worsened joint pain (mild. Does not buy kamagra oral jelly online australia interfere with activity. Moderate. Some interference with buy kamagra oral jelly online australia activity.

Or severe. Prevents daily activity), vomiting (mild buy kamagra oral jelly online australia. 1 to 2 times in 24 hours. Moderate. >2 times in 24 hours.

Or severe. Requires intravenous hydration), and diarrhea (mild. 2 to 3 loose stools in 24 hours. Moderate. 4 to 5 loose stools in 24 hours.

Or severe. 6 or more loose stools in 24 hours). Grade 4 for all events indicated an emergency department visit or hospitalization. Н™¸ bars represent 95% confidence intervals, and numbers above the 𝙸 bars are the percentage of participants who reported the specified reaction.The reactogenicity subset included 8183 participants. Overall, BNT162b2 recipients reported more local reactions than placebo recipients.

Among BNT162b2 recipients, mild-to-moderate pain at the injection site within 7 days after an injection was the most commonly reported local reaction, with less than 1% of participants across all age groups reporting severe pain (Figure 2). Pain was reported less frequently among participants older than 55 years of age (71% reported pain after the first dose. 66% after the second dose) than among younger participants (83% after the first dose. 78% after the second dose). A noticeably lower percentage of participants reported injection-site redness or swelling.

The proportion of participants reporting local reactions did not increase after the second dose (Figure 2A), and no participant reported a grade 4 local reaction. In general, local reactions were mostly mild-to-moderate in severity and resolved within 1 to 2 days. Systemic Reactogenicity Systemic events were reported more often by younger treatment recipients (16 to 55 years of age) than by older treatment recipients (more than 55 years of age) in the reactogenicity subset and more often after dose 2 than dose 1 (Figure 2B). The most commonly reported systemic events were fatigue and headache (59% and 52%, respectively, after the second dose, among younger treatment recipients. 51% and 39% among older recipients), although fatigue and headache were also reported by many placebo recipients (23% and 24%, respectively, after the second dose, among younger treatment recipients.

17% and 14% among older recipients). The frequency of any severe systemic event after the first dose was 0.9% or less. Severe systemic events were reported in less than 2% of treatment recipients after either dose, except for fatigue (in 3.8%) and headache (in 2.0%) after the second dose. Fever (temperature, ≥38°C) was reported after the second dose by 16% of younger treatment recipients and by 11% of older recipients. Only 0.2% of treatment recipients and 0.1% of placebo recipients reported fever (temperature, 38.9 to 40°C) after the first dose, as compared with 0.8% and 0.1%, respectively, after the second dose.

Two participants each in the treatment and placebo groups reported temperatures above 40.0°C. Younger treatment recipients were more likely to use antipyretic or pain medication (28% after dose 1. 45% after dose 2) than older treatment recipients (20% after dose 1. 38% after dose 2), and placebo recipients were less likely (10 to 14%) than treatment recipients to use the medications, regardless of age or dose. Systemic events including fever and chills were observed within the first 1 to 2 days after vaccination and resolved shortly thereafter.

Daily use of the electronic diary ranged from 90 to 93% for each day after the first dose and from 75 to 83% for each day after the second dose. No difference was noted between the BNT162b2 group and the placebo group. Adverse Events Adverse event analyses are provided for all enrolled 43,252 participants, with variable follow-up time after dose 1 (Table S3). More BNT162b2 recipients than placebo recipients reported any adverse event (27% and 12%, respectively) or a related adverse event (21% and 5%). This distribution largely reflects the inclusion of transient reactogenicity events, which were reported as adverse events more commonly by treatment recipients than by placebo recipients.

Sixty-four treatment recipients (0.3%) and 6 placebo recipients (<0.1%) reported lymphadenopathy. Few participants in either group had severe adverse events, serious adverse events, or adverse events leading to withdrawal from the trial. Four related serious adverse events were reported among BNT162b2 recipients (shoulder injury related to treatment administration, right axillary lymphadenopathy, paroxysmal ventricular arrhythmia, and right leg paresthesia). Two BNT162b2 recipients died (one from arteriosclerosis, one from cardiac arrest), as did four placebo recipients (two from unknown causes, one from hemorrhagic stroke, and one from myocardial infarction). No deaths were considered by the investigators to be related to the treatment or placebo.

No erectile dysfunction treatment–associated deaths were observed. No stopping rules were met during the reporting period. Safety monitoring will continue for 2 years after administration of the second dose of treatment. Efficacy Table 2. Table 2.

treatment Efficacy against erectile dysfunction treatment at Least 7 days after the Second Dose. Table 3. Table 3. treatment Efficacy Overall and by Subgroup in Participants without Evidence of before 7 Days after Dose 2. Figure 3.

Figure 3. Efficacy of BNT162b2 against erectile dysfunction treatment after the First Dose. Shown is the cumulative incidence of erectile dysfunction treatment after the first dose (modified intention-to-treat population). Each symbol represents erectile dysfunction treatment cases starting on a given day. Filled symbols represent severe erectile dysfunction treatment cases.

Some symbols represent more than one case, owing to overlapping dates. The inset shows the same data on an enlarged y axis, through 21 days. Surveillance time is the total time in 1000 person-years for the given end point across all participants within each group at risk for the end point. The time period for erectile dysfunction treatment case accrual is from the first dose to the end of the surveillance period. The confidence interval (CI) for treatment efficacy (VE) is derived according to the Clopper–Pearson method.Among 36,523 participants who had no evidence of existing or prior erectile dysfunction , 8 cases of erectile dysfunction treatment with onset at least 7 days after the second dose were observed among treatment recipients and 162 among placebo recipients.

This case split corresponds to 95.0% treatment efficacy (95% confidence interval [CI], 90.3 to 97.6. Table 2). Among participants with and those without evidence of prior SARS CoV-2 , 9 cases of erectile dysfunction treatment at least 7 days after the second dose were observed among treatment recipients and 169 among placebo recipients, corresponding to 94.6% treatment efficacy (95% CI, 89.9 to 97.3). Supplemental analyses indicated that treatment efficacy among subgroups defined by age, sex, race, ethnicity, obesity, and presence of a coexisting condition was generally consistent with that observed in the overall population (Table 3 and Table S4). treatment efficacy among participants with hypertension was analyzed separately but was consistent with the other subgroup analyses (treatment efficacy, 94.6%.

95% CI, 68.7 to 99.9. Case split. BNT162b2, 2 cases. Placebo, 44 cases). Figure 3 shows cases of erectile dysfunction treatment or severe erectile dysfunction treatment with onset at any time after the first dose (mITT population) (additional data on severe erectile dysfunction treatment are available in Table S5).

Between the first dose and the second dose, 39 cases in the BNT162b2 group and 82 cases in the placebo group were observed, resulting in a treatment efficacy of 52% (95% CI, 29.5 to 68.4) during this interval and indicating early protection by the treatment, starting as soon as 12 days after the first dose.Trial Design and Oversight In the Study of Tofacitinib in Hospitalized Patients with erectile dysfunction treatment Pneumonia (STOP-erectile dysfunction treatment), we compared tofacitinib with placebo in patients with erectile dysfunction treatment pneumonia. The trial protocol (available with the full text of this article at NEJM.org) was approved by the institutional ethics board at participating sites. The trial was conducted in accordance with Good Clinical Practice guidelines and the principles of the Declaration of Helsinki. The trial was sponsored by Pfizer and was designed and led by a steering committee that included academic investigators and representatives from Pfizer. The trial operations and statistical analyses were conducted by the Academic Research Organization of the Hospital Israelita Albert Einstein in São Paulo.

An independent data and safety monitoring board reviewed unblinded patient-level data for safety on an ongoing basis during the trial. Pfizer provided the entire trial budget, which covered all trial-related expenses including but not limited to investigator fees, costs related to investigational product suppliers and importation, insurance, applicable taxes and fees, and funding to support the activities of the data and safety monitoring board. All the authors vouch for the accuracy and completeness of the data and for the fidelity of the trial to the protocol. The trial committee members and participating investigators are listed in the Supplementary Appendix, available at NEJM.org. Trial Population The trial included patients 18 years of age or older who had laboratory-confirmed erectile dysfunction as determined on reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay before randomization, who had evidence of erectile dysfunction treatment pneumonia on radiographic imaging (computed tomography or radiography of the chest), and who had been hospitalized for less than 72 hours.

Information regarding the timing of the qualifying RT-PCR assay in relation to symptom onset is provided in Section S3.1 in the Supplementary Appendix. High-flow devices constituted the maximum oxygen support that was allowed for trial inclusion. The main exclusion criteria were the use of noninvasive or invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) on the day of randomization, a history of thrombosis or current thrombosis, known immunosuppression, and any current cancer for which the patient was receiving active treatment. Details of the eligibility criteria are provided in Section S3.2. Written informed consent was obtained from each patient or from the patient’s legally authorized representative if the patient was unable to provide informed consent.

Randomization, Interventions, and Follow-up Eligible patients were randomly assigned in a 1:1 ratio to receive either tofacitinib or placebo. Randomization, with stratification according to site, was performed with the use of a central concealed, Web-based, automated randomization system. Patients received either oral tofacitinib at a dose of 10 mg or placebo twice daily for up to 14 days or until hospital discharge, whichever was earlier. If a participant underwent intubation before the end of the 14-day treatment period (or before discharge), they continued to receive tofacitinib or placebo if it was considered to be clinically appropriate by the treating physicians. A reduced-dose regimen of 5 mg of tofacitinib (or matching placebo) twice daily was administered in patients with an estimated glomerular fiation rate of less than 50 ml per minute per 1.73 m2 of body-surface area, in those with moderate hepatic impairment, and in those with concomitant use of a strong CYP3A4 inhibitor or a combination of a moderate CYP3A4 inhibitor and a strong CYP2C19 inhibitor.

The rationale for the tofacitinib dosage is provided in Section S3.3. All the patients were treated according to local standards of care for erectile dysfunction treatment, which could have included glucocorticoids, antibiotic agents, anticoagulants, and antiviral agents. Concomitant use of other JAK inhibitors, biologic agents, potent immunosuppressants, interleukin-1 inhibitors, interleukin-6 inhibitors, or potent CYP450 inducers was prohibited. Patients were assessed daily (up to day 28) while hospitalized. Follow-up visits occurred on day 14 and on day 28 for participants who were discharged before day 14 or http://patrickjanz.de/releasestruktur-jtl-wawi/ 28.

Prespecified reasons for permanent discontinuation of the trial intervention are described in Section S3.4. Outcomes The primary outcome was death or respiratory failure during the 28 days of follow-up. Death or respiratory failure was determined to occur if participants met the criteria for category 6 (status of being hospitalized while receiving noninvasive ventilation or ventilation through high-flow oxygen devices), 7 (status of being hospitalized while receiving invasive mechanical ventilation or ECMO), or 8 (death) on the eight-level National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity (on a scale from 1 to 8, with higher scores indicating a worse condition) (Table S1 in the Supplementary Appendix). Patients who were enrolled in the trial while they were receiving oxygen through high-flow devices (category 6) were considered to have met the criteria for the primary outcome if they presented with clinical worsening to category 7 or 8. The occurrence of the primary outcome was adjudicated by an independent clinical-events classification committee, whose members were unaware of the group assignments.

The protocol and statistical analysis plan used an inverted ordinal scale, which was reversed in this report to be consistent with previous studies. Secondary efficacy outcomes were the cumulative incidence of death through day 28, the scores on the NIAID ordinal scale of disease severity at day 14 and at day 28, the status of being alive and not using mechanical ventilation or ECMO at day 14 and day 28, the status of being alive and not hospitalized at day 14 and day 28, cure (defined as resolution of fever and cough and no use of ventilatory or oxygen support), the duration of stay in the hospital, and the duration of stay in the intensive care unit (ICU). The occurrence and severity of adverse events were evaluated and coded according to the Medical Dictionary for Regulatory Activities, version 23.1. Details of adverse event reporting, including the reporting of prespecified adverse events of special interest, are described in Section S3.5. Statistical Analysis We estimated that the assignment of 260 patients, with randomization performed in a 1:1 ratio, would provide the trial with 80% power to detect a between-group difference of 15 percentage points in the incidence of the primary outcome, assuming that 15% of the participants in the tofacitinib group and 30% of those in the placebo group would have an event (death or respiratory failure through day 28).

The hypothesis of superiority was tested at a two-tailed alpha level of 5%. The efficacy analyses included all the participants who underwent randomization. Safety analyses included all the participants who underwent randomization and took at least one dose of tofacitinib or placebo. The results for the primary efficacy outcome were analyzed by means of binary regression with Firth correction, with trial group and antiviral therapy for erectile dysfunction treatment as covariates, and are expressed as a risk ratio. The antiviral treatments on day 1 were used in the statistical model.

Dichotomous secondary outcomes were analyzed in a manner similar to that used for the primary outcome. The effect of the intervention on death through day 28 is expressed as a hazard ratio derived from Cox regression. For ordinal data, a proportional-odds model with adjustment for baseline antiviral therapy was used. An odds ratio of less than 1.0 represents a clinical improvement as assessed on the ordinal scale. Odds proportionality was assessed with the use of the method of Pulkstenis–Robinson.9 We created Kaplan–Meier survival curves to express the time until the occurrence of the primary outcome, both overall and stratified according to the use of supplemental oxygen at baseline, and the occurrence of death through 28 days.

As a sensitivity analysis, results for the primary outcome were analyzed by means of binary regression with Firth correction, with use of glucocorticoids and antiviral agents at baseline as covariates. In addition, results for the primary outcome were analyzed by means of logistic regression with Firth correction, with adjustment for baseline antiviral therapy. Prespecified subgroup analyses were performed according to age, sex, concomitant use of antiviral therapy, concomitant use of glucocorticoids, and time from symptom onset to randomization. For the primary outcome, a two-sided P value of less than 0.05 was considered to indicate statistical significance. The 95% confidence intervals were estimated for all effect measures.

The widths of the 95% confidence intervals for the secondary outcomes were not adjusted for multiple comparisons, so the intervals should not be used to infer definitive treatment effects. All the analyses were performed with the use of SAS software, version 9.4 (SAS Institute), and R software, version 3.6.3 (R Foundation for Statistical Computing). Additional details about the statistical analysis are provided in Section S3.6.From the Department of Clinical Sciences Lund, Sections of Cardiology (J. Dankiewicz, D.E.), Neurology (T. Cronberg, G.L.), and Anesthesiology and Intensive Care (H.

Levin, O.B.), Skåne University Hospital Lund, Lund University and Clinical Studies Sweden — Forum South, Skåne University Hospital (S.U.), Lund. The Department of Clinical Sciences Lund, Section of Anesthesia and Intensive Care, Skåne University Hospital Malmö, Malmö, (J. Düring, S.S., H.F.). The Department of Clinical Sciences Lund, Sections of Anesthesiology and Intensive Care (M.A., N.N.) and Clinical Sciences Helsingborg (N.N.), Helsingborg Hospital, Helsingborg. The Department of Clinical Sciences Lund, Section of Anesthesiology and Intensive Care Lund, Hallands Hospital, Halmstad (J.U.).

The Department of Anesthesiology and Intensive Care Medicine, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg (C.R., A. Lundin). The Department of Clinical Science and Education, Center for Resuscitation Science, Karolinska Institutet, Södersjukhuset, Stockholm (P.N., J. Hollenberg, A.A.). And the Department of Anesthesiology, Intensive Care, and Acute Medicine, Linköping University, Linköping (M.S.C.) — all in Sweden.

Copenhagen Trial Unit, Center for Clinical Intervention Research, Copenhagen University Hospital (J.C.J.), and the Section of Biostatistics, Faculty of Health and Medical Sciences (T.L.), University of Copenhagen, Copenhagen, the Department of Regional Health Research, the Faculty of Health Sciences, University of Southern Denmark, Odense (J.C.J.), the Research Center for Emergency Medicine, the Department of Clinical Medicine (H.K.), and the Department of Intensive Care (A.M.G., S.C.), Aarhus University Hospital, Aarhus — all in Denmark. Adult Critical Care, University Hospital of Wales, Cardiff (M.P.W., M.P.G.M., J.M.C.), the Department of Intensive Care, Bristol Royal Infirmary, Bristol (M.T., J. Bewley, K.S.), Essex Cardiothoracic Centre, Basildon (T.R.K., G.V.K.), Anglia Ruskin University School of Medicine, Chelmsford, Essex (T.R.K., G.V.K.), and the Department of Anesthesiology and Intensive Care, Royal Victoria Hospital, Belfast (P.M.) — all in the United Kingdom. Neuroscience Critical Care Research Group and Adult Intensive Care Medicine Service, Centre Hospitalier Universitaire Vaudois–Lausanne University Hospital and University of Lausanne, Lausanne (M. Oddo, S.A.-M.), the Departments of Intensive Care Medicine (M.H.) and Anesthesiology and Pain Medicine, Inselspital (A.

Levis), Bern University Hospital, University of Bern, Bern, the Intensive Care Department, Kantonsspital St. Gallen, St. Gallen (C. Schrag, E.F.), the Institute of Intensive Care Medicine, University Hospital Zurich, Zurich (M.M., P.D.W.G.), and the Cardiac Anesthesia and Intensive Care Department, Instituto Cardiocentro Ticino, Lugano (T. Cassina) — all in Switzerland.

Descartes University of Paris and Cochin University Hospital, Paris (A.C., P.J.), Medical-Surgical Intensive Care Unit, Dupuytren Teaching Hospital, Limoges (P.V.) — all in France. The 2nd Department of Medicine (J. Bělohlávek, O.S.), and the Department of Anesthesiology and Intensive Care Medicine (M. Otáhal), General University Hospital and First Faculty of Medicine, Charles University, Prague, the 1st Department of Internal Medicine–Cardioangiology, University Hospital Hradec Králové, and Faculty of Medicine, Charles University, Hradec Králové (M. Solar) — all in the Czech Republic.

The Department of Anesthesiology, Division of Emergencies and Critical Care, Oslo University Hospital, Rikshospitalet, Oslo (J. Hovdenes), the Department of Anesthesiology, Sørlandet Hospital, Arendal (R.B.O.), the Department of Anesthesiology and Intensive Care Medicine, St. Olav’s University Hospital, and the Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim (H. Langeland) — all in Norway. The Division of Critical Care and Trauma, George Institute for Global Health, and Bankstown–Lidcombe Hospital, South Western Sydney Local Health District, Sydney (M.

Saxena), and the Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine (G.M.E., A.D.N.), and the Department of Intensive Care, Alfred Health (A.D.N.), Monash University, Melbourne — all in Australia. The Medical Research Institute of New Zealand, Intensive Care Unit, Wellington Hospital, Wellington (P.J.Y., L.N.). The Departments of Surgical Sciences and Integrated Diagnostics (P.P.) and Anesthesiology and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neuroscience (P.P., I.B.), University of Genoa, Genoa, Italy. The Department of Nephrology and Medical Intensive Care (C. Storm), and Klinik und Hochschulambulanz für Neurologie (C.L.), Charité Universitätzmedizin, Berlin, Germany.

The Department of Intensive Care, Erasme University Hospital, Université Libre de Bruxelles, Brussels (F.S.T.). The Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Innsbruck, Austria (M.J.). The Department of Emergency Medicine, University of Pittsburgh, Pittsburgh (C.C.). And University College Dublin Clinical Research Centre at St. Vincent’s University Hospital, Dublin, Ireland (A.D.N.).Address reprint requests to Dr.

Nielsen at the Department of Anesthesiology and Intensive Care, Intensive Care Unit, Helsingborg Hospital, S Vallgatan 5, 251 87, Helsingborg, Sweden, or at [email protected].Participants Table 1. Table 1. Characteristics of the Trial Participants at Baseline (Full Analysis Set). The trial began enrollment on September 21, 2020, and the data-cutoff date for the present analysis was January 22, 2021. A total of 44,325 participants underwent randomization, of whom 43,783 received treatment or placebo.

The per-protocol population included 39,321 erectile dysfunction–negative participants, of whom 19,630 received Ad26.COV2.S and 19,691 received placebo (Fig. S3). The demographic characteristics and coexisting conditions of the participants at baseline were balanced across the two groups (Table 1 and S4). A total of 9.6% of the participants were erectile dysfunction–seropositive at baseline. The median follow-up was 58 days (range, 1 to 124), and 55% of participants had at least 8 weeks of follow-up.

Later and slower recruitment of participants 60 years of age or older with coexisting conditions resulted in a shorter duration of follow-up in this subgroup (Table S5). Safety Figure 1. Figure 1. Solicited Local and Systemic Adverse Events Reported within 7 days after the Administration of treatment or Placebo (Safety Subpopulation). Most solicited local and systemic adverse events occurred within 1 to 2 days after the administration of treatment or placebo and had a median duration of 1 to 2 days.

No grade 4 local or systemic adverse events were reported. There were no local or systemic reactogenicity differences between participants who were seronegative at baseline and those who were seropositive (data not shown). Pain was categorized as grade 1 (mild. Does not interfere with activity), grade 2 (moderate. Requires modification of activity or involves discomfort with movement), grade 3 (severe.

Inability to perform usual activities), or grade 4 (potentially life-threatening. Hospitalization or inability to perform basic self-care). Erythema and swelling were categorized as grade 1 (mild. 25 to 50 mm), grade 2 (moderate. 51 to 100 mm), grade 3 (severe.

>100 mm), or grade 4 (potentially life-threatening. Necrosis or leading to hospitalization). Systemic events were categorized as grade 1 (mild. Minimal symptoms), grade 2 (moderate. Notable symptoms not resulting in loss of work or school time), grade 3 (severe.

Incapacitating symptoms resulting in loss of work or school time), or grade 4 (life-threatening. Hospitalization or inability to perform basic self-care). Fever was defined as grade 1 (mild. ‰¥38.0 to 38.4°C), grade 2 (moderate. ‰¥38.5 to 38.9°C), grade 3 (severe.

‰¥39.0 to 40.0°C), or grade 4 (potentially life-threatening. >40°C).The safety subpopulation included 3356 participants in the treatment group and 3380 in the placebo group. During the 7-day period after the administration of treatment or placebo, more solicited adverse events were reported by Ad26.COV2.S recipients than by placebo recipients and by participants 18 to 59 years of age than by those 60 years of age or older (Figure 1). In the treatment group, injection-site pain was the most common local reaction (in 48.6% of the participants). The most common systemic reactions were headache (in 38.9%), fatigue (in 38.2%), myalgia (in 33.2%), and nausea (in 14.2%).

The adverse events of at least grade 3 that were considered by the investigators to be possibly related to Ad26.COV2.S or placebo are listed in Table S6. Serious adverse events, excluding those related to erectile dysfunction treatment, were reported by 83 of 21,895 treatment recipients (0.4%) and by 96 of 21,888 placebo recipients (0.4%). Seven serious adverse events were considered by the investigators to be related to vaccination in the Ad26.COV2.S group (Table S7). A numeric imbalance was observed for venous thromboembolic events (11 in the treatment group vs. 3 in the placebo group).

Most of these participants had underlying medical conditions and predisposing factors that might have contributed to these events (Table S8). Imbalances were also observed with regard to seizure (which occurred in 4 participants in the treatment group vs. 1 in the placebo group) and tinnitus (in 6 vs. 0). A causal relationship between these events and Ad26.COV2.S cannot be determined.

These events will be monitored in the post-marketing setting. Three deaths were reported in the treatment group and 16 in the placebo group, all of which were considered by the investigators to be unrelated to the trial intervention (Table S7). No deaths related to erectile dysfunction treatment were reported in the treatment group, whereas 5 deaths related to erectile dysfunction treatment were reported in the placebo group. Transverse sinus thrombosis with cerebral hemorrhage and a case of the Guillain–Barré syndrome were each seen in 1 treatment recipient. Efficacy Table 2.

Table 2. treatment Efficacy against erectile dysfunction treatment with Onset at Least 14 Days and at Least 28 Days after the Administration of treatment or Placebo (Per-Protocol at-Risk Population). In the per-protocol at-risk population, 468 centrally confirmed cases of symptomatic erectile dysfunction treatment with an onset at least 14 days after administration were observed, of which 464 were moderate to severe–critical (116 cases in the treatment group vs. 348 in the placebo group), which indicated treatment efficacy of 66.9% (adjusted 95% confidence interval [CI], 59.0 to 73.4) (Table 2). In terms of the primary end point of disease onset at least 28 days after administration, 66 cases of moderate to severe–critical erectile dysfunction treatment in the treatment group and 193 cases in the placebo group were observed, which indicated treatment efficacy of 66.1% (adjusted 95% CI, 55.0 to 74.8) (Table 2).

Figure 2. Figure 2. Cumulative Incidence of erectile dysfunction treatment with Onset at Least 1 Day after Vaccination and treatment Efficacy over Time. Panel A shows the cumulative incidence of moderate to severe–critical cases of erectile dysfunction disease 2019 (erectile dysfunction treatment). Circles indicate severe–critical cases.

Panel B shows the cumulative incidence of severe–critical cases. Cases included in the analyses in Panels A and B were centrally confirmed cases in the full analysis set among participants who were seronegative at baseline. Panel C shows the cumulative incidence of severe–critical cases in South Africa among participants who were seronegative at baseline. These cases were those that were positive on reverse-transcriptase–polymerase-chain-reaction (RT-PCR) testing from all sources, whether centrally confirmed or not.Table 3. Table 3.

treatment Efficacy against erectile dysfunction treatment with Onset at Least 14 Days and at Least 28 Days after Administration of treatment or Placebo, According to Country (Per-Protocol at-Risk Population). The cumulative incidence of the first occurrence of moderate to severe–critical erectile dysfunction treatment diverged between the two trial groups at approximately 14 days after the administration of treatment or placebo, which indicates an early onset of protection with the treatment (Figure 2A). Fewer cases in the treatment group were observed after day 14 while cases continued to accrue in the placebo group, which led to increasing treatment efficacy over time (Fig. S4A). Efficacy against disease with an onset at least 28 days after administration was similar across age groups, but efficacy against disease with an onset 14 days after administration was higher among older participants than among younger participants (Table 2).

This discrepancy probably resulted from differences in follow-up duration or from smaller sample sizes in subgroups. The number of primary end-point cases was similar to the number of cases of symptomatic erectile dysfunction treatment as defined according to the FDA harmonized definition (Table 2). Thus, the primary end-point analyses captured most of the cases of symptomatic erectile dysfunction treatment. Estimates of treatment efficacy in the analyses of the two primary end points and the secondary end points of centrally confirmed cases differed by less than 2 percentage points from the estimates in analyses of positive cases from all sources, and the confidence intervals were similar (Table 2 and Table 3). treatment-efficacy estimates in the full analysis set were generally lower than those in the per-protocol population because the estimates included cases that occurred at or after 1 day after administration, when immunity was building (Table S9).

With regard to severe–critical erectile dysfunction treatment, treatment efficacy was 76.7% (adjusted 95% CI, 54.6 to 89.1) against disease with onset at least 14 days after administration and 85.4% (adjusted 95% CI, 54.2 to 96.9) against disease with onset at least 28 days after administration (Table 2). The cumulative-incidence curves began to separate approximately 7 days after administration. treatment efficacy increased with longer follow-up and was 92.4% after day 42 (post hoc calculation) (Figures 2B and S4B). The analysis of treatment efficacy against asymptomatic included all the participants with a newly positive N-immunoassay result at day 71 (i.e., those who had been seronegative or had no result available at day 29 and who were seropositive at day 71). Only 2650 participants had an N-immunoassay result available at day 71, and therefore only a preliminary analysis could be performed.

A total of 18 asymptomatic s were identified in the treatment group and 50 in the placebo group (treatment efficacy, 65.5%. 95% CI, 39.9 to 81.1). treatment efficacy against erectile dysfunction treatment involving medical intervention ranged from 75.0 to 100.0% (Table S10). Two cases of erectile dysfunction treatment with onset at least 14 days after administration in the Ad26.COV2.S group and 29 such cases in the placebo group led to hospitalization (treatment efficacy, 93.1%. 95% CI, 72.7 to 99.2) (Fig.

S5). No hospitalizations for cases with an onset at least 28 days after administration occurred in the treatment group, as compared with 16 hospitalizations in the placebo group (treatment efficacy, 100%. 95% CI, 74.3 to 100.0). Participants with moderate erectile dysfunction treatment who had received Ad26.COV2.S most frequently reported 4 to 6 symptoms, as compared with 7 to 9 symptoms in participants who had received placebo (Fig. S6).

The total mean symptom-severity score as reported on the Symptoms of with erectile dysfunction-19 questionnaire was 24% (95% CI, −1 to 46) lower among treatment recipients than among placebo recipients at day 1 after symptom onset, 47% (95% CI, 23 to 66) lower at day 7 after symptom onset, and 53% (95% CI, 0 to 81) lower at day 14 after symptom onset among participants with an onset of moderate illness at least 28 days after administration (Fig. S1). The estimates of treatment efficacy against severe–critical disease were consistently high across countries that had sufficient cases for analysis (Table 3). On the basis of interim sequencing data from 512 unique RT-PCR–positive samples obtained from 714 participants (71.7%) with erectile dysfunction , the reference sequence (Wuhan-Hu-1 including the D614G mutation) was detected predominantly in the United States (190 of 197 sequences [96.4%]) and the 20H/501Y.V2 variant (also called B.1.351) was detected predominantly in South Africa (86 of 91 sequences [94.5%]), whereas in Brazil, the reference sequence was detected in 38 of 124 sequences (30.6%) and the reference sequence with the E484K mutation (P.2 lineage) was detected in 86 of 124 sequences (69.4%). Despite the high prevalence of the 20H/501Y.V2 variant in South Africa and in erectile dysfunction treatment cases in the trial, treatment efficacy was maintained (52.0% against moderate to severe–critical disease and 73.1% against severe–critical disease with onset ≥14 days after administration.

64.0% against moderate to severe–critical disease and 81.7% against severe–critical disease with onset at ≥28 days after administration) (Figure 2C and Table 3). In South Africa, no hospitalizations of participants with an onset of erectile dysfunction treatment at least 28 days after administration occurred in the treatment group, as compared with 6 hospitalizations in the placebo group. All five erectile dysfunction treatment–related deaths in the trial occurred in the placebo group in South Africa. No meaningful differences in treatment efficacy were observed among subgroups defined according to sex, race, or ethnic group (Fig. S7 and Table S11).

A lower point estimate of treatment efficacy was observed among participants 60 years of age or older with coexisting conditions in the analysis of cases with onset at least 28 days after administration (15 cases of moderate to severe–critical erectile dysfunction treatment among treatment recipients vs. 26 cases among placebo recipients) but not in the analysis of cases with onset at least 14 days after administration (22 vs. 63 cases) (Fig. S7). Estimates of efficacy over time that were based on Kaplan–Meier analysis were similar among participants 60 years of age or older with coexisting conditions and those without coexisting conditions (Figs.

S4C and S8). Two participants 60 years of age or older with coexisting conditions in the treatment group were hospitalized, as compared with 11 such participants in the placebo group (treatment efficacy, 81.6%. 95% CI, 15.8 to 98.0)..