Search

Background The prevention of coronavirus disease 2019 (COVID-19) in vulnerable populations is a global health priority. EVADE was a phase 2/3 multicenter, double-blind, randomized, placebo-controlled trial of adintrevimab, an extended–half-life monoclonal antibody, for postexposure (PEP) and pre-exposure prophylaxis (PrEP) of symptomatic COVID-19. Methods Eligible participants (vaccine-naive, aged ≥12 years) were randomized 1:1 to receive a single 300-mg intramuscular injection of adintrevimab or placebo. Primary efficacy end points were reverse transcription polymerase chain reaction (RT-PCR)–confirmed symptomatic COVID-19 through day 28 in the PEP cohort (RT-PCR-negative at baseline) and through month 3 in the PrEP cohort (RT-PCR-negative and seronegative at baseline) among participants randomized before emergence of the severe acute respiratory syndrome coronavirus 2 Omicron variant (November 30, 2021). Safety was assessed through 6 months. Results Between April 27, 2021, and January 11, 2022, 2582 participants were randomized. In the primary efficacy analysis, RT-PCR-confirmed symptomatic COVID-19 occurred in 3/175 (1.7%) vs 12/176 (6.8%) adintrevimab- and placebo-treated PEP participants, respectively (74.9% relative risk reduction [RRR]; standardized risk difference, −5.0%; 95% CI, −8.87% to −1.08%; P =.0123) and in 12/752 (1.6%) vs 40/728 (5.5%) adintrevimab- and placebo-treated PrEP participants, respectively (71.0% RRR; standardized risk difference, −3.9%; 95% CI, −5.75% to −2.01%; P <.0001). In a prespecified exploratory analysis of 428 PrEP participants randomized after the emergence of Omicron, adintrevimab reduced RT-PCR-confirmed symptomatic COVID-19 by 40.6% (standardized risk difference −8.4%; 95% CI, −15.35% to −1.46%; nominal P =.0177) vs placebo. Adintrevimab was well tolerated, with no serious drug-related adverse events reported. Conclusions A single intramuscular injection of adintrevimab provided prophylactic efficacy against COVID-19 due to susceptible variants without safety concerns. Clinical trial registration. NCT04859517. [ABSTRACT FROM AUTHOR]

Background Safe and effective treatments are needed to prevent severe outcomes in individuals with coronavirus disease 2019 (COVID-19). We report results from STAMP, a phase 2/3, multicenter, double-blind, randomized, placebo-controlled trial of adintrevimab, an extended half-life monoclonal antibody, for treatment of high-risk ambulatory patients with mild to moderate COVID-19. Methods Nonhospitalized, unvaccinated participants aged ≥12 years with mild to moderate COVID-19 and ≥1 risk factor for disease progression were randomized to receive a single intramuscular injection of 300 mg adintrevimab or placebo. Enrollment was paused due to the global emergence of the Omicron BA.1/BA1.1 variants, against which adintrevimab showed reduced activity in vitro. The primary efficacy endpoint was COVID-19–related hospitalization or all-cause death through day 29 in participants with COVID-19 due to laboratory-confirmed or suspected non-Omicron severe acute respiratory syndrome coronavirus 2 variants. Results Between 8 August 2021 and 11 January 2022, 399 participants were randomized to receive adintrevimab (n = 198) or placebo (n = 201), including 336 with COVID-19 due to non-Omicron variants. COVID-19–related hospitalization or all-cause death through day 29 occurred in 8 of 169 (4.7%) participants in the adintrevimab group and 23 of 167 (13.8%) participants in the placebo group, a 66% relative risk reduction in favor of adintrevimab (standardized risk difference, −8.7% [95% confidence interval, −14.71% to −2.67%]; P =.0047). Incidence of treatment-emergent adverse events (TEAEs) was similar between treatment groups (33.9% for adintrevimab and 39.5% for placebo). No adintrevimab-related serious TEAEs were reported. Conclusions Treatment with a single intramuscular injection of adintrevimab provided protection against severe outcomes in high-risk ambulatory participants with COVID-19 due to susceptible variants, without safety concerns. Clinical Trial Registration. NCT04805671. [ABSTRACT FROM AUTHOR]

Familial Mediterranean fever (FMF) is an autosomal recessive hereditary disease which is characterized by recurrent attacks of fever and peritonitis, pleuritis, arthritis, or erysipelas-like skin disease. Mean platelet volume (MPV) is a sign of platelet activation. There are limited studies in the literature about MPV levels in FMF patients. We aimed to investigate MPV levels during the attack period (group 1) and attack-free periods (group 2) in FMF patients, and to compare them with healthy controls (group 3). The study consisted of the data of: 60 group 1 patients, 120 group 2 patients, and 75 group 3 patients. Erythrocyte sedimentation rate, C-reactive protein, white blood cell count, platelet count, and MPV levels were retrospectively recorded from patient files. Statistical analyses showed that MPV was significantly lower in FMF patients both in group 1 and group 2 than in group 3 ( p = 0.004, p = 0.002, respectively); however, there was no difference among group 1 and group 2 in patients with FMF ( p = 0.279). The mean platelet count of group 1 was higher than that of group 3 ( p = 0.010). In conclusion, this study results suggested that MPV level did not increase on the contrary, it decreased in patients with FMF both in group 1 and/or group 2 when compared to group 3. It was concluded that the lower MPV level was an expected result of secondary thrombocytosis in FMF patients. [ABSTRACT FROM AUTHOR]

Aim To expand our understanding of the clinical importance to patients with stress urinary incontinence (SUI) of reductions in incontinence episode frequency (IEF) that fall short of a complete cure. Methods We used an integrated database that included data from 1,913 women with SUI who were enrolled in four randomized, placebo-controlled pharmaceutical clinical trials and examined the relationship between various levels of reduction in IEF and minimally clinical important difference (MCID) levels established for the validated Incontinence Quality of Life (I-QOL) questionnaire. The first decile of IEF reduction to exceed the within-group MCID was considered to be the point at which the reduction in IEF first became clinically important. The between-group MCID was then used to determine when further reductions in incontinence represented clinically relevant incremental improvements for patients. Results Improvements in condition-specific quality of life were not clinically important until the fifth decile of IEF reduction, representing a reduction in IEF >40% to ≤50%. Patients appreciated incremental clinically important benefits when IEF reductions exceeded 70%, with progressive improvements in condition-specific quality of life with higher levels of IEF reduction. The difference between a >70% to ≤80% reduction and a >90% to ≤100% reduction was clinically important. Conclusion Reductions in IEF ≤40% do not appear to be clinically important for women with SUI. Patients appear to recognize important clinical value at reductions of approximately 50% and important incremental clinical value at reductions of approximately 75% and 90-100%. These thresholds may not apply to women seeking non-pharmaceutical treatments for SUI. Neurourol. Urodynam. 29:344-347, 2010. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

To assess the efficacy and safety of duloxetine in women with stress urinary incontinence.Randomised double-blind, placebo-controlled clinical trial.Fort-six centres in seven European countries and Canada.Four hundred and ninety-four women aged 24–83 years identified as having predominant symptoms of stress urinary incontinence using a clinical algorithm that was 100% predictive of urodynamic stress urinary incontinence in a subgroup of 34 women.The case definition included a predominant symptom of stress urinary incontinence with a weekly incontinence episode frequency≥7, the absence of predominant symptoms of urge incontinence, normal diurnal and nocturnal frequencies, a bladder capacity≥400 mL and both a positive cough stress test and positive stress pad test. Subjects completed two urinary diaries prior to randomisation and three diaries during the active treatment phase of the study, each completed during the week prior to monthly visits. Subjects also completed quality of life questionnaires at each visit. Safety was assessed by the evaluation of treatment-emergent adverse events, discontinuation of treatment because of adverse events, serious adverse events, vital sign measurements, electrocardiograms (ECG) and clinical laboratory tests.After a two-week placebo lead-in, women received placebo or duloxetine 40 mg BD for 12 weeks.The percentage decrease in incontinence episode frequency and the change in the Incontinence Quality of Life (I-QOL) questionnaire total score were prespecified as co-primary outcome variables in the protocol.Incontinence episode frequency decreased significantly with duloxetine compared with placebo (median decrease of 50%vs29%;P= 0.002) with comparable improvements in the more severely incontinent subgroup (those experiencing at least 14 incontinence episodes per week at baseline; 56%vs27% decreases;P<0.001). The primary analysis of I-QOL scores did not reveal a significant difference between treatment groups, due primarily to the carrying forward of low scores from patients who discontinued treatment very early due to duloxetine-associated adverse events. The increase in I-QOL scores was significantly greater for duloxetine than for placebo at each of the three postrandomisation visits after 4, 8, and 12 weeks of treatment. Discontinuation rates for adverse events were higher for duloxetine (22%vs5%;P<0.001) with nausea being the most common reason for discontinuation (5.3%). Nausea tended to be mild to moderate, not progressive, and transient.The findings support duloxetine as a potential treatment for women with stress urinary incontinence. [ABSTRACT FROM AUTHOR]

Objective: Familial Mediterranean fever (FMF) is an auto- immune disorder. Long-term complications of the disease include decreased quality of life. The measurement of quality of life in the patients with chronic disease has become an important research topic during the last years. We aimed to evaluate life quality of the FMF patients the short form 36 health survey questionnaire (SF-36), and examine its relationship with the disease parameters. Methods: One hundred voluntary patients (69 female, 31 male) admitted to the rheumatology clinic were included in the study. The control group consisted of 100 healthy individuals. All subjects in the study were asked to completeSF-36. Age of onset of FMF, age at diagnosis, age at the beginning of colchicine therapy, number of attacks per month, family history of FMF and dialysis were inquired to FMF patients. Disease severity was rated using the FMF severity score. Results: The mean age of the patient group was 31±12 years and that of the control group was 29±9. Sixty-nine patients (69%) were female, and 31 patients were male (31%) in both groups. The mean scores of the physical function, physical role function, emotional role function, mental health, and general health parameters of the patients were statistically significantly lower than those of healthy volunteers (p<0.05). The difference in social function and vitality between two groups was found to be insignificant (p>0.05). Conclusion: We have shown that FMF had a negative impact on SF-36. FMF reduces quality of life both in physical and mental dimensions [ABSTRACT FROM AUTHOR]

Background: There are data on the safety of cancer surgery and the efficacy of preventive strategies on the prevention of postoperative symptomatic COVID-19 in these patients. But there is little such data for any elective surgery. The main objectives of this study were to examine the safety of bariatric surgery (BS) during the coronavirus disease 2019 (COVID-19) pandemic and to determine the efficacy of perioperative COVID-19 protective strategies on postoperative symptomatic COVID-19 rates., Methods: We conducted an international cohort study to determine all-cause and COVID-19-specific 30-day morbidity and mortality of BS performed between 01/05/2020 and 31/10/2020., Results: Four hundred ninety-nine surgeons from 185 centres in 42 countries provided data on 7704 patients. Elective primary BS (n = 7084) was associated with a 30-day morbidity of 6.76% (n = 479) and a 30-day mortality of 0.14% (n = 10). Emergency BS, revisional BS, insulin-treated type 2 diabetes, and untreated obstructive sleep apnoea were associated with increased complications on multivariable analysis. Forty-three patients developed symptomatic COVID-19 postoperatively, with a higher risk in non-whites. Preoperative self-isolation, preoperative testing for SARS-CoV-2, and surgery in institutions not concurrently treating COVID-19 patients did not reduce the incidence of postoperative COVID-19. Postoperative symptomatic COVID-19 was more likely if the surgery was performed during a COVID-19 peak in that country., Conclusions: BS can be performed safely during the COVID-19 pandemic with appropriate perioperative protocols. There was no relationship between preoperative testing for COVID-19 and self-isolation with symptomatic postoperative COVID-19. The risk of postoperative COVID-19 risk was greater in non-whites or if BS was performed during a local peak., (© 2021. The Author(s).)

Objective: The safety and tolerability of duloxetine for major depressive disorder (MDD), generalized anxiety disorder (GAD), diabetic peripheral neuropathic pain (DPNP), fibromyalgia, and lower urinary tract disorders (LUTD) (including female stress urinary incontinence [SUI] and other LUTDs) has been established in individual clinical studies. The objective of this manuscript is to characterize the overall safety profile of duloxetine, regardless of indication, based on data from the duloxetine exposures integrated safety database., Research Design and Methods: The duloxetine exposures integrated safety database was examined using pooled data from 23,983 patients randomized to receive duloxetine in 64 studies for MDD, GAD, DPNP, fibromyalgia, or LUTDs. Evaluated aspects of drug safety included treatment-emergent adverse events (TEAEs), adverse events leading to discontinuation, serious adverse events (SAEs), clinical laboratory tests, vital signs, and electrocardiograms., Results: Common TEAEs included nausea, headache, dry mouth, insomnia, constipation, dizziness, fatigue, somnolence, diarrhea, and hyperhidrosis. Most TEAEs emerged early; the majority were mild to moderate in severity, and did not worsen. Overall, discontinuation rates due to AEs were 20.0%. SAEs occurred at a rate of 3.5% and no single event was predominant. Mean pulse increased by < 2 beats per minute. Mean increases in systolic and diastolic blood pressure were < 1 mmHg. Mean alanine transaminase and aspartate transaminase values increased by < 2 U/L., Conclusions: The safety profile for the molecule from the overall duloxetine exposures integrated safety database suggests that benign and common pharmacologic side effects occur with duloxetine treatment. Because these pooled analyses do not allow for statistical comparison to placebo or active comparator, and include data from five different studied indications, these data do not suggest causality for AEs, nor are they necessarily generalizable to each disease stated studied.

Purpose: We primarily compared the effectiveness of combined pelvic floor muscle training (PFMT) and duloxetine with imitation PFMT and placebo for 12 weeks in women with stress urinary incontinence (SUI). In addition, we compared the effectiveness of combined treatment with single treatments, single treatments with each other and single treatments with no treatment., Materials and Methods: This blinded, doubly controlled, randomized trial enrolled 201 women 18 to 75 years old with SUI at 17 incontinence centers in the Netherlands, United Kingdom and United States. Women averaged 2 or more incontinence episodes daily and were randomized to 1 of 4 combinations of 80 mg duloxetine daily, placebo, PFMT and imitation PFMT, including combined treatment (in 52), no active treatment (in 47), PFMT only (in 50) and duloxetine only (in 52). The primary efficacy measure was incontinence episode frequency. Other efficacy variables included the number of continence pads used and the Incontinence Quality of Life questionnaire score., Results: The intent to treat population incontinence episode frequency analysis demonstrated the superiority of duloxetine with or without PFMT compared with no treatment or with PFMT alone. However, pad and Incontinence Quality of Life analyses suggested greater improvement with combined treatment than single treatment. A completer population analysis demonstrated the efficacy of duloxetine with or without PFMT and suggested combined treatment was more effective than either treatment alone., Conclusions: The data support significant efficacy of combined PFMT and duloxetine in the treatment of women with SUI. We hypothesize that complementary modes of action of duloxetine and PFMT may result in an additive effect of combined treatment.