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1.
BMC Med Educ ; 24(1): 407, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38610013

RESUMEN

BACKGROUND: Simulation-based training courses in laparoscopy have become a fundamental part of surgical training programs. Surgical skills in laparoscopy are challenging to master, and training in these skills induces stress responses in trainees. There is limited data on trainees' stress levels, the stress responses related to training on different laparoscopic simulators, and how previous experiences influence trainees' stress response during a course. This study investigates physiologic, endocrine and self-reported stress responses during simulation-based surgical skills training in a course setting. METHODS: We conducted a prospective observational study of trainees attending basic laparoscopic skills training courses at a national training centre. During the three-day course, participants trained on different laparoscopic simulators: Two box-trainers (the D-box and P.O.P. trainer) and a virtual reality simulator (LAPMentor™). Participants' stress responses were examined through heart rate variability (HRV), saliva cortisol, and the State Trait Anxiety Inventory-6 (STAI-6). The correlation between previous laparoscopic experiences and stress response measurements was explored. RESULTS: Twenty-four surgical trainees were included in the study. Compared to resting conditions, stress measures were significantly higher during simulation-training activity (the D-box (SDNN = 58.5 ± 23.4; LF/HF-ratio = 4.58 ± 2.71; STAI-6 = 12.3 ± 3.9, P < 0.05), the P.O.P trainer (SDNN = 55.7 ± 7.4; RMSSD = 32.4 ± 17.1; STAI-6 = 12.1 ± 3.9, P < 0.05), and the LAPMentor™ (SDNN = 59.1 ± 18.5; RMSSD = 34.3 ± 19.7; LF/HF-ratio = 4.71 ± 2.64; STAI-6 = 9.9 ± 3.0, P < 0.05)). A significant difference in endocrine stress response was seen for the simulation-training activity on the D-box (saliva cortisol: 3.48 ± 1.92, P < 0.05), however, no significant differences were observed between the three simulators. A moderate correlation between surgical experience, and physiologic and endocrine stress response was observed (RMSSD: r=-0.31; SDNN: r=-0.42; SD2/SD1 ratio: r = 0.29; Saliva cortisol: r = 0.46; P < 0.05), and a negative moderate correlation to self-reported stress (r=-0.42, P < 0.05). CONCLUSION: Trainees have a significant higher stress response during simulation-training compared to resting conditions, with no difference in stress response between the simulators. Significantly higher cortisol levels were observed on the D-box, indicating that simulation tasks with time pressure stress participants the most. Trainees with more surgical experience are associated with higher physiologic stress measures, but lower self-reported stress scores, demonstrating that surgical experience influences trainees' stress response during simulation-based skills training courses.


Asunto(s)
Laparoscopía , Entrenamiento Simulado , Humanos , Simulación por Computador , Frecuencia Cardíaca , Hidrocortisona , Estudios Prospectivos
2.
Antimicrob Agents Chemother ; 68(5): e0158423, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38526046

RESUMEN

Rezafungin is a long-acting, intravenously administered echinocandin for the treatment of candidemia and invasive candidiasis (IC). Non-inferiority of rezafungin vs caspofungin for the treatment of adults with candidemia and/or IC was demonstrated in the Phase 3 ReSTORE study based on the primary endpoints of day 14 global cure and 30-day all-cause mortality. Here, an analysis of ReSTORE data evaluating efficacy outcomes by baseline Candida species is described. Susceptibility testing was performed for Candida species using the Clinical and Laboratory Standards Institute reference broth microdilution method. There were 93 patients in the modified intent-to-treat population who received rezafungin; 94 received caspofungin. Baseline Candida species distribution was similar in the two treatment groups; C. albicans (occurring in 41.9% and 42.6% of patients in the rezafungin and caspofungin groups, respectively), C. glabrata (25.8% and 26.6%), and C. tropicalis (21.5% and 18.1%) were the most common pathogens. Rates of global cure and mycological eradication at day 14 and day 30 all-cause mortality by Candida species were comparable in the rezafungin and caspofungin treatment groups and did not appear to be impacted by minimal inhibitory concentration (MIC) values for either rezafungin or caspofungin. Two patients had baseline isolates with non-susceptible MIC values (both in the rezafungin group: one non-susceptible to rezafungin and one to caspofungin, classified as intermediate); both were candidemia-only patients in whom rezafungin treatment was successful based on the day 30 all-cause mortality endpoint. This analysis of ReSTORE demonstrated the efficacy of rezafungin for candidemia and IC in patients infected with a variety of Candida species.


Asunto(s)
Antifúngicos , Candidemia , Candidiasis Invasiva , Caspofungina , Equinocandinas , Pruebas de Sensibilidad Microbiana , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antifúngicos/uso terapéutico , Antifúngicos/farmacología , Candida/efectos de los fármacos , Candida albicans/efectos de los fármacos , Candida glabrata/efectos de los fármacos , Candida tropicalis/efectos de los fármacos , Candidemia/tratamiento farmacológico , Candidemia/mortalidad , Candidemia/microbiología , Candidiasis Invasiva/tratamiento farmacológico , Candidiasis Invasiva/microbiología , Candidiasis Invasiva/mortalidad , Caspofungina/uso terapéutico , Caspofungina/farmacología , Equinocandinas/uso terapéutico , Equinocandinas/farmacología , Lipopéptidos/uso terapéutico , Resultado del Tratamiento
3.
Clin Infect Dis ; 78(6): 1473-1481, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38297916

RESUMEN

BACKGROUND: Novel treatments are needed for Staphylococcus aureus bacteremia, particularly for methicillin-resistant S. aureus (MRSA). Exebacase is a first-in-class antistaphylococcal lysin that is rapidly bactericidal and synergizes with antibiotics. METHODS: In Direct Lysis of Staph Aureus Resistant Pathogen Trial of Exebacase (DISRUPT), a superiority-design phase 3 study, patients with S. aureus bacteremia/endocarditis were randomly assigned to receive a single dose of intravenous exebacase or placebo in addition to standard-of-care antibiotics. The primary efficacy outcome was clinical response at day 14 in the MRSA population. RESULTS: A total of 259 patients were randomized before the study was stopped for futility based on the recommendation of the unblinded Data Safety Monitoring Board. Clinical response rates at day 14 in the MRSA population (n = 97) were 50.0% (exebacase + antibiotics; 32/64) versus 60.6% (antibiotics alone; 20/33) (P = .392). Overall, rates of adverse events were similar across groups. No adverse events of hypersensitivity related to exebacase were reported. CONCLUSIONS: Exebacase + antibiotics failed to improve clinical response at day 14 in patients with MRSA bacteremia/endocarditis. This result was unexpected based on phase 2 data that established proof-of-concept for exebacase + antibiotics in patients with MRSA bacteremia/endocarditis. In the antibiotics-alone group, the clinical response rate was higher than that seen in phase 2. Heterogeneity within the study population and a relatively small sample size in either the phase 2 or phase 3 studies may have increased the probability of imbalances in the multiple components of day 14 clinical outcome. This study provides lessons for future superiority studies in S. aureus bacteremia/endocarditis. Clinical Trials Registration.NCT04160468.


Asunto(s)
Antibacterianos , Bacteriemia , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Humanos , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Masculino , Femenino , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Persona de Mediana Edad , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Anciano , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Adulto , Endocarditis Bacteriana/tratamiento farmacológico , Endocarditis Bacteriana/microbiología , Resultado del Tratamiento , Nivel de Atención , Quimioterapia Combinada , Staphylococcus aureus/efectos de los fármacos
4.
Lancet Infect Dis ; 24(3): 319-328, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38008099

RESUMEN

BACKGROUND: Rezafungin, a new US Food and Drug Administration-approved, long-acting echinocandin to treat candidaemia and invasive candidiasis, was efficacious with a similar safety profile to caspofungin in clinical trials. We conducted pooled analyses of the phase 2 STRIVE and phase 3 ReSTORE rezafungin trials. METHODS: ReSTORE was a multicentre, double-blind, double-dummy, randomised phase 3 trial conducted at 66 tertiary care centres in 15 countries. STRIVE was a multicentre, double-blind, double-dummy, randomised phase 2 trial conducted at 44 centres in 10 countries. Adults (≥18 years) with candidaemia or invasive candidiasis were treated with once-a-week intravenous rezafungin (400 mg and 200 mg) or once-a-day intravenous caspofungin (70 mg and 50 mg). Efficacy was evaluated in a pooled modified intent-to-treat (mITT) population. Primary efficacy endpoint was day 30 all-cause mortality (tested for non-inferiority with a pre-specified margin of 20%). Secondary efficacy endpoint was mycological response. Safety was also evaluated. The STRIVE and ReSTORE trials are registered with ClinicalTrials.gov, NCT02734862 and NCT03667690, and both studies are complete. FINDINGS: ReSTORE was conducted from Oct 12, 2018, to Oct 11, 2021, and STRIVE from July 26, 2016, to April 18, 2019. The mITT population, pooling the data from the two trials, comprised 139 patients for rezafungin and 155 patients for caspofungin. Day 30 all-cause mortality rates were comparable between groups (19% [26 of 139] for the rezafungin group and 19% [30 of 155] for the caspofungin group) and the upper bound of the 95% CI for the weighted treatment difference was below 10% (-1·5% [95% CI -10·7 to 7·7]). Mycological eradication occurred by day 5 in 102 (73%) of 139 rezafungin patients and 100 (65%) of 155 caspofungin patients (weighted treatment difference 10·0% [95% CI -0·3 to 20·4]). Safety profiles were similar across groups. INTERPRETATION: Rezafungin was non-inferior to caspofungin for all-cause mortality, with a potential early treatment benefit, possibly reflecting rezafungin's front-loaded dosing regimen. These findings are of clinical importance in fighting active and aggressive infections and reducing the morbidity and mortality caused by candidaemia and invasive candidiasis. FUNDING: Melinta Therapeutics and Cidara Therapeutics.


Asunto(s)
Candidemia , Candidiasis Invasiva , Candidiasis , Adulto , Humanos , Caspofungina/uso terapéutico , Antifúngicos/efectos adversos , Estudios Prospectivos , Resultado del Tratamiento , Equinocandinas/efectos adversos , Candidemia/tratamiento farmacológico , Candidiasis Invasiva/tratamiento farmacológico , Método Doble Ciego , Ensayos Clínicos Controlados Aleatorios como Asunto
5.
Open Forum Infect Dis ; 10(6): ofad279, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37351456

RESUMEN

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.

8.
Lancet ; 401(10370): 49-59, 2023 01 07.
Artículo en Inglés | MEDLINE | ID: mdl-36442484

RESUMEN

BACKGROUND: Rezafungin is a next-generation, once-a-week echinocandin in development for the treatment of candidaemia and invasive candidiasis and for the prevention of invasive fungal disease caused by Candida, Aspergillus, and Pneumocystis spp after blood and marrow transplantation. We aimed to compare the efficacy and safety of intravenous rezafungin versus intravenous caspofungin in patients with candidaemia and invasive candidiasis. METHODS: ReSTORE was a multicentre, double-blind, double-dummy, randomised phase 3 trial done at 66 tertiary care centres in 15 countries. Adults (≥18 years) with systemic signs and mycological confirmation of candidaemia or invasive candidiasis were eligible for inclusion and randomly assigned (1:1) to receive intravenous rezafungin once a week (400 mg in week 1, followed by 200 mg weekly, for a total of two to four doses) or intravenous caspofungin (70 mg loading dose on day 1, followed by 50 mg daily) for no more than 4 weeks. The primary endpoints were global cure (consisting of clinical cure, radiological cure, and mycological eradication) at day 14 for the European Medical Agency (EMA) and 30-day all-cause mortality for the US Food and Drug Administration (FDA), both with a target non-inferiority margin of 20%, assessed in the modified intention-to-treat population (all patients who received one or more doses of study drug and had documented Candida infection based on a culture from blood or another normally sterile site obtained within 96 h before randomisation). Safety was evaluated by the incidence and type of adverse events and deaths in the safety population, defined as all patients who received any amount of study drug. The trial is registered with ClinicalTrials.gov, NCT03667690, and is complete. FINDINGS: Between Oct 12, 2018, and Aug 29, 2021, 222 patients were screened for inclusion, and 199 patients (118 [59%] men; 81 [41%] women; mean age 61 years [SD 15·2]) were randomly assigned (100 [50%] patients to the rezafungin group and 99 [50%] patients to the caspofungin group). 55 (59%) of 93 patients in the rezafungin group and 57 (61%) of 94 patients in the caspofungin group had a global cure at day 14 (weighted treatment difference -1·1% [95% CI -14·9 to 12·7]; EMA primary endpoint). 22 (24%) of 93 patients in the rezafungin group and 20 (21%) of 94 patients in the caspofungin group died or had an unknown survival status at day 30 (treatment difference 2·4% [95% CI -9·7 to 14·4]; FDA primary endpoint). In the safety analysis, 89 (91%) of 98 patients in the rezafungin group and 83 (85%) of 98 patients in the caspofungin group had at least one treatment-emergent adverse event. The most common treatment-emergent adverse events that occurred in at least 5% of patients in either group were pyrexia, hypokalaemia, pneumonia, septic shock, and anaemia. 55 (56%) patients in the rezafungin group and 52 (53%) patients in the caspofungin group had serious adverse events. INTERPRETATION: Our data show that rezafungin was non-inferior to caspofungin for the primary endpoints of day-14 global cure (EMA) and 30-day all-cause mortality (FDA). Efficacy in the initial days of treatment warrants evaluation. There were no concerning trends in treatment-emergent or serious adverse events. These phase 3 results show the efficacy and safety of rezafungin and support its ongoing development. FUNDING: Cidara Therapeutics and Mundipharma.


Asunto(s)
Candidiasis Invasiva , Adulto , Masculino , Humanos , Femenino , Persona de Mediana Edad , Caspofungina/uso terapéutico , Administración Intravenosa , Candidiasis Invasiva/tratamiento farmacológico , Método Doble Ciego , Resultado del Tratamiento
9.
Clin Infect Dis ; 76(1): 78-88, 2023 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-36068705

RESUMEN

BACKGROUND: Sulopenem is a thiopenem antibiotic being developed for the treatment of multidrug-resistant infections. The availability of both intravenous (IV) and oral formulations will facilitate earlier hospital discharge. METHODS: Hospitalized adults with pyuria, bacteriuria, and signs and symptoms of complicated urinary tract infection (cUTI) were randomized to 5 days of IV sulopenem followed by oral sulopenem etzadroxil/probenecid or 5 days of IV ertapenem followed by oral ciprofloxacin or amoxicillin-clavulanate, depending on uropathogen susceptibility. The primary end point was overall combined clinical and microbiologic response at the test-of-cure visit (day 21). RESULTS: Of 1392 treated patients, 444 and 440 treated with sulopenem and ertapenem, respectively, had a positive baseline urine culture and were eligible for the primary efficacy analyses. Extended-spectrum ß-lactamase-producing organisms were identified in 26.6% of patients and fluoroquinolone-nonsusceptible pathogens in 38.6%. For the primary end point, noninferiority of sulopenem to the comparator regimen was not demonstrated, 67.8% vs 73.9% (difference, -6.1%; 95% confidence interval, -12.0 to -.1%). The difference was driven by a lower rate of asymptomatic bacteriuria in the subgroup of ertapenem-treated patients who stepped down to ciprofloxacin. No substantial difference in overall response was observed at any other time point. Both IV and oral formulations of sulopenem were well-tolerated and compared favorably to the comparator. CONCLUSIONS: Sulopenem followed by oral sulopenem-etzadroxil/probenecid was not noninferior to ertapenem followed by oral step-down therapy for the treatment of cUTIs, driven by a lower rate of asymptomatic bacteriuria in those who received ciprofloxacin. Both formulations of sulopenem were well-tolerated. CLINICAL TRIAL REGISTRATION: NCT03357614.


Asunto(s)
Bacteriuria , Pielonefritis , Infecciones Urinarias , Adulto , Humanos , Ertapenem/uso terapéutico , Bacteriuria/tratamiento farmacológico , Infecciones Urinarias/microbiología , Antibacterianos , Pielonefritis/tratamiento farmacológico , Ciprofloxacina/uso terapéutico
10.
Clin Infect Dis ; 76(1): 66-77, 2023 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-36069202

RESUMEN

BACKGROUND: There are limited treatment options for uncomplicated urinary tract infection (uUTI) caused by resistant pathogens. Sulopenem etzadroxil/probenecid (sulopenem) is an oral thiopenem antibiotic active against multidrug-resistant pathogens that cause uUTIs. METHODS: Patients with uUTI were randomized to 5 days of sulopenem or 3 days of ciprofloxacin. The primary endpoint was overall success, defined as both clinical and microbiologic response at day 12. In patients with ciprofloxacin-nonsusceptible baseline pathogens, sulopenem was compared for superiority over ciprofloxacin; in patients with ciprofloxacin-susceptible pathogens, the agents were compared for noninferiority. Using prespecified hierarchical statistical testing, the primary endpoint was tested in the combined population if either superiority or noninferiority was declared in the nonsusceptible or susceptible population, respectively. RESULTS: In the nonsusceptible population, sulopenem was superior to ciprofloxacin, 62.6% vs 36.0% (difference, 26.6%; 95% confidence interval [CI], 15.1 to 7.4; P <.001). In the susceptible population, sulopenem was not noninferior to ciprofloxacin, 66.8% vs 78.6% (difference, -11.8%; 95% CI, -18.0 to 5.6). The difference was driven by a higher rate of asymptomatic bacteriuria (ASB) post-treatment in patients on sulopenem. In the combined analysis, sulopenem was noninferior to ciprofloxacin, 65.6% vs 67.9% (difference, -2.3%; 95% CI, -7.9 to 3.3). Diarrhea occurred more frequently with sulopenem (12.4% vs 2.5%). CONCLUSIONS: Sulopenem was noninferior to ciprofloxacin in the treatment of uUTIs. Sulopenem was superior to ciprofloxacin in patients with uUTIs due to ciprofloxacin-nonsusceptible pathogens. Sulopenem was not noninferior in patients with ciprofloxacin-susceptible pathogens, driven largely by a lower rate of ASB in those who received ciprofloxacin. CLINICAL TRIAL REGISTRATION: NCT03354598.


Asunto(s)
Ciprofloxacina , Infecciones Urinarias , Humanos , Femenino , Ciprofloxacina/uso terapéutico , Infecciones Urinarias/microbiología , Antibacterianos , Lactamas/uso terapéutico
11.
Adv Simul (Lond) ; 7(1): 33, 2022 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-36273197

RESUMEN

INTRODUCTION: Stress can affect the ability to acquire technical skills. Simulation-based training (SBT) courses allow surgical trainees to train their technical skills away from stressful clinical environments. Trainees' subjective experiences of stress during SBT courses on laparoscopic surgery remains understudied. Here, we explored the subjective stress experiences of surgical trainees during mandatory laparoscopic SBT courses. We aimed to obtain a broader understanding of which factors of the simulation training the trainees perceived as eliciting stress. METHODS: A qualitative study with semistructured individual interviews was undertaken to explore trainees' subjective experiences of stress. Twenty surgical trainees participated while attending courses at a national training center for advanced laparoscopic surgery. Questions explored trainees' stress experiences during the SBT courses with a focus on perceived stressors related to laparoscopic simulation training on two box-trainers and one virtual reality simulator. Interview data were analyzed using inductive, qualitative content analysis methods to identify codes, categories, and themes. RESULTS: Findings indicated that trainees have a variety of stress experiences during laparoscopic SBT. Three main themes were identified to be related to stress experiences: simulation task requirements, psychomotor skill levels and internal pressures, with subcategories such as task difficulty and time requirements, unrealistic haptic feedback and realism of graphics, inconsistent and poor technical performance, and self-imposed pressures and socio-evaluative threats. CONCLUSIONS: Insights into surgical trainees' experience of stress during laparoscopic SBT courses showed that some stress experiences were directly related to simulation training, while others were of psychological nature. The technical and efficiency requirements of simulation tasks elicited stress experiences among trainees with less laparoscopic experience and lower levels of psychomotor skills. Self-imposed pressures played an integral part in how trainees mobilized and performed during the courses, suggesting that levels of stress might enhance laparoscopic simulation performance. For course facilitators aiming at optimizing future laparoscopic SBT courses, attending to the realism, providing clarity about learning objectives, and having awareness of individual differences among trainees' technical level when designing the simulation tasks, would be beneficial. Equally important to the laparoscopic SBT is to create a psychological safe learning space in order to reduce the internal pressures of trainees.

12.
JGH Open ; 6(6): 421-426, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35774346

RESUMEN

Background: Irritable bowel syndrome (IBS) is a very common gastrointestinal disorder worldwide, but research regarding this disease is rare in Bangladesh. This study aimed to assess the prevalence of IBS and its associated risk factors among university students in Bangladesh. Methods: This is a cross-sectional study. A total of 300 randomly selected participants were included in this study. By using a structured questionnaire and anthropometric methods, we collected all the required data for our study. The diagnosis of IBS was based on Rome III criteria. Results: The overall prevalence of IBS was 39.3%, but the majority (77.3%) had no basic awareness of IBS. In our study, anxiety and depression (χ 2 = 6.817; odds ratio [OR] = 1.910; 95% confidence interval [CI] = 1.172, 3.113; P = 0.011) had a significant relationship with IBS and IBS had a significant (P < 0.001) relationship with food intolerance (χ 2 = 8.737; OR = 2.130; 95% CI = 1.284, 3.531), chest pain (χ 2 = 7.482; OR = 2.035; 95% CI = 1.218, 3.401), and insomnia (χ 2 = 19.320; OR = 2.907; 95% CI = 1.794, 4.709). In our dietary data, the intake patterns of vegetables (P = 0.000), fast food (P = 0.000), and tea-coffee (P = 0.003) showed a strong significant association with IBS. On the other hand, monthly household income (P = 0.154) and body mass index (BMI) (P = 0.138) showed no significant association with IBS. Among our study subjects, IBS-constipation (54.2%) was more common than IBS-diarrhea (27.1%) and IBS-mixed (18.6%). Moreover, among the 118 IBS respondents, 67.8% had a headache with increased flatulence (95.8%) as the most common IBS-related complication. Conclusion: IBS is common in university students of Bangladesh and is associated with anxiety, depression, and particular dietary patterns.

13.
J Glob Antimicrob Resist ; 29: 434-443, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-34788694

RESUMEN

OBJECTIVES: Lefamulin, a pleuromutilin antibiotic approved for community-acquired bacterial pneumonia (CABP), was evaluated for microbiological efficacy in a prespecified pooled analysis of LEAP 1 and 2 phase 3 clinical trial data in patients with CABP. METHODS: In LEAP 1, adults (PORT risk class III‒V) received intravenous (IV) lefamulin 150 mg every 12 h (q12h) for 5‒7 days or moxifloxacin 400 mg every 24 h (q24h) for 7 days, with optional IV-to-oral switch. In LEAP 2, adults (PORT II‒IV) received oral lefamulin 600 mg q12h for 5 days or moxifloxacin 400 mg q24h for 7 days. Primary outcomes were early clinical response (ECR) at 96 ± 24 h after treatment start and investigator assessment of clinical response (IACR) 5‒10 days after the last dose. Secondary outcomes included ECR and IACR in patients with a baseline CABP pathogen (detected via culture, urinary antigen testing, serology and/or real-time PCR). RESULTS: Baseline CABP pathogens were detected in 709/1289 patients (55.0%; microbiological intention-to-treat population). The most frequently identified pathogens were Streptococcus pneumoniae (61.9% of patients) and Haemophilus influenzae (29.9%); 25.1% had atypical pathogens and 33.1% had polymicrobial infections. Pathogens were identified most frequently by PCR from sputum, followed by culture from respiratory specimens. In patients with baseline CABP pathogens, ECR rates were 89.3% (lefamulin) and 93.0% (moxifloxacin); IACR success rates were 83.2% and 86.7%, respectively. Results were consistent across CABP pathogens, including drug-resistant isolates and polymicrobial infections. CONCLUSION: Lefamulin is a valuable IV and oral monotherapy option for empirical and directed CABP treatment in adults.


Asunto(s)
Coinfección , Infecciones Comunitarias Adquiridas , Neumonía Bacteriana , Adulto , Bacterias , Coinfección/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/microbiología , Diterpenos , Humanos , Pruebas de Sensibilidad Microbiana , Moxifloxacino/uso terapéutico , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Bacteriana/microbiología , Compuestos Policíclicos , Tioglicolatos
14.
Antibiotics (Basel) ; 10(12)2021 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-34943700

RESUMEN

Lefamulin was the first systemic pleuromutilin antibiotic approved for intravenous and oral use in adults with community-acquired bacterial pneumonia based on two phase 3 trials (Lefamulin Evaluation Against Pneumonia [LEAP]-1 and LEAP-2). This pooled analysis evaluated lefamulin efficacy and safety in adults with community-acquired bacterial pneumonia caused by atypical pathogens (Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydia pneumoniae). In LEAP-1, participants received intravenous lefamulin 150 mg every 12 h for 5-7 days or moxifloxacin 400 mg every 24 h for 7 days, with optional intravenous-to-oral switch. In LEAP-2, participants received oral lefamulin 600 mg every 12 h for 5 days or moxifloxacin 400 mg every 24 h for 7 days. Primary outcomes were early clinical response at 96 ± 24 h after first dose and investigator assessment of clinical response at test of cure (5-10 days after last dose). Atypical pathogens were identified in 25.0% (91/364) of lefamulin-treated patients and 25.2% (87/345) of moxifloxacin-treated patients; most were identified by ≥1 standard diagnostic modality (M. pneumoniae 71.2% [52/73]; L. pneumophila 96.9% [63/65]; C. pneumoniae 79.3% [46/58]); the most common standard diagnostic modality was serology. In terms of disease severity, more than 90% of patients had CURB-65 (confusion of new onset, blood urea nitrogen > 19 mg/dL, respiratory rate ≥ 30 breaths/min, blood pressure <90 mm Hg systolic or ≤60 mm Hg diastolic, and age ≥ 65 years) scores of 0-2; approximately 50% of patients had PORT (Pneumonia Outcomes Research Team) risk class of III, and the remaining patients were more likely to have PORT risk class of II or IV versus V. In patients with atypical pathogens, early clinical response (lefamulin 84.4-96.6%; moxifloxacin 90.3-96.8%) and investigator assessment of clinical response at test of cure (lefamulin 74.1-89.7%; moxifloxacin 74.2-97.1%) were high and similar between arms. Treatment-emergent adverse event rates were similar in the lefamulin (34.1% [31/91]) and moxifloxacin (32.2% [28/87]) groups. Limitations to this analysis include its post hoc nature, the small numbers of patients infected with atypical pathogens, the possibility of PCR-based diagnostic methods to identify non-etiologically relevant pathogens, and the possibility that these findings may not be generalizable to all patients. Lefamulin as short-course empiric monotherapy, including 5-day oral therapy, was well tolerated in adults with community-acquired bacterial pneumonia and demonstrated high clinical response rates against atypical pathogens.

15.
Health Expect ; 24(5): 1780-1789, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34289215

RESUMEN

BACKGROUND: Cancer patient pathways (CPPs) were implemented in Norway in 2015-2017 to advance cancer diagnostics and treatment initiation. The aim of CPPs is to ensure standardized waiting times, but also to strengthen patient participation and shared decision-making. This study investigates how patients enrolled in a CPP experienced shared decision-making. METHODS: This study comprised of 19 individual semistructured interviews with patients who had been enrolled in a CPP at three hospitals in Norway. Twelve patients had breast cancer, four patients had prostate cancer and three patients had malignant melanoma. We analyzed their experiences using a narrative approach. FINDINGS: This study showed how participating in a standardized CPP provided different possibilities for shared decision-making. The patients' narratives of shared decision-making in CPPs included stories from the three cancer diagnoses through the following themes: (1) The predictable safeness of standardizations, (2) the ambivalence of making decisions and (3) opposing standardizations and pushing for action. CONCLUSION: Standardized CPPs provided patients with predictability and safety. Shared decision-making was possible when the cancer diagnoses supported preference-sensitive treatment options. Balancing standardizations with individualized care is necessary to facilitate patient participation in CPPs, and the possibility of shared decision-making needs to be discussed for each specific CPP. PATIENT OR PUBLIC CONTRIBUTION: A service user representative from the Norwegian Cancer Society participated in designing this study.


Asunto(s)
Neoplasias de la Mama , Toma de Decisiones Conjunta , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/terapia , Toma de Decisiones , Humanos , Masculino , Noruega , Evaluación del Resultado de la Atención al Paciente , Participación del Paciente
16.
Open Forum Infect Dis ; 8(6): ofab136, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34160473

RESUMEN

In this post hoc analysis of the 63 patients with secondary bacteremia enrolled in the 3 omadacycline phase 3 studies of acute bacterial skin/skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP), we determined that omadacycline is a viable therapeutic option for appropriate patients with secondary bacteremia.

17.
Open Forum Infect Dis ; 8(6): ofab135, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34160474

RESUMEN

BACKGROUND: Severity/mortality risk scores and disease characteristics may assist in deciding whether patients with community-acquired bacterial pneumonia (CABP) require outpatient treatment or hospitalization. The phase 3 OPTIC (Omadacycline for Pneumonia Treatment In the Community) study enrolled patients with Pneumonia Outcomes Research Team (PORT) risk class II-IV. Omadacycline demonstrated noninferiority to moxifloxacin in adults with CABP, at early clinical response (ECR) and posttreatment evaluation (PTE). We assessed efficacy of omadacycline versus moxifloxacin in these patients based on disease severity. METHODS: Patients were randomized 1:1 to receive intravenous (IV) omadacycline (100 mg every 12 hours for 2 doses followed by 100 mg daily [q24h], with optional transition to omadacycline 300 mg orally q24h after 3 days of IV treatment) or moxifloxacin IV 400 mg q24h (with optional transition to 400 mg orally q24h after 3 days of IV treatment). Total treatment duration was 7-14 days. We compared rates of early clinical success (72-120 hours after first dose) and investigator-assessed clinical success at PTE (5-10 days after last dose) in subgroups based (1) on severity/mortality risk scores (PORT, CURB-65, systemic inflammatory response syndrome, quick Sequential [Sepsis-related] Organ Failure Assessment, modified ATS, SMART-COP) and (2) on presence of baseline radiographic characteristics, chronic obstructive pulmonary disease (COPD)/asthma, or bacteremia. RESULTS: Altogether, 774 patients (omadacycline, n = 386; moxifloxacin, n = 388) were randomized. Clinical success rates (ECR/PTE) were similar between treatment groups (across all subgroups). Efficacy across treatment groups was similar in patients with baseline radiographic characteristics or COPD/asthma, but moxifloxacin had higher clinical success rates in patients with bacteremia. CONCLUSIONS: Efficacy of omadacycline was similar to that of moxifloxacin, regardless of disease severity/mortality risk and disease characteristics.

18.
BMC Pulm Med ; 21(1): 154, 2021 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-33964925

RESUMEN

BACKGROUND: Lefamulin, a first-in-class pleuromutilin antibiotic approved for intravenous and oral use in adults with community-acquired bacterial pneumonia (CABP), was noninferior to moxifloxacin in the Lefamulin Evaluation Against Pneumonia (LEAP) 1 intravenous-to-oral switch study and the LEAP 2 oral-only study. Using pooled LEAP 1/2 data, we examined lefamulin efficacy/safety overall and within subgroups of patients presenting with comorbidities typical in CABP management. METHODS: In LEAP 1, adults with CABP were randomized to receive intravenous lefamulin (150 mg every 12 h) for 5‒7 days or moxifloxacin (400 mg every 24 h) for 7 days, with optional intravenous-to-oral switch if predefined improvement criteria were met. In LEAP 2, adults with CABP were randomized to receive oral lefamulin (600 mg every 12 h) for 5 days or moxifloxacin (400 mg every 24 h) for 7 days. Both studies assessed early clinical response (ECR) at 96 ± 24 h after first study drug dose and investigator assessment of clinical response (IACR) at test-of-cure (5‒10 days after last dose). Pooled analyses of the overall population used a 10% noninferiority margin. RESULTS: Lefamulin (n = 646) was noninferior to moxifloxacin (n = 643) for ECR (89.3% vs 90.5%, respectively; difference - 1.1%; 95% CI - 4.4 to 2.2); IACR success rates at test-of-cure were similarly high (≥ 85.0%). High efficacy with both lefamulin and moxifloxacin was also demonstrated across all well-represented patient subgroups, including those with advanced age, diabetes mellitus, a history of cardiovascular diseases (e.g., hypertension, congestive heart failure, or arrhythmia) or chronic lung diseases (e.g., asthma or chronic obstructive pulmonary disease), elevated liver enzymes, or mild-to-moderate renal dysfunction. No new safety signals were identified. CONCLUSIONS: Lefamulin may provide a valuable intravenous/oral monotherapy alternative to fluoroquinolones or macrolides for empiric treatment of patients with CABP, including cases of patients at risk for poor outcomes due to age or various comorbidities. TRIAL REGISTRATION: ClinicalTrials.gov LEAP 1 (NCT02559310; Registration Date: 24/09/2015) and LEAP 2 (NCT02813694; Registration Date: 27/06/2016).


Asunto(s)
Antibacterianos/uso terapéutico , Diterpenos/administración & dosificación , Fluoroquinolonas/administración & dosificación , Moxifloxacino/administración & dosificación , Neumonía Bacteriana/tratamiento farmacológico , Compuestos Policíclicos/administración & dosificación , Tioglicolatos/administración & dosificación , Administración Intravenosa , Administración Oral , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Comorbilidad , Diterpenos/efectos adversos , Método Doble Ciego , Femenino , Fluoroquinolonas/efectos adversos , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Moxifloxacino/efectos adversos , Compuestos Policíclicos/efectos adversos , Tioglicolatos/efectos adversos , Estados Unidos , Adulto Joven
19.
Int J Infect Dis ; 104: 501-509, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33484864

RESUMEN

OBJECTIVE: Community-acquired bacterial pneumonia (CABP) is a major clinical burden worldwide. In the phase III OPTIC study (NCT02531438) in CABP, omadacycline was found to be non-inferior to moxifloxacin for investigator-assessed clinical response (IACR) at post-treatment evaluation (PTE, 5-10 days after last dose). This article reports the efficacy findings, as specified in the European Medicines Agency (EMA) guidance. METHODS: Patients were randomized 1:1 to omadacycline 100 mg intravenously (every 12 h for two doses, then every 24 h) with optional transition to 300 mg orally after 3 days, or moxifloxacin 400 mg intravenously (every 24 h) with optional transition to 400 mg orally after 3 days. The total treatment duration was 7-14 days. The primary endpoint for EMA efficacy analysis was IACR at PTE in patients with Pneumonia Patient Outcomes Research Team (PORT) risk class III and IV. RESULTS: In total, 660 patients were randomized as PORT risk class III and IV. Omadacycline was non-inferior to moxifloxacin at PTE. The clinical success rates were 88.4% and 85.2%, respectively [intent-to-treat population; difference 3.3; 97.5% confidence interval (CI) -2.7 to 9.3], and 92.5% and 90.5%, respectively (clinically evaluable population; difference 2.0; 97.5% CI 3.2-7.4). Clinical success rates with omadacycline and moxifloxacin were similar against identified pathogens and across key subgroups. CONCLUSIONS: Omadacycline was non-inferior to moxifloxacin for IACR at PTE, with high clinical success across pathogen types and patient subgroups.


Asunto(s)
Antibacterianos/uso terapéutico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Moxifloxacino/uso terapéutico , Neumonía Bacteriana/tratamiento farmacológico , Tetraciclinas/uso terapéutico , Administración Intravenosa , Anciano , Antibacterianos/administración & dosificación , Infecciones Comunitarias Adquiridas/microbiología , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Moxifloxacino/administración & dosificación , Neumonía Bacteriana/microbiología , Tetraciclinas/administración & dosificación
20.
Clin Infect Dis ; 73(11): e3647-e3655, 2021 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-32955088

RESUMEN

BACKGROUND: Rezafungin (RZF) is a novel echinocandin exhibiting distinctive pharmacokinetics/pharmacodynamics. STRIVE was a phase 2, double-blind, randomized trial designed to compare the safety and efficacy of RZF once weekly (QWk) to caspofungin (CAS) once daily for treatment of candidemia and/or invasive candidiasis (IC). METHODS: Adults with systemic signs and mycological confirmation of candidemia and/or IC were randomized to RZF 400 mg QWk (400 mg), RZF 400 mg on week 1 then 200 mg QWk (400/200 mg), or CAS 70 mg as a loading dose followed by 50 mg daily for ≤4 weeks. Efficacy assessments included overall cure (resolution of signs of candidemia/IC + mycological eradication) at day 14 (primary endpoint), investigator-assessed clinical response at day 14, and 30-day all-cause mortality (ACM) (secondary endpoints), and time to negative blood culture. Safety was evaluated by adverse events and ACM through follow-up. RESULTS: Of 207 patients enrolled, 183 were in the microbiological intent-to-treat population (~21% IC). Overall cure rates were 60.5% (46/76) for RZF 400 mg, 76.1% (35/46) for RZF 400/200 mg, and 67.2% (41/61) for CAS; investigator-assessed clinical cure rates were 69.7% (53/76), 80.4% (37/46), and 70.5% (43/61), respectively. In total, 30-day ACM was 15.8% for RZF 400 mg, 4.4% for RZF 400/200 mg, and 13.1% for CAS. Candidemia was cleared in 19.5 and 22.8 hours in RZF and CAS patients, respectively. No concerning safety trends were observed; ACM through follow-up was 15.2% (21/138) for RZF and 18.8% (13/69) for CAS. CONCLUSIONS: RZF was safe and efficacious in the treatment of candidemia and/or IC. CLINICAL TRIALS REGISTRATION: NCT02734862.


Asunto(s)
Candidemia , Candidiasis Invasiva , Caspofungina , Equinocandinas , Adulto , Antifúngicos/efectos adversos , Candidemia/tratamiento farmacológico , Candidiasis Invasiva/tratamiento farmacológico , Caspofungina/efectos adversos , Método Doble Ciego , Equinocandinas/efectos adversos , Humanos , Resultado del Tratamiento
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