Weight Loss in Short-Term Interventions for Physical Activity and Nutrition Among Adults With Overweight or Obesity: A Systematic Review and Meta-Analysis.

Introduction: Reaching, enrolling, and retaining participants in lengthy lifestyle change interventions for weight loss is a major challenge. The objective of our meta-analysis was to investigate whether lifestyle interventions addressing nutrition and physical activity lasting 6 months or less are effective for weight loss. Methods: We searched for peer-reviewed studies on lifestyle change interventions of 6 months or less published from 2012 through 2023. Studies were screened based on inclusion criteria, including randomized controlled trials (RCTs) for adults with overweight or obesity. We used a random-effects model to pool the mean difference in weight loss between intervention and control groups. We also performed subgroup analyses by intervention length and control type. Results: Fourteen RCTs were identified and included in our review. Half had interventions lasting less than 13 weeks, and half lasted from 13 to 26 weeks. Seven were delivered remotely, 4 were delivered in person, and 3 used combined methods. The pooled mean difference in weight change was -2.59 kg (95% CI, -3.47 to -1.72). The pooled mean difference measured at the end of the intervention was -2.70 kg (95% CI, -3.69 to -1.71) among interventions lasting less than 13 weeks and -2.40 kg (95% CI, -4.44 to -0.37) among interventions of 13 to 26 weeks. Conclusion: Short-term multicomponent interventions involving physical activity and nutrition can achieve weight loss for adults with overweight or obesity. Offering short-term interventions as alternatives to long-term ones may reach people who otherwise would be unwilling or unable to enroll in or complete longer programs.

Psychometric properties of the World Health Organization WHOQOL-AGE Scale in Singapore.

WHOQOL-AGE is a promising quality of life (QOL) tool that has not been fully validated in Asia. The present study aimed to verify its factor structure and psychometric properties among community-dwelling older adults in Singapore. This study was cross-sectional and used data (N = 593) from the Community Health and Intergenerational study that interviewed older adults between 2018 and 2021. Confirmatory factor analysis (CFA) was used to examine the factor structure of the WHOQOL-AGE, and Cronbach's alpha coefficients were employed to examine internal consistency. Spearman's rho correlations coefficients between WHOQOL-AGE and other related scales (Satisfaction with Life and the Friendship) examined convergent validity. A Pearson's correlation coefficient between WHOQOL-AGE and compassion scale examined discriminant validity. An independent t test was used to demonstrate known-groups validity, examining differences in QOL scores between individuals with and without chronic medical conditions. Findings supported a bifactor model with more satisfactory goodness-of-fit indices than the original two-factor model and the two-correlated factor model. WHOQOL-AGE showed adequate internal consistency (Cronbach's alpha coefficients > .70). Good convergent validity was demonstrated by moderate-to-large correlations between WHOQOL-AGE and satisfaction with life (rs = .54) as well as social connectedness (rs = .33). Discriminant validity was shown by low correlations between WHOQOL-AGE and compassion (r = .19). Findings also indicated good known-groups validity (p < 0.01). The WHOQOL-AGE showed promising psychometric properties using an Asian convenience sample and can be useful in large-scale studies or busy clinical settings.

Socio-demographic and comorbid risk factors for poor prognosis in patients hospitalized with community-acquired bacterial pneumonia in southeastern US.

BACKGROUND: How socio-demographic characteristics and comorbidities affect bacterial community-acquired pneumonia (CAP) prognosis during/after hospitalization is important in disease management. OBJECTIVES: To identify predictors of medical intensive care unit (MICU) admission, length of hospital stay (LOS), in-hospital mortality, and bacterial CAP readmission in patients hospitalized with bacterial CAP. METHODS: ICD-9/10 codes were used to query electronic medical records to identify a cohort of patients hospitalized for bacterial CAP at a tertiary hospital in Southeastern US between 01/01/2013-12/31/2019. Adjusted accelerated failure time and modified Poisson regression models were used to examine predictors of MICU admission, LOS, in-hospital mortality, and 1-year readmission. RESULTS: There were 1956 adults hospitalized with bacterial CAP. Median (interquartile range) LOS was 11 days (6-23), and there were 26 % (513) MICU admission, 14 % (266) in-hospital mortality, and 6 % (117) 1-year readmission with recurrent CAP. MICU admission was associated with heart failure (RR 1.38; 95 % CI 1.17-1.62) and obesity (RR 1.26; 95 % CI 1.04-1.52). Longer LOS was associated with heart failure (adjusted time ratio[TR] 1.27;95 %CI 1.12-1.43), stroke (TR 1.90;95 %CI 1.54,2.35), type 2 diabetes (TR 1.20;95 %CI 1.07-1.36), obesity (TR 1.50;95 %CI 1.31-1.72), Black race (TR 1.17;95 %CI 1.04-1.31), and males (TR 1.24;95 %CI 1.10-1.39). In-hospital mortality was associated with stroke (RR 1.45;95 %CI 1.03-2.04) and age ≥65 years (RR 1.34;95 %CI 1.06-1.68). 1-year readmission was associated with COPD (RR 1.55;95 %CI 1.05-2.27) and underweight BMI (RR 1.74;95 %CI 1.04-2.90). CONCLUSIONS: Comorbidities and socio-demographic characteristics have varying impacts on bacterial CAP in-hospital prognosis and readmission. More studies are warranted to confirm these findings to develop comprehensive care plans and inform public health interventions.

The Prevalence of Urinary Tract Infections and Antibiotic Prescription Treatments Across Three Countries: A Retrospective Study Using an Electronic Medical Record.

Introduction The Clinical Rotation Evaluation and Documentation Organizer (CREDO) is an electronic medical record (EMR) system created by the Edward Via College of Osteopathic Medicine (VCOM). International healthcare providers who partner with VCOM can gain access to CREDO and input their patient data. The objective of this study was to determine the frequency of urinary tract infection (UTI) diagnoses and prescription use over a one-year period in three Latin American countries. Methods Researchers analyzed the frequency of UTI diagnosis with corresponding prescription recommendations over a 12-month period in three Latin American countries (i.e., Dominican Republic, El Salvador, and Honduras) that utilize the CREDO system. For each month between May 2021 and May 2022, the total number of UTI diagnosis codes and prescription codes were summed, graphed, and analyzed. Results In El Salvador, there were 142 UTIs and 126 corresponding prescriptions written for UTIs reported from May 2021 to May 2022 but diagnoses were not consistent each month. Ciprofloxacin was prescribed most frequently at a rate of 43.7% in El Salvador. In Honduras, there were 68 UTIs and 68 corresponding prescriptions written for the UTIs reported from May 2021 until May 2022 with Ciprofloxacin being prescribed most frequently at a rate of 39.7%. Again, diagnosis frequency was not consistent each month. In the Dominican Republic, there were 42 UTIs and 14 corresponding prescriptions written for those UTIs reported, however, data only reflected two months' worth of UTI diagnoses from May 2021 to May 2022. Fosfomycin was prescribed most frequently at a rate of 61.5%.  Conclusion: The findings above suggest that there are inconsistent UTI reports throughout the year with a varied use of antibiotics prescriptions for UTIs. The discovered discrepancies in disease reporting, or lack thereof of reporting, and prescription recommendation suggest inconsistent reporting in CREDO. In the future, focused education or revision on CREDO reporting and uniform coding practices could be implemented to reduce these inconsistencies.

Outpatient Treatment of Confirmed COVID-19: Living, Rapid Practice Points From the American College of Physicians (Version 2).

DESCRIPTION: Evidence for the use of outpatient treatments in adults with confirmed COVID-19 continues to evolve with new data. This is version 2 of the American College of Physicians (ACP) living, rapid practice points focusing on 22 outpatient treatments for COVID-19, specifically addressing the dominant SARS-CoV-2 Omicron variant. METHODS: The Population Health and Medical Science Committee (formerly the Scientific Medical Policy Committee) developed this version of the living, rapid practice points on the basis of a living, rapid review done by the ACP Center for Evidence Reviews at Cochrane Austria at the University for Continuing Education Krems (Danube University Krems). This topic will be maintained as living and rapid by continually monitoring and assessing the impact of new evidence. PRACTICE POINT 1: Consider molnupiravir to treat symptomatic patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 5 days of the onset of symptoms and at a high risk for progressing to severe disease. PRACTICE POINT 2: Consider nirmatrelvir-ritonavir combination therapy to treat symptomatic patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 5 days of the onset of symptoms and at a high risk for progressing to severe disease. PRACTICE POINT 3: Do not use ivermectin to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. PRACTICE POINT 4: Do not use sotrovimab to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting.

Guidelines for Diagnosis and Management of Infective Endocarditis in Adults: A WikiGuidelines Group Consensus Statement.

Importance: Practice guidelines often provide recommendations in which the strength of the recommendation is dissociated from the quality of the evidence. Objective: To create a clinical guideline for the diagnosis and management of adult bacterial infective endocarditis (IE) that addresses the gap between the evidence and recommendation strength. Evidence Review: This consensus statement and systematic review applied an approach previously established by the WikiGuidelines Group to construct collaborative clinical guidelines. In April 2022 a call to new and existing members was released electronically (social media and email) for the next WikiGuidelines topic, and subsequently, topics and questions related to the diagnosis and management of adult bacterial IE were crowdsourced and prioritized by vote. For each topic, PubMed literature searches were conducted including all years and languages. Evidence was reported according to the WikiGuidelines charter: clear recommendations were established only when reproducible, prospective, controlled studies provided hypothesis-confirming evidence. In the absence of such data, clinical reviews were crafted discussing the risks and benefits of different approaches. Findings: A total of 51 members from 10 countries reviewed 587 articles and submitted information relevant to 4 sections: establishing the diagnosis of IE (9 questions); multidisciplinary IE teams (1 question); prophylaxis (2 questions); and treatment (5 questions). Of 17 unique questions, a clear recommendation could only be provided for 1 question: 3 randomized clinical trials have established that oral transitional therapy is at least as effective as intravenous (IV)-only therapy for the treatment of IE. Clinical reviews were generated for the remaining questions. Conclusions and Relevance: In this consensus statement that applied the WikiGuideline method for clinical guideline development, oral transitional therapy was at least as effective as IV-only therapy for the treatment of IE. Several randomized clinical trials are underway to inform other areas of practice, and further research is needed.

Choosing patients over placebos: oral transitional therapy vs. IV-only therapy for bacteraemia and infective endocarditis.

BACKGROUND: The belief that antibiotics must be administered intravenously (IV) to treat bacteraemia and endocarditis has its origins 70 years ago and has engrained itself in the psyche of the medical community and the public at large. This has led to hesitancy in adopting evidence-based strategies utilizing oral transitional therapy for the treatment of these infections. We aim to reframe the narrative around this debate, focusing on patient safety over vestigial psychology. OBJECTIVES: This narrative review summarizes the current state of the literature regarding the use of oral transitional therapy for the treatment of bacteraemia and infective endocarditis, focusing on studies comparing it to the traditional, IV-only approach. SOURCES: Relevant studies and abstracts from PubMed reviewed in April 2023. CONTENT: Treating bacteraemia with oral transitional therapy has been studied in 9 randomized controlled trials (RCTs), totalling 625 patients, as well as numerous large, retrospective cohorts, including 3 published in the last 5 years alone, totalling 4763 patients. We identified 3 large, retrospective cohort studies; one quasi-experimental, pre-post study, and 3 RCTs of patients with endocarditis, totalling 748 patients in the retrospective cohorts and 815 patients in prospective, controlled studies. In all these studies, no worse outcomes were observed in the oral transitional therapy arm as compared with IV-only therapy. The main difference has consistently been longer durations of inpatient hospitalization and increased risk of catheter-related adverse events like venous thrombosis and line-associated blood stream infections in the IV-only groups. IMPLICATIONS: There are ample data showing that choosing oral therapy reduces hospital stay and has fewer adverse events for patients than IV-only therapy, all with similar or better outcomes. In selected patients, choosing IV-only therapy may serve more as an anxiolytic "placebo" for the patient and provider rather than a necessity for treating the actual infection.

Establishment of Skeletal Myogenic Progenitors from Non-Human Primate Induced Pluripotent Stem Cells.

Pluripotent stem (PS) cells enable the scalable production of tissue-specific derivatives with therapeutic potential for various clinical applications, including muscular dystrophies. Given the similarity to human counterparts, the non-human primate (NHP) is an ideal preclinical model to evaluate several questions, including delivery, biodistribution, and immune response. While the generation of human-induced PS (iPS)-cell-derived myogenic progenitors is well established, there have been no data for NHP counterparts, probably due to the lack of an efficient system to differentiate NHP iPS cells towards the skeletal muscle lineage. Here, we report the generation of three independent Macaca fascicularis iPS cell lines and their myogenic differentiation using PAX7 conditional expression. The whole-transcriptome analysis confirmed the successful sequential induction of mesoderm, paraxial mesoderm, and myogenic lineages. NHP myogenic progenitors efficiently gave rise to myotubes under appropriate in vitro differentiation conditions and engrafted in vivo into the TA muscles of NSG and FKRP-NSG mice. Lastly, we explored the preclinical potential of these NHP myogenic progenitors in a single wild-type NHP recipient, demonstrating engraftment and characterizing the interaction with the host immune response. These studies establish an NHP model system through which iPS-cell-derived myogenic progenitors can be studied.

Understanding risk factors and microbial trends implicated in the development of Whipple-related surgical-site infections.

Objective: The purpose of this study is to understand the role of risk factors and postoperative complications seen in patients undergoing Whipple procedures in the development of surgical site infections. Our secondary goal was to evaluate whether microbial patterns differed between preoperative antibiotic classes, offering insight into the effectiveness of current practices while promoting antibiotic stewardship. Design: We performed a retrospective cohort study comparing patients with and without SSIs. Setting: This study was conducted at a tertiary-care center in the southeastern United States. Participants: Patients who underwent a Whipple procedure between 2012 and 2021 were acquired from the National Surgical Quality Improvement Program (NSQIP) database. Results: Patients with a bleeding disorder reported higher SSI rates (P = .04), whereas patients with a biliary stent reported lower surgical site infection (SSI) rates (P = .02) Those with postoperative complications had higher SSI rates, including delayed gastric emptying (P < .001) and pancreatic fistula (P < .001). Patients with longer operative times were 1.002 times more likely to develop SSIs (adjusted odds ratio [aOR], 1.002; 95% confidence interval [CI], 1.001-1.004; P = .006) whereas surgical indications for malignancy correlated with decreased SSIs risk (aOR, 0.578; 95% CI, 0.386-866) when adjusting for body mass index, surgical indication, and duration of surgical procedure. Conclusions: Optimizing preoperative management of modifiable risk factors for patients undergoing pancreatoduodenectomies and decreasing operative times may reduce SSI rates and patient and hospital burden. Further research is needed to understand whether stent placement reduces SSI risk in pancreatoduodenectomy.

Can the Future of ID Escape the Inertial Dogma of Its Past? The Exemplars of Shorter Is Better and Oral Is the New IV.

Like all fields of medicine, Infectious Diseases is rife with dogma that underpins much clinical practice. In this study, we discuss 2 specific examples of historical practice that have been overturned recently by numerous prospective studies: traditional durations of antimicrobial therapy and the necessity of intravenous (IV)-only therapy for specific infectious syndromes. These dogmas are based on uncontrolled case series from >50 years ago, amplified by the opinions of eminent experts. In contrast, more than 120 modern, randomized controlled trials have established that shorter durations of therapy are equally effective for many infections. Furthermore, 21 concordant randomized controlled trials have demonstrated that oral antibiotic therapy is at least as effective as IV-only therapy for osteomyelitis, bacteremia, and endocarditis. Nevertheless, practitioners in many clinical settings remain refractory to adopting these changes. It is time for Infectious Diseases to move beyond its history of eminent opinion-based medicine and truly into the era of evidenced-based medicine.

Short-course antibiotics for common infections: what do we know and where do we go from here?

BACKGROUND: Over the past 25 years, researchers have performed >120 randomized controlled trials (RCTs) illustrating short courses to be non-inferior to long courses of antibiotics for common bacterial infections. OBJECTIVE: We sought to determine whether clinical data from RCTs affirm the mantra of 'shorter is better' for antibiotic durations in 7 common infections: pneumonia, urinary tract infection, intra-abdominal infection, bacteraemia, skin and soft tissue infection, bone and joint infections, pharyngitis and sinusitis. SOURCES: Published RCTs comparing short- versus long-course antibiotic durations were identified through searches of PubMed and clinical guideline documents. CONTENT: Short-course antibiotic durations consistently result in similar treatment success rates as longer antibiotic courses among patients with community-acquired pneumonia, complicated urinary tract infections in women, gram-negative bacteraemia, and skin and soft tissue infections when the diagnosis is confirmed, appropriate antimicrobials are used, and patients show clinical signs of improvement. For patients with osteomyelitis, 6 weeks of antibiotics is adequate for the treatment of osteomyelitis in the absence of implanted foreign bodies and surgical debridement. Whether durations can be further shortened with debridement is unclear, although small studies are promising. IMPLICATIONS: With few exceptions, short courses were non-inferior to long courses; future research should focus on appropriately defining the patient population, ensuring the correct choice and dose of antimicrobials and developing meaningful outcomes relevant for frontline clinicians.

Outpatient Treatment of Confirmed COVID-19: Living, Rapid Practice Points From the American College of Physicians (Version 1).

DESCRIPTION: Strategies to manage COVID-19 in the outpatient setting continue to evolve as new data emerge on SARS-CoV-2 variants and the availability of newer treatments. The Scientific Medical Policy Committee (SMPC) of the American College of Physicians (ACP) developed these living, rapid practice points to summarize the best available evidence on the treatment of adults with confirmed COVID-19 in an outpatient setting. These practice points do not evaluate COVID-19 treatments in the inpatient setting or adjunctive COVID-19 treatments in the outpatient setting. METHODS: The SMPC developed these living, rapid practice points on the basis of a living, rapid review done by the ACP Center for Evidence Reviews at Cochrane Austria at the University for Continuing Education Krems (Danube University Krems). The SMPC will maintain these practice points as living by monitoring and assessing the impact of new evidence. PRACTICE POINT 1: Consider molnupiravir to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 5 to 7 days of the onset of symptoms and at high risk for progressing to severe disease. PRACTICE POINT 2: Consider nirmatrelvir-ritonavir combination therapy to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 5 days of the onset of symptoms and at high risk for progressing to severe disease. PRACTICE POINT 3: Consider remdesivir to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 7 days of the onset of symptoms and at high risk for progressing to severe disease. PRACTICE POINT 4: Do not use azithromycin to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. PRACTICE POINT 5: Do not use chloroquine or hydroxychloroquine to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. PRACTICE POINT 6: Do not use ivermectin to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. PRACTICE POINT 7: Do not use nitazoxanide to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. PRACTICE POINT 8: Do not use lopinavir-ritonavir combination therapy to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. PRACTICE POINT 9: Do not use casirivimab-imdevimab combination therapy to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting unless it is considered effective against a SARS-CoV-2 variant or subvariant locally in circulation. PRACTICE POINT 10: Do not use regdanvimab to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting unless it is considered effective against a SARS-CoV-2 variant or subvariant locally in circulation. PRACTICE POINT 11: Do not use sotrovimab to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting unless it is considered effective against a SARS-CoV-2 variant or subvariant locally in circulation. PRACTICE POINT 12: Do not use convalescent plasma to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. PRACTICE POINT 13: Do not use ciclesonide to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. PRACTICE POINT 14: Do not use fluvoxamine to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting.

Clinical risk factors for admission with Pseudomonas and multidrug-resistant Pseudomonas community-acquired pneumonia.

BACKGROUND: Microbial etiology for community-acquired pneumonia (CAP) is evolving with pathogens known for high CAP mortality e.g., Pseudomonas species. Chronic obstructive pulmonary disease (COPD) patients are at risk for hospitalization for CAP. Understanding regional patterns and risk factors for multidrug-resistant (MDR) Pseudomonas acquisition has implications for antimicrobial stewardship. OBJECTIVES: To evaluate the regional epidemiology of MDR Pseudomonas CAP and its association with COPD. METHODS: We queried the electronic medical records of the University of Alabama at Birmingham Healthcare System to identify patients hospitalized for CAP with Pseudomonas positive respiratory samples between 01/01/2013-12/31/2019. Log binomial regression models were used to examine associations between COPD diagnosis and risk of Pseudomonas/MDR Pseudomonas CAP. RESULTS: Cohort consisted of 913 culture positive CAP cases aged 59-year (IQR:48-68), 61% (560) male, 60% (547) white, 65% (580) current/past smokers, and 42% (384) COPD. Prevalence of Pseudomonas CAP in culture positive CAP was 18% (167), MDR Pseudomonas CAP in Pseudomonas CAP was 22% (36), and yearly incidence of MDR Pseudomonas CAP was stable (p = 0.169). COPD was associated with Pseudomonas CAP (RR 1.39; 95% CI 1.01, 1.91; p = 0.041) but not with MDR Pseudomonas CAP (0.71; 95% CI 0.35, 1.45; p = 0.349). Stroke (RR 2.64; 95% CI 1.51, 4.61; p = 0.0006) and use of supplemental oxygen (RR 2.31; 95% CI 1.30, 4.12; p = 0.005) were associated with MDR Pseudomonas CAP. CONCLUSION: Incidence of MDR Pseudomonas CAP was stable over time. COPD was associated with Pseudomonas CAP but not with MDR Pseudomonas CAP. Larger cohort studies are needed to confirm findings.

Leveraging Technology and Gamification to Engage Learners in a Microbiology Curriculum in Undergraduate Medical Education.

Background: Microbiology is a critical and expansive topic that many medical schools' curriculum must teach in a constrained time frame. We implemented a microbiology question bank smart phone app enhanced with game elements and clinical pearls during a microbiology course for first-year medical students. We hypothesized that these enhancements and clinical pearls would engage the students meaningfully and increase their knowledge base. Methods: Though use was optional, students' game play was recorded through the app, which was compared to test grades retrospectively. A player efficiency rating (PER) was calculated as a function of question response, accuracy, and engagement. Students were separated into tertiles of PER and median exam grades were compared using a non-parametric Kruskal-Wallis (KW) test. An anonymous satisfaction and usability feedback survey was also administered. Results: One hundred eighty-one of the 189 students (96%) answered at least one question, and 165 (87%) completed all 56 questions. The average PER was 84.75. We received feedback surveys from 61 (34%) students in the course, with positive responses regarding the perceived impact on learning microbiology. The KW test found a positive correlation for median exam scores of the player groups when divided into tertiles by PER (p = 0.0002). Conclusions: We leveraged gamification and clinical pearls to design a supplemental microbiology question bank. We found high engagement overall and higher class exam scores associated with greater use of the question bank.

Use of Novel Strategies to Develop Guidelines for Management of Pyogenic Osteomyelitis in Adults: A WikiGuidelines Group Consensus Statement.

Importance: Traditional approaches to practice guidelines frequently result in dissociation between strength of recommendation and quality of evidence. Objective: To construct a clinical guideline for pyogenic osteomyelitis management, with a new standard of evidence to resolve the gap between strength of recommendation and quality of evidence, through the use of a novel open access approach utilizing social media tools. Evidence Review: This consensus statement and systematic review study used a novel approach from the WikiGuidelines Group, an open access collaborative research project, to construct clinical guidelines for pyogenic osteomyelitis. In June 2021 and February 2022, authors recruited via social media conducted multiple PubMed literature searches, including all years and languages, regarding osteomyelitis management; criteria for article quality and inclusion were specified in the group's charter. The GRADE system for evaluating evidence was not used based on previously published concerns regarding the potential dissociation between strength of recommendation and quality of evidence. Instead, the charter required that clear recommendations be made only when reproducible, prospective, controlled studies provided hypothesis-confirming evidence. In the absence of such data, clinical reviews were drafted to discuss pros and cons of care choices. Both clear recommendations and clinical reviews were planned with the intention to be regularly updated as new data become available. Findings: Sixty-three participants with diverse expertise from 8 countries developed the group's charter and its first guideline on pyogenic osteomyelitis. These participants included both nonacademic and academic physicians and pharmacists specializing in general internal medicine or hospital medicine, infectious diseases, orthopedic surgery, pharmacology, and medical microbiology. Of the 7 questions addressed in the guideline, 2 clear recommendations were offered for the use of oral antibiotic therapy and the duration of therapy. In addition, 5 clinical reviews were authored addressing diagnosis, approaches to osteomyelitis underlying a pressure ulcer, timing for the administration of empirical therapy, specific antimicrobial options (including empirical regimens, use of antimicrobials targeting resistant pathogens, the role of bone penetration, and the use of rifampin as adjunctive therapy), and the role of biomarkers and imaging to assess responses to therapy. Conclusions and Relevance: The WikiGuidelines approach offers a novel methodology for clinical guideline development that precludes recommendations based on low-quality data or opinion. The primary limitation is the need for more rigorous clinical investigations, enabling additional clear recommendations for clinical questions currently unresolved by high-quality data.

The contribution of skills to the effectiveness of dialectical behavioral therapy.

OBJECTIVE: The present study investigated the effectiveness of dialectical behavioral therapy (DBT) and the effect of improvement in DBT skills on clinical outcomes. METHOD: Participants included 57 adults who attended a community mental health service and underwent one of two modes of DBT. Twenty-six adults had been diagnosed with borderline personality disorder (BPD) and participated in comprehensive DBT (DBT-C; including group skills training, individual therapy, and phone coaching). Thirty-one adults had BPD traits and participated in DBT skills training (DBT-S; group skills training only). In the present study, the DBT skills examined were mindfulness, emotion regulation, and interpersonal effectiveness; the clinical outcomes examined were borderline symptoms, psychological distress, and quality of life. RESULTS: Six 2 × 2 analysis of covariances indicated significant improvements in psychological distress, quality of life, mindfulness, and interpersonal effectiveness (but not borderline symptoms and emotion regulation), over a 6-month period. Mode of delivery of DBT did not impact on the improvement in DBT skills and clinical outcomes over the 6-month period. Hierarchical multiple regression results indicated that improvement in DBT skills (mindfulness, emotion regulation, and interpersonal effectiveness) were associated with reductions in borderline symptoms and psychological distress, with emotion regulation the only skill uniquely associated with improvements in clinical outcomes. CONCLUSIONS: The results of the present study support the effectiveness of DBT and the specific role of emotion regulation for favorable clinical outcomes over a 6-month period, independent of the mode of delivery of DBT.

Boosting of SARS-CoV-2 immunity in nonhuman primates using an oral rhabdoviral vaccine.

An orally active vaccine capable of boosting SARS-CoV-2 immune responses in previously infected or vaccinated individuals would help efforts to achieve and sustain herd immunity. Unlike mRNA-loaded lipid nanoparticles and recombinant replication-defective adenoviruses, replicating vesicular stomatitis viruses with SARS-CoV-2 spike glycoproteins (VSV-SARS2) were poorly immunogenic after intramuscular administration in clinical trials. Here, by G protein trans-complementation, we generated VSV-SARS2(+G) virions with expanded target cell tropism. Compared to parental VSV-SARS2, G-supplemented viruses were orally active in virus-naive and vaccine-primed cynomolgus macaques, powerfully boosting SARS-CoV-2 neutralizing antibody titers. Clinical testing of this oral VSV-SARS2(+G) vaccine is planned.