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

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

Garetosmab in Fibrodysplasia Ossificans Progressiva: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial

Fibrodysplasia ossificans progressiva (FOP) is a rare disease characterized by heterotopic ossification (HO) in connective tissues and painful flare-ups. In the phase 2 LUMINA-1 trial, adult patients with FOP were randomized to garetosmab, an activin A-blocking antibody (n = 20) or placebo (n = 24) in period 1 (28 weeks), followed by an open-label period 2 (28 weeks; n = 43). The primary end points were safety and for period 1, the activity and size of HO lesions. All patients experienced at least one treatment-emergent adverse event during period 1, notably epistaxis, madarosis and skin abscesses. Five deaths (5 of 44; 11.4%) occurred in the open-label period and, while considered unlikely to be related, causality cannot be ruled out. The primary efficacy end point in period 1 (total lesion activity by PET–CT) was not met (P = 0.0741). As the development of new HO lesions was suppressed in period 1, the primary efficacy end point in period 2 was prospectively changed to the number of new HO lesions versus period 1. No placebo patients crossing over to garetosmab developed new HO lesions (0% in period 2 versus 40.9% in period 1; P = 0.0027). Further investigation of garetosmab in FOP is ongoing

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

Comparison of insect biodiversity between organic and conventional plantations in Kodagu, Karnataka, India

We undertook a comparative analysis of ground insects and fruit eating butterflies on 29 different plantations in Kodagu District of Karnataka which is one of the rich biodiversity zones of the Western Ghats. These included organic and conventional coffee and cardamom plantations using different levels of chemical fertilizers and pesticides. A total number of 457 ground insect species were collected using pit-fall traps which included 92 species of ants and 123 species of beetles, among other insect taxa that we measured. Similarly, 25 species of butterflies belonging to the family Nymphalidae were collected using bait traps. We found a clear negative effect on the ground insect species diversity (Shannon index) and evenness (Shannon evenness index) in pesticide treated plantations as compared to the organic plantations. A similar negative effect was observed for butterfly diversity in plantations using pesticides. Our results corroborate the value of organic plantations in supporting higher levels of biodiversity