A Systematic Review And Meta-Analysis

[Posted 17/May/2022]

AUDIENCE: Emergency Medicine, Pediatric

KEY FINDINGS: The present systematic review and meta-analysis showed that POCUS had high sensitivity and specificity for identifying testicular torsion in paediatric patients although the risk of bias was high in the studies analysed.

BACKGROUND: Previous studies have examined the utility of ultrasonography performed by radiologists for diagnosing paediatric testicular torsion. While point-of-care ultrasound (POCUS) is used in paediatric emergency medicine, its diagnostic accuracy is still unknown. The present systematic review and meta-analysis aimed to clarify the accuracy of POCUS in diagnosing testicular torsion in children.

DETAILS: Following the Preferred Reporting Items for Systematic Review and Meta-analysis of Diagnostic Test Accuracy guidelines, a systematic review was performed. Any study investigating the diagnostic accuracy of POCUS for paediatric testicular torsion was extracted. The primary outcome was the assessment of the diagnostic accuracy of POCUS for paediatric testicular torsion. The pooled sensitivity and specificity were calculated. Quality analysis was conducted using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Four studies enrolling 784 patients in total were included. The pooled sensitivity, specificity, and positive and negative likelihood ratios of POCUS were 98.4% (95% CI: 88.5% to 99.8%), 97.2% (95% CI: 87.2% to 99.4%), 34.7 (95% CI: 7.4 to 164.4) and 0.017 (95% CI: 0.002 to 0.12), respectively. Risk-of-bias assessment using QUADAS-2 revealed that two of the studies had a high risk of bias in patient selection.

Copyright © BMJ Publishing Group Ltd and the College of Emergency Medicine. All rights reserved.

Source: Mori, T., Ihara, T., Nomura, O. (2022). Diagnostic Accuracy Of Point-Of-Care Ultrasound For Paediatric Testicular Torsion: A Systematic Review And Meta-Analysis. Emergency Medicine Journal . 2022; e212281. Published: May 6, 2022. DOI: 10.1136/emermed-2021-212281.

[Posted 13/Jul/2026]

AUDIENCE: Infectious Disease, Internal Medicine

KEY FINDINGS: This review underscores the expanding pipeline of therapeutic strategies targeting Candida auris, ranging from repurposed medications and next-generation antifungal agents to vaccines, antimicrobial peptides, nanoparticle formulations, and innovative environmental control measures. Although no single therapy has emerged as a definitive solution, compounds such as ibrexafungerp (SCY-078), ATI-2307, and fosmanogepix, together with drug repurposing and bioinspired approaches, represent promising avenues for addressing multidrug-resistant C. auris infections. Continued translational research and clinical evaluation remain essential to establish safe and effective treatment options for this increasingly important fungal pathogen.

BACKGROUND: Candida auris has rapidly emerged as a multidrug-resistant fungal pathogen of global concern since its first identification in 2009. The organism is associated with healthcare-associated outbreaks, high transmissibility, frequent misidentification, and severe invasive infections, with reported mortality rates ranging from 35% to 72%. Resistance to currently available antifungal agents further complicates treatment, with approximately 90% of isolates resistant to fluconazole, around 30% resistant to amphotericin B, and fewer than 5% resistant to echinocandins. These challenges have accelerated efforts to identify novel antifungal therapies and alternative treatment strategies.

DETAILS: This publication is a comprehensive narrative review that summarizes advances in antifungal research targeting C. auris over the preceding decade. The authors evaluated emerging therapeutic approaches from a medicinal chemistry perspective, including drug repurposing, combination therapy, novel antifungal agents, natural products, metal-based compounds, nanoparticles, vaccines, antimicrobial peptides, and environmental decontamination strategies. The review also examined chemical and physicochemical characteristics of promising compounds, including lipophilicity and topological polar surface area, to identify structural features that may facilitate future antifungal drug development. The review highlights several promising therapeutic candidates with activity against multidrug-resistant C. auris. Drug repurposing identified multiple agents with antifungal or antibiofilm activity, including sertraline, miltefosine, iodoquinol, octenidine dihydrochloride, taurolidine, and bensulfuron methyl. Miltefosine demonstrated fungicidal and antibiofilm activity, while encapsulation within alginate nanoparticles reduced toxicity and improved survival in an infected Galleria mellonella model. The NDV-3A vaccine generated cross-reactive antibodies against C. auris and protected neutropenic mice, with additive efficacy when combined with micafungin.

Among novel antifungal agents, SCY-078 (ibrexafungerp), an orally available 1,3-ß-D-glucan synthesis inhibitor, demonstrated potent activity against C. auris, with an MIC90 of 1 mg/L and MIC50 and MIC90 values of 0.5 µg/mL and 1 µg/mL, respectively, across 100 isolates representing the four major clades. More than 150 strains with diverse resistance profiles were subsequently shown to be uniformly susceptible to SCY-078, and the agent remained active against pan-resistant isolates while also exhibiting antibiofilm activity.

Additional investigational therapies also demonstrated encouraging preclinical activity. The arylamidine T-2307 (ATI-2307) exhibited in vitro MIC values ranging from 0.125 to 4 µg/mL and improved survival while reducing kidney fungal burden in murine infection models following 3 mg/kg once-daily subcutaneous treatment. Other experimental approaches included antimicrobial peptides, ceragenins, fluorinated hydrazone derivatives, and novel chemical scaffolds designed to overcome existing resistance mechanisms.

Copyright © Skyscape. All rights reserved.

Source: Billamboz, M., Fatima, Z., Hameed, S., et al. Promising Drug Candidates and New Strategies for Fighting against the Emerging Superbug Candida auris. Microorganisms. 2021; 9(3): 634. Published: March 18, 2021. DOI: 10.3390/microorganisms9030634.

[Posted 10/Jul/2026]

AUDIENCE: Infectious Disease, Internal Medicine

KEY FINDINGS: Early initiation of a 5-day oral ensitrelvir regimen within 72 hours after symptom onset in an index patient significantly reduced the risk of developing Covid-19 among household contacts while maintaining a safety profile comparable to placebo. Clinical benefit was observed across major patient subgroups, including individuals at increased risk for severe disease, and treatment was associated with reduced household transmission. These findings support ensitrelvir as an effective postexposure prophylactic option for household contacts and suggest potential utility in other high-risk exposure settings where rapid outbreak control is needed.

BACKGROUND: Household transmission remains a major contributor to the spread of SARS-CoV-2, particularly among individuals at increased risk for severe Covid-19. Although vaccination and prior infection have reduced disease severity, waning immunity and emerging variants continue to sustain transmission. Previous trials evaluating oral antiviral agents for postexposure prophylaxis in household contacts have not demonstrated significant protection, highlighting the need for effective preventive therapies. This phase 3 trial evaluated whether oral ensitrelvir, a SARS-CoV-2 3C-like protease inhibitor, could prevent Covid-19 among household contacts exposed to an infected index patient.

DETAILS: This phase 3, double-blind, randomized, placebo-controlled trial was conducted between June 2023 and mid-September 2024 across the United States, Argentina, Japan, South Africa, and Vietnam. Eligible household contacts were 12 years of age or older, had a negative SARS-CoV-2 test at enrollment, and were randomized within 72 hours after symptom onset in the index patient. Participants received either ensitrelvir 375 mg on day 1 followed by 125 mg once daily on days 2-5 or matching placebo. The primary endpoint was laboratory-confirmed Covid-19 by day 10 in the modified intention-to-treat population, defined as RT-PCR positivity accompanied by at least one prespecified Covid-19 symptom lasting 48 hours or longer. Secondary endpoints included laboratory-confirmed SARS-CoV-2 infection regardless of symptoms, subgroup analyses, and safety outcomes. Overall, 2,387 household contacts were randomized, including 1,030 participants in the ensitrelvir group and 1,011 in the placebo group within the modified intention-to-treat population. The mean participant age was 42.4 years, 71.1% were enrolled within 48 hours after symptom onset in the index patient, and 37.0% had at least one risk factor for severe Covid-19. By day 10, laboratory-confirmed Covid-19 occurred in 2.9% of participants receiving ensitrelvir compared with 9.0% receiving placebo, corresponding to a risk ratio of 0.33 (95% CI, 0.22-0.49; P<0.001) and an approximate 67% relative risk reduction in the modified intention-to-treat population. In the intention-to-treat population, Covid-19 developed in 4.4% and 10.2% of participants, respectively (risk ratio, 0.43; 95% CI, 0.32-0.59; P<0.001). Laboratory-confirmed SARS-CoV-2 infection irrespective of symptoms was also lower with ensitrelvir (14.0% vs. 21.5%; risk ratio, 0.66; 95% CI, 0.55-0.79). Subgroup analyses demonstrated generally consistent efficacy across age groups and participants with risk factors for severe disease. Among participants with risk factors, Covid-19 developed in 2.4% of the ensitrelvir group compared with 9.9% of the placebo group. Ensitrelvir was also associated with a 34% relative reduction in household SARS-CoV-2 transmission. Adverse events occurred at similar frequencies in the ensitrelvir and placebo groups (15.1% vs. 15.5%), with serious adverse events reported in 0.2% of participants in each group. No Covid-19-related hospitalizations or deaths occurred. Transient reductions in high-density lipoprotein concentrations were observed with ensitrelvir but returned toward baseline by day 15 and were not associated with clinical events.

Source: Hayden, F. G., Shinkai, M., Clark, T. W., et al. Ensitrelvir for Covid-19 Postexposure Prophylaxis in Household Contacts. New England Journal of Medicine. 2026; 394(19): 1905-1915. Published: June 22, 2026. DOI: 10.1056/NEJMoa2509306.

Multicenter Evaluation Reveals Persistent Gaps in Guideline-Concordant Care

[Posted 8/Jul/2026]

AUDIENCE: Infectious Disease, Internal Medicine

KEY FINDINGS: This multicenter evaluation demonstrates that antibiotic prescribing for acute sinusitis remains substantially higher than recommended by evidence-based guidelines, with nearly one-third of patients failing to meet prescribing criteria and fewer than half of prescriptions fully adhering to recommended antibiotic selection and duration. Prolonged symptom duration, cough, and incomplete documentation were significant drivers of inappropriate prescribing, while electronic encounters were associated with more judicious antibiotic use. These findings identify important opportunities for antimicrobial stewardship interventions aimed at improving prescribing decisions and optimizing treatment duration in ambulatory care.

BACKGROUND: Acute sinusitis is among the most common indications for antibiotic prescribing in ambulatory practice, despite national guidelines recommending antibiotic therapy only when specific clinical criteria suggest bacterial infection. Inappropriate antibiotic use contributes to adverse drug events, antimicrobial resistance, and unnecessary healthcare expenditures. This multicenter study evaluated the appropriateness of antibiotic prescribing for acute sinusitis, assessed concordance with guideline-recommended agent selection and treatment duration, and identified factors associated with inappropriate prescribing.

DETAILS: This retrospective multicenter cohort study included 1,000 randomly selected adult ambulatory encounters with a primary diagnosis of acute sinusitis between January 1, 2024, and March 31, 2024. Encounters were drawn from emergency departments, urgent care centers, and primary care clinics across seven geographic regions within a large healthcare system. Medical records were reviewed to determine whether patients met national guideline criteria for antibiotic therapy based on symptom duration, severe symptoms, treatment failure, or double worsening. Antibiotic selection and treatment duration were evaluated against institutional recommendations. Multivariable logistic regression was performed to identify predictors of inappropriate antibiotic prescribing, and 30-day repeat respiratory-related healthcare utilization was also assessed. Among the 1,000 encounters, 676 (67.6%) met guideline criteria for antibiotic therapy, whereas 324 (32.4%) did not. Antibiotics were prescribed in 892 (89.2%) encounters overall. Prescribing occurred in 93.5% of encounters meeting treatment criteria but also in 80.2% of encounters where criteria were not satisfied, indicating substantial antibiotic use beyond guideline recommendations. Overall, only 49.2% of antibiotic prescriptions were fully guideline concordant with respect to both agent selection and duration. Guideline-concordant drug selection occurred in 74.1% of prescriptions, while 64.5% met recommended treatment duration. The most frequently prescribed antibiotic was amoxicillin/clavulanate (60.9%), followed by doxycycline (19.1%), and the median treatment duration was 7 days. However, 35.4% of patients received therapy lasting longer than 7 days. Watch-and-wait prescribing was used in only 6.8% of antibiotic-treated encounters. Multivariable analysis demonstrated that the presence of cough (OR 2.15; 95% CI, 1.08-4.29; P = 0.03), symptom duration of 7-9 days compared with 6 days (OR 7.70; 95% CI, 3.24-18.31; P 0.001), and undocumented symptom duration (OR 5.01; 95% CI, 1.41-17.82; P = 0.013) were independently associated with inappropriate antibiotic prescribing. In contrast, electronic encounters were associated with significantly lower odds of inappropriate prescribing than in-person visits (OR 0.03; 95% CI, 0.01-0.09; P 0.001). Unplanned respiratory-related healthcare contact within 30 days occurred in 12.8% of patients and was more frequent among those who did not receive antibiotics (20.4% vs 11.9%; P = 0.013), although antibiotic prescribing was not independently associated with reduced repeat healthcare utilization after multivariable adjustment.

Source: Arensman Hannan, K., Ilges, D., Le, K. T., Cole K, et al. Ambulatory antibiotic prescribing for acute sinusitis: a multicenter, retrospective cohort study evaluating appropriateness. Antimicrobial Stewardship & Healthcare Epidemiology.. 2026; 6(1): e193. Published: June 25, 2026. DOI: 10.1017/ash.2026.10743.

Findings from the PRESIDE Double-Blind Randomized Controlled Trial

[Posted 7/Jul/2026]

AUDIENCE: Family Medicine, Psychiatry

KEY FINDINGS: In this pragmatic double-blind randomized controlled trial conducted in Australian primary care, pharmacogenomic-informed antidepressant prescribing did not improve depressive symptoms compared with prescribing guided by national therapeutic guidelines. Clinical outcomes, medication tolerability, adherence, and quality of life were similar between groups, while cost-effectiveness analyses did not support routine implementation of pharmacogenomic testing in this setting. These findings suggest that broad pharmacogenomic-guided antidepressant prescribing in general practice does not provide additional clinical benefit over guideline-based management, although targeted evaluation in carefully selected patient populations may warrant further investigation.

BACKGROUND: Pharmacogenomic testing has been proposed as a strategy to individualize antidepressant selection by identifying CYP2D6 and CYP2C19 variants that influence drug metabolism. Although previous studies have suggested potential clinical benefits, evidence from pragmatic primary care settings remains limited. The Pharmacogenomic-Informed Antidepressant Prescribing for Moderate-to-Severe Depressive Symptoms in Australian General Practice (PRESIDE) trial evaluated whether pharmacogenomic-guided prescribing improves depression outcomes compared with guideline-based prescribing in routine general practice.

DETAILS: PRESIDE was a multicenter, double-blind, randomized controlled trial conducted in Australian general practice between May 26, 2021, and September 28, 2023. Of 5185 patients approached, 552 were randomized, and 550 participants (275 per group) were included in the intention-to-treat analysis. Participants with moderate-to-severe depressive symptoms were assigned in a 1:1 ratio to receive antidepressant prescribing recommendations based either on pharmacogenomic testing combined with Australian Therapeutic Guidelines or on Australian Therapeutic Guidelines alone. Pharmacogenomic reports incorporated CYP2D6 and CYP2C19 metabolizer phenotypes derived from saliva-based genotyping. The primary endpoint was change in Patient Health Questionnaire-9 (PHQ-9) score from baseline to 12 weeks after the prescribing report was received. Secondary outcomes included remission, treatment response, antidepressant-related adverse effects, medication adherence, prescribing congruence, quality of life, and cost-effectiveness. A total of 479 participants (87%) completed the primary 12-week outcome assessment. Depressive symptoms improved over time in both groups. At 12 weeks, the adjusted between-group difference in PHQ-9 change was 0.90 (95% CI, 0.06-1.75; standardized mean difference 0.23 [95% CI, 0.02-0.45]; p=0.036), indicating a small but greater improvement in depressive symptoms in the guideline-based control group. No significant between-group differences were observed at 4, 8, or 26 weeks. Remission at 12 weeks occurred in 11% of participants receiving pharmacogenomic-guided prescribing compared with 18% in the control group, corresponding to an adjusted difference of -7.22% (95% CI, -13.25 to -1.19) and an odds ratio of 0.530 (95% CI, 0.311-0.903; p=0.020). Treatment response rates did not differ significantly between groups (29% vs 32%; OR 0.874; 95% CI, 0.581-1.315; p=0.518). Approximately two-thirds of participants had an actionable CYP2D6 or CYP2C19 phenotype, yet subgroup analyses demonstrated no differential treatment benefit based on genotype. Antidepressant adherence, side-effect burden, health-related quality of life, and health-care utilization were comparable between groups. Economic analyses indicated that pharmacogenomic-guided prescribing was more costly and less effective than standard guideline-based care, although differences in costs and quality-adjusted life years were not statistically significant. No grade 2-5 adverse events occurred, and only one grade 1 adverse event related to an administrative reporting error was documented.

Source: Saya, S., Chondros, P., Abela, A., et al. Pharmacogenomic-informed antidepressant prescribing for moderate-to-severe depressive symptoms in Australian general practice (PRESIDE): a double-blind, randomised controlled trial. The Lancet Primary Care. 2026; Published: June 25, 2026. DOI: 10.1016/j.lanprc.2026.100158

[Posted 3/Jul/2026]

AUDIENCE: Ob/Gyn, Internal Medicine

KEY FINDINGS: This large cohort study demonstrates that the choice of UA Doppler reference chart can substantially alter both the diagnosis of fetal growth restriction and the prediction of clinically relevant placental disease. Depending on the selected chart, the proportion of SGA fetuses identified as growth restricted varied more than tenfold. Among the evaluated references, the Rahimi et al., Drukker et al., and Flatley et al. charts provided the most favorable balance between sensitivity and specificity for identifying placenta-mediated FGR. Although no single chart is optimal for every clinical setting, these findings support ongoing efforts to standardize UA Doppler interpretation and improve consistency in FGR diagnosis, pending external validation.

BACKGROUND: Umbilical artery (UA) Doppler assessment plays a central role in distinguishing placenta-mediated fetal growth restriction (FGR) from constitutionally small-for-gestational-age (SGA) fetuses. However, clinical interpretation varies considerably because multiple UA pulsatility index (PI) reference charts are currently used, and no guideline recommends a preferred standard. This variability can influence FGRdiagnosis, patient management, referral patterns, and research outcomes. The present study evaluated the comparative performance of 10 widely used UA-PI reference charts to identify which most accurately predicts clinically meaningful indicators of placenta-mediated FGR.

DETAILS: This retrospective cohort study included singleton pregnancies that underwent routine UA Doppler assessment at >=20 weeks' gestation between January 2012 and December 2022 at a tertiary referral center. A total of 15,841 pregnancies with 38,398 ultrasound examinations met the inclusion criteria. Ten published UA-PI reference charts were compared using the conventional threshold of UA-PI >95th percentile.

The investigators assessed two primary outcomes considered specific markers of placenta-mediated FGR: progression to absent or reversed end-diastolic flow (AREDF) in the umbilical artery and maternal vascular malperfusion (MVM) identified on placental pathology. A secondary outcome was a composite adverse perinatal outcome (CAPO), defined by the occurrence of at least one of the following: stillbirth, 5-minute Apgar score <7, umbilical artery pH <7.1, need for neonatal resuscitation, or neonatal intensive care unit admission. Diagnostic performance was compared using sensitivity, specificity, predictive values, likelihood ratios, and the Youden index, while accounting for repeated ultrasound examinations within the same pregnancy.

The selected UA-PI reference chart had a substantial impact on the proportion of SGA fetuses classified as having FGR. Among SGA fetuses, abnormal UA-PI classification ranged from 2.2% to 25.7%, depending on the chart applied.

Performance for predicting late-stage UA Doppler abnormalities also differed markedly across charts. Sensitivity ranged from 20.7% to 76.3%, while specificity ranged from 75.2% to 98.0%. For predicting maternal vascular malperfusion, sensitivity ranged from 6.8% to 42.0% and specificity from 77.5% to 98.6%. Similar trends were observed for prediction of composite adverse perinatal outcomes.

When overall diagnostic performance was ranked using the Youden index, the Rahimi et al., Drukker et al., and Flatley et al. reference charts consistently demonstrated the highest predictive accuracy for placenta-mediated FGR outcomes. These three charts also maintained superior performance in pregnancies evaluated before 32 weeks' gestation. Across most reference charts, diagnostic performance remained relatively consistent between the overall cohort and gestational age subgroups.

Copyright © John Wiley & Sons, Inc. All rights reserved

Source: Vayenas, A., Kingdom, J., Kongkham, N., et al. Optimal Umbilical Artery Doppler Chart for Predicting Placenta-Mediated Fetal Growth Restriction. International Journal of Gynecology and Obstetrics. 2026; 67(6): 783-794. Published: June, 2026. DOI: 10.1002/uog.70222