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During September-December 2020, we conducted a multicenter retrospective study across India to evaluate epidemiology and outcomes among cases of coronavirus disease (COVID-19)-associated mucormycosis (CAM). Among 287 mucormycosis patients, 187 (65.2%) had CAM; CAM prevalence was 0.27% among hospitalized COVID-19 patients. We noted a 2.1-fold rise in mucormycosis during the study period compared with September-December 2019. Uncontrolled diabetes mellitus was the most common underlying disease among CAM and non-CAM patients. COVID-19 was the only underlying disease in 32.6% of CAM patients. COVID-19-related hypoxemia and improper glucocorticoid use independently were associated with CAM. The mucormycosis case-fatality rate at 12 weeks was 45.7% but was similar for CAM and non-CAM patients. Age, rhino-orbital-cerebral involvement, and intensive care unit admission were associated with increased mortality rates; sequential antifungal drug treatment improved mucormycosis survival. The COVID-19 pandemic has led to increases in mucormycosis in India, partly from inappropriate glucocorticoid use.

Cryptococcosis is a major worldwide disseminated invasive fungal infection. Cryptococcosis, particularly in its most lethal manifestation of cryptococcal meningitis, accounts for substantial mortality and morbidity. The breadth of the clinical cryptococcosis syndromes, the different patient types at-risk and affected, and the vastly disparate resource settings where clinicians practice pose a complex array of challenges. Expert contributors from diverse regions of the world have collated data, reviewed the evidence, and provided insightful guideline recommendations for health practitioners across the globe. This guideline offers updated practical guidance and implementable recommendations on the clinical approaches, screening, diagnosis, management, and follow-up care of a patient with cryptococcosis and serves as a comprehensive synthesis of current evidence on cryptococcosis. This Review seeks to facilitate optimal clinical decision making on cryptococcosis and addresses the myriad of clinical complications by incorporating data from historical and contemporary clinical trials. This guideline is grounded on a set of core management principles, while acknowledging the practical challenges of antifungal access and resource limitations faced by many clinicians and patients. More than 70 societies internationally have endorsed the content, structure, evidence, recommendation, and pragmatic wisdom of this global cryptococcosis guideline to inform clinicians about the past, present, and future of care for a patient with cryptococcosis.

We performed a case–control study across 25 hospitals in India for the period of January–June 2021 to evaluate the reasons for an COVID-19–associated mucormycosis (CAM) outbreak. We investigated whether COVID-19 treatment practices (glucocorticoids, zinc, tocilizumab, and others) were associated with CAM. We included 1,733 cases of CAM and 3,911 age-matched COVID-19 controls. We found cumulative glucocorticoid dose (odds ratio [OR] 1.006, 95% CI 1.004–1.007) and zinc supplementation (OR 2.76, 95% CI 2.24–3.40), along with elevated C-reactive protein (OR 1.004, 95% CI 1.002–1.006), host factors (renal transplantation [OR 7.58, 95% CI 3.31–17.40], diabetes mellitus [OR 6.72, 95% CI 5.45–8.28], diabetic ketoacidosis during COVID-19 [OR 4.41, 95% CI 2.03–9.60]), and rural residence (OR 2.88, 95% CI 2.12–3.79), significantly associated with CAM. Mortality rate at 12 weeks was 32.2% (473/1,471). We emphasize the judicious use of COVID-19 therapies and optimal glycemic control to prevent CAM.

Cervical dystonia (CD) is primarily treated with botulinum toxin, at intervals of ≥ 12 weeks. We present efficacy, patient-reported outcomes (PROs), and safety in adults with CD at the last available visit after a single set of abobotulinumtoxinA (aboBoNT-A) injections versus placebo using 500 U in a 2-mL injection volume. In this 12-week, randomized, double-blind trial, patients were ≥ 18 years of age with primary idiopathic CD, had a Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score ≥ 20, and TWSTRS-Severity subscale score > 10 at baseline. Patients (N = 134) were randomized (2:1) to aboBoNT-A (n = 89) or placebo (n = 45), with aboBoNT-A patients treated with 500 units (U) if toxin-naïve, and 250 to 500 U based on previous onabotulinumtoxinA dose if non-naïve. Endpoints included total TWSTRS, Pain Numeric Rating Scale (NRS-Pain; 24-hour), Treatment Satisfaction Questionnaire for Medication, and other PROs for pain, depression, and global health. Results are for the intent-to-treat population, with “Week 12” (Wk12) comprising the last available post-baseline assessment (end-of-study or early withdrawal). Mean TWSTRS total scores improved from 42.5 at baseline to 35.4 at Wk12 with aboBoNT-A and 42.4 to 40.4 with placebo (treatment difference: –4.8; 95% confidence interval [CI]: –8.5, –1.1; p = 0.011). At Wk12, mean (95% CI) change from baseline in NRS-Pain was –1.0 (–1.59, –0.45) for aboBoNT-A and –0.2 (–0.96, 0.65) for placebo. AboBoNT-A demonstrated numeric improvements in other PROs. More aboBoNT-A–treated patients than patients receiving placebo reported being at least “somewhat satisfied” with treatment (60.4% vs 42.2%, respectively), symptom relief (57.0% vs 40.0%), and time for treatment to work (55.8% vs 33.3%). No new adverse events were reported. Results indicate that in patients with CD, treatment with aboBoNT-A using a 2-mL injection provided sustained improvement in the TWSTRS total score and patient-perceived benefits up to 12 weeks. Trial registration: Clinicaltrials.gov Identified: NCT01753310 .

The pooled incidences of treatment-emergent adverse events (TEAEs) were examined by indication using the integrated clinical database of Merz-sponsored, placebo-controlled, or repeat-dose studies of incobotulinumtoxinA in adults with cervical dystonia, blepharospasm, limb spasticity, sialorrhea, or essential tremor of the upper limb. Overall incidences of TEAEs, serious TEAEs, TEAEs leading to discontinuation, fatal TEAEs, TEAEs of special interest (TEAESIs; indicating possible toxin spread), and treatment-related (TR) events were determined for incobotulinumtoxinA and placebo after a single injection and for repeated dose cycles of incobotulinumtoxinA. The most frequent events after a single dose of incobotulinumtoxinA are summarized. After a single cycle, incidences of overall TEAEs were similar between incobotulinumtoxinA and the placebo in most indications, although between-indication differences were observed. Few TEAEs led to incobotulinumtoxinA discontinuation; there were no fatal TEAEs with incobotulinumtoxinA. In general, repeated cycles did not increase the incidence of any event. The most frequent TR-TEAEs were indication-dependent, including dysphagia for indications affecting the head or neck. The TR-TEAESIs across all indications were most commonly muscular weakness, dysphagia and dry mouth. Overall, the results of this pooled analysis support and extend the favorable safety and tolerability profile of incobotulinumtoxinA for the treatment of adult neurological disorders established by individual clinical studies.

Purpose A systematic epidemiological study on intensive care unit (ICU)-acquired candidemia across India. Method A prospective, nationwide, multicentric, observational study was conducted at 27 Indian ICUs. Consecutive patients who acquired candidemia after ICU admission were enrolled during April 2011 through September 2012. Clinical and laboratory variables of these patients were recorded. The present study is an analysis of data specific for adult patients. Results Among 1,400 ICU-acquired candidemia cases (overall incidence of 6.51 cases/1,000 ICU admission), 65.2 % were adult. Though the study confirmed the already known risk factors for candidemia, the acquisition occurred early after admission to ICU (median 8 days; interquartile range 4–15 days), even infecting patients with lower APACHE II score at admission (median 17.0; mean ± SD 17.2 ± 5.9; interquartile range 14–20). The important finding of the study was the vast spectrum of agents (31 Candida species) causing candidemia and a high rate of isolation of Candida tropicalis (41.6 %). Azole and multidrug resistance were seen in 11.8 and 1.9 % of isolates. Public sector hospitals reported a significantly higher presence of the relatively resistant C. auris (8.2 vs. 3.9 %; p  = 0.008) and C. rugosa (5.6 vs. 1.5 %; p  = 0.001). The 30-day crude and attributable mortality rates of candidemia patients were 44.7 and 19.6 %, respectively. Logistic regression analysis revealed significant independent predictors of mortality including admission to public sector hospital, APACHE II score at admission, underlying renal failure, central venous catheterization and steroid therapy. Conclusion The study highlighted a high burden of candidemia in Indian ICUs, early onset after ICU admission, higher risk despite less severe physiology score at admission and a vast spectrum of agents causing the disease with predominance of C. tropicalis.

Background: Dolutegravir (DTG) is widely used for the management of naïve and treatment-experienced HIV-infected patients. Low-level viremia (LLV) is common in patients receiving nonnucleoside reverse transcriptase inhibitor- and protease inhibitor-containing regimens. However, the incidence of LLV associated with DTG-containing regimen is not well known. Objective: The objective of this study was to assess the virological response associated with DTG-containing regimens and explored frequencies of LLV and risk factors for the same. Methods: We performed a retrospective cohort study of HIV-infected patients receiving generic DTG-containing regimen from February 2017 to July 2019. All adult patients (≥18 years), who completed at least the first follow-up after initiating treatment, were included in this study. LLV was defined as plasma viral load between 20 and 200 copies/ml. Results: A total of 597 patients started DTG-containing regimen during the study period, of which 522 patients met the inclusion criteria. The study patients were categorized into five groups: naïve (n = 86), first-line failure (n = 32), second-line failure (n = 53), switch (n = 325), and HIV-2 (n = 26). Complete virological suppression at 6, 12, and 18 months was achieved in 78.5%, 81.1%, and 70.9% of the patients, respectively. Furthermore, 17.9%, 12.9%, and 23.3% of the patients had LLV at 6, 12, and 18 months, respectively. Persistent LLV was found in 2.9% of the patients. Overall, DTG was well tolerated and was discontinued in only three patients due to neuropsychiatric side effects. Conclusion: DTG is well tolerated and effective in suppressing HIV across all antiretroviral treatment categories. The rate of persistent LLV is low in DTG-containing therapy.

[This corrects the article DOI: 10.1371/journal.pone.0245827.].

The therapeutic efficacy remaining from prior treatments with botulinum toxins (BoNTs) when cervical dystonia (CD) patients prefer to be re-treated has not been well characterized. Here, we assessed the residual therapeutic efficacy of BoNT injections at the time of a patient-desired re-treatment. In pivotal trials for daxibotulinumtoxinA (DAXI) in CD, subjects could request re-treatment before returning to pre-treatment symptom levels (defined as ≤20% of peak efficacy remaining). In this post hoc analysis of the Phase 3 ASPEN-OLS trial, the median percent efficacy remaining (based on change in TWSTRS total score) was determined in subjects who requested re-injection before returning to pre-treatment symptoms. Dysphagia and muscle weakness were evaluated in patients requesting re-treatment with efficacy remaining, relative to those waiting to return to baseline. There were 264 (28.7% of 920 total treatments) patient requests for re-treatment before returning to pre-treatment status across the study. The median percent efficacy remaining at the time of requested re-injection was 45.5%, which corresponded to a median of 16.0 weeks (range 10.9–40.3) post-treatment. The rates of dysphagia (≤4.9%) and muscle weakness (≤6.8%) were low and were not significantly different in those who waited for return to pre-treatment symptom status versus subjects who requested re-injection with efficacy remaining. A significant proportion of CD patients wished to be re-treated with efficacy still remaining from prior BoNT injections as early symptoms re-emerged. With the overall clinical profile of DAXI, physicians can safely provide individualized treatment regimens based on the treatment goals or symptomatic needs of their patients.