Symptomatic Adults Research Articles

Practical Approach to Longitudinal Neurologic Care of Adults With X-Linked Adrenoleukodystrophy and Adrenomyeloneuropathy.

Although X-linked adrenoleukodystrophy (ALD) has historically been considered a childhood disease managed by pediatric neurologists, it is one of the most common leukodystrophies diagnosed in adulthood. An increase in both male and female adults reaching diagnosis due to familial cases identified by state newborn screening panels and more widespread use of genetic testing results in a large cohort of presymptomatic or early symptomatic adults. This population is in urgent need of standardized assessments and follow-up care. Adults with ALD/adrenomyeloneuropathy (AMN) may be diagnosed in a variety of ways, including after another family member is identified via genetic testing or newborn screening, presenting for symptomatic evaluation, or following diagnosis with primary adrenal insufficiency. Significant provider, patient, and systems-based barriers prevent adult patients with ALD/AMN from receiving appropriate care, including lack of awareness of the importance of longitudinal neurologic management. Confirmation of and education about the diagnosis should be coordinated in conjunction with a genetic counselor. Routine surveillance for adrenal insufficiency and onset of cerebral ALD (CALD) in men should be performed systematically to avoid preventable morbidity and mortality. While women with ALD do not usually develop cerebral demyelination or adrenal insufficiency, they remain at risk for myeloneuropathy and are no longer considered "carriers." After diagnosis, patients should be connected to the robust support networks, foundations, and research organizations available for ALD/AMN. Core principles of neurologic symptom management parallel those for patients with other etiologies of progressive spastic paraplegia. Appropriate patient candidates for hematopoietic stem cell transplant (HSCT) and other investigational disease-modifying strategies require early identification to achieve optimal outcomes. All patients with ALD/AMN, regardless of sex, age, or symptom severity, benefit from a multidisciplinary approach to longitudinal care spearheaded by the neurologist. This review proposes key strategies for diagnostic confirmation, laboratory and imaging surveillance, approach to symptom management, and guidance for identification of appropriate candidates for HSCT and investigational treatments.

Endoscopic therapy for gastrointestinal angiodysplasia.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the benefits and harms of the different endoscopic management approaches for gastrointestinal angiodysplasia in symptomatic adults.

Helicobacter pylori Infection among Symptomatic Adults in a Tertiary Hospital in Southwestern Nigeria: A Retrospective Study

Aim: To determine the prevalence of Helicobacter pylori (H. pylori) infection among symptomatic adults in a tertiary hospital in a peri-urban setting in Southwestern Nigeria. Methodology: It was a retrospective, cross-sectional study conducted in the Medical Microbiology Laboratory, Department of Medical Microbiology and Parasitology, Babcock University Teaching Hospital, Ilisan-Remo, Ogun State, Nigeria, between January 2022 and June 2024. The study involved a review of the medical microbiology laboratory records to evaluate the H. pylori stool antigen results of samples obtained from adults with gastrointestinal symptoms suggestive of H. pylori infection. Results: A total of 1061 adults were included in the study with females accounting for 56.2% of the participants. The age range of the participants was 18 – 95 years with a mean age of 34.59 + 15.51. The prevalence rate of H. pylori infection was 32.4% (344/1061). The infection was higher in females (50.6%) than in males (49.4%) and it was statistically significant (P = 0.011). However, a higher proportion (36.6%) of males had the infection than females (29.2%). The age group 21 – 30 years accounted for 23.3% of the H. pylori-positive participants while 37.6% of participants in the age group 41 -50 years were H. pylori-positive, however it was not statistically significant. Conclusion: H. pylori infection is prevalent among symptomatic adults in this locality. Hence, screening for H. pylori is recommended for detection, prompt treatment and eradication of H. pylori infection to prevent long-term complications.

Effect of Aficamten on Health Status Outcomes in Obstructive Hypertrophic Cardiomyopathy: Results From SEQUOIA-HCM

BackgroundA primary goal in treating obstructive hypertrophic cardiomyopathy (oHCM) is to improve patients’ health status: their symptoms, function, and quality of life. The health status benefits of aficamten, a novel cardiac myosin inhibitor, have not been comprehensively described. ObjectivesThis study sought to determine the effect of aficamten on patient-reported health status, including symptoms of fatigue, shortness of breath, chest pain, physical and social limitations, and quality of life. MethodsSEQUOIA-HCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM) randomized symptomatic adults with oHCM to 24 weeks of aficamten (n = 142) or placebo (n = 140), followed by a 4-week washout. The Kansas City Cardiomyopathy Questionnaire (KCCQ) and Seattle Angina Questionnaire 7-item (SAQ7) were serially administered. Changes in mean KCCQ—Overall Summary Score (KCCQ-OSS) and SAQ7—Summary Score (SAQ7-SS) from baseline to 24 weeks and following treatment withdrawal were compared using linear regression adjusted for baseline scores and randomization strata. Proportions of patients with clinically important changes were compared. ResultsAmong 282 participants, the mean age was 59 ± 13 years, 115 (41%) were female, and 223 (79%) were White. Baseline KCCQ-OSS (69.3 ± 20.1 vs 67.3 ± 18.8) and SAQ7-SS (72.0 ± 21.0 vs 72.4 ± 18.3) were similar between aficamten and placebo groups. Treatment with aficamten, compared with placebo, improved both the mean KCCQ-OSS (13.3 ± 16.3 vs 6.1 ± 12.6; mean difference: 7.9; 95% CI: 4.8-11.0; P < 0.001) and SAQ7-SS (11.6 ± 17.4 vs 3.8 ± 14.4; mean difference: 7.8; 95% CI: 4.7-11.0; P < 0.001) at 24 weeks, with benefits emerging within 4 weeks. No heterogeneity in treatment effect was found across subgroups. A much larger proportion of participants experienced a very large health status improvement (≥20 points) with aficamten vs placebo (KCCQ-OSS: 29.7% vs 12.4%, number needed to treat: 5.8; SAQ7-SS: 31.2% vs 13.9%, number needed to treat: 5.8). Participants’ health status worsened significantly more after withdrawal from aficamten than placebo (KCCQ-OSS: −16.2 ± 19.0 vs −3.0 ± 9.6; P < 0.001; SAQ7-SS: −17.4 ± 21.4 vs −2.5 ± 13.3), further confirming a causal effect of aficamten. ConclusionsIn patients with symptomatic oHCM, treatment with aficamten resulted in markedly improved health status, including significant improvement in chest pain-related health status, than placebo. (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM [SEQUOIA-HCM]; NCT05186818)

Pfizer-BioNTech (BNT162b2) Vaccine Effectiveness against Symptomatic Laboratory-Confirmed COVID-19 Infection among Outpatients in Sentinel Sites, Lebanon, July-December 2021.

On 14 February 2021, Lebanon implemented nationwide vaccination, offering the Pfizer-BioNTech (BNT162b2) vaccine to adults over 50 years of age. We estimated the effectiveness of the Pfizer-BioNTech vaccine in preventing symptomatic laboratory-confirmed COVID-19. We conducted a test-negative case-control (TND) study among symptomatic adults aged 50 years and older who presented with influenza-like illness (ILI) or COVID-19-like illness (CLI) in surveillance sentinel sites between 1 July and 31 December 2021. Unvaccinated participants did not receive any vaccine dose before symptom onset. Vaccinated participants received at least one dose within 14 days before onset of symptoms. We estimated vaccine effectiveness against symptomatic laboratory-confirmed COVID-19, adjusted for demographic and behavioral factors, using multivariable logistic regression. Out of 457 participants with symptoms, 150 (33%) were positive and 307 (67%) were negative for SARS-CoV-2. Adjusted vaccine effectiveness was 22% (95% CI: -70-65%) for those partially vaccinated and 44% (95% CI: 6-67%) for those fully vaccinated. Vaccination with two doses of the Pfizer-BioNTech vaccine was effective in preventing COVID-19 symptomatic illness in the older population. Vaccine effectiveness was lower for those partially vaccinated. We recommend enhancing vaccine uptake with at least one dose among risk groups for COVID-19 and keeping general recommendations on contact and droplet precautions in the general population.

Race, Ethnicity, and Gender Differences in Patient Reported Well-Being and Cognitive Functioning Within 3 Months of Symptomatic Illness During COVID-19 Pandemic.

Differences in acute COVID-19 associated morbidity based on race, ethnicity, and gender have been well described; however, less is known about differences in subsequent longer term health-related quality of life and well-being. This prospective cohort study included symptomatic adults tested for SARS-CoV-2 who completed baseline and 3-month follow-up surveys. Using the PROMIS-29 tool, a validated measure of health and well-being, we compared outcomes at 3months and change in outcomes from baseline to 3months among groups with different races, ethnicities, and/or sexes. Among 6044 participants, 4113 (3202 COVID +) were included. Among COVID + participants, compared to non-Hispanic White participants, Black participants had better PROMIS T-scores for cognitive function (3.6 [1.1, 6.2]) and fatigue (- 4.3 [- 6.6, - 2.0]) at 3months and experienced more improvement in fatigue over 3months (- 2.7 [- 4.7, - 0.8]). At 3months, compared with males, females had worse PROMIS T-scores for cognitive function (- 4.1 [- 5.6, - 2.6]), physical function (- 2.1 [- 3.1, - 1.0]), social participation (- 2.8 [- 4.2, - 1.5]), anxiety (2.8 [1.5, 4.1]), fatigue (5.1 [3.7, 6.4]), and pain interference (2.0 [0.9, 3.2]). Females experienced less improvement in fatigue over 3months (3.1 [2.0, 4.3]). Transgender/non-binary/other gender participants had worse 3-month scores in all domains except for sleep disturbance and pain interference. Three months after the initial COVID-19 infection, Black participants reported better cognitive function and fatigue, while females and other gender minoritized groups experienced lower well-being. Future studies are necessary to better understand how and why social constructs, specifically race, ethnicity, and gender, influence differences in COVID-19-related health outcomes. Trials Registration ClinicalTrials.gov Identifier: NCT04610515.

Effect of spirulina on risk of hospitalization among patients with COVID-19: the TOGETHER randomized trial

BackgroundAlgae-derived nutraceuticals, such as spirulina, have been reported to have biological activities that may minimize clinical consequences to COVID-19 infections. ObjectivesThis study aimed to determine whether spirulina is an effective treatment for high-risk patients with early COVID-19 in an outpatient setting. MethodsThe TOGETHER trial is a placebo-controlled, randomized, platform trial conducted in Brazil. Eligible participants were symptomatic adults with a positive rapid test for SARS-CoV-2 older than 50 y or with a known risk factor for disease severity. Patients were randomly assigned to receive placebo or spirulina (1 g twice daily for 14 d). The primary end point was hospitalization defined as either retention in a COVID-19 emergency setting for >6 h or transfer to tertiary hospital owing to COVID-19 at 28 d. Secondary outcomes included time-to-hospitalization, mortality, and adverse drug reactions. We used a Bayesian framework to compare spirulina with placebo. ResultsWe recruited 1126 participants, 569 randomly assigned to spirulina and 557 to placebo. The median age was 49.0 y, and 65.3% were female. The primary outcome occurred in 11.2% in the spirulina group and 8.1% in the placebo group (odds ratio [OR]: 1.24; 95% credible interval: 0.84, 1.86). There were no differences in emergency department visit (OR: 1.21; 95% credible interval: 0.81, 1.83), nor time to symptom relief (hazard ratio: 0.90; 95% credible interval: 0.79, 1.03). Spirulina also not demonstrate important treatment effects in the prespecified subgroups defined by age, sex, BMI, days since symptom onset, or vaccination status. ConclusionsSpirulina has no any clinical benefits as an outpatient therapy for COVID-19 compared with placebo with respect to reducing the retention in an emergency setting or COVID-19–related hospitalization. There are no differences between spirulina and placebo for other secondary outcomes.This trial was registered at clinicaltrials.gov as NCT04727424.

Efficacy and acceptability of long-acting antipsychotics in acutely ill individuals with schizophrenia-spectrum disorders: A systematic review and network meta-analysis

To assess the effect of Long-acting injectable (LAI) antipsychotics in acutely ill patients, we systematically searched major databases for randomized controlled trials (RCTs) comparing LAIs with other LAIs, oral antipsychotics, or placebo in acutely symptomatic adults with schizophrenia-spectrum disorders. Data were analyzed with a random-effects network meta-analysis. Co-primary outcomes were efficacy (mean change in psychopathology rating scales) and acceptability (all-cause discontinuations) at study endpoint.Of 25 RCTs, 19 studies tested second-generation LAIs (SGA-LAIs) and six first-generation LAIs (FGA-LAIs). Due to a disconnected network, FGA-LAIs were analyzed separately, with poor data quality. The SGA-LAIs network included 8,418 individuals (males=63%, mean age=39.3 years). All SGA-LAIs outperformed placebo in reducing acute symptoms at study endpoint (median follow-up=13 weeks). They were more acceptable than placebo with the only exception of olanzapine, for which no differences with placebo emerged. Additionally, we distinguished between different LAI formulations of the same antipsychotic to explore potential pharmacokinetic differences. Most formulations outperformed placebo in the very short-term (2 weeks or less), regardless of the need for initial oral supplementation.SGA-LAIs are evidence-based treatments in acutely ill individuals with schizophrenia-spectrum disorders. Findings support the use of SGA-LAIs to manage psychopathology and improve adherence right from the acute phases of illness.

Synergistic effects of GFAP and Aβ42: Implications for white matter integrity and verbal memory across the cognitive spectrum

BackgroundPlasma glial fibrillary acidic protein (GFAP), an astrocytic biomarker, has previously been linked with Alzheimer's disease (AD) status, amyloid levels, and memory performance in older adults. The neuroanatomical pathways by which astrogliosis/astrocyte reactivity might impact cognitive outcomes remains unclear. We evaluated whether plasma GFAP and amyloid levels had a synergistic effect on fornix structure, which is critically involved in AD-associated cholinergic pathways. We also examined whether fornix structure mediates associations between GFAP and verbal memory. MethodsIn a cohort of both asymptomatic and symptomatic older adults (total n = 99), we assessed plasma GFAP, amyloid-β42 (Aβ42), other AD-related proteins, and vascular markers, and we conducted comprehensive memory testing. Tractography-based methods were used to assess fornix structure with whole brain diffusion metrics to control for diffuse alterations in brain white matter. ResultsIn individuals in the low plasma amyloid-β42 (Aβ42) group, higher plasma GFAP was associated with lower fractional anisotropy (FA; p = 0.007), higher mean diffusivity (MD; p < 0.001), higher radial diffusivity (RD; p < 0.001), and higher axial diffusivity (DA; p = 0.001) in the left fornix. These associations were independent of APOE gene status, plasma levels of total tau and neurofilament light, plasma vascular biomarkers, and whole brain diffusion metrics. In a sub-analysis of participants in the low plasma Aβ42 group (n = 33), fornix structure mediated the association between higher plasma GFAP levels and lower verbal memory performance. DiscussionHigher plasma GFAP was associated with altered fornix microstructure in the setting of greater amyloid deposition. We also expanded on our prior GFAP-verbal memory findings by demonstrating that in the low plasma Aβ42 group, left fornix integrity may be a primary white matter conduit for the negative associations between GFAP and verbal memory performance. Overall, these findings suggest that astrogliosis/astrocyte reactivity may play an early, pivotal role in AD pathogenesis, and further demonstrate that high GFAP and low Aβ42 in plasma may reflect a particularly detrimental synergistic role in forniceal-memory pathways.

Proportions and Seasonal Patterns of Respiratory Viruses via Rapid Tests in Adults at a Greek Hospital (Oct. 2023-Mar. 2024).

Respiratory infections pose a major public health threat. The predominant viruses causing viral respiratory infections are influenza A and B (Flu-A, Flu-B), coronaviruses, respiratory syncytial virus (RSV), and adenovirus. This study aims to investigate the proportion of these cases via rapid antigen tests and assess seasonal patterns. Clinical samples were collected from symptomatic adults presenting to the Emergency and Respiratory Medicine Departments of the University Hospital of Larissa (UHL), Greece from 16 October 2023 to 31 March 2024. Nasal specimens were antigen-tested for Flu-A/B, SARS-CoV-2, RSV, and adenovirus. The total sample of specimens collected was 1434, of which 739 (51.5%) were female and 695 were male (48.5%). The mean age of participants was 57 ± 5.5 years. Among the positive results, we recorded a proportion of 40.18% and 11.40% for influenza A and B, respectively, followed by 35.79% for SARS-CoV-2, 10.70% for RSV, and 1.93% for adenovirus. In Greece, surveillance systems in infection control are underutilized. Rapid tests via multiple antigens can quickly identify viral infections, making them a valuable tool with financial benefits for health systems. Early detection of respiratory infections helps allocate resources efficiently, ensures adequate staff and facilities are available, and improves patient care through refined clinical management.

Osgood-Schlatter Disease: Ossicle Resection and Patellar Tendon Repair in a Symptomatic Adult

Chronic Osgood-Schlatter disease can cause significant knee pain and can result in severe functional deficits. For large, painful Osgood-Schlatter disease ossicles refractory to conservative management, surgical ossicle excision can provide resolution of symptoms. After diagnostic arthroscopy and intra-articular debridement, our preferred excision technique uses an open incision for direct visualization and removal of intratendinous ossicles, followed by distal patellar tendon repair and subsequent fixation with FiberTape sutures and knotless anchors to the tibial tubercle.

Factors affecting meibomian gland area loss in symptomatic adults.

To characterize the distribution of meibomian gland (MG) area loss (MGL) and its relationship with demographic characteristics, mites, and symptoms. This retrospective observational study included patients who visited the Dry Eye Clinic of Shenzhen Eye Hospital between June 2020 and August 2021. General patient characteristics, ocular symptoms, Demodex test results of the eyelid edges, and the results of a comprehensive ocular surface analysis were collected. MGL was analyzed using Image J software. This study enrolled 1204 outpatients aged 20-80 (40.70±13.44)y, including 357 males (29.65%) and 847 females (70.35%). The patients were classified into mild (n=155; 12.87%), moderate (n=795; 66.03%), severe (n=206; 17.11%), and extremely severe (n=48; 3.99%) MGL groups. MGL was significantly larger in female than in male (P=0.006). The degree of MGL also significantly differed in age (P<0.001) and the more numbers of mites with severity (P<0.001). Multivariate disordered multinomial logistic regression analysis identified that female sex, older age, secretory symptoms, and a large number of mites were risk factors for MGL (P<0.05). Patients with MGL are more likely to be older, female, more numbers of mites, and increased secretion.

Development and validation of reference equations for dual-energy X-ray absorptiometry-derived measures of fat-free mass in adults aged 45-85 years: results from the Canadian Longitudinal Study on Aging.

Reference equations for fat-free mass (FFM) and lean soft tissue mass (LM) measures obtained from dual-energy X-ray absorptiometry (DEXA) are important for the interpretation of body composition. This study developed and validated reference equations for FFM and LM using DEXA from the Canadian Longitudinal Study on Aging. Reference equations were developed using data from a random population-based sample of ostensibly healthy and functionally independent adults aged 45-85 years. Reference equations for absolute (accounting for age, sex, height, and body mass) and height-adjusted aka index (accounting for age, sex, and body mass index) measures of FFM and LM were developed using quantile regression. Reference equations were respectively developed and validated in derivation (80%) and validation cohorts (20%). Reference equations were applied to symptomatic adults with self-reported chronic obstructive pulmonary disease (COPD) or heart disease to assess discriminant validity; and compared with other published equations to assess performance. Bland-Altman analyses and Lin's concordance correlation coefficients were utilised to assess agreement. Reference equations for 5th, 10th, 50th, 90th, and 95th percentiles were developed for DEXA-derived estimates of FFM and LM based on 1881 healthy participants (57% male) aged 55 [IQR: 50-61] years. Reference equations performed comparably in the validation cohort and discriminated reference values between ostensibly healthy adults and people with symptomatic COPD or heart disease. Previously published reference equations tended to over- or under-predict estimates of LM compared with the current reference equations. This study provides a comprehensive and validated set of reference equations for estimating and interpreting FFM and LM from DEXA in Canadian adults aged 45-85 years, although additional validation may be required for those>75 years.

Management of obstructive sleep apnoea in primary care.

Obstructive sleep apnoea (OSA) is common in the community and is increasing in prevalence. Primary care plays a pivotal role in the diagnosis and management of OSA. This article focuses on the management options for a patient with an established diagnosis of OSA and provides a guide for driving licensing requirements. Indications for continuous positive airway pressure (CPAP) are discussed and tips provided toconsider when conducting a review appointment, including trouble shooting. There are several treatment options available for patients with an established diagnosis of OSA. Selecting the optimal therapy involves aligning the symptoms and severity of OSA with the presence of comorbidities. CPAP is a highly effective therapy for symptomatic adults with moderate-to-severe OSA and for some symptomatic patients with mild OSA. Early trouble shooting of side effects and using supportive interventions increases the probability of long-term adherence, which is key to symptomatic improvement.

Assessment of Oculomotor Functions as a Biomarker in Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI), or concussion, is a major public health problem, and ambiguity still exists regarding its diagnosis. While functional magnetic resonance imaging (fMRI) has been identified as a helpful screening tool for concussion, its limited accessibility in clinical or field settings necessitates a more efficient alternative. Oculomotor function deficit is an often-reported pathology in mTBI. Due to the neuroanatomical overlap between eye-movement circuitry and mTBI pathophysiology, visual deficits are expected. In this study, we investigate the possibility of using an oculomotor assessment tool for finding biomarkers in concussion. We used fMRI with tasks evaluating oculomotor functions: smooth pursuit (SP), saccades, anti-saccades, and optokinetic nystagmus (OKN). Before the scanning, the testing with a system of virtual reality goggles with integrated eye- and head-tracking was used where subjects performed the same tasks as those used in fMRI. Twenty-nine concussed symptomatic adults (CSA) within 1-month postconcussion and 29 age- and sex-matched healthy controls (HCS) were tested to examine blood oxygen level-dependent (BOLD) fMRI alterations associated with performances in oculomotor function after mTBI and evaluate the efficacy of the oculomotor assessment in detecting oculomotor and gaze deficits following mTBI. Comparing CSA with HCS, significant differences were observed in anti-saccades and OKN performance. CSA group exhibited elevated %BOLD signal change on each task compared with HCS: in the superior frontal gyrus during the smooth pursuit, inferior frontal gyrus during the saccades, putamen and dorsolateral prefrontal cortex (DLPFC) during the anti-saccades, and lingual gyrus and IFG during the OKN. Key findings include the following: (1) oculomotor deficits in concussed subjects compared with controls, (2) abnormal activation patterns in areas related to the regulation and control of oculomotor movements, suggesting concussion-induced disruptions, and (3) the potential of oculomotor assessment as a promising approach for mTBI biomarkers, with anti-saccades and OKN identified as the most sensitive tasks.

Oral mouthwashes for asymptomatic to mildly symptomatic adults with COVID-19 and salivary viral load: a randomized, placebo-controlled, open-label clinical trial

BackgroundRecent randomized clinical trials suggest that the effect of using cetylpyridinium chloride (CPC) mouthwashes on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load in COVID-19 patients has been inconsistent. Additionally, no clinical study has investigated the effectiveness of on-demand aqueous chlorine dioxide mouthwash against COVID-19.MethodsWe performed a randomized, placebo-controlled, open-label clinical trial to assess for any effects of using mouthwash on the salivary SARS-CoV-2 viral load among asymptomatic to mildly symptomatic adult COVID-19-positive patients. Patients were randomized to receive either 20 mL of 0.05% CPC, 10 mL of 0.01% on-demand aqueous chlorine dioxide, or 20 mL of placebo mouthwash (purified water) in a 1:1:1 ratio. The primary endpoint was the cycle threshold (Ct) values employed for SARS-CoV-2 salivary viral load estimation. We used linear mixed-effects models to assess for any effect of the mouthwashes on SARS-CoV-2 salivary viral load.ResultsOf a total of 96 eligible participants enrolled from November 7, 2022, to January 19, 2023, 90 were accepted for the primary analysis. The use of 0.05% CPC mouthwash was not shown to be superior to placebo in change from baseline salivary Ct value at 30 min (difference vs. placebo, 0.640; 95% confidence interval [CI], -1.425 to 2.706; P = 0.543); 2 h (difference vs. placebo, 1.158; 95% CI, -0.797 to 3.112; P = 0.246); 4 h (difference vs. placebo, 1.283; 95% CI, -0.719 to 3.285; P = 0.209); 10 h (difference vs. placebo, 0.304; 95% CI, -1.777 to 2.385; P = 0.775); or 24 h (difference vs. placebo, 0.782; 95% CI, -1.195 to 2.759; P = 0.438). The use of 0.01% on-demand aqueous chlorine dioxide mouthwash was also not shown to be superior to placebo in change from baseline salivary Ct value at 30 min (difference vs. placebo, 0.905; 95% CI, -1.079 to 2.888; P = 0.371); 2 h (difference vs. placebo, 0.709; 95% CI, -1.275 to 2.693; P = 0.483); 4 h (difference vs. placebo, 0.220; 95% CI, -1.787 to 2.226; P = 0.830); 10 h (difference vs. placebo, 0.198; 95% CI, -1.901 to 2.296; P = 0.854); or 24 h (difference vs. placebo, 0.784; 95% CI, -1.236 to 2.804; P = 0.447).ConclusionsIn asymptomatic to mildly symptomatic adults with COVID-19, compared to placebo, the use of 0.05% CPC and 0.01% on-demand aqueous chlorine dioxide mouthwash did not lead to a significant reduction in SARS-CoV-2 salivary viral load. Future studies of the efficacy of CPC and on-demand aqueous chlorine dioxide mouthwash on the viral viability of SARS-CoV-2 should be conducted using different specimen types and in multiple populations and settings.

Xpert MTB/RIF Ultra versus mycobacterial growth indicator tube liquid culture for detection of Mycobacterium tuberculosis in symptomatic adults: a diagnostic accuracy study

Xpert MTB/RIF Ultra (Ultra) is an automated molecular test for the detection of Mycobacterium tuberculosis in sputum. We compared the sensitivity of Ultra to that of mycobacterial growth indicator tube (MGIT) liquid culture, considered the most sensitive assay in routine clinical use. In this prospective, multicentre, cross-sectional diagnostic accuracy study, we used a non-inferiority design to assess whether the sensitivity of a single Ultra test was non-inferior to that of a single liquid culture for detection of Mtuberculosis in sputum. We enrolled adults (age ≥18 years) with pulmonary tuberculosis symptoms in 11 countries and each adult provided three sputum specimens with a minimum volume of 2 mL over 2 days. Ultra was done directly on sputum 1, and Ultra and MGIT liquid culture were done on resuspended pellet from sputum 2. Results of MGIT and solid media cultures done on sputum 3 were considered the reference standard. The pre-defined non-inferiority margin was 5·0%. Between Feb 18, 2016, and Dec 4, 2019, we enrolled 2906 participants. 2600 (89%) participants were analysed, including 639 (25%) of 2600 who were positive for tuberculosis by the reference standard. Of the 2357 included in the non-inferiority analysis, 877 (37%) were HIV-positive and 984 (42%) were female. Sensitivity of Ultra performed directly on sputum 1 was non-inferior to that of sputum 2 MGIT culture (MGIT 91·1% vs Ultra 91·9%; difference -0·8 percentage points; 95% CI -2·8 to 1·1). Sensitivity of Ultra performed on sputum 2 pellet was also non-inferior to that of sputum 2 MGIT (MGIT 91·1% vs Ultra 91·9%; difference -0·8 percentage points; -2·7 to 1·0). For the detection of M tuberculosis in sputum from adults with respiratory symptoms, there was no difference in sensitivity of a single Ultra test to that of a single MGIT culture. Highly sensitive, rapid molecular approaches for M tuberculosis detection, combined with advances in genotypic methods for drug resistance detection, have potential to replace culture. US National Institute of Allergy and Infectious Diseases.

Evaluating Malaria Rapid Diagnostic Tests and Microscopy for Detecting Plasmodium Infection and Status of Plasmodium falciparum Histidine-Rich Protein 2/3 Gene Deletions in Southeastern Nigeria.

Delays in malaria diagnosis increase treatment failures and deaths. In endemic regions, standard diagnostic methods are microscopy and malaria rapid diagnostic tests (mRDTs) detecting Plasmodium falciparum histidine-rich protein 2/3 (PFHRP2/PFHRP3), but gene deletions can allow certain parasites to remain undetected. We enlisted a cohort comprising 207 symptomatic individuals, encompassing both children and adults, at a hospital in Nnewi, Nigeria. The prevalence of parasites was determined using a highly sensitive, species-specific quantitative polymerase chain reaction (SS-qPCR). Within a subset of 132 participants, we assessed the sensitivity and specificity of microscopy and HRP2-mRDTs in comparison to SS-qPCR for the detection of P. falciparum. We also investigated the prevalence of pfhrp2/pfhrp3 gene deletions. Greater sensitivity was achieved with mRDTs (95%) compared with microscopy (77%). Also, mRDTs exhibited greater specificity (68%) than microscopy (44%). The positive predictive value of mRDTs (89%) surpassed that of microscopy (80%), suggesting a greater probability of accurately indicating the presence of infection. The negative predictive value of mRDTs (82%) was far greater than microscopy (39%). Of the 165 P. falciparum-positive samples screened for pfhrp2/pfhrp3 gene deletions, one gene deletion was detected in one sample. Regarding infection prevalence, 84% were positive for Plasmodium spp. (by reverse transcription [RT]-qPCR), with P. falciparum responsible for the majority (97%) of positive cases. Thus, exclusive reliance on microscopy in endemic areas may impede control efforts resulting from false negatives, underscoring the necessity for enhanced training and advocating for high-throughput molecular testing such as RT-qPCR or qPCR at referral centers to address limitations.

Feasibility of a "No-Biopsy" Approach for the Diagnosis of Celiac Disease in Symptomatic Adults.

It was a retrospective analysis of medical records of all biopsy-diagnosed CD patients with available anti-tTGA antibodies reports from 2019 to 2023. The patients were divided into three groups based on Marsh grading and anti-tTGA antibody levels were compared using various statistical tests. A total of 94 biopsy-diagnosed symptomatic CD patients with anti-tTGA antibody reports available formed the study group. Of these, 54 had biopsy findings consistent with Marsh 3 lesion, three had Marsh 2 lesion, and 37 had Marsh 1 lesion. A significant correlation existed between Marsh grading 3 lesion and anti-tTGA antibody levels above the upper limit of normal (ULN) x 10. Serum levels of anti-tTGA antibodies greater than 10 x ULN can be used to identify symptomatic patients with Marsh grade 3 CD lesions.

Seroprevalence of dengue IgG and associated risk factors in symptomatic and asymptomatic adults in Posadas (Misiones, Argentina), 2017-2019

BackgroundDengue represents a major public health problem in the Americas in general, and in Posadas (Misiones, Argentina) in particular. This study aimed to assess the seroprevalence of dengue virus infection, analyze associated factors, and determine the proportion of asymptomatic cases. MethodsThis prospective cross-sectional study took place from November 2017 to April 2019 in the High Complexity Laboratory of Misiones, at the School Hospital Dr. Ramón Madariaga in Posadas. A random sample of 301 adults (≥ 15 years) was selected from the electoral registry and stratified by geographical area of residence. Sociodemographic, clinical, and laboratory data were collected by means of a survey and serology. Results were analyzed using multivariable logistic regression. ResultsThe median age of the sample was 33 years; 66% were women, and 46.5% had completed at least secondary school. Anti-dengue IgG antibodies were present in 40.2% of the sample (95% confidence interval [CI] 34.5–45.9%), including 90% of those who reported dengue and 20.5% who did not (odds ratio [OR] 33.25, 95% CI 15.46–71.51, p < 0.001). In the multivariable analysis, adjusted for age, group, gender, and vaccination against yellow fever, seropositivity was associated with having relatives with dengue (adjusted OR 3.96, 95% CI 2.18–7.23; p < 0.001). ConclusionSeroprevalence for dengue in Posadas was higher than estimates based on the notification records, and there was a high proportion of asymptomatic cases. Educational level and having a family member who had suffered from dengue were associated with positive serology.