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Background The mortality rate of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) patients is a major challenge in all healthcare systems worldwide. Because the MERS-CoV risk-standardized mortality rates are currently unavailable in the literature, the author concentrated on developing a method to estimate the risk-standardized mortality rates using MERS-CoV 3- and 30-day mortality measures. Methods MERS-CoV data in Saudi Arabia is publicly reported and made available through the Saudi Ministry of Health (SMOH) website. The author studied 660 MERS-CoV patients who were reported by the SMOH between December 2, 2014 and November 12, 2016. The data gathered contained basic demographic information (age, gender, and nationality), healthcare worker, source of infection, pre-existing illness, symptomatic, severity of illness, and regions in Saudi Arabia. The status and date of mortality were also reported. Cox-proportional hazard (CPH) models were applied to estimate the hazard ratios for the predictors of 3- and 30-day mortality. Results 3-day, 30-day, and overall mortality were found to be 13.8%, 28.3%, and 29.8%, respectively. According to CPH, multivariate predictors of 3-day mortality were elderly, non-healthcare workers, illness severity, and hospital-acquired infections (adjusted hazard ratio (aHR) =1.7; 8.8; 6.5; and 2.8, respectively). Multivariate predictors of 30-day mortality were elderly, non-healthcare workers, pre-existing illness, severity of illness, and hospital-acquired infections (aHR =1.7; 19.2; 2.1; 3.7; and 2.9, respectively). Conclusions Several factors were identified that could influence mortality outcomes at 3 days and 30 days, including age (elderly), non-healthcare workers, severity of illness, and hospital-acquired infections. The findings can serve as a guide for healthcare practitioners by appropriately identifying and managing potential patients at high risk of death.

Malaria is spread by the transmission of sexual stage parasites, called gametocytes. However, with Plasmodium falciparum , gametocytes can only be detected in peripheral blood when they are mature and transmissible to a mosquito, which complicates control efforts. Here, we identify the set of genes overexpressed in patient blood samples with high levels of gametocyte-committed ring stage parasites. Expression of all 18 genes is regulated by transcription factor AP2-G, which is required for gametocytogenesis. We select three genes, not expressed in mature gametocytes, to develop as biomarkers. All three biomarkers we validate in vitro using 6 different parasite lines and develop an algorithm that predicts gametocyte production in ex vivo samples and volunteer infection studies. The biomarkers are also sensitive enough to monitor gametocyte production in asymptomatic P. falciparum carriers allowing early detection and treatment of infectious reservoirs, as well as the in vivo analysis of factors that modulate sexual conversion. Malaria gametocytes are sexual-stage parasites transmitted from mammalian host’s blood back to their insect vector. Here, Prajapati et al. identify gametocyte-committed ring-stage biomarkers allowing to forecast malaria transmission potential.

Background Chagas disease (CD)-a parasitic infection caused by Trypanosoma cruzi , affects ~7 million people worldwide. Current first line therapies like Benznidazole and Nifurtimox have significant side effects, and limited data to support their efficacy when used to treat CD in its chronic indeterminate (asymptomatic) phase. This study aimed to critically assess and meta-analyze all clinical trials to date that address this specific phase of CD. Methods PubMed, Cochrane, ClinicalTrials.gov, EBSCOhost, and SciELO (inception - December 2024) were searched for randomized, controlled trials (RCTs) including the efficacy or safety of treatment in adults with indeterminate form, chronic CD. English abstracts were required, with full text in English, Spanish or Portuguese. Studies had to have the potential to report disease progression (primary) or parasitological cure and adverse events (secondary) by treatment regimen. We define parasitological cure as T. cruzi PCR negativity. Meta-analysis was conducted using random effects models with inverse-variance weighting of study-specific risk ratios (95% CI). Publication bias was assessed via funnel plots. Results Five out of 132 studies were unique RCTs that met the inclusion criteria. Inter-rater agreement on study selection was high (κ=0.83). Of all participants, most were female (428/653 or 66%). Summary estimates revealed significant benefit for achieving parasitological cure in treatment versus control groups (overall RR 5.93 [95% CI: 3.96, 8.86, p < 0.001]). A direct comparison of adverse events (AEs) experienced across trials was challenging (overall RR 1.47 [(95% CI: 0.90, 2.38), p <0.12]). Among all participants, 8.1% (53/653) discontinued treatment for various reasons after treatment initiation. Notably, no prospective RCTs of indeterminate form CD were identified that assessed for development of long-term cardiac or gastrointestinal complications. Conclusion Antitrypanosomal treatment can significantly improve parasitological cure rates in indeterminate (asymptomatic) form, chronic phase CD, despite high risk of bias and aggregated data limitations. Our analysis underscores the need for more rigorous, standardized randomized controlled trials with consistent inclusion criteria based on indeterminate form, chronic phase CD and clinical endpoints. This study provides a focused, clinically relevant perspective by emphasizing randomized trial data, complementing broader CD research. PROSPERO registration CRD42024512886.

Background Tuberculosis (TB) continues to be a public health challenge in Saudi Arabia, particularly for the elderly. This study was conducted to estimate mortality per 1000 person-year among TB and resistant TB cases and to identifying factors associated with mortality. Methods This is a retrospective cohort study of 713 new TB cases at King Abdulaziz Medical City in Riyadh diagnosed between January 1, 2000, and December 31, 2016. Patient medical records and microbiology lab databases were used to identify TB cases. Through reviews were conducted of patients’ medical records, including physician notes, physical examinations, radiology (scans and imaging), laboratory tests, and follow-up notes. Collected data include demographic information, clinical features, diagnoses, comorbidities, and death rates. Results Of the 713 TB patients included in this study, 110 died, giving an average mortality rate of 22 per 1000 person-years (PY; 95% CI: 18.2–26.4). Elderly patients (≥ 60 years) had a higher mortality rate of 36.5 per 1000 PY (95% CI: 28.9–45.5). As age increases by one year, the hazard of mortality increase by 2.4% (aHR: 1.024 [95% CI: 1.009–1.039, P  = 0.002]). Higher hazard of mortality was found among males (aHR: 2.014 [95% CI: 1.186–3.418, P  = 0.010]). Patients with respiratory and other types of comorbidities and cancer had a higher mortality hazard (aHR: 1.898 [95% CI: 1.005–3.582, P  = 0.048]; aHR: 2.346 [95% CI: 1.313–4.192, P  = 0.004]; aHR: 3.292 [95% CI: 1.804–6.006, P  = 0.001]), respectively. Multidrug-resistant TB (MDR-TB) was found in 2 cases (0.28%) (95% CI: 0.08–1.02), 1.68% were resistant to only one antibiotic, 0.14% had rifampicine-resistant TB (RR-TB), 0.28% had MDR-TB, and 0.14% had extensively drug-resistant TB (XDR-TB). Conclusions The mortality rate among TB patients was found to be 22 per 1000 person-year at our center. TB was associated with high mortality rates among males, the elderly, and patients with cancer, respiratory illness, and other comorbidities. Future clinical practice should include establishing an efficient TB diagnostic program and continued hazard assessment of TB treatment options.

Infections with rabies virus (RABV) and related lyssaviruses are uniformly fatal once virus accesses the central nervous system (CNS) and causes disease signs. Current immunotherapies are thus focused on the early, pre‐symptomatic stage of disease, with the goal of peripheral neutralization of virus to prevent CNS infection. Here, we evaluated the therapeutic efficacy of F11, an anti‐lyssavirus human monoclonal antibody (mAb), on established lyssavirus infections. We show that a single dose of F11 limits viral load in the brain and reverses disease signs following infection with a lethal dose of lyssavirus, even when administered after initiation of robust virus replication in the CNS. Importantly, we found that F11‐dependent neutralization is not sufficient to protect animals from mortality, and a CD4 T cell‐dependent adaptive immune response is required for successful control of infection. F11 significantly changes the spectrum of leukocyte populations in the brain, and the FcRγ‐binding function of F11 contributes to therapeutic efficacy. Thus, mAb therapy can drive potent neutralization‐independent T cell‐mediated effects, even against an established CNS infection by a lethal neurotropic virus. Synopsis Rabies is a fatal viral disease of humans, with uniform mortality once central nervous system (CNS) invasion occurs and symptoms appear. This study demonstrates that a single‐dose monoclonal (mAb) therapy can yield a functional cure for rabies, even after robust CNS replication. Peripheral administration of mAb F11 reduces CNS viral replication and prevents mortality, following infection of mice with a lethal dose of either Australian bat lyssavirus (ABLV) or rabies virus (RABV). Therapeutic efficacy of F11, a human IgG1, requires a functional antibody Fc region, implicating the mechanistic involvement of immune cells bearing FcRγ. F11 efficacy requires an intact host adaptive immune response, particularly CD4 T cells. Administration of F11 alters both the proportions and phenotypes of immune cells in the brains of ABLV‐infected animals. Virus persists chronically at a low level in the brains of F11‐treated animals, but animals remain free of disease signs. Graphical Abstract Rabies is a fatal viral disease of humans, with uniform mortality once central nervous system (CNS) invasion occurs and symptoms appear. This study demonstrates that a single‐dose monoclonal (mAb) therapy can yield a functional cure for rabies, even after robust CNS replication.

The clinical utility of the ratio of the apnea–hypopnea index (AHI) occurring during rapid eye movement (REM) and non‐REM (NREM) sleep (AHI REM /AHI NREM ratio) has been debated. We investigated the heterogeneity of REM and NREM sleep behaviors to identify unobserved distinct subtypes of sleep‐disordered breathing (SDB) and examine their demographic and clinical features. The present study used a sample of 3626 adult patients who underwent diagnostic polysomnography evaluations at the Sleep Disorders Center of King Abdulaziz Medical City in Riyadh, Saudi Arabia. Latent profile analysis was performed to categorize subjects into distinct profiles of SDB based on AHI REM , AHI NREM , and AHI REM /AHI NREM ratio. A multinomial logistic model estimated the odds ratio of SDB profiles. Four distinct subtypes of SDB were identified: Class I (low AHI REM ; 75.9%) included patients with normal SDB events during REM sleep, serving as the reference group; Class II (REM‐OSA, 1.2%) included patients with high AHI during REM sleep but lowest AHI during NREM sleep, resulting in the largest AHI REM /AHI NREM ratio; Class III (AHI NREM < 30 events per hour, 17.4%); and Class IV (AHI NREM ≥ 30 events per hour, 5.5%). Compared to Class I, factors related to Class IV included older age, high BMI, large neck circumference, hypertension, reduced total sleep time, reduced REM sleep, poor sleep efficiency, high desaturation index, low SpO2, high arousal index, and high Epworth Sleepiness Scale. As hypothesized, the study characterized several subtypes of SDB based on the AHI REM , AHI NREM , and their ratio (AHI REM /AHI NREM ) in a large cohort and identified their demographic and clinical features. These subtypes might be clinically useful for defining SDB among adult patients referred to sleep clinics who may have varying responses to treatment depending on their subtype of the disease.

Sleep is a modifiable factor affecting chronic diseases and conditions in the Active-Duty (AD) United States (US) military population. This study assesses the impact of reported sleep health behaviors and sleep profiles on reported multimorbidity in active-duty service members (ADSMs). The study used a military representative sample of 17,166 active duty SMs from the 2018 Department of Defense (HRBS) to explore sleep patterns and profiles, and medical conditions. Multimorbidity was defined as the presence of two or more medical conditions which we limited to include obesity, hypertension, and hyperlipidemia. The adjusted odds ratios for six sleep-related health behaviors and their unobservable sleep profiles were calculated using a weighted multinomial logistic model. Sleep-related health behaviors were associated with increased odds of obesity, hypertension, and hyperlipidemia. We found higher odds of reported multimorbidity in SMs who reported lack of energy due to poor sleep (adjusted odds ratio [aOR] = 2.35, 95% CI:1.88-2.93), sleep 6 hours or less per night (aOR = 1.95, 95% CI:1.53-2.50), trouble sleeping (aOR = 2.19, 95% CI:1.76-2.72), and use of sleep medications (aOR = 2.10, 95% CI:1.64-2.68). Latent class analysis (LCA) identified three unobservable sleep profiles in SMs: minimal or low-risk sleep patterns (37.43%), moderate-risk sleep patterns (31.11%), and high-risk sleep patterns (31.46%). SMs with high-risk sleep patterns were significantly associated with reported multimorbidity (adjusted odds ratio [aOR] = 3.54, 95% CI:2.75-4.56). We found a strong association between sleep-related health behaviors and their unobservable sleep profiles with multimorbidity in this AD population. Future studies should investigate whether other chronic diseases may be influenced by sleep impairment in the US military population.

Background Despite the fact that several scabies outbreaks emerged in schools in Saudi Arabia in 2018, no study has investigated the risk of scabies recurrence among children in Saudi Arabia. This study aimed to estimate the rate of scabies recurrence and identify factors that were associated with an increased risk of recurrence among children. Methods This is a multi-center retrospective study of children (age < 14 years) who were diagnosed between May 20, 2015 and September 12, 2018 with one or multiple recurrent scabies at the Ministry of National Guard Health Affairs (MNGHA) hospitals and clinics in Saudi Arabia. Data were obtained from an electronic health system, BestCare database. Results A sample of 264 children analyzed (mean age of 6.7 years) resulted in a cumulative number of 316 scabies diagnoses in which 86 (27.2%) experienced scabies recurrence (at least once). Independent factors associated with a high risk of scabies recurrence: older children (adjusted hazard ratio [aHR], 1.036; 95% CI, 1.002–1.072; P  = 0.039), female gender (aHR, 1.734; 95% CI, 1.329–2.262; P  = 0.001), Western region of Saudi Arabia (aHR, 1.548; 95% CI, 1.115–2.151; P  = 0.009), and 2nd tertile season [May to August] (aHR, 2.368; 95% CI, 1.706–3.288; P = 0.001). Conclusions The study demonstrated that the recurrence rate of scabies among children is high. Older children, the female gender, the Western region of Saudi Arabia, and the seasonality were independently associated with an increased risk of scabies recurrence. High temperature and low humidity should be explored as leading factors for scabies infestations in Saudi Arabia. Findings derived from this study may be useful for clinicians and governments in optimizing clinical management of scabies cases and contacts.

Background The peritonitis rate among children treated with peritoneal dialysis (PD) has not been widely reported in Saudi Arabia. The study aim was to estimate the peritonitis rate per patient-year and investigate the factors associated with higher peritonitis rates in a sample of PD children at King Abdullah Specialist Children’s Hospital-Riyadh (KASCH-R), Saudi Arabia. Methods This retrospective cohort study included 27 PD children treated between September 2007 and December 2017 at KASCH-R. We recorded the children’s demographic and clinical data, and the frequency of peritonitis. Results The 27 PD children reviewed (63% girls; mean age = 7.32 years old; range, 1–14 years), resulted in 86 peritonitis diagnoses in which the overall recurrence rate (in at least one episode) was 58/86 (67.4%) with a 95% confidence interval (CI), 56.5 to 77.2%. The rate of peritonitis episodes per patient-year was 0.76 (1 episode per 1.31 patient-year). The generalized Poisson model identified older children (age >  10 years) (adjusted rate ratios [aRR] = 7.273, 95% CI: 1.562–33.860), congenital nephrosis (aRR = 4.677, 95% CI: 1.443–15.155), height below 3rd percentile (aRR = 4.689, 95% CI: 1.874–11.735), weight below 3rd percentile (aRR = 5.388, 95% CI: 1.678–17.302), low albumin level (aRR = 4.041, 95% CI: 2.053–7.956), two-week duration of antibiotic therapy (aRR = 2.947, 95% CI: 1.163–7.468), which were independently associated with a high peritonitis rate. Conclusions This study showed a high peritonitis rate in our center. Older children, congenital nephrosis, height and weight below the 3rd percentile, low albumin level, and long duration of antibiotic therapy were associated with a higher rate of peritonitis. An optimal peritonitis prevention strategy or best-practice guideline is needed to reduce and prevent peritonitis occurrence in our center.