medRxiv : serveur de preprint pour les sciences médicales

Background: Profound sex differences exist in the prevalence and clinical manifestation of several mental disorders, suggesting that sex-specific brain phenotypes may play key roles. Previous research used machine learning models to classify sex from imaging data of the whole brain and studied the association of class probabilities with mental health, potentially overlooking regional specific characteristics. Methods: We here investigated if a regionally constrained model of brain volumetric imaging data may provide estimates that are more sensitive to mental health than whole brain-based estimates. Given its known role in emotional processing and mood disorders, we focused on the limbic system. Using two different cohorts of healthy subjects, the Human Connectome Project and the Queensland Twin IMaging, we investigated sex differences and heritability of brain volumes of limbic structures compared to non-limbic structures. We applied regionally constrained machine learning models for brain sex classification based solely on limbic or non-limbic features and compared the results with a whole brain model. To investigate the biological underpinnings of such models, we assessed the heritability of the obtained estimates, and we investigated the association with major depression diagnosis in an independent clinical sample. Results: Limbic structures show greater sex differences and are more heritable compared to non-limbic structures. Consequently, machine learning models performed well at classifying sex based solely on limbic structures and achieved performance as high as those on non-limbic or whole brain data, despite the much smaller amount of features in the limbic system. The resulting class probabilities were heritable, suggesting potentially meaningful underlying biological information. Applied to an independent population with major depressive disorder, we found that depression is significantly associated with male-female class probabilities, with largest effects obtained using the limbic model. Conclusions: Overall, our results highlight the potential utility of regionally constrained models of brain sex to better understand the link between sex differences in the brain and mental disorders.

Attention deficit hyperactivity disorder (ADHD) has been characterized by impairments among distributed functional brain networks, e.g., the frontoparietal network (FPN), default mode network (DMN), and reward and motivation-related circuits (RMN). In the current study, we evaluated the complexity and functional connectivity (FC) of resting state fMRI (rsfMRI) in pre-adolescents with ADHD for pathology-relevant networks. We leveraged data from the Adolescent Brain and Cognitive Development (ABCD) Study. The final study sample included 63 children with ADHD and 92 healthy control children matched on age, sex, and pubertal development status. For selected regions in relevant networks, ANCOVA compared multiscale entropy (MSE) and FC between the groups. Finally, differences in the association between MSE and FC were evaluated. We found significantly reduced MSE along with increased FC within the FPN of pre-adolescents with ADHD compared to matched healthy controls. Significant partial correlations between MSE and FC emerged in fewer regions in the participants with ADHD than in the controls. The observation of reduced entropy is consistent with existing literature using rsfMRI and other neuroimaging modalities. The current findings of complexity and FC in ADHD support hypotheses of altered function of inhibitory control networks in ADHD.

Introduction: Traumatic Brain Injury (TBI) is any injury to the brain resulting from an external force leading to complications. TBI affects 27-69 million yearly, with high incidence in Africa and LMICs, and is attributed to motor traffic accidents. Within three to six months following moderate-to-severe TBI, the relative risk of any psychiatric disorder is significantly higher than in the general population. Post-TBI neuropsychiatric disorders include; depression with a prevalence of over 50%, apathy up to 72%, Post-traumatic stress disorder (26%), anxiety (9%), manic symptoms (5 - 9%) and psychosis (3 to 8%). This study aims to determine the incidence and predictors of post-TBI neuropsychiatric manifestations among patients admitted at Referral hospitals in Dodoma. Methods and analysis: This is a prospective longitudinal observational study in which patients admitted after moderate to severe TBI will be recruited after obtaining informed consent. Patients will be followed for six months; the diagnostic MINI International Neuropsychiatric Interview (M.I.N.I) tool will assess psychiatric disorders, and severity and progression of symptoms will be assessed using PHQ-9 for depressive symptoms, GAD7 for anxiety symptoms, PCL-5 for Post-traumatic Stress Disorders (PTSD), MoCA for cognitive assessment, AES for apathy and YMRS for manic symptoms at one, three and six months. The analysis will use logistic regression to determine the association between predictors and neuropsychiatric outcomes. Ethics and dissemination The ethical clearance has been secured from the institutional Research Review committee and ethical committee of the University of Dodoma with the reference number MA.84/261/12. The respective authorities provided permission to conduct the study within the premises of BMH and DRRH. Keywords: Traumatic Brain Injury, Neuropsychiatric manifestations, Dodoma Tanzania

ABSTRACT Background and rationale. Digestive diseases are common and lead to significant morbidity, mortality, and health care utilization. We used national survey and claims databases to expand on earlier findings and investigate current trends in the digestive disease burden in the United States. Methods. The National Ambulatory Medical Care Survey, Nationwide Emergency Department Sample, National Inpatient Sample, Vital Statistics of the U.S., Surveillance, Epidemiology, and End Results Program, Optum Clinformatics Data Mart, and Centers for Medicare and Medicaid Services Medicare 5% Sample databases were used to estimate medical care, mortality, cancer incidence, and claims-based prevalence with a digestive disease diagnosis. Rates were age-adjusted (for national databases) and shown per 100,000 population. Results. For all digestive diseases, prevalence (claims-based, all-listed diagnoses) was 30.5% among commercial insurance enrollees (2020) and 53.1% among Medicare beneficiaries (2019). In the U.S. population, digestive diseases contributed to approximately 126 million ambulatory care visits (2015), 41 million emergency department visits (2018), 16 million hospital discharges (2018), and 472,000 deaths (2019) annually. Prevalence, medical care, and mortality rates with a digestive disease diagnosis were higher among children and younger adults (except for emergency department visits) and then increased with age. Women had higher prevalence and medical care rates with a digestive disease diagnosis, but mortality rates were higher among men. Prevalence and medical care rates with a digestive disease diagnosis were higher among Blacks, followed by Whites, then Hispanics, and lowest among Asians. Mortality rates were higher among Blacks compared with Whites and lower among Hispanics compared with non-Hispanics. Between 2004 and the most recent year, ambulatory care visit rates with a digestive disease diagnosis increased by 4%, hospital discharge rates decreased by 3%, and mortality rates decreased by 7%. Among commercial insurance enrollees, rates were higher compared with national data for ambulatory care visits and hospital discharges, but lower for emergency department visits. The medical care use and mortality burdens varied among individual digestive diseases. Conclusion. The digestive disease burden in the United States is substantial, particularly among Blacks and older adults.

Background: Decisions to impose temporary travel measures are less common as the global epidemiology of COVID-19 evolves. Risk-based travel measures may avoid the need for a complete travel ban, however evaluations of their effects are lacking. Here we investigated the public health effects of a temporary traffic light system introduced in the United Kingdom (UK) in 2021, imposing red-amber-green (RAG) status based on risk assessment. Methods: We analysed data on international flight passengers arriving into Scotland, COVID-19 testing surveillance, and SARS-CoV-2 whole genome sequences to quantify effects of the traffic light system on (i) international travel frequency, (ii) travel-related SARS-CoV-2 case importations, (iii) national SARS-CoV-2 case incidence, and (iv) importation of novel SARS-CoV-2 variants. Results: International flight passengers arriving into Scotland had increased by 754% during the traffic light period. Amber list countries were the most frequently visited and ranked highly for SARS-CoV-2 importations and contribution to national case incidence. Rates of international travel and associated SARS-CoV-2 cases varied significantly across age, health board, and deprivation groups. Multivariable logistic regression revealed SARS-CoV-2 cases detections were less likely among travellers than non-travellers, although increasing from green-to-amber and amber-to-red lists. When examined according to travel destination, SARS-CoV-2 importation risks did not strictly follow RAG designations, and red lists did not prevent establishment of novel SARS-CoV-2 variants. Conclusions: Our findings suggest that country-specific post-arrival screening undertaken in Scotland did not prohibit the public health impact of COVID-19 in Scotland. Travel rates likely contributed to patterns of high SARS-CoV-2 case importation and population impact.

Background Rapid economic growth in Southeast Asian countries has led to a significant gap between supply and demand of emergency care, which may negatively affect the health outcomes of local populations. The purpose of this study was to identify current challenges faced by emergency care systems in Indonesia and Malaysia. Methods An online survey was conducted between August and November 2022. Survey participants consisted of emergency department (ED) doctors, nurses, and other medical staff in 11 hospitals in Indonesia and Malaysia. The survey collected information on respondents' characteristics, factors associated with the quality of prehospital or ED care, missing clinical information, and factors associated with patients' length of stay at the ED. Results A total of 83 and 109 respondents from Indonesia and Malaysia, respectively, answered the survey. The most important factor affecting prehospital care quality in both countries was "inadequate amount of clinical information from the ambulance." The most important factor affecting ED care quality was "crowdedness in the emergency room during night shifts." The clinical information most frequently missing was family history, followed by estimated time of arrival to the hospital or medication history. The primary factor affecting the length of ED stay was diagnostic studies and their turnaround time. Conclusions This study identified common challenges in the emergency care systems of Indonesia and Malaysia. Our findings highlight the importance of recognizing both common and country-specific challenges to improve the quality of emergency care in Southeast Asia.

Significance: Gaining insights into the efficacy of topical wound treatments for biofilm eradication is pivotal to enhancing wound management strategies. Despite numerous available agents claiming anti-biofilm properties, the substantiating evidence remains inconclusive. This study aimed to assess the immediate impact of topical wound treatments on wound biofilm and healing outcomes in acute and chronic ulcers. Recent Advances: We comprehensively searched PubMed, ClinicalTrials.gov, and Google Scholar. Additionally, eligible grey literature was incorporated. English-language randomized controlled trials, observational, cohort, and case-control studies targeting biofilm prevention, inhibition, or elimination across diverse wound types were included. Primary outcomes included biofilm presence and elimination, supplemented by secondary outcomes encompassing reduced wound size, complete closure, and diminished infection indicators. Bacterial load reduction and biofilm presence were also assessed. Critical Issues: Twenty-eight articles met the inclusion criteria. Various modalities were identified, including biofilm-visualization techniques like wound blotting and handheld autofluorescence imaging. A notable high bias risk was observed across all studies. Pooled analysis for the primary outcomes was infeasible due to limited eligible studies and data reporting challenges. The primary source of bias is the lack of consensus on objectively evaluating the biofilm. As for the secondary outcomes, the pooled analysis for complete wound closure (6 RCTs, yielding n=439) and presence of infection/inflammation (2 RCTs, yielding n=284) showed no significant difference, with log odds ratio (LOD) 0.03 (95% CI: -1.02-1.09; {tau}2=1.09, SE: 1.10, Q=14.33, p=.014) and LOD -0.95 (95% CI: -3.54-1.64; {tau}2=2.32, Q=2.71, p=.10), respectively. Future Direction: Our findings suggest insufficient evidence to support anti-biofilm claims of topical modalities. Clinicians' skill appears to play a pivotal role in biofilm elimination and wound healing enhancement, with potential optimization through visual-guided techniques like wound blotting and autofluorescence imaging. More rigorous clinical trials are warranted to ascertain the efficacy of these techniques.

Background: Dental caries is a global health crisis. School-based sealant programs are effective strategies to increase access to care and reduce the risk of caries, but are limited by financial restraints and/or dental workforce barriers. The CariedAway trial was a study of alternative minimally-invasive treatments that can be used in a school-based caries prevention program. Methods: CariedAway was a longitudinal, cluster-randomized, single-blind, pragmatic non-inferiority trial comparing silver diamine fluoride (SDF) to glass ionomer sealants and atraumatic restorations (ART) for dental caries. All subjects also received fluoride varnish. Our subject population included children enrolled in New York City primary schools with a student population of at least 50% Hispanic/Latino or black and 80% from low-income families. Subjects were treated by dental hygienists or registered nurses under the supervision of a licensed pediatric dentist. We report on the four-year cumulative incidence and prevalence of caries. Results: We show that repeated application of a combinative therapy for dental caries consisting of SDF and fluoride varnish had similar effects compared to the standard of care sealants and atraumatic restorations over an approximate four year period. The crude incidence of caries in children treated with SDF was 9.2 per 1,000 tooth-years, versus 8.9 per 1,000 tooth-years in children treated with sealants and ART. The odds of decay prevalence decreased longitudinally (OR = 0.79, 95% CI = 0.753, 0.828) and SDF was non-inferior compared to sealants with ART (OR = 0.94, 90% CI = 0.795, 1.11). Conclusion: For high-risk, underserved populations, a minimally-invasive treatment of SDF with fluoride varnish resulted in similar caries prevalence and incidence compared to the standard of care over four years. Integration of silver diamine fluoride into school-based caries prevention may offer an attractive alternative to traditional school sealant programs.

Background: Repolarization alternans, defined as period-2 oscillation in the repolarization phase of the action potentials, provides a mechanistic link between cellular dynamics and ventricular fibrillation (VF). Theoretically, higher-order periodicities (e.g., periods 4, 6, 8...) are expected but have minimal experimental evidence. Methods: We studied explanted human hearts obtained from recipients of heart transplantation at the time of surgery. Optical mapping of the transmembrane potential was performed after staining the hearts with voltage-sensitive fluorescent dyes. Hearts were stimulated at an increasing rate until VF was induced. Signals recorded from the right ventricle endocardial surface prior to induction of VF and in the presence of 1:1 conduction were processed using the Principal Component Analysis and a combinatorial algorithm to detect and quantify higher-order dynamics. Results were correlated to the underlying electrophysiological characteristics as quantified by restitution curves and conduction velocity. Results: A prominent and statistically significant global 1:4 peak (corresponding to period-4 dynamics) was seen in three of the six studied hearts. Local (pixel-wise) analysis revealed the spatially heterogeneous distribution of periods 4, 6, and 8, with the regional presence of periods greater than two in all the hearts. There was no significant correlation between the underlying restitution properties and the period of each pixel. Discussion: We present evidence of higher-order periodicities and the co-existence of such regions with stable non-chaotic areas in ex-vivo human hearts. We infer from the independence of the period to the underlying restitution properties that the oscillation of the excitation-contraction coupling and calcium cycling mechanisms is the primary mechanism of higher-order dynamics. These higher-order regions may act as niduses of instability that can degenerate into chaotic fibrillation and may provide targets for substrate-based ablation of VF.

Background Acute rheumatic fever (ARF) and its chronic sequelae, rheumatic heart disease (RHD) contributes to valvular dysfunction and significant cardiovascular disability and endocardial damage is considered the primary pathophysiological mechanism underlying ARF. This study examined peripheral blood markers of endothelial injury and function in ARF and RHD patients and compared them to healthy controls. Method In this prospective observational study, the levels of collagen intermediates, matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases, brain natriuretic peptide, Anti-DNaseB, VEGF, E-selectin, VCAM, and ICAM in circulation were estimated. The study also isolated hemangioblastic and monocytic endothelial progenitor cells and their respective microvesicles from the peripheral blood of patients and control samples. Results Procollagen type I carboxy-terminal propeptide, cross-linked c-telopeptide of type I, and procollagen III c-terminal propeptide levels were higher in RHD subjects compared to patients with ARF. The ARF patients had the highest levels of matrix metalloproteinases 10 (MMP-10) followed by chronic patients and healthy controls. The ratio of tissue inhibitors of matrix metalloproteinases TIMP-1 and MMP-10 was lowest in healthy controls. At the cellular level, there were higher number of monocytic endothelial progenitor cells (EPCs) in ARF subjects as compared to healthy controls. For hemangioblastic EPCs, there was no significant difference between chronic subjects and healthy controls, though their early subtype was higher in chronic subjects. The hemangioblastic EPCs microvesicles were more abundant in ARF compared to RHD patients. Conclusion The greater number of EPCs and respective microvesicles confirm the continued disruption of the endothelium in ARF, and during the progression of the disease, the majority of EPCs undergo apoptosis.

Background: Takotsubo Syndrome (TTS) generally presents like a form of acute coronary syndrome, with variable extents of coronary flow retardation and concomitant release of markers from damaged endothelial glycocalyx (eGC). Whilst systemic hypotension often develops early, there is also rapid emergence and slow resolution of left ventricular (LV) dysfunction. It remains uncertain whether these hypotensive and LV functional complications reflect severity of early coronary vasculitis. Methods: 284 patients admitted to 3 South Australian hospitals from May 2008 to May 2021 with a diagnosis of TTS were evaluated. Coronary flow velocity was measured using the corrected TIMI frame count. Putative correlations between extent of acute coronary flow retardation and that of acute impairment of LV systolic function, as measured on global longitudinal strain (GLS: primary hypothesis), were determined. Other parameters of acute disturbance of homeostasis, including extent of eGC shedding and of myocardial edema, and residual impairment in GLS and quality of life at 3-months' follow-up, were correlated with extent of flow retardation. We also evaluated correlates of extent of acute systemic hypotension. Results were analysed via univariate followed by multivariate analyses. Results: The patients studied exhibited mild coronary flow retardation relative to previously described norms at early angiography. On univariate analyses, corrected TIMI frame count correlated with extent of acute impairment of GLS (r=0.31, p=0.003) and this association persisted on backwards stepwise multiple logistic regression ({beta}=0.52, p=0.03). Flow retardation also correlated with preservation of renal function ({beta}=0.50, p=0.02), but tended to vary inversely with C-reactive protein (CRP) concentrations ({beta}=-0.44, p=0.06). There were no significant associations between acute TIMI frame count and other acute or 3-months' parameters. Neither TIMI frame count nor acute GLS predicted minimal systolic blood pressure. Conclusions: The data demonstrated a strong association between extent of early coronary flow reduction in TTS and that of LV functional impairment, thus establishing some commonality of causation of the coronary and acute myocardial manifestations of TTS. However, neither extent of coronary vasculitis nor that of acute LV systolic dysfunction predict acute hypotensive changes in TTS.

Background: The incidence and possible implications of coronary artery anomalies (CAA) in patients undergoing transcatheter aortic valve replacement (TAVR) are uncertain. Aims: To evaluate the impact of CAA on TAVR outcomes, and to suggest possible strategies to prevent CAA related complications. Methods: Among 2,164 consecutive patients who underwent TAVR in our center, 15 (0.69%) were identified to have a CAA, based on pre-operative Computed Tomography (CT) scans. Results: CT-angiography revealed the following features of CAA: the majority of anomalous CAA concerned the right coronary artery (80%), followed by the left main (13.3%) and the left circumflex (6.7%). An intramural course was observed only in 26.7% patients, whereas an acute take-off was detected in more than half of the study cohort (53.3%). High-risk sudden cardiac death features were observed in 6 (40%) patients. Technical success was 86.7%, device success was 80%. One patient experienced a cardiac arrest 15 minutes after procedure, resulting from occlusion of the anomalous right coronary artery with the ostium located at the right-to-non coronary commissure. There were no cases of ? moderate paravalvular leak or stroke. One non-cardiac related death was recorded 4 months after the procedure. Conclusions: The interaction between transcatheter bioprosthesis and different CAA types could lead to ominous sequelae, if not promptly recognized and treated accordingly.

Aims: To investigate the prevalence of cognitive impairment among elderly Chinese patients with hypertension and explore the relationship between blood pressure and cognitive impairment. Additionally, the study examined the characteristics of cognitive impairment in hypertensive patients and its impact on blood pressure control. Methods: A cross-sectional study was conducted involving 23,271 subjects. Data collection involved questionnaires, physical examinations, and blood tests. AD8 questionnaire, MMSE questionnaire, and neurologist interview, was used to screen patients for cognitive disabilities. Risk factors and prevalence of cognitive impairment were compared between hypertensive and non-hypertensive groups. The prevalence of cognitive impairment at different blood pressure levels was analyzed within the hypertension group. Differences in MMSE scores across dimensions were compared between hypertensive and non-hypertensive groups. Results: The hypertensive group exhibited additional risk factors for cognitive impairment and a higher prevalence of cognitive impairment. The prevalence of cognitive impairment among hypertensive patients followed a U-shaped curve with increasing blood pressure, with the lowest rate observed among patients with blood pressure in the range of 120-139/80-89 mmHg. Several dimensions of cognitive function were significantly diminished in individuals with hypertension. Patients with cognitive impairment demonstrated lower compliance with hypertension treatment and poorer blood pressure control. Conclusion: Cognitive decline across multiple dimensions is typical among older Chinese patients with hypertension, and cognitive impairment has detrimental effects on blood pressure management. Maintaining blood pressure in the 120-139/80-89 mmHg range appears to be more favorable for preserving cognitive function in hypertensive patients.

Background: Non-invasive cardiac testing (NICT) has been associated with decreased long-term risks of major adverse cardiac events (MACE) among emergency department (ED) patients at high coronary risk. It is unclear whether this association extends to patients without evidence of myocardial injury on initial electrocardiogram and cardiac troponin testing. Methods: Retrospective cohort study of patients presenting with chest pain between 2013-2019 to 21 EDs within an integrated health care system, excluding patients with ST-elevation myocardial infarction or myocardial injury by serum troponin testing. To account for confounding by indication, we grouped patient encounters by the NICT referral rate of the initially assigned emergency physician, relative to local peers within discrete time periods. The primary outcome was MACE within two years. Secondary outcomes were coronary revascularization and MACE inclusive of all-cause mortality (MACE-ALL). Associations between NICT referral group (low, intermediate, or high) and outcomes were assessed using risk-adjusted proportional hazards methods with censoring for competing events. Results: Among 144,577 eligible patient encounters, 30-day NICT referral was 13.0%, 19.9% and 27.8% in low, intermediate, and high NICT referral groups, respectively, with good balance of baseline covariates between groups. Compared with the low group, there was no significant decrease in the adjusted hazard ratio (aHR) of MACE within the intermediate (aHR 1.08, 95% CI 1.02-1.14, adjusted p = 0.024) or high (aHR 1.05, 95% CI 0.99-1.11, adjusted p = 0.13) NICT referral groups. Results were similar for MACE-ALL and coronary revascularization, as well as subgroup analyses stratified by estimated risk (HEART score; 48.2% low-risk, 49.2% moderate-risk, 2.7% high-risk). Conclusion: Increased NICT referral was not associated with a decreased hazard of MACE within two years following ED visits for chest pain without evidence of acute myocardial injury. These findings further highlight the need for evidence-based guidance regarding appropriate use of NICT in this population.

Purpose: In July 2018, the Food and Drug Administration recalled valsartan due to carcinogenic impurities, leading to an unprecedented drug shortage leading to management challenges impacting a large population of valsartan users. However, the extent to which the valsartan recall impacted clinical outcomes is unknown. Our objective was to compare the risk of adverse events between patients with hypertension using valsartan and a propensity-score-matched group of patients using non-recalled angiotensin receptor blockers (ARBs) and angiotensin converting enzyme-inhibitors (ACE-Is). Methods: We conducted a retrospective cohort analysis of Optum's de-identified Clinformatics(R) Datamart (July 2017-January 2019). Adults with hypertension who received valsartan were compared to persons who received non-recalled ARBs and ACE-Is for 1 year prior to and on the recall date. The primary outcomes were measured in the 6 months following the recall date included: 1) a composite measure of all-cause hospitalization, all-cause emergency department (ED) and all-cause urgent care (UC) visit, 2) a composite cardiac event measure of hospitalizations for acute myocardial infarction and hospitalizations/ED/UC visits for stroke/transient ischemic attack, heart failure or hypertension. Cox proportional hazard models compared the risk of outcomes between propensity-score-matched treatment groups. Results: Of adults with hypertension, 76,934 received valsartan at the time of the recall and 509,742 received a non-recalled ARB/ACE-I. Valsartan use at the time of the recall was associated with a combined increased risk of all-cause hospitalization, ED or UC use (HR 1.02; 95% CI: 1.00-1.04) and of the composite of cardiac events (HR 1.22; 95% CI: 1.15-1.29) within six-months after the recall. Conclusions: The national valsartan recall and subsequent shortage had negative consequences for patients with hypertension. As the threat of shortages increases for drugs that treat common outpatient conditions, systems at the local- and national-levels need to be strengthened to protect patients from drug shortages by providing them with safe and reliable alternatives.

Background: Fractional flow reserve (FFR) is routinely used to assess the ischemic potential of a coronary artery lesion. However, recently published randomized control trials have questioned the advantage of FFR over angiography to guide revascularization. Whether FFR guided revascularization provides clinical benefit over angiography remains unclear. Methods: We performed a meta-analysis in patients with stable coronary artery disease (CAD), acute coronary syndrome (ACS), multivessel or single vessel CAD undergoing revascularization comparing FFR versus angiography to guide revascularization. Randomized control trials comparing FFR angiography guided revascularization were searched through PubMed, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central, Scopus, Google Scholar, and Web of Science databases. The primary endpoints included cardiovascular mortality, repeat revascularization, myocardial infarction, major adverse cardiac events, stroke or transient ischemic attack and target lesion revascularization. We also evaluated the procedural outcomes including the average number of stents used between the two groups, procedure time and contrast volume used. Event rates were compared using a forest plot of odds ratios using a random-effects model assuming interstudy heterogeneity. Results: The meta-analysis included 13 trials in which 7415 patients met the eligibility criteria. There was no significant difference between the FFR versus angiography guided revascularization groups across all clinical measures including all-cause mortality (OR = 1.06, 95% CI = 0.74-1.53, P = 0.74, I2= 27%), cardiovascular mortality (OR = 0.81, 95% CI = 0.43-1.52, P = 0.51, I2= 44%), repeat revascularization (OR = 1.02, 95% CI = 0.83-1.26, P = 0.83, I2= 17%), myocardial infarction (OR = 0.92, 95% CI = 0.69-1.21, P = 0.54, I2= 36%), major adverse cardiac event (OR = 0.82, 95% CI = 0.62-1.08, P = 0.15, I2= 41%), stroke or transient ischemic attack (OR = 1.49, 95% CI = 0.87-2.55, P = 0.15, I2= 0%) and target lesion revascularization (OR = 0.86, 95% CI = 0.44-1.69, P = 0.67, I2= 0%). A sensitivity analysis was performed for studies that included patients exclusively with an ACS and studies that used FFR coronary artery bypass grafting as a revascularization strategy. There was no difference in any of the clinical outcomes between the two groups in the sensitivity analysis. In terms of procedural outcomes, the average number of stents used was lower in the FFR group as compared to the angiography group, mean difference (MD) of -0.79 (95% CI = - 1.10, - 0.48), P < 0.00001) with no difference in procedure time or contrast volume used. Conclusion: This meta-analysis suggests that FFR when used in conjunction with angiography prevents unnecessary PCI without any difference in clinical outcomes between the two groups.

Background: Septic shock is a severe form of sepsis that has a high mortality rate, and a substantial proportion of these patients will develop cardiac dysfunction, often termed septic cardiomyopathy (SCM). Some SCM patients may develop frank cardiac failure, termed sepsis-related cardiogenic shock (SeRCS). Little is known of SeRCS. This study describes baseline characteristics of patients with SCM and SeRCS compared to patients with septic shock without cardiac dysfunction. We compare clinical outcomes among SCM, SeRCS, and septic shock, and identify risk factors for the development of SCM and SeRCS. Methods: Septic patients admitted to the ICU with an echocardiogram obtained within 72 hours were included. Left ventricular ejection fraction of [≤]55% was used to define SCM, and cardiac index [≤]2.1 L/min/m2 among patients with SCM defined SeRCS. Machine learning was used to identify risk factors for development of SCM and SeRCS. Logistic regression was used to compare mortality among groups. Results: Among 1229 patients, 977 patients had septic shock without cardiac dysfunction, 207 had SCM, and 45 had SeRCS. In patients with septic shock, the strongest predictor for developing SCM and SeRCs was a prior history of cardiac dysfunction. Mortality did not significantly differ among the three groups. Conclusions: SCM and SeRCS affect a minority of patients with septic shock, disproportionately affecting individuals with a history of cardiac disease. We did not identify a mortality difference associated with SCM or SeRCS. Additional work is needed to define further subtypes and treatment options for this patient population.

We administered BNT162b2 as a third dose to 314 adults [≥]30 years of age who had previously received 2 doses of inactivated vaccine. We collected blood samples before the third dose and again after 1, 6 and 12 months, and found stable levels of antibody responses to the ancestral strain and Omicron BA.2 at 6-12 months after receipt of the BNT162b2 third dose, with increased antibody levels in individuals who also received a fourth vaccine dose or reported a SARS-CoV-2 infection during follow-up.

People with immunocompromising conditions are at increased risk of SARS-CoV-2 infection and mortality, however early in the pandemic it was challenging to collate data on this heterogenous population. We conducted a registry study of immunocompromised individuals with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection from March - October 2020 in Sydney, Australia to understand clinical and laboratory outcomes in this population prior to the emergence of the Delta variant. 27 participants were enrolled into the study including people with a haematologic oncologic conditions (n=12), secondary immunosuppression (N=8) and those with primary or acquired immunodeficiency (i.e. HIV; N=7). All participants had symptomatic COVID-19 with the most common features being cough (64%), fever (52%) and headache (40%). Five patients demonstrated delayed SARS-CoV-2 clearance lasting three weeks to three months. The mortality rate in this study was 7% compared to 1.3% in the state of New South Wales Australia during the same period. This study provides data from the first eight months of the pandemic on COVID-19 outcomes in at-risk patient groups.

Background: The global Viral hepatitis elimination by 2030 is uncertain in resource-limited settings (RLS), due to high burdens and poor diagnostic coverage. This sounds more challenging for hepatitis C virus (HCV) given that antibody (HCVAb) sero-positivity still lacks wide access to HCV RNA molecular testing. This warrants context-specific strategies for appropriate management of liver impairment in RLS. We herein determine the association between anti-HCV positivity and liver impairment in an African RLS. Methods: A facility-based observational study was conducted from July-August 2021 among individuals attending the St Monique Health Center at Ottou, a rural community of Yaounde,Cameroon. Following a consecutive sampling, consenting individuals were tested for anti-HCV antibodies, hepatitis B surface antigen (HBsAg) and HIV antibodies (HIVAb) as per the national guidelines. After excluding positive cases for HBsAg and/or HIVAb, liver function tests (ALT/AST) were performed on eligible participants (HBsAg and HIVAb negative) and outcomes were compared according to HCVAb status; with p<0.05 considered statistically significant. Results: Out of 306 eligible participants (negative for HBsAg and HIVAb) enrolled, the mean age was 34.35{+/-}3.67 years. 252(82.35%) were female and 129 (42.17%) were single. The overall HCVAb sero-positivity was 15.68%(48/306), with 17.86% (45/252) among women vs. 5.55%(3/54) among men [OR (95%CI)=3.69(2.11-9.29),p=0.04]. HCVAb Carriage was greater among participants aged >50 years compared to younger ones [38.46%(15/39) versus 12.36% (33/267) respectively, OR(95%CI)=4.43(2.11-9.29), p<0.000] and in multipartnership [26.67%(12/45)vs.13.79%(36/261) monopartnership, OR (95%CI)= 2.27(1.07-4.80),p=0.03]. The liver impairment rate (abnormal ALT+AST levels) was 30.39%(93/306), with 40.19%(123/306) of abnormal ALT alone. Moreover, the burden of Liver impairment was significantly with aged>50 versus younger ones [69.23% (27/39) versus 24.72%(66/267) respectively, p<0.000). Interestingly, the burden of liver impairment (abnormal AST+ALAT) was significantly higher in HCVAb positive (62.5%, 30/48) versus HCVAb negative (24.42%, 63/258) participants, OR: 3.90 [1.96; 7.79], p=0.0001. Conclusions: In this rural health facility, HCVAb is highly endemic and the burden of liver impairment is concerning. Interestingly, HCVAb carriage is associated with abnormal liver levels of enzyme (ALT/AST), especially among the elderly populations. Hence, in the absence of nuclei acid testing, ALT/AST are relevant sentinel markers to screen HCVAb carriers who require monitoring/care for HCV-associated hepatocellular carcinoma in RLS. Keywords Hepatitis C Virus antibodies (HCVAb), ASAT/ALAT, liver impariment, hepatotoxicity, Cameroon.