COVID-19 vaccination in low and middle-income countries: Creating a sustainable roadmap for promoting public health intervention.

The Coronavirus Disease 2019 (COVID-19) pandemic is a global public health threat ravaging the health systems. In low and middle-income countries (LMICs), COVID-19 and several other challenges concurrently worsen the health outcome indicators. Interestingly, vaccines have been identified as the most reliable and cost-effective public health intervention, and the governments in LMICs have instituted an array of plans to ensure every eligible person gets vaccinated. However, there is still considerable apathy around the use of the available COVID-19 vaccines in LMICs which is impeding the fight against the COVID-19 pandemic. In this paper, we explore the multiple interrelated factors behind low COVID-19 vaccination coverage in LMICs. It is therefore recommended that the governments in LMICs embrace multicomponent and wide-ranging strategies. This should involve utilising community-based approaches such as community pharmacy-led vaccination to promote community access to COVID-19 vaccines and to revive trust in national health authorities by offering population-specific, target-driven, transparent, and timely communication to the community who they serve about the safety and efficacy of the COVID-19 vaccine. Communication strategies should be tailored to reflect diverse political orientations as this can enhance vaccine acceptance. Additionally, local political parties and representative should be engaged in broad alliances to facilitate community mobilisation and support for vaccination campaigns. Also, relevant Nongovernmental Organisations and Community-based Organisations should institute programs at the grassroots that incorporate the gatekeepers to the community aimed at influencing population behaviour regarding COVID-19 vaccine hesitancy. Besides, the public health department in the ministry of health in LMICs should create more awareness, through social and mass media, particularly in the rural, semi-urban, and slum communities about the pivotal role of vaccination. Thus, we opined that these strategies will help LMICs achieve the COVID-19 vaccination target and further reposition the healthcare systems, and promote other public health interventions now and in the future.

Community use of oral antibiotics transiently reprofiles the intestinal microbiome in young Bangladeshi children.

Antibiotics may alter the gut microbiome, and this is one of the mechanisms by which antimicrobial resistance may be promoted. Suboptimal antimicrobial stewardship in Asia has been linked to antimicrobial resistance. We aim to examine the relationship between oral antibiotic use and composition and antimicrobial resistance in the gut microbiome in 1093 Bangladeshi infants. We leverage a trial of 8-month-old infants in rural Bangladesh: 61% of children were cumulatively exposed to antibiotics (most commonly cephalosporins and macrolides) over the 12-month study period, including 47% in the first 3 months of the study, usually for fever or respiratory infection. 16S rRNA amplicon sequencing in 11-month-old infants reveals that alpha diversity of the intestinal microbiome is reduced in children who received antibiotics within the previous 7 days; these samples also exhibit enrichment for Enterococcus and Escherichia/Shigella genera. No effect is seen in children who received antibiotics earlier. Using shotgun metagenomics, overall abundance of antimicrobial resistance genes declines over time. Enrichment for an Enterococcus-related antimicrobial resistance gene is observed in children receiving antibiotics within the previous 7 days, but not earlier. Presence of antimicrobial resistance genes is correlated to microbiome composition. In Bangladeshi children, community use of antibiotics transiently reprofiles the gut microbiome.

Sural flap reconstruction of lateral malleolus following undifferentiated pleomorphic sarcoma resection with 1-year follow-up.

We report a case of a 54-year-old female who presents with a gradually expanding mass at the right lateral malleolus. The diagnosis of undifferentiated pleomorphic sarcoma was made after a histopathological examination of the mass following a wide tumor excision. The defected soft tissue area was reconstructed using a local flap, reverse sural artery flap. Following the surgical management, multiple radiotherapy sessions were completed. The patient's follow-up result showed no signs of local recurrence or metastasis, and the wound was well-healed with no complications other than paresthesia in a small area at the posterolateral aspect of the ankle under the lateral malleolus. This case represents a rare form of malignant neoplasm and emphasizes the effectiveness and safety of the reverse sural artery flap reconstruction technique, especially in places where microsurgery is unavailable or when the patient's status does not allow for prolonged anesthesia.

Risk of acute coronary syndrome and relationship with the use of khat and tobacco products in the Jazan region, Saudi Arabia: A prospective case-control study.

INTRODUCTION: Previous studies have identified several risk factors for acute coronary syndrome (ACS). This study was intended to examine the potential risk of ACS associated with khat and tobacco use. METHODS: A case-control study of 344 people (172 cases and 172 controls) was conducted at Prince Mohammed Bin Nasser Hospital in Jazan, Saudi Arabia, from April to September 2019. The cases and controls were matched for age (±5 years) and gender. Data were analyzed using descriptive, inferential, and modeling analyses. We utilized the adjusted odds ratio (AOR) to express the results. RESULTS: The prevalence of ever khat chewing among all study participants was 29.1%, significantly higher for the cases with ACS than for the control group (43.6% vs 14.5%, p<0.001). Cigarette smokers accounted for 33.4% of the study participants, and 22.1% were ACS cases, which is a significantly higher percentage than the control group. The prevalence of smokeless tobacco was 20.3% among ACS cases and 14.5% among controls, with no statistically significant differences (p>0.05). In the final model, tobacco use was more likely to be reported among cases with myocardial infarction (MI) (AOR=4.58; 95% CI: 1.01-4.73, p<0.05) as was khat chewing (AOR=3.4; 95% CI: 1.55-7.46, p<0.05), after controlling for other traditional risk factors. CONCLUSIONS: Khat chewing was reported more by those who reported ACS. ACS cases were more likely to be frequent khat users with chewing sessions of five or more days per week. Regular tobacco use was also reported in those who reported ACS, and this increases with the amount of tobacco used. Implementing early intervention strategies can help mitigate the impact of khat chewing and smoking on the development of ACS.

Diagnostic and prognostic value of heparin-binding protein in sepsis: A systematic review and meta-analysis.

BACKGROUND: Sepsis remains a leading cause of death worldwide. In this context, heparin-binding protein (HBP) has emerged as a possible biomarker, drawing significant attention for its diagnostic and prognostic usefulness in septic patients. Despite this advancement, the literature yields conflicting results. This study is intended to critically evaluate the diagnostic and prognostic value of HBP in critically ill septic patients. METHODS: We searched multiple databases, including PubMed, SCOPUS, Web of Science, and EBSCO, to identify relevant studies on April 27, 2023. We included studies investigating sepsis or its severe outcomes that reported HBP levels and the required data to create 2 × 2 tables. We used R version 4.2.2 and R Studio to analyze the pooled diagnostic accuracy outcomes. The diagmeta package was utilized to calculate the optimum cutoff value. RESULTS: In our meta-analysis, we incorporated 28 studies including 5508 patients. The analysis revealed that HBP has a sensitivity of 0.71 (95% CI: 0.60; 0.79) and a specificity of 0.68 (95% CI: 0.51; 0.81) in diagnosing sepsis, respectively. HBP demonstrated moderate prognostic accuracy for mortality at a cutoff value of 161.415 ng/mL, with a sensitivity and specificity of 72%, and for severe sepsis outcomes at a cutoff value of 58.907 ng/mL, with a sensitivity and specificity of 71%. CONCLUSION: Our findings indicate a relatively moderate diagnostic and prognostic accuracy of HBP for sepsis. Future studies are required to verify the accuracy of HBP as a biomarker for sepsis.

Persistence of COVID-19 Human Milk Antibodies After Maternal COVID-19 Vaccination: Systematic Review and Meta-Regression Analysis.

The World Health Organization (WHO) declared COVID-19 a pandemic. The Centers for Disease Control and Prevention (CDC), WHO, and American College of Obstetricians and Gynecologists (ACOG) recommend vaccination of pregnant and lactating women, aiming to protect both mothers and their infants through transplacental and human milk antibody transmission. This study aims to assess the quantity of antibodies in human milk and determine the effect of time, vaccine type, and dose on antibody level. Single-arm prospective observational studies reporting the COVID-19-specific antibody level in human milk after COVID-19 vaccination during pregnancy or lactation were included. PubMed, Scopus, Cochrane, EBSCO, and Web of Science were searched from December 2019 to November 22, 2022. Data were extracted in a uniform Google sheet. A total of 2657 studies were identified. After the removal of duplicates and screening, 24 studies were included in the systematic review and meta-regression. Human milk COVID-19-specific antibody levels increased with subsequent vaccine doses, as reflected by a positive relationship for the second (coefficient=0.91, P-value 0.043 for IgA and coefficient=1.77, P-value 0.009 for IgG) and third (coefficient=1.23, P-value 0.0029 for IgA and coefficient=3.73, P-value 0.0068 for IgG) doses. The antibody level exhibited a weak positive relationship with the follow-up time (coefficient=0.13, P-value 0.0029 for IgA and coefficient=0.18, P-value 0.016 for IgG). Only one of the 38 infants showed detectable COVID-19 IgM and IgA antibody levels in their blood. There was an increase in the neutralizing activity of COVID-19 antibodies in human milk following the COVID-19 vaccination. From the analysis of published data, we found high positive levels of antibodies in human milk that increased with subsequent doses. Additionally, the human milk antibodies exhibit a positive neutralizing effect. Only one infant had detectable COVID-19 IgM+IgA antibodies in the blood. Further research is needed to discuss infant protection through a mother's vaccination.

Role of biomarkers in the diagnosis and management of HCC.

For many cancers, biomarkers have served as an important tool across the cancer care continuum from risk stratification and early detection to diagnosis and treatment. Alpha-fetoprotein (AFP) remains one of the few validated biomarkers for patients with HCC. Although AFP has shown potential for each of these steps, its performance, when used alone, has often been suboptimal. There continue to be discordant recommendations about AFP's value when combined with ultrasound for surveillance, as well as its role in diagnostic algorithms. Conversely, high AFP levels are associated with aggressive tumor biology and survival, so it remains a key factor for the selection of candidates for liver transplant. There have been immense efforts to identify and validate additional biomarkers for each of these steps in the HCC care continuum. Indeed, biomarker panels have shown promising data for HCC risk stratification and surveillance among patients with cirrhosis, as well as prognostication and detection of minimal residual disease in patients undergoing HCC treatment. Several large prospective studies are currently ongoing to evaluate the role of these emerging biomarkers in clinical practice.

Safety of Nonselective Beta-Blockers in Decompensated Liver Cirrhosis and Their Role in Inducing Hepatorenal Syndrome.

Background Nonselective beta-blockers (NSBBs) have been used in the management of portal hypertension and the prevention of initial and recurrent variceal bleeding in patients with liver cirrhosis. However, there is controversy regarding the use of NSBBs in patients with decompensated cirrhosis (DC) due to concerns over potential adverse effects, such as worsening of hepatic function and risk of hepatorenal syndrome (HRS). HRS is a serious complication of DC characterized by acute kidney injury (AKI) and progressive renal failure, and its development can lead to significant morbidity and mortality in this setting. Therefore, using NSBBs in patients with DC remains an area of ongoing research and debate. Our study aims to investigate the potential effect of NSBBs on HRS development. Methodology A retrospective chart review of 404 patients with cirrhosis was performed across all Northwell Health institutions between January 01, 2019, and December 31, 2020. An analysis was done on 516 patient encounters. Inclusion criteria included patients with an established International Classification of Diseases 10th Revision code of cirrhosis and AKI. After adjusting for clinical predictors, the Student's t-test or Mann-Whitney U-test was used to compare variables between the two outcome groups (HRS vs. no HRS) for the continuous variables. Pearson's chi-square test or Fisher's exact test was used for the categorical variables to test if an association existed between the use of NSBBs at home and HRS. A two-sided p-value <0.05 was considered statistically significant. SAS 9.4 (SAS Institute Inc., Cary, NC, USA) was used for statistical analysis. Results The primary outcome was the development of HRS during the hospital stay. With a total of 109 visits with HRS, we had 21 (23.60%) reported HRS in the 89 visits where NSBBs were used at home before the hospitalization, while 88 (20.61%) HRS were observed in the 427 visits with no NSBB use at home. The use of NSBBs at home was not significantly associated with the development of HRS (odds ratio = 1.1, 95% confidence interval = 0.6-1.9, p = 0.7321). We also found that higher serum albumin on admission is associated with lower odds of HRS. In contrast, increased serum creatinine, bilirubin, presence of ascites, and use of pressors were associated with a higher risk of HRS. Conclusions Our study highlights the relevant safety of NSBB use in end-stage liver disease. Their use did not appear to increase the risk of developing HRS during hospitalization with DC. Further randomized controlled trials are warranted to shed more light on the efficacy, dose tolerance limits, and safety of NSBBs in decompensated end-stage liver disease.

Laser Therapy in Hypertrophic and Keloid Scars: A Systematic Review and Network Meta-analysis.

BACKGROUND: Laser therapy has emerged as a promising treatment modality for improving the appearance and symptoms associated with hypertrophic and keloid scars. In this network meta-analysis, we aimed to evaluate the efficacy of different laser types in treating hypertrophic and keloid scars. METHODS: A comprehensive search of four databases was conducted to identify relevant studies published up until July 2023. Data were extracted from eligible studies and pooled as mean difference (MD) for continuous outcomes and risk ratio (RR) for dichotomous data in a network meta-analysis (NMA) model, using R software. RESULTS: A total of 18 studies, comprising 550 patients, were included in the analysis. Pooling our data showed that fractional carbon dioxide (FCO2) plus 5-fluorouracil (5-FU) was superior to control in terms of Vancouver Scar Scale (VSS), pliability score, and thickness; [MD = - 5.97; 95% CI (- 7.30; - 4.65)], [MD = - 2.68; 95% CI (- 4.03; - 1.33)], [MD = - 2.22; 95% CI (- 3.13; - 1.31)], respectively. However, insignificant difference was observed among FCO2 plus 5-FU compared to control group in terms of erythema, vascularity, redness and perfusion, and pigmentation [MD = - 0.71; 95% CI (- 2.72; 1.30)], [MD = - 0.44; 95% CI (- 1.26; 0.38)], respectively. CONCLUSION: Our NMA found that the FCO2 plus 5-FU was the most effective intervention in decreasing the VSS and thickness, while FCO2 plus CO2 was the most effective intervention in decreasing the pliability score. Further research is needed to determine the optimal laser parameters and long-term efficacy of laser therapy in hypertrophic and keloid scars. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Mobile Stroke Units in Acute Ischemic Stroke: A Comprehensive Systematic Review and Meta-Analysis of 5 "T Letter" Domains.

Intravenous thrombolysis (IVT) may be administered to stroke patients requiring immediate treatment more quickly than emergency medical services if certain conditions are met. These conditions include the presence of mobile stroke units (MSUs) with on-site treatment teams and a computed tomography scanner. We compared clinical outcomes of MSU conventional therapy by emergency medical services through a systematic review and meta-analysis. We searched key electronic databases from inception till September 2021. The primary outcomes were mortality at 7 and 90 days. The secondary outcomes included the modified Rankin Scale score at 90 days, alarm to IVT or intra-arterial recanalization, and time from symptom onset or last known well to thrombolysis. We included 19 controlled trials and cohort studies to conduct our final analysis. Our comparison revealed that 90-day mortality significantly decreased in the MSU group compared with the conventional care group [risk ratio = 0.82; 95% confidence interval (CI), 0.71-0.95], while there was no significant difference at 7 days (risk ratio = 0.89; 95% CI, 0.69-1.15). MSU achieved greater functional independence (modified Rankin Scale = 0-2) at 90 days (risk ratio = 1.08; 95% CI, 1.01-1.16). MSU was associated with shorter alarm to IVT or intra-arterial recanalization time (mean difference = -29.69; 95% CI, -34.46 to -24.92), treating patients in an earlier time window, as shown through symptom onset or last known well to thrombolysis (mean difference = -36.79; 95% CI, -47.48 to -26.10). MSU-treated patients had a lower rate of 90-day mortality and better 90-day functional outcomes by earlier initiation of IVT compared with conventional care.

Therapeutic potential of clinically proven natural products in the management of dementia.

Dementia is a common neurodegenerative disorder connected to damage to nerve cells in the brain. Although some conventional drugs are available for dementia treatments and are still sanctified for dementia patients, their short- and long-term side effects and other limitations make treating patients more challenging. The authors aimed to explain novel options for treating dementia with natural products and unravel some clinically proven natural products. This article systematically reviewed recent studies that have investigated the role of natural products and their bioactive compounds for dementia. PubMed Central, Scopus, and Google Scholar databases of articles were collected, and abstracts were reviewed for relevance to the subject matter.In this review, we provide mechanistic insights of clinically validated natural products, including like- Yokukansan, Souvenaid, BDW, Hupergene, Bacopa monnier, Omega-3, Tramiprostate and Palmitoylethanolamide with which have therapeutic efficacy against dementia in the management of dementia. As shown by studies, certain natural ingredients could be used to treat and prevent dementia. We strongly believe that the medicinal plants and phytoconstituents alone or in combination with other compounds would be effective treatments against dementia with lesser side effects as compared to currently available treatments. Moreover, these products should be studied further in order to develop novel dementia medications.

Switching the on-surface orientation of oxygen-functionalized helicene.

Helicenes represent an important class of chiral organic material with promising optoelectronic properties. Hence, functionalization of surfaces with helicenes is a key step toward new organic materials devices. The deposition of a heterohelicene containing two furano groups and two hydroxyl groups onto copper(111) surface in ultrahigh vacuum leads to different adsorbate modifications. At low coverage and low temperature, the molecules tend to lie on the surface in order to maximize van der Waals contact with the substrate. Thermal treatment leads to deprotonation of the hydroxyl groups and in part into a reorientation from lying into a standing adsorbate mode.

The diagnostic utility of heparin-binding protein among patients with bacterial infections: a systematic review and meta-analysis.

BACKGROUND: Bacterial infections are considered a leading cause of hospitalization and death globally. There is still a need for a rapid and feasible biomarker for bacterial infections. Heparin-binding protein (HBP) was shown to be related to bacterial infections. The objective of the study is to investigate the diagnostic accuracy of HBP in bacterial infections. METHODS: Articles were screened in PubMed, SCOPUS, Web of Science, and Cochrane to recognize eligible studies. We included studies investigating the diagnostic accuracy of HBP and reported the necessary data to construct 2 × 2 tables. A univariate analysis was conducted to determine the pooled sensitivity and specificity, and a bivariate diagnostic random-effects model was used to calculate the optimal cut-off point. RESULTS: The analysis comprised sixteen studies in total. Plasma HBP showed a sensitivity of 0.90 (95% CI: [0.79, 0.96]) and a specificity of 0.87 (95% CI: [0.66, 0.96]) in diagnosing bacterial infections using blood samples. Pooling data from seven studies revealed that HBP in cerebrospinal fluid (CSF) has sensitivity and specificity of 96% (95% CI: [0.85, 0.99]), and 95% (95% CI: [0.89, 0.97]), respectively, for the diagnosis of bacterial meningitis. In urinary tract infections (UTI), urine-HBP was revealed to have a high diagnostic value in discriminating bacterial from non-bacterial UTI infection at a cut-off value of 32.868 ng/ml with sensitivity and specificity of 87%. CONCLUSION: HBP has shown a high diagnostic accuracy of bacterial infections, including UTI and meningitis. Further studies are needed to determine its prognostic value and whether it could guide antibiotic therapy.

Are we well prepared for public health emergencies? COVID-19 pandemic effect on cancer care in Saudi Arabia: A qualitative study.

BACKGROUND: COVID-19 pandemic has significantly disrupted healthcare systems worldwide, raising concerns about its impact on cancer patients' access to healthcare services. This study aims to explore the experiences of cancer patients and assess effect of restrictions, delays, and changes in healthcare delivery on their health. METHODS: A qualitative study was performed through individual interviews and focus group discussions (FGDs) with cancer patients and key informants (KI). Participants with different cancer types, treatment stages, and residency regions in Saudi Arabia were recruited. Thematic analysis identified four major themes: access to healthcare services; impact on appointments, diagnosis, and treatment; healthcare delivery; and cancer condition deterioration due to the pandemic. RESULTS: Cancer patients reported variable responses to the pandemic and its effects on their healthcare seeking behavior. Several patients faced challenges in accessing healthcare services and experienced difficulties in continuing their treatment, others encountered obstacles in seeking timely diagnosis and care. Lockdown measures and travel restrictions posed barriers, affecting patients' ability to reach treatment centers. Delays in appointments, diagnosis, and treatment were also reported. In contrast, some participants did not report any negative impact but received improved care and condition prioritization. Healthcare delivery underwent a shift towards virtual appointments, online access to lab results and medication's home delivery service. Despite these adaptations, a small group of participants experienced health deterioration due to delays in treatment and difficulties in reaching their treating physicians. CONCLUSION: COVID-19 pandemic has had a multifaceted impact on cancer patients. Some participants faced challenges such as care delays and disruptions in accessing healthcare services. Yet others reported positive experiences such as improved communication and utilization of new healthcare delivery modalities. These findings underscore the need for resilient and adaptable healthcare systems to safeguard the well-being of cancer patients in times of crises and public health emergencies.

Rehabilitation in the intensive care unit: How amount of physical and occupational therapy affects patients' function and hospital length of stay.

BACKGROUND: Patients in the intensive care unit (ICU) often experience extended periods of immobility. Following hospital discharge, many face impaired mobility and never return to their baseline function. Although the benefits of physical and occupational rehabilitation are well established in non-ICU patients, a paucity of work describes effective practices to alleviate ICU-related declines in mobility. OBJECTIVE: To assess how rehabilitation with physical and occupational therapy (PT-OT) during ICU stays affects patients' mobility, self-care, and length of hospital stay. DESIGN: Retrospective cohort study. SETTING: Inpatient ICU. PARTICIPANTS: A total of 6628 adult patients who received physical rehabilitation across multiple sites (Arizona, Florida, Minnesota, and Wisconsin) of a single institution between January 2018 and December 2021. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Descriptive statistics, linear regression models, and gradient boosting machine methods were used to determine the relationship between the amount of PT-OT received and outcomes of hospital length of stay (LOS), Activity Measure for Post-Acute Care Daily Activity and Basic Mobility scores. RESULTS: The 6628 patients who met inclusion criteria received an average (median) of 23 (range: 1-89) minutes of PT-OT per day. Regression analyses showed each additional 10 minutes of PT-OT per day was associated with a 1.0% (95% confidence interval [CI]: 0.41-1.66, p < .001) higher final Basic Mobility score, a 1.8% (95% CI: 1.30%-2.34%, p < .001) higher final Daily Activity score, and a 1.2-day (95% CI: -1.28 to -1.09, p < .001) lower hospital LOS. One-dimensional partial dependence plots revealed an exponential decrease in predicted LOS as minutes of PT-OT received increased. CONCLUSION: Higher rehabilitation minutes provided to patients in the ICU may reduce the LOS and improve patients' functional outcomes at discharge. The benefits of rehabilitation increased with increasing amounts of time of therapy received.

Survival After Single-Stage Repair of Truncus Arteriosus and Associated Defects.

BACKGROUND: The goal of this study was to describe in-hospital and long-term mortality after single-stage repair of truncus arteriosus communis (TAC) and explore factors associated with these outcomes. METHODS: This was a cohort study of consecutive patients undergoing single-stage TAC repair between 1982 and 2011 reported to the Pediatric Cardiac Care Consortium registry. In-hospital mortality was obtained for the entire cohort from registry records. Long-term mortality was obtained for patients with available identifiers by matching with the National Death Index through 2020. Kaplan-Meier survival estimates were created for up to 30 years after discharge. Cox regression models estimated hazard ratios for the associations with potential risk factors. RESULTS: A total of 647 patients (51% male) underwent single-stage TAC repair at a median age of 18 days; 53% had type I TAC, 13% had interrupted aortic arch, and 10% underwent concomitant truncal valve surgery. Of these, 486 (75%) patients survived to hospital discharge. After discharge, 215 patients had identifiers for tracking long-term outcomes; 30-year survival was 78%. Concomitant truncal valve surgery at the index procedure was associated with increased in-hospital and 30-year mortality. Concomitant interrupted aortic arch repair was not associated with increased in-hospital or 30-year mortality. CONCLUSIONS: Concomitant truncal valve surgery but not interrupted aortic arch was associated with higher in-hospital and long-term mortality. Careful consideration of the need and timing for truncal valve intervention may improve TAC outcomes.

Efficacy and safety of polyethylene glycol loxenatide in type 2 diabetic patients: a systematic review and meta-analysis of randomized controlled trials.

Polyethylene glycol loxenatide (PEX168) is a novel glucagon-like peptide-1 receptor agonist with a longer half-life developed by modifying the chemical structure of exenatide. This study aims to assess the efficacy and safety of PEX168 and determine the best dose. We searched PubMed, Scopus, Cochrane Library, and Web of Science databases from inception to April 25, 2023, for randomized controlled trials (RCTs) comparing PEX168 therapy alone or in combination with metformin versus other therapies. We used the risk ratio (RR) for dichotomous outcomes and the mean difference (MD) for continuous outcomes, both with 95% confidence intervals (CI). Six RCTs, including 1248 participants, were included. PEX168 added to metformin was significantly better than metformin alone regarding fasting blood glucose (MD = -1.20, 95% CI (-1.78, - 0.62), p < 0.0001), HbA1c (MD = -1.01, 95% CI (-1.48, - 0.53), p < 0.0001), and postprandial glycemia (MD = -1.94, 95% CI (-2.99, - 0.90), p = 0.0003). Similarly, for glycemic control, PEX168 monotherapy was superior to placebo (P < 0.05). No significant effects were noticed in terms of triglycerides, low-density lipoprotein, or high-density lipoprotein (p > 0.05). Body weight was significantly reduced in obese diabetic patients receiving PEX168 compared to the control group (MD = -5.46, 95% CI (-7.90, - 3.01), p < 0.0001) but not in non-obese patients (MD = 0.06, 95% CI (-0.47, 0.59), p = 0.83). People who received PEX168 alone or with metformin showed more common gastrointestinal adverse effects, especially nausea and vomiting (p < 0.05). PEX168 100, 200, and 300 ug monotherapy demonstrated comparable safety and diabetes control to metformin, but when combined with metformin, PEX168 100 and 200 ug showed significant effects on diabetes control; however, only the latter showed a significantly higher incidence of nausea and vomiting (p < 0.05). PEX168 could be a viable option for treating diabetic patients whose metformin control is inadequate or who cannot tolerate metformin. PEX168 at 100 ug in combination with metformin was found to be safe and more effective compared to metformin; however, due to the small number of trials included, these findings should be interpreted with caution, and additional trials are required.

Are congenital heart defects connected to more severe attention-deficit/hyperactivity disorder?: A systematic review and meta-analysis.

BACKGROUND: Congenital heart defects (CHDs) are the most common cause of birth defect-related infant morbidity and mortality, affecting 1% of 40,000 births per year in the United States. On the other side, the etiology of attention-deficit/hyperactivity disorder (ADHD) is multifactorial. Multiple studies have found that cardiac surgery patients have higher morbidity of having this disorder. Many studies have investigated the prevalence of ADHD in different subtypes of CHD, but few have focused on the severity of ADHD symptoms. Thus, we conducted this systematic review and meta-analysis to investigate the severity of ADHD symptoms in CHD patients. METHODS: We searched PubMed, Embase, Scopus, and Web of Science were searched from inception to March 6, 2023 without any restrictions. We included observational studies published in English language that evaluated burden of symptom of ADHD in CHD patients. Moreover, the standardized mean difference (SMD) for continuous outcomes with 95% confidence interval (CI) was pooled. P-values <.05 are considered as significant, and we performed all statistical analyses using RevMan software Version 5.4.1. RESULTS: Eight studies were included in our review with a total number of 120,158 patients. CHD was associated with a statistically significant increase in both ADHD index T score and ADHD Hyperactivity-Impulsivity Subscale (informant) with (SMD = 0.65, 95% CI [0.40, 0.90], P < .00001, I2 = 81%) and (SMD = 0.16, 95% CI [0.04, 0.28], P = .008, I2 = 0%). Regarding ADHD Inattention Subscale (informant), the pooled data showed that a significant increase of this score in the CHD group (SMD = 0.25, 95% CI [0.13, 0.37], P < .001, I2 = 0%), and ADHD Combined Score (informant) showed a significant increase of this score in the CHD group (SMD = 0.23, 95% CI [0.11, 0.35], P = .0002, I2 = 0%). CONCLUSION: Our study revealed a strong association between CHD and not only ADHD, but also the severity of ADHD, making early diagnosis of ADHD in children with CHD a mandatory step in the clinical evaluation practice to improve these children on both clinical and psychological aspects.

The Effect of Molecular Adsorbent Recirculating System in Patients With Liver Failure: A Case Series of 44 Patients.

BACKGROUND: Liver failure is associated with a high mortality rate, with many patients requiring transplant for definitive treatment. The Molecular Adsorbent Recirculating System (MARS) is a nonbiologic system that provides extracorporeal support. Literature on MARS therapy is mixed: outcomes support MARS therapy for patients with isolated acute liver failure, but data on patients with chronic disease is varied. Several case studies report success using MARS as a bridging treatment for patients awaiting transplant. The purpose of this case series is to present the outcomes of 44 patients who underwent MARS therapy for liver failure, 19 of whom used MARS therapy as a bridging therapy to transplant. METHODS: This study retrospectively identified 44 patients who underwent MARS therapy for liver failure at Mayo Clinic, Jacksonville, between January 2014 and April 2021. Variables of interest included changes in laboratory markers of hepatic functioning, number and length of MARS therapy sessions, transplantation status, and mortality. RESULTS: Following MARS therapy, there were improvements in mean serum bilirubin, ammonia, urea, creatinine, International Normalized Ratio, alanine aminotransferase, and aspartate aminotransferase levels. Twenty-seven patients (61.36%) survived the hospital stay; 17 (38.63%) died in the hospital. The majority of surviving patients (n = 19; 73.07%) received liver transplant. Six did not require transplant (22.22%). All but 1 patient who received MARS as a bridging treatment to transplant survived the follow-up period (n = 18; 94.74%). CONCLUSIONS: Outcomes of these 44 cases suggest that MARS improves liver failure-associated laboratory parameters and may be effective therapy as a bridge to liver transplant.

Empowering Low- and Middle-Income Countries to Combat AMR by Minimal Use of Antibiotics: A Way Forward.

Antibiotic overuse poses a critical global health concern, especially in low- and middle-income countries (LMICs) where access to quality healthcare and effective regulatory frameworks often fall short. This issue necessitates a thorough examination of the factors contributing to antibiotic overuse in LMICs, including weak healthcare infrastructure, limited access to quality services, and deficiencies in diagnostic capabilities. To address these challenges, regulatory frameworks should be implemented to restrict non-prescription sales, and accessible point-of-care diagnostic tools must be emphasized. Furthermore, the establishment of effective stewardship programs, the expanded use of vaccines, and the promotion of health systems, hygiene, and sanitation are all crucial components in combating antibiotic overuse. A comprehensive approach that involves collaboration among healthcare professionals, policymakers, researchers, and educators is essential for success. Improving healthcare infrastructure, enhancing access to quality services, and strengthening diagnostic capabilities are paramount. Equally important are education and awareness initiatives to promote responsible antibiotic use, the implementation of regulatory measures, the wider utilization of vaccines, and international cooperation to tackle the challenges of antibiotic overuse in LMICs.