The efficacy and safety of Zuranolone for treatment of depression: A systematic review and meta-analysis.

RATIONALE: Zuranolone, a newly FDA-approved synthetic neurosteroid, shows promise in treating depression. OBJECTIVES: Our aim is to evaluate Zuranolone's efficacy and safety in treating depression. METHODS: Five databases were searched until September 2023 for relevant randomized clinical trials evaluating the efficacy and safety of zuranolone. The potential risk of bias in the included trials was evaluated by the Cochrane Risk of Bias II guideline Data were extracted and pooled using Review Manager Software (RevMan 5.3). RESULTS: An analysis of eight studies highlights Zuranolone's efficacy in treating depression compared to placebo across most of the outcomes. Notably, the 30mg and 50mg doses demonstrated significant improvements in reducing HAM-D scores by over 50% within a 15-day follow-up (RR) of 1.46 (95% CI [1.27, 1.68], p < 0.0001) and 1.14 (95% CI [1.01, 1.3], p = 0.04). Additionally, the HAM-D ≤ 7% score analysis revealed significant enhancements with the 30mg dose over both 15-day (RR = 1.82, 95% CI [1.44, 2.31], p < 0.0001) and 45-day (RR = 1.43, 95% CI [1.16, 1.77], p = 0.0008) durations. Adverse Events Drug Discontinuation demonstrated no overall significant difference (OR = 1.33, 95% CI: [0.79, 2.23], p = 0.282). Further, specific adverse events, such as headache, showed no significant overall difference between Zuranolone and placebo (OR = 1.11, 95% CI: [0.84, 1.47], p = 0.47), with dose-dependent analysis revealing less headache in the 30 mg group. CONCLUSION: Zuranolone demonstrates favorable tolerability and safety, particularly at 30mg and 50mg doses after 15 days, suggesting its potential and effective treatment for depression.

Seroprevalence of dengue, Japanese encephalitis and Zika among long-term expatriates in Thailand.

BACKGROUND: Travel to Southeast Asia increases the likelihood of acquiring mosquito-borne Flavivirus infections such as dengue (DENV), Japanese encephalitis (JEV) and Zika viruses (ZIKV). Expatriates are long-term travellers who have a higher risk of mosquito-borne illness at their destination country. The purpose of this study was to evaluate the seroprevalence of DENV, JEV and ZIKV infections and the determinants contributing to seropositivity among expatriates living in Thailand. METHODS: A cross-sectional study was performed from December 2017 to February 2020. Expatriates from non-Flavivirus endemic countries were recruited. 5 mL of blood was collected for DENV 1-4, JEV and ZIKV antibody testing by plaque reduction neutralization test (PRNT50). Individuals with vaccination histories or diagnoses for dengue, Japanese encephalitis, yellow fever and tick-borne encephalitis were excluded. RESULTS: Among 254 participants, most participants (83.1%) were male, the mean age was 65 years and the median duration of stay in Thailand was 6 years. Seroprevalence rate of any Flavivirus, non-specific DENV, DENV1-4, JEV and ZIKV were 34.3, 30.7, 20.5, 18.1, 18.9, 10.6, 4.7 and 2.8%, respectively. The presence of neutralizing antibodies against DENV1-4 positively correlates with the duration of stay in Thailand. DENV seropositivity was associated with living in urban areas (aOR 2.75, 95% CI 1.36-5.57). Expatriates were unlikely to have detectable anti-JEV antibodies regardless of time spent in a JEV-endemic area. No risk factors were identified that were significantly associated with JEV or ZIKV seropositivity. Only 48.4% received pre-travel counselling services, while only 18.9% visited a travel medicine specialist. CONCLUSIONS: A high proportion (34.3%) of long-term expatriates living in Thailand were seropositive for flavivirus, mainly from dengue (30.7%). To minimize risk, travel medicine practitioners should provide adequate pre-travel health risk information on mosquito-borne flavivirus infection and offer advice on mosquito bite prevention strategies. Dengue vaccine might be considered in high-risk travellers such as long-term expatriate.

Anterolateral advancement pharyngoplasty versus barbed reposition pharyngoplasty in patients with obstructive sleep apnea.

OBJECTIVES: To compare functional outcomes and complication rates of anterolateral advancement pharyngoplasty (ALA) versus barbed reposition pharyngoplasty (BRP) in the treatment of obstructive sleep apnea patients with palatal and lateral pharyngeal wall collapse. STUDY DESIGN: Prospective study. SETTING: University hospitals. SUBJECTS AND METHODS: Forty-six patients were included in this study. Patients were divided into two groups randomly, group 1 (23 cases) underwent anterolateral advancement pharyngoplasty and group 2 (23 cases) underwent barbed relocation pharyngoplasty. According to the following criteria: both sex, age between 18 and 65 years, body mass index ≤ 32 kg/m2, Friedman stage II or III, type I Fujita, nocturnal polysomnography study diagnostic for OSA, retropalatal and lateral pharyngeal wall collapse, diagnosis with flexible nasoendoscopy during a Muller's maneuver based on a 5-point scale and drug-induced sleep endoscopy. Patients who suffered from retroglossal airway collapse were rolled out. RESULTS: Apnea-hypopnea index decreased from 27.50 ± 11.56 to 11.22 ± 7.63 (P ≤ .001) in group 1 and from 33.18 ± 10.94 to 12.38 ± 6.77 (P ≤ .001) in group 2. Retropalatal posterior airway space increased from 9.84 ± 1.29 mm to 21.48 ± 2.8 mm (P ≤ .001) in group 1 and increased from 10.26 ± 1.2 mm to 22.86 ± 2.62 mm (P ≤ .001) in group 2. Retropalatal space volume increased from 1.9 ± 0.68 cm3 to 2.75 ± 0.7 cm3 (P ≤ .001) in group 1 and increased from 1.96 ± 0.88 cm3 to 2.82 ± 0.83 cm3 (P ≤ .001) in group 2. Surgical success was 86.95% in group 1 compared to 82.6% in group 2. CONCLUSIONS: Both techniques appear to be effective with a high surgical success rate in the treatment of OSA patients with retropalatal and lateral pharyngeal wall collapse.

Medical students' perceptions, experiences, and barriers towards research implementation at the faculty of medicine, Tanta university.

BACKGROUND: Research is essential for advancing medical knowledge and improving patient care. However, research capacity and output are low in low- and middle-income countries due to various challenges, including a lack of research training among medical students. Integrating research training into undergraduate medical curricula can help address this issue. METHODS: A cross-sectional study was conducted between December 2022 and March 2023 among 462 undergraduate medical students at Tanta University, Egypt to assess their knowledge, attitudes, and perceived barriers toward conducting research. Data were collected using a self-administered questionnaire and analyzed using SPSS. RESULTS: Nearly half (49.8%) of the students had an acceptable level of knowledge about research concepts while over two-thirds (66.2%) had a positive attitude. The most common barriers were lack of funding, time, and training in research methods. Previous research training was reported by 66.7% of students, but less than half had participated in or presented research. Students in the competency-based program had significantly higher knowledge and more positive attitudes than those in the mainstream program. Knowledge level was positively correlated with attitude. CONCLUSION: While attitudes were generally positive, improvements are needed in research training and opportunities among undergraduate medical students at Tanta University to help address low research capacity challenges in low- and middle-income countries. Integration of formal research training into the curriculum may help increase knowledge and participation in research.

Concurrent Infection with SARS-CoV-2 and Orientia tsutsugamushi during the COVID-19 Pandemic in the Maldives.

The COVID-19 pandemic was the worst public-health crisis in recent history. The impact of the pandemic in tropical regions was further complicated by other endemic tropical diseases, which can cause concurrent infections along with COVID-19. Here, we describe the clinical course of a patient with concurrent COVID-19 and scrub typhus infection. The patient's de-identified clinical data were retrieved retrospectively. The patient had progressive breathlessness at the time of presentation and was hospitalized for COVID-19. Respiratory examination revealed dyspnea, tachypnea, and coarse crepitations bilaterally over the entire lung field. Oxygenation was impaired, and a PaO2/FiO2 ratio of 229 suggested acute respiratory distress syndrome. Laboratory tests indicated leukocytosis, thrombocytopenia, ferritinemia, hypoalbuminemia, and transaminitis. Upon revaluation for persistent fever, physical examination revealed an eschar in the right antecubital fossa. Serology further confirmed scrub typhus, with IgM and IgG antibody positivity. A remarkable clinical recovery was achieved with doxycycline. The COVID-19 pandemic might have masked endemic tropical diseases. Clinicians working in endemic regions must always consider common tropical diseases that may present as a co-infection, as in our case. Travel and exposure history are critical guides for narrowing down a differential diagnosis. Early diagnosis and treatment can prevent complications.

A Fatal Case of Native Valve Endocarditis with Multiple Embolic Phenomena and Invasive Methicillin-Resistant Staphylococcus aureus Bacteremia: A Case Report from the Maldives.

Infective endocarditis (IE) is a life-threatening condition caused by infection within the endocardium of the heart and commonly involves the valves. The subsequent cascading inflammation leads to the appearance of a highly friable thrombus that is large enough to become lodged within the heart chambers. As a result, fever, fatigue, heart murmurs, and embolization phenomena may be seen in patients with IE. Embolization results in the seeding of bacteria and obstruction of circulation, causing cell ischemia. Of concern, bacteria with the potential to gain pan-drug resistance, such as methicillin-resistant Staphylococcus aureus (MRSA), are increasingly being identified as the causative agent of IE in hospitals and among intravenous drug abusers. We retrospectively reviewed de-identified clinical data to summarize the clinical course of a patient with MRSA isolated using an automated blood culture system. At the time of presentation, the patient showed a poor consciousness level, and the calculated Glasgow scale was 10/15. A high-grade fever with circulatory shock indicated an occult infection, and a systolic murmur was observed with peripheral signs of embolization. This case demonstrated the emerging threat of antimicrobial resistance in the community and revealed clinical findings of IE that may be helpful to clinicians for the early recognition of the disease. The management of such cases requires a multi-specialty approach, which is not widely available in small-island developing states such as the Maldives.

Use of continuous glucose monitor as a motivational device for lifestyle modifications to improve glycaemic control in patients with type 2 diabetes treated with non-insulin therapies.

The efficacy of continuous glucose monitors (CGM) to improve glycaemic control in individuals on intensive insulin therapy (basal and prandial) has been well established in several studies; however, there is limited evidence on its usage and efficacy in patients with type 2 diabetes (T2D) who are on non-insulin therapies. Lifestyle modifications and glucose monitoring are essential components of the management of T2D. We report a case that demonstrates the impact of CGM use as an effective tool for patient education and motivation to implement and adhere to lifestyle modifications in improving glycaemic control in a patient with long-standing poorly controlled T2D who was on oral glucose-lowering medications. CGM use is associated with high level of patient satisfaction which can improve quality of life and has the potential to reduce long-term complications related to poor glycaemic control. These observations emphasise the need to broaden the use of CGM in this patient population.

Multisystem Inflammatory Syndrome in a Young Adult Following COVID-19 Infection: A Case Report.

Multisystem inflammatory syndrome (MIS) after a primary infection with coronavirus disease 2019 (COVID-19) was first recognized in 2020 and presents with similar symptoms as Kawasaki disease, toxic shock syndrome, and macrophage activation syndrome/secondary hemophagocytic lymphohistiocytosis. In children, it is called multisystem inflammatory syndrome in children (MIS-C); in adults, it is termed multisystem inflammatory syndrome in adults (MIS-A). This case offers a unique presentation of MIS in a 20-year-old young adult, who turned 21 years old one week after his presentation. He fits the criteria for MIS-C and MIS-A according to the Centers for Disease Control and World Health Organization, respectively. Initial symptoms in the emergency department included headache, neck stiffness, and fever with diffuse rash. Other symptoms consistent with MIS-C/A developed rapidly later during the course of the disease.

Perceptions and experiences of COVID-19 vaccines' side effects among healthcare workers at an Egyptian University Hospital: a cross-sectional study.

BACKGROUND: A safe and effective vaccine is the ultimate key to mitigating the COVID-19 pandemic. Vaccine acceptance is influenced by various factors, including perceptions about the vaccine's safety and side effects. The side effects vary depending on the type of the vaccine, but they are mainly mild, local, temporary, and self-limiting. METHODS: A cross-sectional study was carried out at Tanta University Hospitals, including 1246 healthcare workers who received either the first or the second dose of the COVID-19 vaccine, selected via a systematic random sampling technique using a self-administered structured validated questionnaire for data collection from November 2021 to January 2022. Qualitative data were presented as frequencies and percentages and analyzed using Chi-square and Fisher's exact tests. RESULTS: The prevalence of one or more side effects was 91.3%. Among participants, about two-thirds believed in vaccine safety and its necessity (65.4% and 63.6%, respectively). Significantly more participants (46.9%) were concerned about AstraZeneca thrombotic complications than other vaccine types. The top five side effects reported by participants were injection site pain (64.8%), sense of fatigue (57.1%), headache (49.9%), muscle pain (48.7%), and fever (46.5). Most of the side effects were significantly higher among participants vaccinated with AstraZeneca. Side effects impacted work capacity of 23.4%, which was significantly higher among participants who received AstraZeneca (33.6%). CONCLUSION: Participants had a good level of belief in vaccination safety and necessity. Healthcare workers who got the AstraZeneca vaccination reported more adverse effects than other vaccines. Injection site pain, fatigue, headache, muscle pains, and fever were the most frequently reported side effects. More research on vaccination safety is needed to understand the long-term adverse effects of vaccinations better, improve the public trust, and accelerate vaccine adoption.

A Case Report of Secondary Syphilis Co-Infected with Measles: A Diagnostic Dilemma with Fever and Rash.

Fever and rash as manifestations of infection by microorganisms are collectively known as febrile exanthem. Since viruses are more frequently associated with fever and rash, these symptoms are thus impetuously termed viral exanthem. However, bacteria represent a frequently overlooked infectious etiology causing rash in humans. In addition, certain microbes may exhibit pathognomonic features that erupt during illness and facilitate clinical diagnosis. Conversely, coinfections often obscure the clinical characteristics of the primary disease and further challenge clinicians attempting to reach a diagnosis. We retrospectively looked at de-identified clinical data of a patient who presented to the Hospital for Tropical Diseases in Bangkok in July 2019 with complaints of fever and rash. The case involved a 35-year-old who presented with a 3-day history of fever, respiratory symptoms, myalgia, conjunctivitis, diarrhea, and a generalized maculopapular rash. On examination, the patient was febrile, tachycardic, and tachypneic, with a mean arterial pressure of 95 mmHg. A differential white blood cell count showed: leukocytes, 5800/µL; neutrophils, 4408/µL; lymphocytes, 406/µL; and platelets, 155,000/µL. Striking findings involving the integumentary system included Koplik's spots and generalized maculopapular rash. Further serology revealed positive immunoglobulin (Ig)M and IgG for both measles and rubella virus, including reactive serology for Treponema pallidum. Here we describe the clinical course and management of this patient.

A review of adverse effects of COVID-19 vaccines.

The COVID-19 pandemic has led to unanticipated pressures on all aspects of human life. Multiple approaches to eliciting protective immunity must be rapidly evaluated. Numerous efforts have been made to develop an effective vaccine for this novel coronavirus, resulting in a race for vaccine development. To combat COVID-19, all nations must focus their efforts on widespread vaccination with an effective and safe vaccine. Globally, concerns about potential long-term adverse effects of vaccines have led to some apprehension about vaccine use. A vaccine's adverse effect has an integral role in the public's confidence and vaccine uptake. This article reviews the current primary literature regarding adverse effects associated with different COVID-19 vaccines in use worldwide.

Acalculous Cholecystitis in a Young Adult with Scrub Typhus: A Case Report and Epidemiology of Scrub Typhus in the Maldives.

Scrub typhus is a neglected tropical disease predominantly occurring in Asia. The causative agent is a bacterium transmitted by the larval stage of mites found in rural vegetation in endemic regions. Cases of scrub typhus frequently present as acute undifferentiated febrile illness, and without early diagnosis and treatment, the disease can develop fatal complications. We retrospectively reviewed de-identified data from a 23-year-old woman who presented to an emergency department with complaints of worsening abdominal pain. On presentation, she appeared jaundiced and toxic-looking. Other positive findings on abdominal examination were a positive Murphey's sign, abdominal guarding and hepatosplenomegaly. Magnetic resonance cholangiopancreatography demonstrated acalculous cholecystitis. Additional findings included eschar on the medial aspect of the left thigh with inguinal regional lymphadenopathy. Further, positive results were obtained for immunoglobulins M and G, confirming scrub typhus. The workup for other infectious causes of acute acalculous cholecystitis (AAC) detected antibodies against human herpesvirus 4 (Epstein-Barr virus), suggesting an alternative cause of AAC. Whether that represented re-activation of the Epstein-Barr virus could not be determined. As other reports have described acute acalculous cholecystitis in adult scrub typhus patients, we recommend doxycycline to treat acute acalculous cholecystitis in endemic regions while awaiting serological confirmation.

Granulomatous Polyangiitis With Renal Involvement: A Case Report and Review of Literature.

Granulomatosis with polyangiitis (GPA), formerly named Wegner's granulomatosis is an antineutrophilic cytoplasmic antibody (ANCA) associated vasculitis of the small vessels. GPA can affect several organ systems even though predominantly affects respiratory and renal systems. Pathogenesis is initiated by activation of the immune system to produce ANCA, Cytoplasmic (C-ANCA) antibody, which thereby leads to widespread necrosis and granulomatous inflammation. Multisystem involvement with varied symptomatology makes GPA diagnosis more challenging. Early diagnosis and management are vital and can alter the prognosis of the disease. We present a literature review and a clinical scenario of a 26-year-old male with a history of chronic sinusitis, testicular carcinoma in remission, recent onset of worsening cough, epistaxis, hoarseness of voice, weight loss, and dark-colored urine. Workup revealed high titers of C-ANCA, C-reactive protein, procalcitonin, CT chest evidence of mass-like consolidation, and bronchoscopy findings of friable tissue that was not amenable for biopsy. Methylprednisolone and rituximab (RTX) were administered, which resulted in marked clinical improvement. Therefore, a keen eye for details is necessary to diagnose GPA early, which can improve disease outcomes dramatically.

Multisystem Inflammatory Syndrome Associated with SARS-CoV-2 Infection in an Adult: A Case Report from the Maldives.

The multisystem inflammatory syndrome in adults (MIS-A) is a novel syndrome observed during COVID-19 outbreaks. This hyper-inflammatory syndrome is seen predominantly in children and adolescents. The case of an adult from the Maldives who had asymptomatic SARS-CoV-2 infection three weeks before presenting to the hospital with fever, rash, and shock is presented. De-identified clinical data were retrospectively collected to summarize the clinical progression and treatment during hospitalization and the six-month follow-up. SARS-CoV-2 infection was confirmed by RT-PCR. Other laboratory findings included anemia (hemoglobin: 9.8 g/dL), leukocytosis (leukocytes: 20,900/µL), neutrophilia (neutrophils: 18,580/µL) and lymphopenia (lymphocytes: 5067/µL), and elevated inflammatory markers, including C-reactive protein (34.8 mg/dL) and ferritin (2716.0 ng/dL). The electrocardiogram had low-voltage complexes, and the echocardiogram showed hypokinesia, ventricular dysfunction, and a pericardial effusion suggestive of myocardial dysfunction compromising hemodynamics and causing circulatory shock. These findings fulfilled the diagnostic criteria of MIS-A. The case was managed in the intensive care unit and required non-invasive positive pressure ventilation, inotropes, and steroids. With the new surges of COVID-19 cases, more cases of MIS-A that require the management of organ failure and long-term follow-up to recovery are anticipated. Clinicians should therefore be vigilant in identifying cases of MIS-A during the pandemic.

Evaluation of Sickle Cell Module for Quality of Life in Egyptian Children and Adolescents Patients: Impact of Psychiatric and Disease Specific Variables.

Sickle cell disease (SCD) impacts the physical, emotional, and psychological aspects of life. We aimed to study the quality of life (QoL) in Egyptian children and adolescents with SCD using the sickle cell module in relations to social, psychological and disease variables. A cross sectional study included 40 patients with SCD between 5 and 18 years. Details of diagnosis, SCD related complications, socioeconomic status were revised. Psychological assessment was done using children depression inventory, revised Children's Manifest anxiety scale and Health related QoL for both patients and parents using a validated Arabic age specific version of sickle cell module. Significant better scores for communication problems in mothers with college degree was found compared with other academic levels with no significant difference in QoL in relation to father education and significant higher communication problems with high rate of hospitalization (P = .021). Pain score was higher in 8-13 years compared with 13-18 years age groups. Significant worse scores for worrying was found in females, P = 0.033; Depression was found in 90% of studied patients. The main determinants of QoL in patients with SCD were maternal education and frequency of hospitalization. Depression is of alarming frequency for intervention.

Clinical Features of Acute Chikungunya Virus Infection in Children and Adults during an Outbreak in the Maldives.

The chikungunya virus is an arthritogenic arbovirus that has re-emerged in many tropical and subtropical regions, causing explosive outbreaks. This re-emergence is due to a genomic polymorphism that has increased the vector susceptibility of the virus. The majority of those infected with chikungunya virus exhibit symptoms of fever, rash, and debilitating polyarthralgia or arthritis. Symptoms can persist for weeks, and patients can relapse months later. Fatalities are rare, but individuals of extreme age can develop severe infection. Here, we describe the 2019 outbreak, the second-largest since the virus re-emerged in the Maldives after the 2004 Indian Ocean epidemic, in which a total of 1,470 cases were reported to the Health Ministry. Sixty-seven patients presenting at the main referral tertiary care hospital in the Maldives capital with acute undifferentiated illness were recruited following a negative dengue serology. A novel point-of-care antigen kit was used to screen suspected cases, 50 of which were subsequently confirmed using real-time reverse transcription-polymerase chain reaction. We describe the genotype and polymorphism of Maldives chikungunya virus using phylogenetic analysis. All isolates were consistent with the East Central South African genotype of the Indian Ocean lineage, with a specific E1-K211E mutation. In addition, we explored the clinical and laboratory manifestations of acute chikungunya in children and adults, of which severe infection was found in some children, whereas arthritis primarily occurred in adults. Arthritides in adults occurred irrespective of underlying comorbidities and were associated with the degree of viremia.

Antibody-dependent enhancement representing in vitro infective progeny virus titer correlates with the viremia level in dengue patients.

Dengue virus (DENV) causes dengue fever (DF) and dengue hemorrhagic fever in humans. Some DF patients suddenly develop severe symptoms around the defervescent period. Although the pathogenic mechanism of the severe symptoms has not been fully elucidated, the viremia level in the early phase has been shown to correlate with the disease severity. One of the hypotheses is that a phenomenon called antibody-dependent enhancement (ADE) of infection leads to high level of viremia. To examine the plausibility of this hypothesis, we examined the relationship between in vitro ADE activity and in vivo viral load quantity in six patients with dengue diseases. Blood samples were collected at multiple time points between the acute and defervescent phases, and the balance between neutralizing and enhancing activities against the autologous and prototype viruses was examined. As the antibody levels against DENV were rapidly increased, ADE activity was decreased over time or partially maintained against some viruses at low serum dilution. In addition, positive correlations were observed between ADE activity representing in vitro progeny virus production and viremia levels in patient plasma samples. The measurement of ADE activity in dengue-seropositive samples may help to predict the level of viral load in the subsequent DENV infection.