The impact of vitamin D administration on mortality in COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Vitamin D, known for its role in bone health, is now being explored for its immunomodulatory effects. This study aimed to evaluate the impact of vitamin D supplementation on mortality in coronavirus disease 2019 (COVID-19) patients through a systematic review and meta-analysis of randomized controlled trials. METHODS: A comprehensive search was conducted across PubMed, Scopus, Web of Science, and preprint servers for eligible trials up to July 8, 2024. Two investigators independently screened the records and assessed the risk of bias using the Cochrane Risk of Bias Tool. Trials were eligible if they compared vitamin D with control interventions in adults with COVID-19. Data extraction and analysis were carried out independently, employing a random-effects model to estimate pooled odds ratios for mortality. RESULTS: Nineteen randomized controlled trials with 2495 participants were included. The meta-analysis showed a significant reduction in all-cause mortality with vitamin D supplementation (pooled OR 0.72, 95% CI 0.53-0.98; I2 = 20%). Subgroup analysis for severe COVID-19 cases also indicated significant mortality reduction (pooled OR 0.57, 95% CI 0.35-0.92; I2 = 18%). CONCLUSION: Vitamin D supplementation appears to reduce mortality in COVID-19 patients, especially in severe cases. These findings highlight the potential benefits of vitamin D as an adjunct treatment in COVID-19, though further large-scale trials are needed to confirm these effects and determine optimal dosing.

Assessing disintegration effectiveness: A thorough evaluation using the SeDeM-ODT expert system for doxylamine succinate orodispersible formulation.

BACKGROUND: The SeDeM-ODT expert system is designed to assess the suitability of the pharmaceutical ingredients for their conversion into an orodispersible formulation by direct compression. The tool can be utilized to select the most appropriate excipients that improve the compressibility and buccodispersibility of the formulation. OBJECTIVE: This study aimed to utilize the SeDeM-ODT expert system to evaluate the performance of superdisintegrants and select an appropriate superdisntegrant for Doxylamine Succinate orodispersible formulation. METHOD: The SeDeM-ODT expert system scrutinized the excipients to develop an orodispersible Doxylamine Succinate formulation. Among the 15 parameters of the tool, some of them were determined through experimental work, while the remaining were calculated through the experimental values of other parameters. The central composite design approach was used for formulation development. The prepared powder blends were compressed using the direct compression method and evaluated for different parameters (hardness, thickness, diameter, friability, weight variation, water absorption ratio, wetting time, and disintegration time). RESULTS: The results of the SeDeM-ODT expert system were correlated with the values obtained by the post-compression tests. The Crospovidone formulation (F7) was found to be an optimized formulation as it disintegrated quickly compared with the other formulations containing other superdisintegtrants. The results perfectly endorsed the SeDeM-ODT expert system evaluation, as Crospovidone showed the highest IGCB value of 6.396. CONCLUSION: The study observed the effectiveness of the expert system in accurately examining the performance of disintegrating agents. The study observed the effectiveness of the expert system in accurately examining the performance of disintegrating agents. The assessment proved Crospovidone to produce quicker disintegration in Doxylamine Succinate orodispersible formulation.

Anatomic Characteristics of Eyes With Fuchs Endothelial Corneal Dystrophy.

PURPOSE: The purpose of this study was to evaluate and compare the anatomic characteristics of eyes with Fuchs endothelial corneal dystrophy (FECD) with eyes without FECD. METHODS: This study was a retrospective chart review performed at an academic medical center. Patients with FECD were identified through a search of the electronic medical records. Eligible patients underwent Scheimpflug imaging and optical biometry and were compared with age and sex-matched control subjects who underwent similar testing in preparation for cataract surgery. Several measurements of the cornea, anterior chamber, and eyes were evaluated using multivariable linear regression models and multivariable logistic regression models. RESULTS: A total of 404 eyes (202 eyes with FECD and 202 control eyes) were included in this study. Compared with controls, eyes with FECD had shallower AC depths, lower AC volumes, and narrower angles. Conversely, the spherical equivalent before cataract surgery, corneal pachymetry, and corneal volume were higher in eyes with FECD. On Scheimpflug imaging analysis, these anatomical differences were present in FECD eyes with and without corneal edema. After adjusting for sex, these differences remained statistically significant. Shorter axial length was found to be statistically significant in male eyes but not in female eyes with FECD. CONCLUSIONS: This study reports new ocular characteristics in FECD eyes with and without edema. Optical biometry and Scheimpflug imaging established that the anatomic findings in eyes with FECD were not simply due to the larger volume of an edematous cornea but rather unique to eyes with FECD. These findings will provide reliable, normative data for future studies examining surgical, medical, and anatomical factors in FECD.

Bringing back Galium aparine L. from forgotten corners of traditional wound treatment procedures: an antimicrobial, antioxidant, and in-vitro wound healing assay along with HPTLC fingerprinting study.

BACKGROUND: The wound healing process, restoring the functionality of the damaged tissue, can be accelerated by various compounds. The recent experimental analysis highlights the beneficial effects of phytochemicals in improving skin regeneration and wound healing. In traditional medicine, one of the widespread plants used for treating different injuries or skin afflictions is Galium aparine L. (GA). Besides, previously reported chemical compounds of GA suggested its therapeutic effects for the wound healing process, yet its regulatory effects on the cellular and molecular stages of the wound healing process have not been investigated. METHODS: In the present study, the phytochemical profile of the GA extract was analyzed using HPTLC fingerprinting, and further scientific evaluation of its phytochemicals was done. The wound-healing effects of GA extract were explored at the cellular and molecular levels while accounting for cell toxicity. The wound closure enhancing effect, antibacterial activity, and antioxidant activity were assessed. RESULTS: The HPTLC fingerprinting of the GA extract proved its previously reported phytochemical profile including phenols, flavonoids, tannins, plant acids, ergot alkaloids, flavonoids, anthraquinones, terpenoids, sterols, salicin, lipophilic compounds, saponins, iridoids, and heterocyclic nitrogen compounds. Antimicrobial assessment, of the extract, indicated the more susceptibility of S. aureus to the inhibitory effects of GA rather than E. coli and S. epidermidis. DPPH test results revealed the antioxidant property of GA extract, which was comparable to ascorbic acid. The results of the viability assay showed no cytotoxicity effects on human umbilical endothelial cell (HUVEC) and normal human dermal fibroblast (NHDF) cell lines treated with different concentrations of whole plant extract and cell viability increased in a dose-dependent manner. The results of the scratch assay showed improved cell migration and wound closure. CONCLUSIONS: This study shows the anti-oxidant, anti-microbial, and in vitro wound healing wound-healing effects of GA hydroalcoholic extract, which aligns with its use in traditional medicine. No cytotoxicity effects were shown. The results from this study can be the basis for further investigations such as animal models and phytochemical studies. Further evaluation of its effects on mechanisms and signaling pathways involved in the wound healing processes such as angiogenesis and cell proliferation can provide novel insights into the potential therapeutic effects of the GA extract.

Effect of intravenous immunoglobulin on mortality in hospitalized patients with COVID-19: A systematic review and meta-analysis of randomized controlled trials.

Background and Aims: We performed a meta-analysis of randomized controlled trials (RCTs) to summarize the overall effect of intravenous immunoglobulin (IVIG) on mortality outcomes among hospitalized coronavirus disease 2019 (COVID-19) patients. Methods: We systematically searched electronic databases up to June 1, 2023. Pooled odds ratio (OR) of mortality with a 95% confidence interval (CI) was generated using a random-effects model. The risk of bias was appraised using the Cochrane risk-of-bias Version 2 tool for randomized trials. Results: Nine RCTs were included: three RCTs had an overall low risk of bias, four RCTs had some concerns in the overall risk of bias, and two RCTs trials had an overall high risk of bias. The use of IVIG indicated a significant reduction in the odds of mortality (pooled OR = 0.69; 95% CI 0.50-0.96) relative to nonuse of IVIG. Subgroup analysis in patients with a severe course of COVID-19 revealed no significant reduction in the odds of mortality (pooled OR = 0.58; 95% CI 0.29-1.16). Conclusions: We suggest exercising caution when interpreting effectiveness of IVIG in reducing mortality among hospitalized patients with COVID-19. Our findings emphasize for larger trials with rigorous study designs to better understand the impact of IVIG, particularly in those with severe COVID-19.

Cardiorespiratory dynamics of type 2 diabetes mellitus: An extensive view of breathing and fitness challenges in a diabetes prevalent population.

BACKGROUND: Diabetes mellitus (DM) is well known for related micro and macrovascular complications. Uncontrolled hyperglycemia in diabetes mellitus leads to endothelial dysfunction, inflammation, microvascular impairment, myocardial dysfunction, and skeletal muscle changes which affect multiple organ systems. This study was designed to take an extensive view of cardiorespiratory dynamics in patients with type 2 DM. METHODS: One hundred healthy controls (HC) and 100 DM patients were enrolled. We measured and compared the breathing patterns (spirometry), VO2 max levels (heart rate ratio method) and self-reported fitness level (international fitness scale) of individuals with and without diabetes. Data was analyzed in SPSS v.22 and GraphPad Prism v8.0. RESULTS: We observed restrictive spirometry patterns (FVC <80%) in 22% of DM as compared to 2% in HC (p = 0.021). There was low mean VO2 max in DM as compared to HC(32.03 ± 5.36 vs 41.91 ± 7.98 ml/kg/min; p value <0.001). When evaluating physical fitness on self-reported IFiS scale, 90% of the HC report average, good, or very good fitness levels. In contrast, only 45% of the DM shared this pattern, with a 53% proportion perceiving their fitness as poor or very poor (p = <0.05). Restrictive respiratory pattern, low VO2 max and fitness level were significantly associated with HbA1c and long-standing DM. CONCLUSION: This study shows decreased pulmonary functions, decreased cardiorespiratory fitness (VO2 max) and IFiS scale variables in diabetic population as compared to healthy controls which are also associated with glycemic levels and long-standing DM. Screening for pulmonary functions can aid optimum management in this population.

Phase-specific strategies and interventions to enhance medication adherence across different phases in ADHD: a systematic review and meta-analysis.

INTRODUCTION: This systematic review and meta-analysis assessed the characteristics, types, and impact of interventions to improve adherence to attention-deficit hyperactivity disorder (ADHD) medications within the context of the three phases of adherence, namely, initiation, implementation, and discontinuation. METHODS: PubMed, Psychological Information Database, Embase, International Pharmaceutical Abstracts, and Google Scholar were systematically searched for relevant trials using appropriate search terms. Interventions were classified as educational, behavioural, affective, and multifaceted. Data was pooled using odds ratios and proportions. RESULTS: Seventeen studies were included in this review. In a pooled analysis of four RCTs, interventions did not significantly improve medication adherence (OR = 2.32; 95%-Confidence Interval=CI = 0.91-5.90; p = 0.08). In seven non-randomized trials, a pooled proportion of people who adhered to ADHD medication was considerably higher in the intervention group (85%, 95%CI = 78%-91%) than in the control group (47%, 95%CI = 33%-61%). Interventions varied in terms of study design, methods and their impact on different phases of adherence. CONCLUSIONS: Despite some promising results, the lack of consideration of phase-specific adherence factors may limit the effectiveness and sustainability of interventions to improve adherence in clinical practice. Future interventions should be phase-specific, guided by factors which are pertinent to each phase. Meanwhile, clinicians should choose or tailor interventions based on individual needs and preferences.

Effect of JAK Inhibitors on the Risk of Death in Patients with Moderate to Severe COVID-19: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: The pathophysiology of COVID-19 involves a signalling pathway based on the Janus kinases (JAKs) and the signal transducer and activator of transcription (STAT) family of proteins. As such, there has been growing interest in exploring JAK inhibitors as potential therapeutic agents for this disease. Objective: To provide a comprehensive summary of the efficacy of JAK inhibitors in the treatment of COVID-19 through a systematic review and meta-analysis. Data Sources: A systematic literature search was conducted in multiple electronic databases (PubMed, Scopus, and the Cochrane Central Register of Controlled Trials) and preprint repositories, without language restrictions, to identify relevant studies published up to December 31, 2023. Study Selection and Data Extraction: The primary outcome of interest was all-cause mortality. Randomized controlled trials (RCTs) investigating the administration of JAK inhibitors in patients with COVID-19 were included. Data Synthesis: Through the systematic literature search, a total of 20 RCTs meeting the inclusion criteria were identified. A random-effects model was employed to estimate the pooled odds ratio for death with administration of a JAK inhibitor relative to non-administration of such an agent, with 95% confidence interval. Meta-analysis of these trials revealed a significant reduction in mortality among patients with COVID-19 who received JAK inhibitors relative to those who did not receive these agents (pooled odds ratio 0.70, 95% confidence interval 0.58-0.84). Conclusions: The results of this systematic review and meta-analysis suggest that JAK inhibitors, specifically baricitinib, may address the urgent need for effective treatments in the ongoing COVID-19 pandemic by reducing the risk of death among affected patients. However, further research, including larger-scale RCTs, is needed to establish the efficacy and safety of other JAK inhibitors in the treatment of COVID-19 and to generate more robust evidence regarding their use in this specific patient population.

Contexte: La physiopathologie de la COVID-19 implique une voie de signalisation basée sur les Janus kinases (JAK) et les protéines STAT (pour signal transducer and activator of transcription en anglais, soit, les protéines transductrices de signal et activatrices de transcription). C'est pourquoi l'étude des inhibiteurs de JAK en tant qu'agents thérapeutiques potentiels pour cette maladie suscite un intérêt croissant. Objectif: Fournir un résumé complet de l'efficacité des inhibiteurs de JAK dans le traitement de la COVID-19 grâce à une revue systématique et une méta-analyse. Sources des données: Une recherche systématique de la littérature a été menée dans plusieurs bases de données électroniques (PubMed, Scopus et le Cochrane Central Register of Controlled Trials) et dans les référentiels de prépublications, sans restrictions linguistiques, pour identifier les études pertinentes publiées jusqu'au 31 décembre 2023. Sélection des études et extraction des données: Le principal résultat d'intérêt était la mortalité, toutes causes confondues. Des essais contrôlés randomisés (ECR) portant sur l'administration d'inhibiteurs de JAK chez des patients atteints de COVID-19 ont été inclus. Synthèse des données: Grâce à la recherche documentaire systématique, un total de 20 ECR répondant aux critères d'inclusion ont été identifiés. Un modèle à effets aléatoires a été utilisé pour estimer le rapport de cotes groupé de décès avec l'administration d'un inhibiteur de JAK par rapport à la non-administration d'un tel agent, avec un intervalle de confiance de 95 %. La méta-analyse de ces essais a révélé une réduction significative de la mortalité chez les patients atteints de COVID-19 ayant reçu des inhibiteurs de JAK par rapport à ceux n'ayant pas reçu ces agents (rapport de cotes groupé 0,70, intervalle de confiance à 95 % 0,58­0,84). Conclusions: Les résultats de cette revue systématique et méta-analyse indiquent que les inhibiteurs de JAK, en particulier le baricitinib, pourraient répondre au besoin urgent de traitements efficaces dans le cadre de la pandémie de COVID-19 en cours en réduisant le risque de décès parmi les patients touchés. Cependant, des recherches supplémentaires, y compris des ECR à plus grande échelle, sont nécessaires pour établir l'efficacité et l'innocuité d'autres inhibiteurs de JAK dans le traitement de la COVID-19 et pour générer des éléments probants plus solides concernant leur utilisation dans cette population de patients en particulier.

Ocular Syphilis as a Primary Manifestation of Neurosyphilis: A Case Report.

Sexually transmitted infectious diseases could affect a variety of organs, generating significant symptomatology. In the elderly population, infectious causes for vision problems are not generally considered. We present the case of an elderly patient with blurred vision and darkening of visual fields. He underwent an unsuccessful biopsy of the temporal artery as his vision disturbances presented also with episodic headaches. He was found to have an elevated rapid plasma reagin (RPR) and venereal disease research laboratory (VDRL) test in his cerebrospinal fluid (CSF) analysis. He was treated for ocular syphilis with a total resolution of his vision loss.

Potentiality of phosphide-based nanotubes for breast cancer detection: A DFT investigation.

Breast cancer is one of the most basilisk cancers for women due to its high mortality rate which can be prevented drastically with early-stage detection. In this work, the adsorption mechanism of two volatile organic compounds that are present in the breath of breast cancer patients, 2-Methyloctane and 3, 3-Dimethylpentane, has been investigated on aluminum phosphide nanotubes (AlPNT) and gallium phosphide nanotubes (GaPNT) in order to understand their feasibility as sensor materials to diagnosis breast cancer at early stage. We have used the quantum mechanical approach by employing density functional theory using B3LYP-D3 hybrid potential for noncovalent interaction along with the LanL2DZ basis in the Gaussian 09 software package. The adsorption properties analyses suggest that GaPNT exhibits better sensing behavior as well as proclaims 12.6% greater adsorption energy for 2-Methyloctane and 9.4% greater adsorption energy for 3, 3-Dimethylpentane than AlPNT. Other structural and electric properties analyses satisfy this conclusion and suggest that GaPNT exhibits higher stability than AlPNT and could possibly be a potential candidate for developing biosensors to detect breast cancer at the preliminary stages.

Formulation of sumatriptan succinate orodispersible tablets using chitosan and sodium starch glycolate for immediate migraine relief.

Migraine is one of the common neurological disease affecting around 23% of the Pakistani population. Prompt treatment is required to regain the functional ability of patients. The present study was designed to develop sumatriptan succinate orodispersible tablets that would quickly overcome acute migraine episodes using 22 full-factorial design. The chitosan and sodium starch glycolate were taken as independent variables; friability, disintegration, dispersion time and water absorption ratio as response variables. Eight trial formulations were generated by Design Expert® software. The main effect plots were used to check the interaction of formulations with response variables. All trial formulations showed good micromeritic properties in terms of angle of repose (19.59o-24.57°), Carr's index (17.08-24.90%) and Hausner's ratio (1.20-1.33). The tablets wetted quickly (17.1- 39 sec) in dispersion medium, showed higher water absorption ratio (188-341 sec) and disintegrated quickly (13-20 sec) with an excellent dissolution rate (94-99%). The main effect plots show interactions between the independent variables against most of the study responses. A 22 full-factorial model was found to be effective in studying the influence of formulation variables on response parameters. Both chitosan and sodium starch glycolate can be used in combination to fabricate an effective orodispersible formulation of sumatriptan succinate.

Trends in prescription and cost of Sativex, a cannabinoid-based medicine, in treating patients with multiple sclerosis in England.

Aim: Cannabis-based medication has recently been made available in the NHS for reducing pain and spasticity in patients with multiple sclerosis (MS). The currently available preparation of Sativex (nabiximols) contains a combination of botanical cannabis extracts with cannabidiol (CBD) and tetrahydrocannabinol (THC) with almost equal amounts in addition to minor cannabinoids and terpenoids and is delivered via an oro-mucosal spray. The present study aims to examine the use and trends in prescribing cannabinoid-based Sativex to control pain in patients diagnosed with MS. Methods: Primary care prescribing data for cannabinoid-based Sativex (2013-2022) from the Prescription Cost Analysis were extracted and analysed. Linear regression analyses were performed to examine prescription trends and prescription costs (average change per year). Results: There was a general increasing trend in the number of prescriptions each year, from 4.42 items dispensed per 100,000 people in 2013 to 5.15 in 2022. Overall, prescription items for cannabinoid-based Sativex increased by 0.34% per year (95% CI:-3.98, 4.67, p = 0.860) on average between 2013 and 2022. On average, a 2.43% (95% CI: -5.78, 0.92, p = 0.133) increase per year was observed for the costs of cannabinoid-based Sativex from 2013 to 2022. Conclusion: The results suggested that cannabinoid-based Sativex should be considered an option due to its effectiveness, acceptable tolerance, and safety profile in the prescribing of Sativex.

Long-term outcomes of titanium-nitride-oxide coated stents and drug-eluting stents in acute coronary syndrome: A systematic review and meta-analysis.

BACKGROUND: In severe cases of coronary artery disease, percutaneous coronary intervention provide promising results. The stent used could be a drug-eluting stent (DES) or a titanium-nitride-oxide coated stent (TiNOS). AIM: To compare the 5-year effectiveness and safety of the two stent types. METHODS: The following systematic review and meta-analysis was conducted in accordance with the preferred reporting items for systematic reviews and meta-analysis guidelines, and PubMed/MEDLINE, Scopus, and Cochrane Central were searched from inception till August 2023. Primary outcomes were major adverse cardiac events (MACE), cardiac death, myocardial infarction (MI), cardiac death or MI, and ischemia-driven total lesion revascularization (ID-TLR). RESULTS: Four randomized controlled trials (RCT), which analyzed a sum total of 3045 patients with acute coronary syndrome (ACS) after a median follow-up time of 5 years were included. Though statistically insignificant, an increase in the ID-TLR was observed in patients receiving TiNOSs vs DESs. In addition, MI, cardiac death and MI, and definite stent thrombosis (DST) were significantly decreased in the TiNOS arm. Baseline analysis revealed no significant results with meta-regression presenting non-ST elevated MI (NSTEMI) as a statistically significant covariate in the outcome of MACE. CONCLUSION: TiNOS was found to be superior to DES in terms of MI, cardiac death or MI, and DST outcomes, however, the effect of the two stent types on ID-TLR and MACE was not significant. A greater number of studies are required to establish an accurate comparison of patient outcomes in TiNOS and DES.