Humoral and T cell responses to SARS-CoV-2 reveal insights into immunity during the early pandemic period in Pakistan.

BACKGROUND: Protection against SARS-CoV-2 is mediated by humoral and T cell responses. Pakistan faced relatively low morbidity and mortality from COVID-19 through the pandemic. To examine the role of prior immunity in the population, we studied IgG antibody response levels, virus neutralizing activity and T cell reactivity to Spike protein in a healthy control group (HG) as compared with COVID-19 cases and individuals from the pre-pandemic period (PP). METHODS: HG and COVID-19 participants were recruited between October 2020 and May 2021. Pre-pandemic sera was collected before 2018. IgG antibodies against Spike and its Receptor Binding Domain (RBD) were determined by ELISA. Virus neutralization activity was determined using a PCR-based micro-neutralization assay. T cell - IFN-γ activation was assessed by ELISpot. RESULTS: Overall, the magnitude of anti-Spike IgG antibody levels as well as seropositivity was greatest in COVID-19 cases (90%) as compared with HG (39.8%) and PP (12.2%). During the study period, Pakistan experienced three COVID-19 waves. We observed that IgG seropositivity to Spike in HG increased from 10.3 to 83.5% during the study, whilst seropositivity to RBD increased from 7.5 to 33.3%. IgG antibodies to Spike and RBD were correlated positively in all three study groups. Virus neutralizing activity was identified in sera of COVID-19, HG and PP. Spike reactive T cells were present in COVID-19, HG and PP groups. Individuals with reactive T cells included those with and without IgG antibodies to Spike. CONCLUSIONS: Antibody and T cell responses to Spike protein in individuals from the pre-pandemic period suggest prior immunity against SARS-CoV-2, most likely from cross-reactive responses. The rising seroprevalence observed in healthy individuals through the pandemic without known COVID-19 may be due to the activation of adaptive immunity from cross-reactive memory B and T cells. This may explain the more favourable COVID-19 outcomes observed in this population.

Understanding the facilitators and barriers to barcode medication administration by nursing staff using behavioural science frameworks. A mixed methods study.

INTRODUCTION: Barcode medication administration (BCMA) technology helps ensure correct medications are administered by nursing staff through scanning of patient and medication barcodes. In many hospitals scanning rates are low, limiting the potential safety benefits. We aimed to explore the barriers and facilitators to BCMA use in a London hospital. METHODS: In this mixed methods study we used local quantitative data on BCMA scanning rates to identify clinically similar wards (in terms of patient acuity and workload) with different scanning rates for qualitative exploration. Interviews designed to elicit barriers to using BCMA technology were conducted with nursing staff, supported by observations of medication administration. Qualitative data were analysed inductively and a thematic framework constructed housing key themes, subsequently categorised into barriers and facilitators. To explore patient perspectives of BCMA scanning, a purposive sample of patients were also interviewed. These patient data were analysed deductively according to the thematic framework. Themes were mapped to behavioural science frameworks to further understand the behaviours involved. RESULTS: BCMA was operational on 15 wards, with only six having medication scan rates of more than 10% of scannable doses. Of three wards selected for qualitative investigation, the lowest scan rate was 6.7%. Twenty-seven nurses and 15 patients were interviewed. Eleven key themes were identified, encompassing both barriers and facilitators to BCMA use. Barriers included poor trolley ergonomics and perceived time inefficiency. Facilitators included a streamlined process and thorough training. All nurses described BCMA as positive for patient safety. Patients described BCMA as making them "feel safer". Behavioural science frameworks highlighted the importance of professional role and an individual's belief in their capability. CONCLUSION: We present a novel exploration of facilitators and barriers to BCMA use from the viewpoint of both patients and nursing staff, highlighting a strong perception that BCMA enhances safety. Barriers were reported on both high and low usage wards, demonstrating the importance of behaviours and motivations. These findings provide a detailed understanding from which to design interventions to support behaviour change and increase BCMA use.

Validation and clinical interpretation of the St George's respiratory questionnaire for COPD (SGRQ-C) after adaptation to Malaysian language and culture, in patients with COPD.

BACKGROUND: Cultural differences affect the administration and results of health status questionnaires. "Cross cultural adaptation" ensures retention of psychometric properties such as validity and reliability at an item and/or scale level. OBJECTIVE: To develop a Malaysian version of St George's respiratory COPD specific questionnaire (SGRQ-CM), to evaluate the full spectrum of psychometric properties (reliability, validity and responsiveness), to test the factor structure and to assess minimum clinically important difference for the SGRQ-CM, to be used in population of Malaysia. METHODOLOGY: SGRQ-C was translated to Bahasa Malaysia using a standard protocol. 240 COPD patients were included in the study. All patients were followed-up for six months. Construct validity, internal consistency, item convergent validity, test-retest ability, responsiveness, factor analysis and MCID of the Malaysian version of SGRQ-C to be used in population of Malaysia were evaluated. RESULTS: The Cronbach alpha coefficient and intraclass correlation coefficients (ICC) for SGRQ-CM were reported as 0.87, and 0.88 respectively. Correlation of SGRQ-CM with CAT, EQ-5D-5 L, mMRC dyspnea scales and FEV1%predicted were reported as 0.86, - 0.82, 0.72 and - 0.42 respectively. Correlation coefficient between the subscales and other clinical and health status measures ranged from r = - 0.35 to r = - 0.87. The MCID was reported as 5.07 (- 2.54-12.67). CONCLUSION: The Malaysian version of SGRQ-C has a good psychometric property comparable to those of the original version and has a strong evidence of validity, reliability and responsiveness towards disease severity in Malaysian COPD patients. It can be recommended as a reliable quality of life measure for future research.

Vitamin D status and risk of incident tuberculosis disease: A nested case-control study, systematic review, and individual-participant data meta-analysis.

BACKGROUND: Few studies have evaluated the association between preexisting vitamin D deficiency and incident tuberculosis (TB). We assessed the impact of baseline vitamins D levels on TB disease risk. METHODS AND FINDINGS: We assessed the association between baseline vitamin D and incident TB in a prospective cohort of 6,751 HIV-negative household contacts of TB patients enrolled between September 1, 2009, and August 29, 2012, in Lima, Peru. We screened for TB disease at 2, 6, and 12 months after enrollment. We defined cases as household contacts who developed TB disease at least 15 days after enrollment of the index patient. For each case, we randomly selected four controls from among contacts who did not develop TB disease, matching on gender and year of age. We also conducted a one-stage individual-participant data (IPD) meta-analysis searching PubMed and Embase to identify prospective studies of vitamin D and TB disease until June 8, 2019. We included studies that assessed vitamin D before TB diagnosis. In the primary analysis, we defined vitamin D deficiency as 25-(OH)D < 50 nmol/L, insufficiency as 50-75 nmol/L, and sufficiency as >75nmol/L. We estimated the association between baseline vitamin D status and incident TB using conditional logistic regression in the Lima cohort and generalized linear mixed models in the meta-analysis. We further defined severe vitamin D deficiency as 25-(OH)D < 25 nmol/L and performed stratified analyses by HIV status in the IPD meta-analysis. In the Lima cohort, we analyzed 180 cases and 709 matched controls. The adjusted odds ratio (aOR) for TB risk among participants with baseline vitamin D deficiency compared to sufficient vitamin D was 1.63 (95% CI 0.75-3.52; p = 0.22). We included seven published studies in the meta-analysis and analyzed 3,544 participants. In the pooled analysis, the aOR was 1.48 (95% CI 1.04-2.10; p = 0.03). The aOR for severe vitamin D deficiency was 2.05 (95% CI 0.87-4.87; p trend for decreasing 25-(OH)D levels from sufficient vitamin D to severe deficiency = 0.02). Among 1,576 HIV-positive patients, vitamin D deficiency conferred a 2-fold (aOR 2.18, 95% CI 1.22-3.90; p = 0.01) increased risk of TB, and the aOR for severe vitamin D deficiency compared to sufficient vitamin D was 4.28 (95% CI 0.85-21.45; p = 0.08). Our Lima cohort study is limited by the short duration of follow-up, and the IPD meta-analysis is limited by the number of possible confounding covariates available across all studies. CONCLUSION: Our findings suggest vitamin D predicts TB disease risk in a dose-dependent manner and that the risk of TB disease is highest among HIV-positive individuals with severe vitamin D deficiency. Randomized control trials are needed to evaluate the possible role of vitamin D supplementation on reducing TB disease risk.

Enhancing Eu(3+) magnetic dipole emission by resonant plasmonic nanostructures.

We demonstrate the enhancement of magnetic dipole spontaneous emission from Eu3+ ions by an engineered plasmonic nanostructure that controls the electromagnetic environment of the emitter. Using an optical microscope setup, an enhancement in the intensity of the Eu3+ magnetic dipole emission was observed for emitters located in close vicinity to a gold nanohole array designed to support plasmonic resonances overlapping with the emission spectrum of the ions.

Mortality in Sepsis and its relationship with Gender.

BACKGROUND AND OBJECTIVE: Sepsis remains a leading cause of death across the world, carrying a mortality rate of 20-50%. Women have been reported to be less likely to suffer from sepsis and to have a lower risk of mortality from sepsis compared to men. The objective of this study was to determine the relationship between gender and mortality in sepsis, and compare cytokine profiles of male and female patients. METHODS: This was a prospective case series on 97 patients admitted with sepsis. Clinical and microbiological data was gathered, blood samples were collected for cytokine (IL-10, IL-6 and TNFα) levels and patients were followed up for clinical outcome. RESULTS: There were 54% males and 46% females, with no significant difference of age or comorbids between genders. Respiratory tract infection was the commonest source of sepsis, and was more common in females (60%) compared to males (39%) (p=0.034). Males had a higher mortality (p=0.048, RR 1.73) and plasma IL-6 level(p=0.040) compared to females. Mean IL-6 plasma level was significantly (p<0.01) higher in patients who died vs. who recovered. CONCLUSION: Our study shows that males with sepsis have a 70% greater mortality rate, and mortality is associated with a higher IL-6 plasma level.

BCG activation of trained immunity is associated with induction of cross reactive COVID-19 antibodies in a BCG vaccinated population.

BACKGROUND: Pakistan is endemic to a diverse set of parasitic, mycobacterial and viral diseases. The recognition of BCG Trained Immunity (TI) led us to postulate that the continued presence of BCG-TI may play a protective role, previously reported for both infectious and noninfectious conditions. Most of the previous studies have addressed the issue of BCG-TI in the paediatric populations. This study addressed the key issue of maintenance of BCG-TI in a wider age range (adolescent and adults) to identify the strength and quality of the immune responses. OBJECTIVE: To assess the BCG-induced recall responses in healthy individuals by cytokines secreted from the TI network and its potential role in providing cross-protection against COVID-19 and other viral infections. STUDY DESIGN: In this cross-sectional study, healthy young adults and adolescents (n = 20) were recruited from 16-40 years of age, with no prior history of TB treatment, autoimmune, or chronic inflammatory condition. METHODS: BCG-induced cytokine responses were assessed using prototypic markers for cells of the TI network [macrophages [M1 (TNFα, IFNγ), M2 (IL10)], NK (IL2), Gamma delta (γδ) T (IL17, IL4)] and SARS CoV2 IgG antibodies against RBD using short-term (12 hrs.) cultures assay. RESULTS: Significant differences were observed in the magnitude of recall responses to BCG with macrophage cytokines showing the highest mean levels of TNFα (9148 pg/ml) followed by IL10 (488 pg/ml) and IFNγ (355 pg/ml). The ratio of unstimulated vs.BCG-stimulated cytokines was 132 fold higher for TNFα, 40 fold fo r IL10, and 27 fold for IFNγ. Furthermore, SARS-CoV-2 antibodies were also detected in unstimulated plasma which showed cross reactivity with BCG. CONCLUSION: The presence of cross reactive antibodies to SARS-CoV-2 and the relative ratio of pro- and anti-inflammatory cytokines secreted by activated TI cellular network may play a pivotal role in protection in the early stages of infection as observed during the COVID-19 pandemic in the younger age groups resulting in lower morbidity and mortality.

Impact of bevacizumab on clinical outcomes and its comparison with standard chemotherapy in metastatic colorectal cancer patients: a systematic review and meta-analysis.

Background: Advances in targeted therapies have expanded the treatment options for colorectal cancer (CRC), allowing for more tailored and effective approaches to managing the disease. In targeted therapy, Bevacizumab is a commonly prescribed anti-VEGF monoclonal antibody that has a direct anti-vascular impact in cancer patients. Vascular Endothelial Growth Factors (VEGFs), especially VEGF-A, are significant agents in promoting tumour angiogenesis. Objective: To assess the impact of adding Bevacizumab to chemotherapy on progression-free survival (PFS) and overall survival (OS) in patients with metastatic colorectal cancer. Methodology: Comprehensive searches have been performed on electronic databases such as PubMed, and Google Scholar using the following terms: colorectal cancer, adenocarcinoma, Bevacizumab, chemotherapy, and monoclonal antibody. Results: In the meta-analysis, 16 out of the 24 included studies were analysed. In the final analysis, incorporating Bevacizumab with chеmothеrapy demonstrated favourable outcomes for OS with a hazard ratio (HR = 0.689,95%CI: 0.51-0.83, I² = 39%, p <0.01) and for PFS with a hazard ratio (HR = 0.77 95% CI: 0.60-0.96, I² = 54%, p < 0.01). The subgroup analysis of PFS, categorised by study dеsign (prospеctivе vs rеtrospеctivе), reveals that the Hazard Ratio (HR = 0.82, 95% CI: 0.62-0.97, I² = 21%, p < 0.01) and for OS with a hazard ratio (HR = 0.73, 95% CI: 0.52-0.86, I² = 17%, p < 0.01). Conclusion: Our findings indicate that combining Bevacizumab with chemotherapy enhances clinical outcomes and results in a significant increase in PFS and OS in patients with metastatic colorectal cancer. Positive outcomes are demonstrated by a substantial 23% increase in PFS and 31% increase in OS in patients with metastatic colorectal cancer who undergo Bevacizumab in conjunction with chemotherapy.

A qualitative study exploring community pharmacists' awareness, attitudes and perceptions about drive-thru community pharmacy service in Malaysia during COVID-19.

Introduction: Drive-thru services are not given sufficient focus in the community pharmacy setting which was highlighted during COVID-19, particularly in Malaysia. This study aimed to explore the community pharmacists' perspectives regarding drive-thru community pharmacy service during COVID-19 in Malaysia. Methods: In-depth online semi-structured individual interviews were conducted among 25 community pharmacists working in Malaysia. All interviews were conducted between March 2022 and May 2022 and were audio-recorded and transcribed verbatim, and then analysed by thematic analysis. Results: Thematic analysis yielded seven major themes, 1-familiarity with drive-thru community pharmacy service during COVID-19, 2-willingness toward this service during COVID-19, 3-perceived benefits toward drive-thru community pharmacy service during COVID-19, 4-perceived disadvantages toward this service, 5-barriers toward drive-thru community pharmacy service, 6-factors affecting the preference toward this service, and 7-facilitators to drive-thru community pharmacy service. Enhancing social distancing and preventing the spread of COVID-19 were the major perceived benefits of this service during COVID-19 as reported by participants. Conclusion: Overall, community pharmacists reported positive attitudes toward drive-thru community pharmacy service during COVID-19. However, concerns about poor communication between the pharmacist and the patient, limited counselling, and dispensing errors were acknowledged. These concerns would need to be addressed to improve the provision of drive-thru community pharmacy service.

Management, risk factors and treatment outcomes of rhegmatogenous retinal detachment associated with giant retinal tears: scoping review.

BACKGROUND: Rhegmatogenous retinal detachment (RRD) is a serious condition that occurs when the retina detaches from its underlying retinal pigment epithelium. RRDs associated with giant retinal tears (GRTs) are caused by retinal tears at least 90° or one-quarter of the circumferential extent. This scoping review systematically identifies and summarizes clinical studies evaluating surgical techniques for the management of GRT-related RRDs, discusses functional and visual outcomes and the risk factors affecting treatment outcomes. METHODS: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Scopus, Google Scholar, and Springer Link databases were searched for relevant papers (from January 2001 to March 2023). Studies that were published in the English language and reported the risk factors, management, and treatment outcomes of GRT-related RRDs were included in the review. The outcome measures included anatomic success rates, changes in BCVA (logMAR) from baseline to the final follow-up, and adverse events. RESULTS: A total of 11,982 articles were identified. After the title and abstract review, 71 studies were deemed eligible for full-text review. Thirty-six studies that met the eligibility criteria were included in the final review. Four surgical techniques were identified: pars plana vitrectomy (PPV), combined PPV and scleral buckling, scleral buckling alone, and pneumatic retinopexy. Various types of tamponades, including gas, silicone oil, and air, have been used. PPV was the most commonly used surgical technique in 33.1-100% of patients. Among the 20 studies that used PPV alone, 17 were associated with preoperative PVR. In addition, scleral buckling alone or in combination with PPV was reported as a treatment option in 10 studies, with 2-100% of patients experiencing scleral buckling alone and 13.6-100% experiencing combined PPV and complementary scleral buckling. Primary anatomic success (PAS) was achieved with retinal reattachment via a single operation with no residual tamponade, whereas final anatomic success (FAS) was achieved via more than one operation with no residual tamponade. Reported single surgery anatomic success (SSAS) rates range from 65.51 to 100%. The preoperative best-corrected visual acuity (BCVA) ranged from 0.067 to 2.47 logMAR, whereas the postoperative BCVA ranged from 0.08 to 2.3 logMAR. An improvement in visual acuity was observed in 29 studies. Cataracts (3.9-28.3%) were the most common postoperative complication, followed by high IOP (0.01-51.2%) and PVR (0.8-31.57%). CONCLUSION: PPV is the most common surgical technique, and currently microincision vitrectomy surgery (MIVS) systems are commonly employed. Silicone oil is the most frequently used tamponade in RRD repair. Risk factors for GRT-related RRD include age, sex, lens status, high myopia status, proliferative vitreoretinopathy (PVR), presenting visual acuity, the extent of the GRT and retinal detachment, and macular involvement. Future research areas include guidelines to reduce variability in the reporting of surgical methodology, choice of tamponades, and reporting of functional and visual outcomes to inform the best therapeutic interventions in GRT-related RRD.

Oxidized alginate-gelatin (ADA-GEL)/silk fibroin/Cu-Ag doped mesoporous bioactive glass nanoparticle-based hydrogels for potential wound care treatments.

The present work focuses on developing 5% w/v oxidized alginate (alginate di aldehyde, ADA)-7.5% w/v gelatin (GEL) hydrogels incorporating 0.25% w/v silk fibroin (SF) and loaded with 0.3% w/v Cu-Ag doped mesoporous bioactive glass nanoparticles (Cu-Ag MBGNs). The microstructural, mechanical, and biological properties of the composite hydrogels were characterized in detail. The porous microstructure of the developed ADA-GEL based hydrogels was confirmed by scanning electron microscopy, while the presence of Cu-Ag MBGNs in the synthesized hydrogels was determined using energy dispersive x-ray spectroscopy. The incorporation of 0.3% w/v Cu-Ag MBGNs reduced the mechanical properties of the synthesized hydrogels, as investigated using micro-tensile testing. The synthesized ADA-GEL loaded with 0.25% w/v SF and 0.3% w/v Cu-Ag MBGNs showed a potent antibacterial effect againstEscherichia coliandStaphylococcus aureus. Cellular studies using the NIH3T3-E1 fibroblast cell line confirmed that ADA-GEL films incorporated with 0.3% w/v Cu-Ag MBGNs exhibited promising cellular viability as compared to pure ADA-GEL (determined by WST-8 assay). The addition of SF improved the biocompatibility, degradation rate, moisturizing effects, and stretchability of the developed hydrogels, as determinedin vitro. Such multimaterial hydrogels can stimulate angiogenesis and exhibit desirable antibacterial properties. Therefore further (in vivo) tests are justified to assess the hydrogels' potential for wound dressing and skin tissue healing applications.

Patients' knowledge, attitude, and practices toward unused medications in Qatar: A cross-sectional survey.

Background: Global evidence has linked unused medications and their inappropriate disposal to adverse health, economic, environmental, and ethical impacts. However, such evidence is scarce in Qatar. This study explored patients' knowledge and attitude toward unused medications and their practices toward medication supply and disposal (KAP) in Qatar.Materials and methods. Study design: A cross-sectional survey using a pretested questionnaire was performed between February 2020 and October 2020. Descriptive statistics, Man Whitney U, and Kruskal-Wallis Rank-Sum tests were applied. The Chi square test assessed the association between socio-demographic characteristics and KAP scores. Characteristics that were found significantly associated with KAP (i.e., p-values <0.05) were further included as predictor variables in the multiple linear regression model. Results: All items pertaining to patients' knowledge were found to be good (mean score > 3), except for "awareness of unwanted medication return policy" (mean score < 3), i.e., the lowest level of patient agreement (31 %) (median (M) = 3, Interquartile Range (IQR) = 3). Their attitude was generally good (mean score > 3). Conversely, their practice toward medication supply was poor (mean score < 3). Possible future use was the most reported reason (79 %) for keeping medications at home, and home trash was the most widely disposing place of unused ones (76 %). Knowledge was significantly higher among non-laborers and other occupations than among patients with no work (p < 0.001) and (p = 0.005), respectively. The attitude was significantly lower among patients with healthcare providers (HCPs) in their household than among those without (p = 0.001). Practices were also significantly lower among those aged 40-49 years and those with HCPs in their household than those aged 18-29 years (p = 0.012) and those without HCPs, (p < 0.001), respectively. Conclusions: Overall, patients' knowledge and attitude toward unused medications seem good, while their practices toward medication supply and disposal are bad. To mitigate the health, economic, and environmental impacts of unused medications, interventions including rationalizing drug supply, use, disposal, prescribing, manufacturing, and promotion are recommended.

3D-printed polyether-ether ketone/carboxymethyl cellulose scaffolds coated with Zn-Mn doped mesoporous bioactive glass nanoparticles.

Patient-specific fabrication of scaffold/implant requires an engineering approach to manufacture the ideal scaffold. Herein, we design and 3D print scaffolds comprised of polyether-ether-ketone (PEEK) and sodium-carboxymethyl cellulose (Na-CMC). The fabricated scaffold was dip coated with Zn and Mn doped bioactive glass nanoparticles (Zn-Mn MBGNs). The synthesized ink exhibit suitable shear-thinning behavior for direct ink write (DIW) 3D printing. The scaffolds were crafted with precision, featuring 85% porosity, 0.3 mm layer height, and 1.5 mm/s printing speed at room temperature. Scanning electron microscopy images reveal a well-defined scaffold with an average pore size of 600 ± 30 µm. The energy dispersive X-ray spectroscopy analysis confirmed a well dispersed/uniform coating of Zn-Mn MBGNs on the PEEK/Na-CMC scaffold. Fourier transform infrared spectroscopy approved the presence of PEEK, CMC, and Zn-Mn MBGNs. The tensile test revealed a Young's modulus of 2.05 GPa. Antibacterial assays demonstrate inhibition zone against Staphylococcus aureus and Escherichia Coli strains. Chick Chorioallantoic Membrane assays also present significant angiogenesis potential, owing to the antigenic nature of Zn-Mn MBGNs. WST-8 cell viability assays depicted cell proliferation, with a 103% viability after 7 days of culture. This study suggests that the PEEK/Na-CMC scaffolds coated with Zn-Mn MBGNs are an excellent candidate for osteoporotic fracture treatment. Thus, the fabricated scaffold can offer multifaceted properties for enhanced patient outcomes in the bone tissue regeneration.

Tuberculosis (TB) treatment challenges in TB-diabetes comorbid patients: a systematic review and meta-analysis.

BACKGROUND: The Directly Observed Treatment-Short Course (DOTS) Programme was implemented by WHO and includes a combination of four anti-tuberculosis (TB) drugs (isoniazid, pyrazinamide, ethambutol and rifampicin) for a period of six months to eradicate the TB infection completely. Diabetes mellitus (DM) is recognized as one of a strong contributor of TB according to World Health Organization (WHO). The presence of diabetes mellitus type 2 (DM type 2) makes TB treatment complicated. Thus, the objective of the current meta-analysis was to identify and quantify the impact of type 2 DM on treatment outcomes of TB patients treated under the DOTS Programme. METHODS: This meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Through a systematic review of relevant literature, we focused on studies investigating treatment outcomes including extended treatment duration and recurrence for individuals with both TB and DM undergoing DOTS therapy. The extracted information included study designs, sample sizes, patient characteristics and reported treatment results. RESULTS: In 44 studies from different parts of the world, the pooled HR for the impact of DM on extended treatment duration and reoccurrence were HR 0.72, 95% CI 0.56-0.83, p < .01 and HR 0.93, 95% CI 0.70-1.04, p = .08, respectively. The pooled HR for impact of DM on composite TB treatment outcomes was calculated as 0.76 (95% CI 0.60-0.87), p < .01 with an effect size of 41.18. The heterogeneity observed among the included studies was moderate (I2 = 55.79%). CONCLUSIONS: A negative impact of DM was found on recurrence and extended treatment duration in TB patients treated with DOTS therapy. DM type 2 is responsible for the TB treatment prolongation and TB recurrence rates. By implementing effective management strategies and advancing research, the challenges can be mitigated, arising due to the complex interaction between DM and TB.

Expression of M. tuberculosis-induced suppressor of cytokine signaling (SOCS) 1, SOCS3, FoxP3 and secretion of IL-6 associates with differing clinical severity of tuberculosis.

BACKGROUND: Appropriate immune activation of T cells and macrophages is central for the control of Mycobacterium tuberculosis infections. IFN-γ stimulated responses are lowered in tuberculosis (TB), while expression of Suppressor of Cytokine Signaling (SOCS) molecules - 1 and 3 and CD4+CD25+FoxP3+T regulatory cells is increased. Here we investigated the association of these molecules in regard to clinical severity of TB. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from patients with pulmonary TB (PTB, n = 33), extra-pulmonary TB (ETB, n = 33) and healthy endemic controls (EC, n = 15). Cases were classified as moderately advanced or far advanced PTB, and less severe or severe disseminated ETB. M. tuberculosis -stimulated IFN-γ, SOCS1, SOCS3 and FoxP3 gene expression and secretion of Th1 and Th2 cytokines was measured. Statistical analysis was performed using Mann-Whitney U, Wilcoxon Rank and Kruskal Wallis non-parametric tests. RESULTS: In un-stimulated PBMCs, IL-6 (p = 0.018) and IL-10 (p = 0.013) secretion levels were increased in PTB while IL-10 was also increased in ETB (p = 0.003), all in comparison with EC. M. tuberculosis-stimulated IL-6 (p = 0.003) was lowered in ETB as compared with EC. SOCS1 mRNA expression in M. tuberculosis stimulated PBMCs levels in moderately advanced PTB (p = 0.022), far advanced (p = 0.014) PTB, and severe ETB (p = 0.009) were raised as compared with EC. On the other hand, SOCS1 mRNA titers were reduced in less severe ETB, in comparison with severe ETB (p = 0.027) and far advanced PTB (p = 0.016). SOCS3 mRNA accumulation was reduced in far advanced PTB (p = 0.007) and FoxP3 mRNA expression was increased in less severe ETB as compared with EC (p = 0.017). CONCLUSIONS: The lowered SOCS1 mRNA levels in patients with less severe extra-pulmonary TB as compared to those with more severe ETB and PTB may lead to elevated IFN-γ pathway gene expression in the latter group. As localized ETB has shown to be associated with more effective Th1 immunity and adaptive responses, this suggests a role for SOCS1 in determining disease outcome in extra-pulmonary TB.

Global landscape of community pharmacy services remuneration: a narrative synthesis of the literature.

Community pharmacists form a vital part of the health system all around the globe. Pharmacy remuneration models are aimed to ensure that pharmacies are sustained, and pharmacists could provide cost-effective services to the patients. This review summarizes the pharmacy services remuneration systems from different parts of the globe. Some countries have well-established reimbursement systems that recognize and compensate community pharmacies for their services, others are in the process of expanding the scope of reimbursable services. It further concludes by highlighting the ongoing efforts to incorporate pharmacist-provided services into reimbursement schemes and the need for standardized and consistent approaches to pharmacy remuneration globally.

Awareness, attitudes, and perceptions of drive-thru community pharmacy services among the general public in Malaysia during COVID-19: A cross-sectional study.

INTRODUCTION: There is a lack of attention to drive-thru services in the community pharmacy setting, particularly during the COVID-19 period in Malaysia. The main objective of this study was to assess the public awareness, attitudes, and perceptions towards drive-thru community pharmacy services among during COVID-19 in Malaysia. METHODS: A cross-sectional study was conducted using a self-administrated, web-based survey (Google form) among the public in Malaysia between May and June 2022. Descriptive statistics were used to summarize the socio-demographic characteristics of the participants. Associations between the socio-demographic characteristics of the participants and the use of drive-thru community pharmacy services were assessed using a chi-square test. Regression analyses were carried out to determine whether the socio-demographic characteristics of the participants were associated with perceptions towards drive-thru community pharmacy services. RESULTS: A total of 565 (70.6%) of the general public completed the survey instrument. The median age of study participants was 40.0 (IQR = 36.0) and about half of them were males (50.6%, n = 286). Although 18.6% (n = 105) of the participants reported the presence of DTCPS in their cities, only 9.0% (n = 51) reported having used this service. Most of the participants were supportive to establish drive-thru services at community pharmacies in the country. Most of the believed advantages among participants were that DTCPS are helpful during COVID-19 and quarantine time 48.0% (n = 271) by enhancing social distancing and reducing the spread of the COVID-19 virus 48.5% (n = 274). Among sociodemographic factors, non-Malaysian nationality (p<0.001), and age above 55 years (p = 0.01) were found to negatively affect participants' perceptions towards drive-thru community pharmacy services. CONCLUSION: This study showed positive awareness, attitudes, and perceptions toward drive-thru community pharmacy services during COVID-19 in Malaysia among the public. The participants believed that those services were helpful during COVID-19 to enhance social distancing and to reduce the spread of the COVID-19 virus.

Attitudes, awareness, and perceptions of general public and pharmacists toward the extended community pharmacy services and drive-thru pharmacy services: a systematic review.

BACKGROUND: Several extended and newly added pharmacy services were evaluated in different countries. This review aims to provide a summary of studies on attitudes, awareness, or perceptions toward various extended and drive-thru pharmacy services at community settings among pharmacists and the general public. METHODS: To find qualitative and descriptive quantitative studies, that reported on the attitudes, awareness, or perceptions of the general public and pharmacists toward the practice of any extended community pharmacy service and drive-thru pharmacy services in a community setting and conducted from March 2012 to March 2022. Researchers used databases such as Embase, Medline PubMed, Scopus, Web of Science, and Science Direct. The reviewers extracted data independently using the PRISMA checklist. RESULTS: There were 55 studies found according to the inclusion criteria. Various extended pharmacy services (EPS) and drive-thru pharmacy services were noted in the community setting. Pharmaceutical care services and healthcare promotion services were the noticeable performed extended services. There were positive perceptions and attitudes toward extended and drive-thru pharmacy services among pharmacists and the public. However, some factors, such as lack of time and shortage of staff, affect the practice of those services. CONCLUSION: Understanding the major concerns toward the provision of extended and drive-thru community pharmacy services and improving pharmacists' skills through more training programs to provide such services efficiently. In the future, more reviews for EPS practice barriers are recommended to faceup all concerns and find standardized guidelines by stakeholders and organizations for efficient EPS practices.

Development and validation of an assessment tool for public perceptions toward drive-thru community pharmacy services in Malaysia during COVID-19.

Introduction: Community pharmacists' roles have expanded and undergone a significant transition over the last few years. Consequently, new and different pharmacy services, such as drive-thru pharmacy services, have emerged. Drive-thru pharmacy services began three decades ago and continued even during outbreaks such as the COVID-19 pandemic. Patients' perceptions are essential to the successful implementation and satisfaction with any new service. This study examines the reliability and validity of the assessment tool of public perceptions toward drive-thru community pharmacy services in Malaysia during COVID-19. Methods: A cross-sectional study was conducted. The developed tool consists of 28 items to evaluate believed advantages toward drive-thru community pharmacy services, believed disadvantages toward drive-thru community pharmacy services, differences between drive-thru community pharmacy services and instore drug refill services, perceptions toward drive-thru community pharmacy services and feelings regarding how the introduction of drive-thru pharmacy services may affect the image of community pharmacists. Exploratory factor analysis (EFA) was performed to identify the factors of the developed tool, and confirmatory factor analysis (CFA) evaluated the model fitness. Results: The EFA identified five elements and 25 items for the tool, and through CFA results, the observed model of the 25 items structure of the tool was verified as an excellent fit for the data [χ2 (265, N = 565) = 819.586, p < 0.001, IFI = 0.931, CFI = 0.93, RMSEA = 0.064]. The results of the CFA indicated a good model fit between the observed model and the proposed model. The internal reliability of the entire tool and each factor was very satisfactory as Cronbach's Alpha for the whole structured tool was 0.843 and for each factor was as follows, first factor (believed advantages) = 0.909, second factor (believed disadvantages) = 0.921, third factor (differences between drive-thru and instore refill) = 0.647, fourth factor (perceptions) = 0.926, and fifth factor (feelings) = 0.681. Conclusion: The developed and validated tool would be valuable for assessing the public's perceptions of the drive-thru community pharmacy service during COVID-19 and future pandemics.