Explore the vast range of titles available.

EGFR is critical for tumor angiogenesis and cancer progression, but existing treatments like erlotinib face limitations such as acquired resistance and side effects. To address these issues, this study employs structure-based drug design techniques including virtual screening, molecular docking, and molecular dynamics simulations to identify new small molecule inhibitors targeting the EGFR kinase domain. From an initial selection of 633,000 compounds from diverse databases, top candidates were identified based on their binding affinity and stability. The virtual screening and docking analyses revealed compounds with higher binding scores than erlotinib. Molecular dynamics simulations and Anisotropic Network Model (ANM) analysis uniquely report that EGFR undergoes significant conformational shifts: inward flap movements in the bound state stabilize a closed conformation, while outward movements in the free state result in a more open conformation. Among the identified inhibitors, compounds such as JFD00243, NPA015124, and others exhibited strong binding affinities and stable interactions with both active and inactive forms of EGFR. Notably, JFD00243 was effective in targeting EGFR in both active and inactive conformations. These findings suggest that the identified inhibitors could potentially overcome current treatment limitations and improve targeted cancer therapies by effectively inhibiting EGFR-mediated tumor angiogenesis.

Many women are affected by anxiety and depression after armed conflict in low-income and middle-income countries, yet few scalable options for their mental health care exist. We aimed to establish the effectiveness of a brief group psychological intervention for women in a conflict-affected setting in rural Swat, Pakistan. In a single-blind, cluster, randomised, controlled trial, 34 community clusters in two union councils of rural Swat, Pakistan, were randomised using block permutation at a 1:1 ratio to intervention (group intervention with five sessions incorporating behavioural strategies facilitated by non-specialists) or control (enhanced usual care) groups. Researchers responsible for identifying participants, obtaining consent, enrolment, and outcome assessments were masked to allocation. A community cluster was defined as neighbourhood of about 150 households covered by a lady health worker. Women aged 18–60 years who provided written informed consent, resided in the participating cluster catchment areas, scored at least 3 on the General Health Questionnaire-12, and at least 17 on the WHO Disability Assessment Schedule were recruited. The primary outcome, combined anxiety and depression symptoms, was measured 3 months after the intervention with the Hospital Anxiety and Depression Scale (HADS). Modified intention-to-treat analyses were done using mixed models adjusted for covariates and clusters defined a priori. The trial is registered with the Australian New Zealand Clinical Trials Registry, number 12616000037404, and is now closed to new participants. From 34 eligible community clusters, 306 women in the intervention group and 306 women in the enhanced usual care (EUC) group were enrolled between Jan 11, 2016, and Aug 21, 2016, and the results of 288 (94%) of 306 women in the intervention group and 290 (95%) of 306 women in the EUC group were included in the primary endpoint analysis. At 3 months, women in the intervention group had significantly lower mean total scores on the HADS than women in the control group (10·01 [SD 7·54] vs 14·75 [8·11]; adjusted mean difference [AMD] −4·53, 95% CI −7·13 to −1·92; p=0·0007). Individual HADS anxiety scores were also significantly lower in the intervention group than in the control group (5·43 [SD 4·18] vs 8·02 [4·69]; AMD −2·52, 95% CI −4·04 to −1·01), as were depression scores (4·59 [3·87] vs 6·73 [3·91]; AMD −2·04, −3·19 to −0·88). No adverse events were reported in either group. Our group psychological intervention resulted in clinically significant reductions in anxiety and depressive symptoms at 3 months, and might be a feasible and effective option for women with psychological distress in rural post-conflict settings. WHO through a grant from the Office for Foreign Disaster Assistance.

Background Violence against healthcare personnel is a major public health problem. Healthcare personnel are at the frontline dealing with people in stressful and unpredictable situations. Therefore, this study was conducted to determine the prevalence and associated factors of violence against health care personnel. Methods A cross sectional study was conducted in the district Peshawar. Healthcare personnel from public and private sectors working in both the primary and tertiary levels of healthcare were invited to participate. Violence was assessed through a structured questionnaire previously used in Pakistan and was defined as experiencing and/or witnessing any form of violence in the last 12 months. Mental health was assessed through the General Health Questionnaire. Logistic regression was used to estimate the association of violence against healthcare personnel with psychological distress and demographic characteristics. Data entry and analysis were conducted in STATA 14. Results A total of 842 healthcare personnel participated in the study. The prevalence of violence experienced and/or witnessed by healthcare personnel in Peshawar was 51%. Verbal violence remained the predominant form of violence and almost half of the healthcare personnel (45%) were exposed to it. A quarter of the respondents (24%) reported physical violence alone or in combination with other forms of violence. In almost two third of the incidents the perpetrators were either attendants, relatives or the patients. The emergency unit and wards within healthcare facilities were the most common places where violent events took place. The major factors responsible for the violent incidents were communication failure, unreasonable expectations and perceived substandard care. No uniform policy/procedure existed to manage the incidents and the healthcare personnel adopted different responses in the wake of violent events targeting health care. Working in public healthcare facilities and having a larger number of co-workers/colleagues significantly increased the risk of violence in the healthcare settings while being a paramedic significantly reduced the risk as compared to physicians. Conclusions Violence against healthcare personnel is a serious public health issue and the prevalence is quite high. A holistic effort is needed by all stakeholders including healthcare community, the administration, lawmakers, law enforcement, civil society, and international organizations.

IntroductionRegulatory compliance in the retail environment is integral to the success of tobacco control. We assessed compliance among naswar (smokeless tobacco product widely used in South Asia) vendors with tobacco control laws. We also assessed their awareness of tobacco-related harms and policies and perceived effect of policies on their sales.MethodsWe surveyed 286 naswar vendors in three districts of the Khyber Pakhtunkhwa province of Pakistan. We recruited general and specialty vendors from urban and rural areas through multistage cluster sampling. Compliance was measured for promotion, sale to/by minors and tax paid on naswar. We used logistic regression analyses for assessing the association between the outcome variables (awareness of tobacco harms and laws, perceptions about the effect of policies on business and compliance with laws) and their predictors.ResultsMost vendors (70%) were aware of tobacco-related harms of naswar. Although educated vendors were more aware of tobacco control policies, the greatest awareness was for a ban on sales to/by minors (21% overall). The majority of vendors (76%) violated this policy (measured by self-report), and violations were more common among rural than urban vendors (OR 2.27, 95% CI 1.05 to 4.96). Most vendors (71%) violated a ban on promotion of naswar. Vendors perceived tax increases and sales ban to/by minors as most detrimental for business.ConclusionsThere was poor awareness and compliance among naswar vendors in Pakistan with tobacco control laws. This study finds potential areas for policy interventions that can reduce urban/rural disparities in implementation of and compliance with tobacco control laws.

Hyperlipidemia significantly contributes to the risk of developing cardiovascular diseases. However, about half of the patients do not adhere to their antihyperlipidemic medications, leading to healthcare costs and premature mortality. This study's objective was to determine the prevalence and associated factors of non-adherence to antihyperlipidemic medications. The study covered hypertensive patients (21,451) aged 21–75 years, presenting to the primary and secondary healthcare facilities across Pakistan (covering 21 divisions) from January 2022 to April 2023. The outcome intended was non-adherence to antihyperlipidemic medication, which was assessed by SEAMS and pill-counting methods (non-adherence < 80%). The study found overall non-adherence to antihyperlipidemic medication of 60.6% across Pakistan, with the highest non-adherence rates found in Azad Jammu and Kashmir (71.9%) and the lowest in Islamabad (47.7%). Multivariable logistic regression analysis revealed that female, no health card (Sehat Sahulat Program government insurance), < 5 years of illness, < 5 daily medications, and dose frequency of twice daily revealed a positively significant association with non-adherence. While monthly income 51,000–100,000, graduation level of education, Muhajir, and hyperlipidemia with one comorbid condition had a significant negative association with the non-adherence. Antihyperlipidemic non-adherence is a multifaceted, multifactorial, profound problem requiring a multipronged approach.

Background: Circadian Syndrome (CircS) encompasses cardiometabolic risk factors and comorbidities, indicating an elevated susceptibility to cardiovascular disease and type 2 diabetes. Methods: This cross-sectional study aimed to investigate the association between vitamin D levels and each of the following: CircS, metabolic syndrome (MetS), and the individual components of CircS. Data from 14,907 adults who participated in the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018 were utilized. CircS was defined based on MetS components, alongside depression, short sleep, and non-alcoholic fatty liver disease (NAFLD). Results: Our results indicated that low vitamin D levels exhibited meaningful associations with CircS, with vitamin D deficiency and inadequacy demonstrating 2.21-fold (95% CI 1.78–2.74, p < 0.001) and 1.33-fold (95% CI 1.14–1.54, p < 0.001) increases in CircS odds, respectively. The association between vitamin D deficiency and CircS was stronger than that with MetS. Additionally, a dose-response gradient in odds of CircS components, particularly with short sleep duration, was noted as serum vitamin D levels decreased. Conclusions: our findings highlight a significant association between low serum vitamin D levels and CircS and its components, particularly with short sleep. This suggests a potentially pivotal role of vitamin D in the pathogenesis of Circadian syndrome.

Background Hypertension is the leading modifiable risk factor for cardiovascular diseases, contributing significantly to global morbidity and mortality. Despite advancements in antihypertensive therapies, adherence to medication remains alarmingly low, particularly in low- and middle-income countries. There is limited representative research in Pakistan on adherence rates and associated factors, necessitating a comprehensive investigation. Objective To determine the prevalence of adherence to antihypertensive medication and identify factors influencing adherence among hypertensive patients across Pakistan. Methods A nationwide cross-sectional study was conducted between September 2021 and January 2023 across 225 healthcare facilities in Pakistan. A multistage random sampling strategy recruited 32,197 hypertensive patients. Adherence was assessed using the Self-Efficacy for Appropriate Medication Scale (SEAMS) and pill count methods. Multivariable binary regression analysis identified sociodemographic and clinical predictors of adherence. Results Adherence to antihypertensive medication was observed in only 36.6% of hypertensive patients, with significant regional and demographic variations. Factors positively associated with adherence to antihypertensive medications include male gender (AOR = 4.64, 95% CI [1.53–14.11]), graduate education compared to postgraduate education (AOR = 1.23, 95% CI [1.08–1.39]), higher daily medication (> 9) compared to less (< 5) medications (AOR = 2.00; 95% CI [1.84–2.19]), higher daily dose frequency compared to single dose, and higher monthly income compared to less than 25,000/month. Conversely, negative associations include primary/secondary education to postgraduate (AOR = 0.16, 95% CI [0.14–0.18]), single marital status compared to married (AOR = 0.02 95% CI [0.01–0.04]), more than one comorbid condition (AOR = 0.81, 95% CI [0.74–0.89], smoking (AOR = 0.09, 95% CI[0.08–0.10]), uncontrolled hypertension (AOR = 0.74, 95% CI [0.69–0.78), and the rest of the regions compared to Islamabad. Conclusion These findings highlight the complex interplay of demographics, medication patterns, and economic factors in medication adherence with very low adherence rates in Pakistan. Targeted, context-specific interventions—addressing affordability, education, and better awareness could potentially improve the adherence rates.

Undernutrition is a major public health problem in developing countries. Around 40·2 % of children are stunted in Pakistan. This longitudinal study aimed to assess the effectiveness of locally produced ready-to-use supplementary foods in the prevention of stunting by detecting change in of children in intervention v. control arm against the 2006 WHO growth reference. A community-based non-randomised cluster-controlled trial was conducted from January 2018 to December 2020 in the district of Kurram, Khyber Pakhtunkhwa, Pakistan. A total of 80 clusters (each cluster comprising ≈ 250–300 households) were defined in the catchment population of twelve health facilities. Children aged 6–18 months were recruited n 1680. The intervention included a daily ration of 50 g – locally produced ready-to-use-supplementary food (Wawa-Mum). The main outcome of this study was a change in length for age z-score (LAZ) v. WHO growth standards. Comparison between the interventions was by t test and ANOVA. Cox proportional hazard models were used to assess the association between stunting occurrence and the utilisation of locally produced supplement. Out of the total 1680, fifty-one out of the total 1680, 51·1 out of the total 1680 and 51·1 % (n 859) were male. Mean age 13·9 months (sd + 859) were male. Mean age 13·9 months (sd + –4·4). At baseline, 36·9 % (n 618) were stunted. In the intervention group, mean LAZ score significantly increased from −1·13(2·2 sd) at baseline to −0·93(1·8 sd) at 6-month follow-up (P value 0·01) compared with the control group. The incidence rate of stunting in the intervention arm was 1·3 v. 3·4 per person year in the control arm. The control group had a significantly increased likelihood of stunting (Hazard Ratio (HR) 1·7, 95 % CI 1·46, 2·05, P value < 0·001) v. the intervention group. Locally produced ready-to-use supplementary food is an effective intervention for reducing stunting in children below 2 years of age. This can be provided as part of a malnutrition prevention package to overcome the alarming rates of stunting in Pakistan.

ObjectiveTo obtain insights into the perceptions of barriers and facilitators to implementation of the WHO Framework Convention on Tobacco Control (FCTC) among smokeless tobacco (SLT) supply chain actors in the Khyber Pakhtunkhwa province of Pakistan.MethodsWe conducted a qualitative study to investigate the perceptions about SLT control policy formulation and implementation among exclusive Naswar sellers and point of sale vendors. We conducted five focus group discussions in three districts of Khyber Pakhtunkhwa using combined deductive-inductive thematic analyses.ResultsWe identified three central themes that potentially impact policy formulation, its implementation and application. The first theme examines the role of children in the Naswar business: as potential customers, and as potential heirs to a Naswar-selling business. A second theme targets the ‘business of Naswar’, which includes a specific identity of Naswar sellers, its potential to generate profits and the special case of Naswar regulation as a socially accepted and culturally rooted product. The third theme addresses the unusual ingredients of Naswar and its production process, making Naswar a health risk for consumers and producers. We also report conflicting views regarding SLT control among the supply chain actors.ConclusionsThis study provides insights into the perceptions of important SLT supply-side stakeholders regarding various SLT control policy options based on the FCTC. While there is some opposition to policy approaches like taxation and switching of business, implementing a ban on selling SLT to minors may be a viable option for policymakers in the short term.

ObjectivesThe primary objective of this study was to evaluate the effectiveness of a half-day training on de-escalation of violence against healthcare personnel regarding prevention and management of violence incidents versus a similar tertiary-level hospital with no such training. Secondary objectives were to compare the overall satisfaction, burnout, fear of violence and confidence in coping with patients’ aggression of the healthcare personnel in the two hospitals.DesignMixed method design, with a comparative cross-sectional (quantitative) and focus group discussions (qualitative) components.SettingEmergency departments of the two tertiary care hospitals in district Peshawar over 6 months starting from May 2018.ParticipantsHealthcare personnel in the emergency departments of the two hospitals (trained vs untrained).Outcome measuresViolence exposure (experienced/witnessed) assessed through a previously validated tool in the past 5 months. Burnout, confidence in coping with patient aggression and overall job satisfaction were also assessed through validated tools. The qualitative component explored the perceptions of healthcare personnel regarding the management of violence and the importance of training on de-escalation of violence through focus group discussions in the two hospitals.ResultsThe demographic characteristics of the healthcare personnel within the two hospitals were quite similar. The de-escalation training did not lead to a reduction in the incidences of violence; however, confidence in coping with patient aggression and the overall satisfaction were significantly improved in the intervention hospital. The de-escalation training was lauded by the respondents as led to an improvement in communication skills, and the healthcare personnel suggested for scale-up to all the cadres and hospitals.ConclusionThe study found significant improvements in the confidence of healthcare personnel in coping with patient aggression, along with better job satisfaction and less burnout in the intervention hospital following the de-escalation training.