Aga Khan University

INTRODUCTION: The Asian Pacific Association for the Study of the Liver (APASL) convened an international working party on the management of hepatocellular carcinoma (HCC) in December 2008 to develop consensus recommendations. METHODS: The working party consisted of expert hepatologist, hepatobiliary surgeon, radiologist, and oncologist from Asian-Pacific region, who were requested to make drafts prior to the consensus meeting held at Bali, Indonesia on 4 December 2008. The quality of existing evidence and strength of recommendations were ranked from 1 (highest) to 5 (lowest) and from A (strongest) to D (weakest), respectively, according to the Oxford system of evidence-based approach for developing the consensus statements. RESULTS: Participants of the consensus meeting assessed the quality of cited studies and assigned grades to the recommendation statements. Finalized recommendations were presented at the fourth APASL single topic conference on viral-related HCC at Bali, Indonesia and approved by the participants of the conference.

CONTEXT: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation more accurately estimates glomerular filtration rate (GFR) than the Modification of Diet in Renal Disease (MDRD) Study equation using the same variables, especially at higher GFR, but definitive evidence of its risk implications in diverse settings is lacking. OBJECTIVE: To evaluate risk implications of estimated GFR using the CKD-EPI equation compared with the MDRD Study equation in populations with a broad range of demographic and clinical characteristics. DESIGN, SETTING, AND PARTICIPANTS: A meta-analysis of data from 1.1 million adults (aged ≥ 18 years) from 25 general population cohorts, 7 high-risk cohorts (of vascular disease), and 13 CKD cohorts. Data transfer and analyses were conducted between March 2011 and March 2012. MAIN OUTCOME MEASURES: All-cause mortality (84,482 deaths from 40 cohorts), cardiovascular mortality (22,176 events from 28 cohorts), and end-stage renal disease (ESRD) (7644 events from 21 cohorts) during 9.4 million person-years of follow-up; the median of mean follow-up time across cohorts was 7.4 years (interquartile range, 4.2-10.5 years). RESULTS: Estimated GFR was classified into 6 categories (≥90, 60-89, 45-59, 30-44, 15-29, and <15 mL/min/1.73 m(2)) by both equations. Compared with the MDRD Study equation, 24.4% and 0.6% of participants from general population cohorts were reclassified to a higher and lower estimated GFR category, respectively, by the CKD-EPI equation, and the prevalence of CKD stages 3 to 5 (estimated GFR <60 mL/min/1.73 m(2)) was reduced from 8.7% to 6.3%. In estimated GFR of 45 to 59 mL/min/1.73 m(2) by the MDRD Study equation, 34.7% of participants were reclassified to estimated GFR of 60 to 89 mL/min/1.73 m(2) by the CKD-EPI equation and had lower incidence rates (per 1000 person-years) for the outcomes of interest (9.9 vs 34.5 for all-cause mortality, 2.7 vs 13.0 for cardiovascular mortality, and 0.5 vs 0.8 for ESRD) compared with those not reclassified. The corresponding adjusted hazard ratios were 0.80 (95% CI, 0.74-0.86) for all-cause mortality, 0.73 (95% CI, 0.65-0.82) for cardiovascular mortality, and 0.49 (95% CI, 0.27-0.88) for ESRD. Similar findings were observed in other estimated GFR categories by the MDRD Study equation. Net reclassification improvement based on estimated GFR categories was significantly positive for all outcomes (range, 0.06-0.13; all P < .001). Net reclassification improvement was similarly positive in most subgroups defined by age (<65 years and ≥65 years), sex, race/ethnicity (white, Asian, and black), and presence or absence of diabetes and hypertension. The results in the high-risk and CKD cohorts were largely consistent with the general population cohorts. CONCLUSION: The CKD-EPI equation classified fewer individuals as having CKD and more accurately categorized the risk for mortality and ESRD than did the MDRD Study equation across a broad range of populations.

BACKGROUND: Coronavirus disease (COVID-19) pandemic has spread to 198 countries, with approximately 2.4 million confirmed cases and 150,000 deaths globally as of April 18. Frontline healthcare workers (HCWs) face a substantially higher risk of infection and death due to excessive COVID-19 exposure. This review aimed at summarizing the evidence of the physical and mental health impacts of COVID-19 pandemic on health-care workers (HCWs). METHODS: We used the Arksey O'Malley framework to conduct a scoping review. A systematic literature search was conducted using two databases: PubMed and Google Scholar. We found 154 studies, and out of which 10 met our criteria. We collected information on the date of publication, first author's country, the title of the article, study design, study population, intervention and outcome, and key findings, and divided all research articles into two domains: physical and mental health impact. RESULTS: We reviewed a total of 154 articles from PubMed (126) and Google Scholar (28), of which 58 were found to be duplicate articles and were excluded. Of the remaining 96 articles, 82 were excluded after screening for eligibility, and 4 articles did not have available full texts. Ten full-text articles were reviewed and included in this study. Our findings identified the following risk factors for COVID-19-related health impact: working in a high-risk department, diagnosed family member, inadequate hand hygiene, suboptimal hand hygiene before and after contact with patients, improper PPE use, close contact with patients (≥ 12 times/day), long daily contact hours (≥ 15 h), and unprotected exposure. The most common symptoms identified amongst HCWs were fever (85%), cough (70%), and weakness (70%). Prolonged PPE usage led to cutaneous manifestations and skin damage (97%), with the nasal bridge (83%) most commonly affected site. HCWs experienced high levels of depression, anxiety, insomnia, and distress. Female HCWs and nurses were disproportionately affected. CONCLUSION: The frontline healthcare workers are at risk of physical and mental consequences directly as the result of providing care to patients with COVID-19. Even though there are few intervention studies, early data suggest implementation strategies to reduce the chances of infections, shorter shift lengths, and mechanisms for mental health support could reduce the morbidity and mortality amongst HCWs.

BACKGROUND: Of the 3.7 million neonatal deaths and 3.3 million stillbirths each year, 98% occur in developing countries. An evaluation of community-based interventions designed to reduce the number of these deaths is needed. METHODS: With the use of a train-the-trainer model, local instructors trained birth attendants from rural communities in six countries (Argentina, Democratic Republic of Congo, Guatemala, India, Pakistan, and Zambia) in the World Health Organization Essential Newborn Care course (which focuses on routine neonatal care, resuscitation, thermoregulation, breast-feeding, "kangaroo" [skin-to-skin] care, care of the small baby, and common illnesses) and (except in Argentina) in a modified version of the American Academy of Pediatrics Neonatal Resuscitation Program (which teaches basic resuscitation in depth). The Essential Newborn Care intervention was assessed among 57,643 infants with the use of a before-and-after design. The Neonatal Resuscitation Program intervention was assessed as a cluster-randomized, controlled trial involving 62,366 infants. The primary outcome was neonatal death in the first 7 days after birth. RESULTS: The 7-day follow-up rate was 99.2%. After birth attendants were trained in the Essential Newborn Care course, there was no significant reduction from baseline in the rate of neonatal death from all causes in the 7 days after birth (relative risk with training, 0.99; 95% confidence interval [CI], 0.81 to 1.22) or in the rate of perinatal death; there was a significant reduction in the rate of stillbirth (relative risk with training, 0.69; 95% CI, 0.54 to 0.88; P=0.003). In clusters of births in which attendants had been randomly assigned to receive training in the Neonatal Resuscitation Program, as compared with control clusters, there was no reduction in the rates of neonatal death in the 7 days after birth, stillbirth, or perinatal death. CONCLUSIONS: The rate of neonatal death in the 7 days after birth did not decrease after the introduction of Essential Newborn Care training of community-based birth attendants, although the rate of stillbirths was reduced. Subsequent training in the Neonatal Resuscitation Program did not significantly reduce the mortality rates. (ClinicalTrials.gov number, NCT00136708.)

OBJECTIVE: To determine the prevalence, attitude and knowledge of self-medication amongst university students of Karachi, Pakistan. METHODS: This cross-sectional, study was conducted from Jan-Feb 2007. A convenience sample was taken from 2 medical and 2 non-medical universities of the city of Karachi, Pakistan. Data was analyzed using SPSS v 14 and associations were tested using the Chi square test. RESULTS: Of the 572 participants (mean age=21 +/- 1.8 years, Male: Female ratio=1:1.5), 295 were medical and 277 were non-medical students. The prevalence of self-medication was 76%. Forty three percent students stated that they alter the regimen of prescribed medicines while 61.9% stated that they stop taking a prescribed medicine without consulting a doctor. The most common reason for self-medication was previous experience (50.1%) and the most common symptoms were headache (72.4%), flu (65.5%), and fever (55.2%). Commonly used medicines were analgesics (88.3%), antipyretics (65.1%) and antibiotics (35.2%). Eighty seven percent of students thought self-medication could be harmful and 82.5% students thought that it was necessary to consult a doctor before taking a new medicine. There was no significant difference between the self medication practices of medical and non medical students (p=0.8) CONCLUSION: Prevalence of self-medication is high in the educated youth, despite majority being aware of its harmful effects. There is a need to educate the youth to ensure safe practices. Strict policies need to be implemented on the advertising and selling of medications to prevent this problem from escalating.

OBJECTIVE: To determine if vitamin A supplementation is associated with reductions in mortality and morbidity in children aged 6 months to 5 years. DESIGN: Systematic review and meta-analysis. Two reviewers independently assessed studies for inclusion. Data were double extracted; discrepancies were resolved by discussion. Meta-analyses were performed for mortality, illness, vision, and side effects. DATA SOURCES: Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, Medline, Embase, Global Health, Latin American and Caribbean Health Sciences, metaRegister of Controlled Trials, and African Index Medicus. Databases were searched to April 2010 without restriction by language or publication status. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised trials of synthetic oral vitamin A supplements in children aged 6 months to 5 years. Studies of children with current illness (such as diarrhoea, measles, and HIV), studies of children in hospital, and studies of food fortification or β carotene were excluded. RESULTS: 43 trials with about 215,633 children were included. Seventeen trials including 194,483 participants reported a 24% reduction in all cause mortality (rate ratio=0.76, 95% confidence interval 0.69 to 0.83). Seven trials reported a 28% reduction in mortality associated with diarrhoea (0.72, 0.57 to 0.91). Vitamin A supplementation was associated with a reduced incidence of diarrhoea (0.85, 0.82 to 0.87) and measles (0.50, 0.37 to 0.67) and a reduced prevalence of vision problems, including night blindness (0.32, 0.21 to 0.50) and xerophthalmia (0.31, 0.22 to 0.45). Three trials reported an increased risk of vomiting within the first 48 hours of supplementation (2.75, 1.81 to 4.19). CONCLUSIONS: Vitamin A supplementation is associated with large reductions in mortality, morbidity, and vision problems in a range of settings, and these results cannot be explained by bias. Further placebo controlled trials of vitamin A supplementation in children between 6 and 59 months of age are not required. However, there is a need for further studies comparing different doses and delivery mechanisms (for example, fortification). Until other sources are available, vitamin A supplements should be given to all children at risk of deficiency, particularly in low and middle income countries.

CONTEXT: Helicopter emergency medical services and their possible effect on outcomes for traumatically injured patients remain a subject of debate. Because helicopter services are a limited and expensive resource, a methodologically rigorous investigation of its effectiveness compared with ground emergency medical services is warranted. OBJECTIVE: To assess the association between the use of helicopter vs ground services and survival among adults with serious traumatic injuries. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study involving 223,475 patients older than 15 years, having an injury severity score higher than 15, and sustaining blunt or penetrating trauma that required transport to US level I or II trauma centers and whose data were recorded in the 2007-2009 versions of the American College of Surgeons National Trauma Data Bank. INTERVENTIONS: Transport by helicopter or ground emergency services to level I or level II trauma centers. MAIN OUTCOME MEASURES: Survival to hospital discharge and discharge disposition. RESULTS: A total of 61,909 patients were transported by helicopter and 161,566 patients were transported by ground. Overall, 7813 patients (12.6%) transported by helicopter died compared with 17,775 patients (11%) transported by ground services. Before propensity score matching, patients transported by helicopter to level I and level II trauma centers had higher Injury Severity Scores. In the propensity score-matched multivariable regression model, for patients transported to level I trauma centers, helicopter transport was associated with an improved odds of survival compared with ground transport (odds ratio [OR], 1.16; 95% CI, 1.14-1.17; P < .001; absolute risk reduction [ARR], 1.5%). For patients transported to level II trauma centers, helicopter transport was associated with an improved odds of survival (OR, 1.15; 95% CI, 1.13-1.17; P < .001; ARR, 1.4%). A greater proportion (18.2%) of those transported to level I trauma centers by helicopter were discharged to rehabilitation compared with 12.7% transported by ground services (P < .001), and 9.3% transported by helicopter were discharged to intermediate facilities compared with 6.5% by ground services (P < .001). Fewer patients transported by helicopter left level II trauma centers against medical advice (0.5% vs 1.0%, P < .001). CONCLUSION: Among patients with major trauma admitted to level I or level II trauma centers, transport by helicopter compared with ground services was associated with improved survival to hospital discharge after controlling for multiple known confounders.

BACKGROUND: There is no standardized approach to comparing socioeconomic status (SES) across multiple sites in epidemiological studies. This is particularly problematic when cross-country comparisons are of interest. We sought to develop a simple measure of SES that would perform well across diverse, resource-limited settings. METHODS: A cross-sectional study was conducted with 800 children aged 24 to 60 months across eight resource-limited settings. Parents were asked to respond to a household SES questionnaire, and the height of each child was measured. A statistical analysis was done in two phases. First, the best approach for selecting and weighting household assets as a proxy for wealth was identified. We compared four approaches to measuring wealth: maternal education, principal components analysis, Multidimensional Poverty Index, and a novel variable selection approach based on the use of random forests. Second, the selected wealth measure was combined with other relevant variables to form a more complete measure of household SES. We used child height-for-age Z-score (HAZ) as the outcome of interest. RESULTS: Mean age of study children was 41 months, 52% were boys, and 42% were stunted. Using cross-validation, we found that random forests yielded the lowest prediction error when selecting assets as a measure of household wealth. The final SES index included access to improved water and sanitation, eight selected assets, maternal education, and household income (the WAMI index). A 25% difference in the WAMI index was positively associated with a difference of 0.38 standard deviations in HAZ (95% CI 0.22 to 0.55). CONCLUSIONS: Statistical learning methods such as random forests provide an alternative to principal components analysis in the development of SES scores. Results from this multicountry study demonstrate the validity of a simplified SES index. With further validation, this simplified index may provide a standard approach for SES adjustment across resource-limited settings.

Candida species are the predominant cause of fungal infections in patients treated in hospital, contributing substantially to morbidity and mortality. Candidaemia and other forms of invasive candidiasis primarily affect patients who are immunocompromised or critically ill. In contrast, mucocutaneous forms of candidiasis, such as oral thrush and vulvovaginal candidiasis, can occur in otherwise healthy individuals. Although mucocutaneous candidiasis is generally not life-threatening, it can cause considerable discomfort, recurrent infections, and complications, particularly in patients with underlying conditions such as diabetes or in those taking immunosuppressive therapies. The rise of difficult-to-treat Candida infections is driven by new host factors and antifungal resistance. Pathogens, such as Candida auris (Candidozyma auris) and fluconazole-resistant Candida parapsilosis, pose serious global health risks. Recent taxonomic revisions have reclassified several Candida spp, potentially causing confusion in clinical practice. Current management guidelines are limited in scope, with poor coverage of emerging pathogens and new treatment options. In this Review, we provide updated recommendations for managing Candida infections, with detailed evidence summaries available in the appendix.

BACKGROUND: Anxiety and depression contribute to poor disease outcomes among individuals with diabetes. This study aimed to assess the prevalence of anxiety and depression and to identify their associated factors including metabolic components among people with type 2 diabetes. METHODS: We conducted a cross-sectional, multi-center study in four out-patient clinics in Karachi, Pakistan. In all, 889 adults with type-2 diabetes were included in this study. Anxiety and depression were measured by using the Hospital Anxiety and Depression Scale (HADS). Multivariable analysis using multiple logistic regression was carried out to evaluate the combined effect of various factors associated with anxiety and depression, while adjusting for confounding variables. RESULTS: Overall, 57.9% (95% CI = 54.7%, 61.2%) and 43.5% (95% CI = 40.3%, 46.8%) study participants had anxiety and depression respectively. Factors found to be independently associated with anxiety were physical inactivity, having hypertension and ischemic heart disease. For depression, being female, of older age, having hypertension and ischemic heart disease were significantly associated. Metabolic components found to be independently associated with both anxiety and depression were systolic blood pressure, fasting blood glucose and fasting blood triglycerides. Body mass index was independently associated with depression but not with anxiety. CONCLUSION: This study identified that a large proportion of adults with diabetes had anxiety and/or depression, and identified factors associated with these entities. These results alert clinicians to identify and treat anxiety and depression as common components of diabetes care. Additional studies are needed to establish the directional nature of this relationship and to test interventions.

OBJECTIVE: To understand the rates, causes and risk factors for stillbirth in developing countries as well as the strategies that have been evaluated to reduce stillbirth. METHODS: We searched the English literature for 2003-2008 for all articles related to stillbirth and perinatal mortality in developing countries and reviewed all related publications. RESULTS: Despite the large number of stillbirths worldwide, the topic of stillbirths in developing countries has received very little research, programmatic or policy attention. In many developing countries, almost half of the deliveries occur at home, and under-reporting of stillbirths is a significant problem. Reliable data about rates and causes are unavailable in many areas of the world. Nevertheless, of the estimated 3.2 million stillbirths that occur yearly world-wide, the vast majority occur in developing countries. Rates in many developing countries are 10-fold greater or more than in developed countries. There is not a standard international classification system that defines cause of death, nor is there agreement about the lower limits of birthweight or gestational age that define stillbirth, making comparisons of causes of stillbirth or rates over time or between sites problematic. From available data, prolonged and obstructed labour, pre-eclampsia and various infections, all without adequate treatment, appear to account for the majority of stillbirths in developing countries. Identification and treatment of maternal syphilis has been effective in reducing stillbirth risk, as has improvements in access to emergency obstetrical services and particularly caesarean section. CONCLUSIONS: Further research is needed to understand the causes and the best preventive strategies for stillbirth specific to geographic areas. However, based on current data, better access to appropriate obstetric care, particularly during labour and delivery and better screening and treatment of syphilis should reduce developing country stillbirth rates dramatically.

BACKGROUND: Anemia affects almost two-thirds of pregnant women in developing countries and contributes to maternal morbidity and mortality and to low birthweight. OBJECTIVE: To determine the prevalence of anemia and the dietary and socioeconomic factors associated with anemia in pregnant women living in an urban community setting in Hyderabad, Pakistan. METHODS: This was a prospective, observational study of 1,369 pregnant women enrolled at 20 to 26 weeks of gestation and followed to 6 weeks postpartum. A blood sample was obtained at enrollment to determine hemoglobin levels. Information on nutritional knowledge, attitudes, and practice and dietary history regarding usual food intake before and during pregnancy were obtained by trained interviewers within 1 week of enrollment. RESULTS: The prevalence of anemia (defined by the World Health Organization as hemoglobin < 11.0 g/dL) in these subjects was 90.5%; of these, 75.0% had mild anemia (hemoglobin from 9.0 to 10.9 g/dL) and 14.8% had moderate anemia (hemoglobin from 7.0 to 8.9 g/dL). Only 0.7% were severely anemic (hemoglobin < 7.0 g/ dL). Nonanemic women were significantly taller, weighed more, and had a higher body mass index. Multivariate analysis after adjustment for education, pregnancy history, iron supplementation, and height showed that drinking more than three cups of tea per day before pregnancy (adjusted prevalence odds ratio [aPOR], 3.2; 95% confidence interval [CI], 1.3 to 8.0), consumption of clay or dirt during pregnancy (aPOR, 3.7; 95% CI, 1.1 to 12.3), and never consuming eggs or consuming eggs less than twice a week during pregnancy (aPOR, 1.7; 95% CI, 1.1 to 2.5) were significantly associated with anemia. Consumption of red meat less than twice a week prior to pregnancy was marginally associated with anemia (aPOR, 1.2; 95% CI, 0.8 to 1.8) but was significantly associated with lower mean hemoglobin concentrations (9.9 vs. 10.0 g/dL, p = .05) during the study period. A subanalysis excluding women with mild anemia found similar associations to those of the main model, albeit even stronger. CONCLUSIONS: A high percentage of women at 20 to 26 weeks of pregnancy had mild to moderate anemia. Pica, tea consumption, and low intake of eggs and red meat were associated with anemia. Women of childbearing age should be provided nutritional education regarding food sources of iron, especially prior to becoming pregnant, and taught how food choices can either enhance or interfere with iron absorption.

BACKGROUND: Because large, prospective, population-based data sets describing maternal outcomes are typically not available in low- and middle-income countries, it is difficult to monitor maternal mortality rates over time and to identify factors associated with maternal mortality. Early identification of risk factors is essential to develop comprehensive intervention strategies preventing pregnancy-related complications. Our objective was to describe maternal mortality rates in a large, multi-country dataset and to determine maternal, pregnancy-related, delivery and postpartum characteristics that are associated with maternal mortality. METHODS: We collected data describing all pregnancies from 2010 to 2013 among women enrolled in the multi-national Global Network for Women's and Children's Health Research Maternal and Neonatal Health Registry (MNHR). We reported the proportion of mothers who died per pregnancy and the maternal mortality ratio (MMR). Generalized linear models were used to evaluate the relationship of potential medical and social factors and maternal mortality and to develop point and interval estimates of relative risk associated with these factors. Generalized estimating equations were used to account for the correlation of outcomes within cluster to develop appropriate confidence intervals. RESULTS: We recorded 277,736 pregnancies and 402 maternal deaths for an MMR of 153/100,000 live births. We observed an improvement in the total MMR from 166 in 2010 to 126 in 2013. The MMR in Latin American sites (91) was lower than the MMR in Asian (178) and African sites (125). When adjusted for study site and the other variables, no formal education (RR 3.2 [1.5, 6.9]), primary education only (RR 3.4 [1.6, 7.5]), secondary education only (RR 2.5 [1.1, 5.7]), lack of antenatal care (RR 1.8 [1.2, 2.5]), caesarean section delivery (RR 1.9 [1.3, 2.8]), hemorrhage (RR 3.3 [2.2, 5.1]), and hypertensive disorders (RR 7.4 [5.2, 10.4]) were associated with higher risks of death. CONCLUSIONS: The MNHR identified preventable causes of maternal mortality in diverse settings in low- and middle-income countries. The MNHR can be used to monitor public health strategies and determine their association with reducing maternal mortality. TRIAL REGISTRATION: clinicaltrials.gov NCT01073475.

To determine the prevalence and routes of transmission of hepatitis C virus (HCV) infection in Hafizabad, Pakistan, we collected sera in 1993 from a geographically based random sample of residents, and in 1994 identified 15 HCV-infected individuals (cases) and 67 age and sex matched uninfected individuals (controls). Initially we approached 504 households, and collected serum from a randomly selected household member in 309 (64%). Twenty persons (6.5%) had anti-HCV antibody; 31% percent had hepatitis B core antibodies, and 4.3% had hepatitis B surface antigen. In the case-control study, persons who received more therapeutic injections (categorized as averaging 1, 2-4, 5-9 or > 10 injections per year in the previous 10 years) were more likely to be infected with HCV (odds ratio 0, 1.5, 2.5 and 6.9 respectively, P = 0.008) compared to persons averaging 0 injections per year. Efforts to limit therapeutic injections to only those that are medically indicated and that use sterile equipment are essential in order to prevent transmission of HCV.

BACKGROUND: Pakistan is a patriarchal society where men are the primary authority figures and women are subordinate. This has serious implications on women's and men's life prospects. OBJECTIVE: The aim was to explore current gender roles in urban Pakistan, how these are reproduced and maintained and influence men's and women's life circumstances. DESIGN: Five focus group discussions were conducted, including 28 women representing employed, unemployed, educated and uneducated women from different socio-economic strata. Manifest and latent content analyses were applied. FINDINGS: TWO MAJOR THEMES EMERGED DURING ANALYSIS: 'Reiteration of gender roles' and 'Agents of change'. The first theme included perceptions of traditional gender roles and how these preserve women's subordination. The power gradient, with men holding a superior position in relation to women, distinctive features in the culture and the role of the extended family were considered to interact to suppress women. The second theme included agents of change, where the role of education was prominent as well as the role of mass media. It was further emphasised that the younger generation was more positive to modernisation of gender roles than the elder generation. CONCLUSIONS: This study reveals serious gender inequalities and human rights violations against women in the Pakistani society. The unequal gender roles were perceived as static and enforced by structures imbedded in society. Women routinely faced serious restrictions and limitations of autonomy. However, attainment of higher levels of education especially not only for women but also for men was viewed as an agent towards change. Furthermore, mass media was perceived as having a positive role to play in supporting women's empowerment.

In tuberculosis, Mycobacterium tuberculosis (MTB)-stimulated T-cell responses are depressed transiently, whereas antibody levels are increased. Lymphoproliferative responses of peripheral blood mononuclear cells (PBMCs) from Pakistani tuberculosis (TB) patients to both mycobacterial and candidal antigens were suppressed by approximately 50% when compared to healthy purified protein derivative (PPD)-positive household contacts. Production of interferon gamma (IFN-gamma) in response to PPD also was depressed by 78%. Stimulation with PPD and the 30-kDa alpha antigen of MTB (30-kDa antigen) induced greater secretion of transforming growth factor beta (TGF-beta), but not interleukin 10 (IL-10) or tumor necrosis factor alpha (TNF-alpha), by PBMCs from TB patients compared to healthy contacts. The degree of suppression correlated with the duration of treatment; patients treated for <1 month had significantly lower T-cell blastogenesis and IFN-gamma production and higher levels of TGF-beta than did patients treated for >1 month. Neutralizing antibody to TGF-beta normalized lymphocyte proliferation in response to PPD, partially restored blastogenesis to candidal antigen, and significantly increased PPD-stimulated production of IFN-gamma in TB patients but not in contacts. Neutralizing antibody to IL-10 augmented, but did not normalize, T-cell responses to both PPD and candida in TB patients and candidal antigen in contacts. TGF-beta, produced in response to MTB antigens, therefore plays a prominent role in down-regulating potentially protective host effector mechanisms and looms as an important mediator of immunosuppression in TB.

Working in Afghanistan's capital city of Kabul, the authors assessed the relative contribution of daily stressors and war-related experiences of violence and loss to levels of depression, PTSD, impaired functioning, and a culturally specific measure of general psychological distress. For women, daily stressors were a better predictor than war experiences of all mental health outcomes except for PTSD; for men, daily stressors were a better predictor of depression and functional impairment, while war experiences and daily stressors were similarly predictive of general distress. For men, daily stressors moderated the relationship between war experiences and PTSD, which was significant only under conditions of low daily stress. The study's implications for research and intervention in conflict and post-conflict settings are considered.

Ginger (Zingiber officinale Roscoe), a well-known spice plant, has been used traditionally in a wide variety of ailments including hypertension. We report here the cardiovascular effects of ginger under controlled experimental conditions. The crude extract of ginger (Zo.Cr) induced a dose-dependent (0.3-3 mg/kg) fall in the arterial blood pressure of anesthetized rats. In guinea pig paired atria, Zo.Cr exhibited a cardiodepressant activity on the rate and force of spontaneous contractions. In rabbit thoracic aorta preparation, Zo.Cr relaxed the phenylephrine-induced vascular contraction at a dose 10 times higher than that required against K+ (80 mM)-induced contraction. Ca2+ channel-blocking (CCB) activity was confirmed when Zo.Cr shifted the Ca2+ dose-response curves to the right similar to the effect of verapamil. It also inhibited the phenylephrine (1 μM) control peaks in normal-Ca2+ and Ca2+-free solution, indicating that it acts at both the membrane-bound and the intracellular Ca2+ channels. When tested in endothelium-intact rat aorta, it again relaxed the K+-induced contraction at a dose 14 times less than that required for relaxing the PE-induced contraction. The vasodilator effect of Zo.Cr was endothelium-independent because it was not blocked by L-NAME (0.1 mM) or atropine (1 μM) and also was reproduced in the endothelium-denuded preparations at the same dose range. These data indicate that the blood pressure-lowering effect of ginger is mediated through blockade of voltage-dependent calcium channels.

BACKGROUND: Despite convincing evidence that lowering blood pressure decreases cardiovascular morbidity and mortality, the hypertension burden remains high and control rates are poor in developing countries. OBJECTIVE: To assess the effectiveness of 2 community-based interventions on blood pressure in hypertensive adults. DESIGN: Cluster randomized, 2 x 2 factorial, controlled trial. (ClinicalTrials.gov registration number: NCT00327574) SETTING: 12 randomly selected communities in Karachi, Pakistan. PATIENTS: 1341 patients 40 years or older with hypertension (systolic blood pressure >or=140 mm Hg, diastolic blood pressure >or=90 mm Hg, or already receiving treatment). MEASUREMENTS: Reduction in systolic blood pressure from baseline to end of follow-up at 2 years. INTERVENTION: Family-based home health education (HHE) from lay health workers every 3 months and annual training of general practitioners (GPs) in hypertension management. RESULTS: The age, sex, and baseline blood pressure-adjusted decrease in systolic blood pressure was significantly greater in the HHE and GP group (10.8 mm Hg [95% CI, 8.9 to 12.8 mm Hg]) than in the GP-only, HHE-only, or no intervention groups (5.8 mm Hg [CI, 3.9 to 7.7 mm Hg] in each; P < 0.001). The interaction between the main effects of GP training and HHE on the primary outcome approached significance (interaction P = 0.004 in intention-to-treat analysis and P = 0.044 in per-protocol analysis). LIMITATIONS: Follow-up blood pressure measurements were missing for 22% of patients. No mechanism was detected by which interventions lowered blood pressure. CONCLUSION: Family-based HHE delivered by trained lay health workers, coupled with educating GPs on hypertension, can lead to significant blood pressure reductions among patients with hypertension in Pakistan. Both strategies in combination may be feasible for upscaling within the existing health care systems of Indo-Asian countries. PRIMARY FUNDING SOURCE: Wellcome Trust.

BACKGROUND: The most common geriatric psychiatric disorder is depression. The role of family systems in depression among the elderly has not been studied extensively. It has been suggested that urbanization promotes nucleation of family systems and a decrease in care and support for the elderly. We conducted this study in Karachi, a large urban city of Pakistan, to determine the relationship between the type of family system and depression. We also determined the prevalence of depression in the elderly, as well as correlation of depression with other important socio-demographic variables. METHODS: A cross-sectional study was carried out in the premises of a tertiary care hospital in Karachi, Pakistan. Questionnaire based interviews were conducted among the elderly people visiting the hospital. Depression was assessed using the 15-item Geriatric Depression Scale. RESULTS: Four hundred subjects aged 65 and above were interviewed. The age of majority of the subjects ranged from 65 to 74 years. Seventy eight percent of the subjects were male. The prevalence of depression was found to be 19.8%. Multiple logistic regression analysis revealed that the following were significant (p < 0.05) independent predictors of depression: nuclear family system, female sex, being single or divorced/widowed, unemployment and having a low level of education. The elderly living in a nuclear family system were 4.3 times more likely to suffer from depression than those living in a joint family system (AOR = 4.3 [95% CI = 2.4-7.6]). CONCLUSION: The present study found that residing in a nuclear family system is a strong independent predictor of depression in the elderly. The prevalence of depression in the elderly population in our study was moderately high and a cause of concern. The transition in family systems towards nucleation may have a major deleterious effect on the physical and mental health of the elderly.