Global primary care research challenges

Healthcare needs are changing globally as people live longer, but not necessarily in better health. Increased population migration is leading to culturally diverse patient populations with more diverse health needs and expectations. The provision of accessible and equitable primary care poses workforce, infrastructure and management challenges for high- and lower-middle income countries that transcend national borders. In this special issue, we describe ‘global primary care’ as primary care training, research and service delivery that places a priority on the needs and overall health of individuals and their communities, to advance health equity worldwide. Given this nascent definition, what should ‘global primary care research’ look like? The following case demonstrates the breadth of physical, mental, and social issues a primary care practitioner must consider when faced with a patient from a marginalised group in an inner-city practice and why training and research must have a focus on equity

Validation Study of the Mini-Mental State Examination in Urdu Language for Pakistani Population

Validation study of the Mini-Mental State Examination in Urdu language for Pakistani population. Objective: This study was conducted primarily to validate and determine the optimal cutoff score in the diagnosis of dementia among Pakistani’s and study the effects of gender and education on the MMSE performance in our population. Methods: Four hundred participants took part in the study. Patient with dementia recruited from five major hospitals from Pakistan. The MMSE was translated into Urdu. Results: There were 61 men and 39 women in dementia group and 225 men and 75 women in the control group. The mean score of Urdu MMSE were lower in patients with dementia 18.5 ± 5.6 (range 0-30) as compared to the controls 26.8 ± 2.6 (range 7-30). This difference between groups was statistically significant (p\u3c0.001). Educational based MMSE score below 15 yielded perfect sensitivity and specificity for the diagnosis of dementia. Conclusions: These finding confirm the influence of level of education on MMSE score and education stratified cutoff scores should be used while screening for cognitive impairment in this population

Validation Study of the Mini-Mental State Examination in Urdu Language for Pakistani Population

Validation study of the Mini-Mental State Examination in Urdu language for Pakistani population. Objective: This study was conducted primarily to validate and determine the optimal cutoff score in the diagnosis of dementia among Pakistani’s and study the effects of gender and education on the MMSE performance in our population. Methods: Four hundred participants took part in the study. Patient with dementia recruited from five major hospitals from Pakistan. The MMSE was translated into Urdu. Results: There were 61 men and 39 women in dementia group and 225 men and 75 women in the control group. The mean score of Urdu MMSE were lower in patients with dementia 18.5 ± 5.6 (range 0-30) as compared to the controls 26.8 ± 2.6 (range 7-30). This difference between groups was statistically significant (p\u3c0.001). Educational based MMSE score below 15 yielded perfect sensitivity and specificity for the diagnosis of dementia. Conclusions: These finding confirm the influence of level of education on MMSE score and education stratified cutoff scores should be used while screening for cognitive impairment in this population

Range for Normal Body Temperature in Hemodialysis Patients and Its Comparison with That of Healthy Individuals

Background/Aims: Patients with chronic kidney disease undergoing hemodialysis have an altered homeostasis leading to altered body temperatures. We aimed to determine the range for normal body temperature in hemodialysis Patients and compared it to healthy individuals. Also, we determined how much axillary temperatures differed from oral temperatures in both groups and whether axillary temperature is affected by the presence of an arteriovenous fistula (AVF) in hemodialysis Patients. Methods: Oral and axillary (left & right) temperatures were recorded using an ordinary mercury-in-glass thermometer in 400 subjects (200 hemodialysis Patients, 200 healthy individuals) at the Sindh Institute of Urology and Transplantation from mid-May to mid-June 2006. Comparisons were made between the temperatures of both groups. Results: Mean oral temperature in hemodialysis Patients was higher than in healthy individuals [98.7 degrees F (37 degrees C) vs. 98.4 degrees F (36.8 degrees C), p \u3c 0.001], as was the mean average axillary temperature [97.7 degrees F (36.5 degrees C) vs. 97.5 degrees F (36.3 degrees C), p = 0.02] and mean left axillary temperature [97.9 degrees F (36.6 degrees C) vs. 97.6 degrees F (36.4 degrees C), p \u3c 0.001]. The fistula arm had higher axillary temperature in 77 (44%) hemodialysis Patients. The difference between oral and axillary temperatures varied widely, making it impossible to obtain an accurate correction factor in both groups. Conclusion: Hemodialysis Patients have higher normal body temperatures than healthy individuals. Axillary temperatures require cautious interpretation. In hemodialysis Patients, the non-fistula arm should be preferred for recording axillary temperatures, as the presence of AVF may cause discrepancies in temperature measurements

Quality of life in individuals surgically treated for congenital hydrocephalus during infancy: A single-institution experience

Background: Congenital hydrocephalus (CH) is a frequently encountered birth anomaly that can hinder long-term neurologic maturity and social well-being of affected children. This study was undertaken to assess quality of life (QOL) 10-15 years after surgical treatment for primary CH during infancy at a tertiary care hospital in a developing country.Methods: This retrospective cohort study included individuals who presented to Aga Khan University Hospital, Karachi, Pakistan, between 1995 and 2005 at QOL.Results: Of 118 patients, 90 patients participated in the study. Mean age at first admission was 6.2 months. Mean length of follow-up was 5.4 years. Of these, 28 patients had died after surgery. Shunt infection (P = 0.012) and delayed milestones (P = 0.003) were found to be statistically significant factors affecting mortality in the patients who died. The mean overall health score was 0.67 ± 0.30. Age (P = 0.039).Conclusions: In our analysis, we assessed the QOL associated with CH. We hope that these results will provide insight for future prospective work with the ultimate goal of improving long-term QOL in children with CH

ADIPONECTIN VERSUS THIAZOLIDINEDIONES AND ANGIOTENSIN RECEPTOR BLOCKERS

Adipose tissue has gained great attention during the last decade. It represents not only a depot for energy stores, but also releases adipocytokines regulating energy disposal and can therefore be considered from therapeutic point of view. Hypoadiponectemia is an independent threat for development of metabolic syndrome. When subjects treated with antidiabetic (Thiazolidinediones) and antihypertensive (angiotensin receptor blocker) agents , the plasma concentration of adiponectin, the only component of adipocytokines, directly proportional to plasma values of these drugs. The prevalance of hypertension and T2DM is mounting with unprecedented degree in both developing and advanced countries, therefore, there is a dire need to find safer and economical therapeutic regimes for the treatment of these ailments, and intensive research is also underway for this purpose. PPARγ serves as a common link in the actions of ADN, TZDs and ARBs when exerting their effects, and it is responsible for stimulation of adiponectin receptors, thus ultimately enhancing the levels of adiponectin in plasma. This review aims to elucidate the role, link and use of ARBs, ADN and TZDs as a safer and convenient approach for the treatment of these co-morbidities as a unanimous or single remedy from comparative point of view

TREATMENT OF BOVINE SCHISTOSOMIASIS WITH MEDICINAL PLANT VERONIA ANTHELMINTICA (KALIZIRI), AN ALTERNATIVE APPROACH

Background: Veronia anthelmintica (Kaliziri) is a medicinally very important plant as being reported for remarkable therapeutic potential. The present research evaluates its antischistosomal activity. Methods and Materials: 54 buffaloes naturally infected with Schistosomiasis were used for anthelmintic trails. All animals for the study were tagged so as to distinguish from others. The animals were checked up on routine basis by a veterinary doctor. Preparation of samples of herbal drug and experiment was design according to available literature. Results: During present studies, buffalos naturally infected with Schistosomiasis were treated with Veronia anthelmintica (Kaliziri), with dose 75 mg/kg, 150 mg/kg and 225 mg/kg body weight respectively, and their impact on various parameters like eggs reduction, milk production, weight gain and feed intake was noted. Furthermore, their efficiency (%) was compared with standard drug “Praziquantel” (allopathic drug) at “10mg/Kg” body weight dose level. The effectiveness (%) of “Praziquantel” was noted as hundred after first dose, while the effectiveness for the herbal drug get to this level after injecting of second dose of “225mg/kg body weight”. Statistically significant (

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

Pro-renin receptor suppresses mitochondrial biogenesis and function via AMPK/SIRT-1/ PGC-1α pathway in diabetic kidney.

Abnormal mitochondrial biogenesis and function has been linked to multiple diseases including diabetes. Recently, we demonstrated the role of renal (Pro)renin receptor (PRR) in the dysregulation of mitochondria. We hypothesized that PRR contributes to the reduction of mitochondrial biogenesis and function in diabetic kidney via PGC-1α/AMPK/SIRT-1 signaling pathway. In vivo and in vitro studies were conducted in C57BL/6 mouse and mouse renal mesangial cells (mRMCs). Control and streptozotocin-induced diabetic mice were injected with scramble or PRR shRNA and followed for a period of eight weeks. PRR mRNA and protein expression increased by 44% and 39% respectively (P<0.05) in kidneys of diabetic mice, and in mRMCs exposed to high glucose by 43 and 61% respectively compared to their respective controls. These results were accompanied by reduced mRNA and protein expressions of PGC-1α (67% and 75%), nuclear respiratory factors (NRF-1, 48% and 53%), mitochondrial transcriptional factor A (mtTFA, 56% and 40%), mitochondrial DNA copy number by 75% (all, P<0.05), and ATP production by 54%, respectively in diabetic kidneys and in mRMCs exposed to high glucose. Compared to non-diabetic control mice, PRR knockdown in diabetic mice and in mRMCs, not only attenuated the PRR mRNA and protein expression but also normalized mRNA and protein expressions of PGC-1α, NRF-1, mtTFA, mitochondrial DNA copy number, and ATP production. Treatment with AMPK inhibitor, Compound C, or SIRT-1 inhibitor, EX-527, alone, or combined with PRR siRNA caused marked reduction of mRNA expression of PGC-1α, NRF-1 and mtTFA, and ATP production in mRMCs exposed to high glucose. In conclusion, our study demonstrated the contribution of the PRR to the reduction of mitochondrial biogenesis and function in diabetic kidney disease via decreasing AMPK/SIRT-1/ PGC-1α signaling pathway