Assessment of pediatric surgical needs, health-seeking behaviors, and health systems in a rural district of Pakistan.

Surgical conditions are responsible for up to 15% of total Disability-Adjusted Life Years (DALY) lost globally. Approximately 4.8 billion people have no access to surgical care and this studies aim is to assess the surgical disease burden in children under the age of five years. We used Surgeons OverSeas Assessment of Surgical Need (SOSAS) and Pediatric Personnel, Infrastructure, Procedures, Equipment, and Supplies (PediPIPES) survey tools in Tando Mohammad Khan (TMK). A set of photographs of lesions were also taken for review by experts. All the data was recorded electronically via an android application. The current surgical need was defined as the caregiver's reported surgical problems in their children and the unmet surgical need was defined as a surgical problem for which the respondent did not access care. Descriptive analysis was performed. Information of 6,371 children was collected. The study identified 1,794 children with 3,072 surgical lesions. Categorization of the lesions by the six body regions suggested that head and neck accounted for the greatest number of lesions (55.2%) and the most significant unmet surgical need (16.6%). The chest region had the least unmet surgical need of 5.9%. A large percentage of the lesions were managed at a health care facility, but the treatment essentially consisted of mainly medical management (87%), and surgical treatment was provided for only 11% of lesions. The health facility assessment suggested that trained personnel including surgeons, anesthetic, or trained nurses were only available at one hospital. Basic procedures such as suturing and wound debridement were only performed frequently. This study suggests a high rate of unmet surgical need and a paucity of trained health staff and resources in this rural setting of Pakistan. The government needs to make policies and ensure funding so that proper trained staff and supplies can be ensured at district level.

Performance and Determinants of Serum Creatinine and Cystatin C-Based GFR Estimating Equations in South Asians.

INTRODUCTION: The creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rate (eGFR) equation was calibrated for the general Pakistan population (eGFRcr-PK) to eliminate bias and improve accuracy. Cystatin C-based CKD-EPI equations (eGFRcys and eGFRcr-cys) have not been assessed in this population, and non-GFR determinants of cystatin C are unknown. METHODS: We assessed eGFRcys, eGFRcr-cys, and non-GFR determinants of cystatin C in a cross-sectional study of 557 participants (≥40 years of age) from Pakistan. We compared bias (median difference in measured GFR [mGFR] and eGFR), precision (interquartile range [IQR] of differences), accuracy (percentage of eGFR within 30% of mGFR), root mean square error (RMSE), and classification of mGFR <60 ml/min/1.73 m2 (area under the receiver operating characteristic curve [AUC] and net reclassification index [NRI]) among eGFR equations. RESULTS: We found that eGFRcys underestimated mGFR (bias, 12.7 ml/min/1.73 m2 [95% confidence interval {CI} 10.7-15.2]). eGFRcr-cys did not improve performance over eGFRcr-PK in precision (P = 0.52), accuracy (P = 0.58), or RMSE (P = 0.49). Results were consistent among subgroups by age, sex, smoking, body mass index (BMI), and eGFR. NRI was 7.31% (95% CI 1.52%-13.1%; P < 0.001) for eGFRcr-cys versus eGFRcr-PK, but AUC was not improved (0.92 [95% CI 0.87-0.96] vs. 0.90 [95% CI 0.86-0.95]; P = 0.056). Non-GFR determinants of higher cystatin C included male sex, smoking, higher BMI and total body fat, and lower lean body mass. CONCLUSION: eGFRcys underestimated mGFR in South Asians and eGFRcr-cys did not offer substantial advantage compared with eGFRcr-PK. Future studies are warranted to better understand the large bias in eGFRcys and non-GFR determinants of cystatin C in South Asians.

Control of Blood Pressure and Risk Attenuation: Post Trial Follow-Up of Randomized Groups.

BACKGROUND: Evidence on long term effectiveness of public health strategies for lowering blood pressure (BP) is scarce. In the Control of Blood Pressure and Risk Attenuation (COBRA) Trial, a 2 x 2 factorial, cluster randomized controlled trial, the combined home health education (HHE) and trained general practitioner (GP) intervention delivered over 2 years was more effective than no intervention (usual care) in lowering systolic BP among adults with hypertension in urban Pakistan. However, it was not clear whether the effect would be sustained after the cessation of intervention. We conducted 7 years follow-up inclusive of 5 years of post intervention period of COBRA trial participants to assess the effectiveness of the interventions on BP during extended follow-up. METHODS: A total of 1341 individuals 40 years or older with hypertension (systolic BP 140 mm Hg or greater, diastolic BP 90 mm Hg or greater, or already receiving treatment) were followed by trained research staff masked to randomization status. BP was measured thrice with a calibrated automated device (Omron HEM-737 IntelliSense) in the sitting position after 5 minutes of rest. BP measurements were repeated after two weeks. Generalized estimating equations (GEE) were used to analyze the primary outcome of change in systolic BP from baseline to 7- year follow-up. The multivariable model was adjusted for clustering, age at baseline, sex, baseline systolic and diastolic BP, and presence of diabetes. FINDINGS: After 7 years of follow-up, systolic BP levels among those randomised to combined HHE plus trained GP intervention were significantly lower (2.1 [4.1-0.1] mm Hg) compared to those randomised to usual care, (P = 0.04). Participants receiving the combined intervention compared to usual care had a greater reduction in LDL-cholesterol (2.7 [4.8 to 0.6] mg/dl. CONCLUSIONS: The benefit in systolic BP reduction observed in the original cohort assigned to the combined intervention was attenuated but still evident at 7- year follow-up. These findings highlight the potential for scaling-up simple strategies for cardiovascular risk reduction in low- and middle- income countries. TRIAL REGISTRATION: ClinicalTrials.gov NCT00327574.

Prevalence, determinants, and management of chronic kidney disease in Karachi, Pakistan - a community based cross-sectional study.

BACKGROUND: Chronic kidney disease (CKD) is increasing being recognized as a global public health problem. However, there is dearth of information on the prevalence, determinants, and management of CKD from low- and middle-income countries. The objectives of the study were to determine the 1) prevalence of CKD; 2) socio-demographic and clinical factors associated with CKD; and 3) the existing management of these patients with regards to blood pressure control, and use of antihypertensive medications. METHODS: We conducted a cross-sectional study on 2873 participants aged ≥ 40 years in 12 representative communities in Karachi, Pakistan. The primary outcome was clinically significant CKD defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 estimated by CKD-EPI (CKD Epidemiology Collaboration) Pakistan equation (0.686 × CKD-EPI1.059) or urinary albumin to creatinine ratio ≥ 3 mg/mmol (i.e. KDOQI CKD stage G3, A2 or worse). RESULTS: The overall prevalence (95% CI) of CKD was 12.5% (11.4 - 13.8%). The factors independently associated with CKD were older age, hypertension, diabetes, elevated systolic blood pressure, raised fasting plasma glucose, raised triglycerides, and history of stroke (p<0.05 for each). About 267 (74.4%, 69.5 - 78.8%) adults with CKD had concomitant hypertension. Of these, 130 (48.7%, 42.6 - 54.9%) were on antihypertensive medications, and less than 20% had their BP controlled to conventional target of ≤ 140/90 mm Hg, and only 16.9% (12.6 - 21.9%) were on blockers of renin-angiotensin system alone or in combination with other drugs. CONCLUSIONS: Clinically significant CKD is common among Pakistani adults. The conventional risk factors for CKD and poor control of blood pressure among patients with CKD highlight the need to integrate CKD prevention and management in the primary care infrastructure in Pakistan, and possibly neighbouring countries.

Association of parental blood pressure with retinal microcirculatory abnormalities indicative of endothelial dysfunction in children.

OBJECTIVE: Microcirculatory abnormalities precede the onset of hypertension and may explain its familial nature. We examined the relationship between parental blood pressure (BP) and offspring retinal microvasculature in Pakistani trios [father, mother, and child (aged 9-14 years)]. METHODS: This is a substudy of a population-based trial of BP reduction. Data were available on 358 normotensive, and 410 offspring of at least one hypertensive parent. Retinal vessel characteristics were measured from digital images. Multivariable linear regression models were built to assess the associations between maternal and paternal BP and offspring retinal microvasculature. RESULTS: Optimality deviation was greatest in offspring of two hypertensive parents, compared with those with one or no hypertensive parent (P=0.030 for trend). Paternal SBP and DBP were each significantly associated with optimality deviation in offspring (P=0.023 and P=0.006, respectively). This relationship persisted after accounting for offspring cardiovascular risk factors [increase in optimality deviation (95% confidence interval, CI) 0.0053 (0.0001-0.0106, P=0.047) and 0.0109 (0.0025-0.0193, P=0.011), for each 10 mmHg increase in paternal SBP and DBP, respectively]. Maternal DBP was inversely associated with offspring arteriovenous ratio -0.0102 (-0.0198 to -0.0007, P=0.035). CONCLUSION: Microvascular endothelial dysfunction in children is associated with increasing levels of parental hypertension. The association with paternal BP is independent of other cardiovascular risk factors, including the child's BP. Higher maternal DBP is associated with evidence of arteriolar narrowing in offspring. These early microcirculatory changes may help explain familial predisposition to hypertension in people of Pakistani origin at an early age. VIDEO ABSTRACT: :

Estimation of GFR in South Asians: a study from the general population in Pakistan.

BACKGROUND: South Asians are at high risk for chronic kidney disease. However, unlike those in the United States and United Kingdom, laboratories in South Asian countries do not routinely report estimated glomerular filtration rate (eGFR) when serum creatinine is measured. The objectives of the study were to: (1) evaluate the performance of existing GFR estimating equations in South Asians, and (2) modify the existing equations or develop a new equation for use in this population. STUDY DESIGN: Cross-sectional population-based study. SETTING & PARTICIPANTS: 581 participants 40 years or older were enrolled from 10 randomly selected communities and renal clinics in Karachi. PREDICTORS: eGFR, age, sex, serum creatinine level. OUTCOMES: Bias (the median difference between measured GFR [mGFR] and eGFR), precision (the IQR of the difference), accuracy (P30; percentage of participants with eGFR within 30% of mGFR), and the root mean squared error reported as cross-validated estimates along with bootstrapped 95% CIs based on 1,000 replications. RESULTS: The CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation performed better than the MDRD (Modification of Diet in Renal Disease) Study equation in terms of greater accuracy at P30 (76.1% [95% CI, 72.7%-79.5%] vs 68.0% [95% CI, 64.3%-71.7%]; P < 0.001) and improved precision (IQR, 22.6 [95% CI, 19.9-25.3] vs 28.6 [95% CI, 25.8-31.5] mL/min/1.73 m(2); P < 0.001). However, both equations overestimated mGFR. Applying modification factors for slope and intercept to the CKD-EPI equation to create a CKD-EPI Pakistan equation (such that eGFRCKD-EPI(PK) = 0.686 × eGFRCKD-EPI(1.059)) in order to eliminate bias improved accuracy (P30, 81.6% [95% CI, 78.4%-84.8%]; P < 0.001) comparably to new estimating equations developed using creatinine level and additional variables. LIMITATIONS: Lack of external validation data set and few participants with low GFR. CONCLUSIONS: The CKD-EPI creatinine equation is more accurate and precise than the MDRD Study equation in estimating GFR in a South Asian population in Karachi. The CKD-EPI Pakistan equation further improves the performance of the CKD-EPI equation in South Asians and could be used for eGFR reporting.

Cost-effectiveness of community-based strategies for blood pressure control in a low-income developing country: findings from a cluster-randomized, factorial-controlled trial.

BACKGROUND: Evidence on economically efficient strategies to lower blood pressure (BP) from low- and middle-income countries remains scarce. The Control of Blood Pressure and Risk Attenuation (COBRA) trial randomized 1341 hypertensive subjects in 12 randomly selected communities in Karachi, Pakistan, to 3 intervention programs: (1) combined home health education (HHE) plus trained general practitioner (GP); (2) HHE only; and (3) trained GP only. The comparator was no intervention (or usual care). The reduction in BP was most pronounced in the combined group. The present study examined the cost-effectiveness of these strategies. METHODS AND RESULTS: Total costs were assessed at baseline and 2 years to estimate incremental cost-effectiveness ratios based on (1) intervention cost; (2) cost of physician consultation, medications, diagnostics, changes in lifestyle, and productivity loss; and (3) change in systolic BP. Precision of the incremental cost-effectiveness ratio estimates was assessed by 1000 bootstrapping replications. Bayesian probabilistic sensitivity analysis was also performed. The annual costs per participant associated with the combined HHE plus trained GP, HHE alone, and trained GP alone were $3.99, $3.34, and $0.65, respectively. HHE plus trained GP was the most cost-effective intervention, with an incremental cost-effectiveness ratio of $23 (95 confidence interval, 6-99) per mm Hg reduction in systolic BP compared with usual care, and remained so in 97.7 of 1000 bootstrapped replications. CONCLUSIONS: The combined intervention of HHE plus trained GP is potentially affordable and more cost-effective for BP control than usual care or either strategy alone in some communities in Pakistan, and possibly other countries in Indochina with similar healthcare infrastructure.

Level and determinants of kidney function in a South Asian population in Pakistan.

BACKGROUND: People of South Asian origin are at high risk of chronic kidney disease. Some have suggested that the usual level of glomerular filtration rate (GFR) in South Asians may be lower than in populations of European origin. However, measured GFR in a general adult population of South Asian origin has not been studied. DESIGN: Cross-sectional observational study. SETTING & PARTICIPANTS: 530 patients 40 years or older randomly selected from communities in Karachi, Pakistan, using multistage cluster sampling. Patients with both diabetes and hypertension were excluded. PREDICTOR: Age, sex, diabetes, and hypertension. OUTCOME: Measured GFR using urinary clearance of inulin. RESULTS: Mean age of participants was 49.7 ± 9.5 (standard deviation [SD]) years, 51% were men, 34.9% had hypertension, and 30.5% had diabetes. Mean measured GFR was 94.1 ± 28.6 mL/min/1.73 m(2). GFR was lower by 0.79 ± 0.11 mL/min/1.73 m(2) for each 1-year older age. The 5-year age- and sex-specific mean GFR of the study population generally was within 1 SD of the mean of previously reported values for US adults. Factors independently associated with GFR were younger age (ß coefficient, -3.84 [95% CI, -5.46 to -2.21] mL/min/1.73 m(2) per 5 years older), higher serum albumin level (4.58 [95% CI, 0.74-8.42] mL/min/1.73 m(2) per 0.5-g/dL increase), higher fasting plasma glucose level (0.81 [95% CI, 0.44-1.18] mL/min/1.73 m(2) per 10-mg/dL increase), high versus low meat intake (7.81 [95% CI, 1.14-14.48] mL/min/1.73 m(2) for ≥11 vs ≤5 servings/wk), and higher estimated protein intake (1.46 [95% CI, 0.41-2.51] mL/min/1.73 m(2) per 1.0-g/d increase) from urine urea nitrogen. LIMITATIONS: Moderate sample size, lack of validation of some items in the dietary assessment for this study population. CONCLUSIONS: Mean measured GFR in South Asian adults from the general population in Karachi, Pakistan, is only modestly lower than in European-origin counterparts, with similar age association. This may reflect lower dietary protein intake in South Asians.

Community based lifestyle intervention for blood pressure reduction in children and young adults in developing country: cluster randomised controlled trial.

OBJECTIVE: To assess the effectiveness of a community based lifestyle intervention on blood pressure in children and young adults in a developing country setting. DESIGN: Cluster randomised controlled trial. SETTING: 12 randomly selected geographical census based clusters in Karachi, Pakistan. PARTICIPANTS: 4023 people aged 5-39 years. INTERVENTION: Three monthly family based home health education delivered by lay health workers. MAIN OUTCOME MEASURE: Change in blood pressure from randomisation to end of follow-up at 2 years. RESULTS: Analysed using the intention to treat principle, the change in systolic blood pressure (adjusted for age, sex, and baseline blood pressure) was significant; it increased by 1.5 (95% confidence interval 1.1 to 1.9) mm Hg in the control group and by 0.1 (-0.3 to 0.5) mm Hg in the home health education group (P for difference between groups=0.02). Findings for diastolic blood pressure were similar; the change was 1.5 mm Hg greater in the control group than in the intervention group (P=0.002). CONCLUSIONS: Simple, family based home health education delivered by trained lay health workers significantly ameliorated the usual increase in blood pressure with age in children and young adults in the general population of Pakistan, a low income developing country. This strategy is potentially feasible for up-scaling within the existing healthcare systems of Indo-Asia. TRIAL REGISTRATION: Clinical trials NCT00327574.

Community-based interventions to promote blood pressure control in a developing country: a cluster randomized trial.

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.

Life style related risk factors for cardiovascular disease among patients at a teaching hospital in Karachi.

BACKGROUND: Cardiovascular disease is a leading cause for morbidity and mortality all over the world. It is important to study life style related, modifiable cardiovascular risk factors among patients, in order to devise preventive strategies. METHODS: We surveyed family practice patients visiting the out-patient clinics of Aga Khan University Hospital, Karachi. The interview was questionnaire-based and recorded the demographic profile of the patients, in addition to information on life style related cardiovascular risk factors. The ethical requirements for the study were met. SPSS computer software was used for data management. RESULTS: Fifty patients were surveyed and included 28 (56%) men and 22 (44%) women. Thirty seven (74%) respondents were married, nineteen (38%) had graduate education, twenty five (50%) were in private service, and twelve (24%) were housewives. Twenty six (52%) respondents were overweight or obese. Butter, cream, margarine and red meat was consumed by 17 (34%) and 32 (64%) respondents respectively. White meat, fresh fruits and vegetables were consumed by 30 (60%), 29 (58%) and 38 (76%) respondents respectively. Oil from vegetable sources was used by 49 (98%) respondents. Addition of table salt was found occasionally and always in 18 (36%) and 09 (18%) respondents respectively. Twenty seven (54%) respondents exercised at least twenty minutes, three times a week, while eleven (22%) were current smokers. CONCLUSIONS: Life style related modifiable risk factors are prevalent in patients reporting to our hospital. This offers an opportunity for preventive strategies, to prevent cardiovascular disease. Such surveys, followed by interventional strategies, are recommended to be followed by all Primary care facilities.