Highlights of Cardiovascular Disease Prevention Studies Presented at the 2024 American College of Cardiology Conference.

PURPOSE OF REVIEW: To summarize selected late-breaking science on cardiovascular (CV) disease prevention presented at the 2024 Scientific Session of the American College of Cardiology (ACC) conference. RECENT FINDINGS: The LIBerate-HR trial showed the efficacy and safety of lerodalcibep, a subcutaneous injection that prevents binding of Pro-Protein Convertase Subtilisin/Kexin (PCSK) 9 to low-density lipoprotein (LDL)-receptors resulting in LDL-cholesterol (LDL-C) lowering in patients at very high risk or high risk of atherosclerotic CV disease (ASCVD). The AEGIS-II randomized patients with type 1 myocardial infarction (MI) with multivessel coronary artery disease and additional CV risk factors and found no benefit in major adverse CV events (MACE) with CSL112, an apolipoprotein A1 infusion shown to increase cholesterol efflux capacity. The Bridge-TIMI 73a trial showed a significant reduction in triglyceride (TG) levels with olezarsen, an antisense mRNA, in patients with moderate hyperTG with elevated CV risk. The BE ACTIVE trial showed significant improvement in step counts in patients given behavioral and financial incentives. The DRIVE study showed a significant increase in the prescription of either sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus (T2DM) at elevated CV or renal risk with a remote team-based, non-licensed navigator and clinical pharmacist approach. The TACTiC trial showed increased and sustained use of statin therapy by patient-driven use of a web-based portal that calculated the ASCVD risk score and gave prompts. The VICTORIAN-INITIATE trial showed efficacy and safety in early use of inclisiran in patients with ASCVD who did not reach target LDL-C < 70 mg/dL despite maximally tolerated statin therapy. The ARISE-HF trial showed no difference in change of peak oxygen consumption with the use of an oral aldose reductase inhibitor, AT-001, in patients with well-controlled T2DM and diabetic cardiomyopathy with high-risk features compared to placebo. The PREVENT trial showed a significant reduction in target vessel failure at 2 years in patients with non-flow limiting vulnerable plaques with percutaneous coronary intervention and optimal medical therapy (OMT) compared to OMT alone. The late-breaking clinical science presented at the 2024 Scientific Session of the ACC paves the way for an evidence-based alternative to statin therapy and provides data on several common clinical scenarios encountered in daily practice.

Highlights of Cardiovascular Disease Prevention Studies Presented at the 2023 American Heart Association Scientific Sessions.

PURPOSE OF REVIEW: Focused review highlighting ten select studies presented at the 2023 American Heart Association (AHA) Scientific Sessions. RECENT FINDINGS: Included studies assessed semaglutide and cardiovascular outcomes in overweight or obese patients without diabetes (SELECT); dapagliflozin in patients with acute myocardial infarction without diabetes (DAPA-MI); effects of dietary sodium on systolic blood pressure in middle-aged individuals (CARDIA-SSBP); long-term blood pressure control after hypertensive pregnancy with physician guided self-management (POP-HT); effect and safety of zilebesiran, an RNA interference therapy, for sustained blood pressure reduction (KARDIA-1); recaticimab add-on therapy in patients with non-familial hypercholesterolemia and mixed hyperlipidemia (REMAIN-2); efficacy and safety of lepodisiran an extended duration short-interfering RNA targeting lipoprotein(a); safety and pharmacodynamic effects of an investigational DNA base editing medicine that inactivates the PCSK9 gene and lowers LDL cholesterol (VERVE-101); automated referral to centralized pharmacy services for evidence-based statin initiation in high-risk patients; and effects of intensive blood pressure lowering in reducing risk of cardiovascular events (ESPRIT). Research presented at the 2023 AHA Scientific Sessions emphasized innovative strategies in cardiovascular disease prevention and management.

Presentation, management, and early outcomes of young acute coronary syndrome patients- analysis of 23,560 South Asian patients from 2012 to 2021.

BACKGROUND: There is dearth of literature addressing early outcomes of acute coronary syndrome (ACS) among young patients, particularly South Asians descent who are predisposed to premature coronary artery disease (CAD). Therefore, we compared presentation, management, and early outcomes of young vs. old ACS patients and explored predictors of in-hospital mortality. METHODS: We extracted data of 23,560 ACS patients who presented at Tabba Heart Institute, Karachi, Pakistan, from July 2012-June 2020, from the Chest pain-MI-Registry™. We categorized data into young ≤ 45 and old ACS patients > 45 years. Chi-sq/Fischer exact tests were used to assess the difference between presentation, disease management, and in-hospital mortality between both groups. Logistic regression was used to determine odds ratio along with 95% confidence interval of factors associated with early mortality. RESULTS: The younger patients were 12.2% and women 23.5%. The prevalence of dyslipidemia (34.5% vs. 22.4%), diabetes (52.1% vs. 27.4%), and hypertension (68.3% vs. 42.9%) was higher in older patients. Family history of premature CAD (18.1% vs. 32.7%), smoking (40.0% vs. 22.9%), and smokeless tobacco use (6.5% vs. 8.4%) were lower in older patients compared to younger ones. Younger patients were more likely to present with STEMI (33.2% vs. 45%). The median symptom-to-door time was 125 min longer (p-value < 0.01) in the young patients compared to the older age group. In-hospital mortality (4.3% vs. 1.7%), cardiac arrest (1.9% vs. 0.7%), cardiogenic shock (1.9% vs. 0.9%), and heart failure (1% vs. 0.6%) were more common in older patients. After adjusting for other factors, younger age (AOR 0.6, 95% CI 1.5-3.7) had significantly lesser odds of in-hospital mortality. Other factors associated with early mortality included women, family history of premature CAD, STEMI, Killip class III and IV, coronary angiography, revascularization, CABG, and use of aspirin and beta blockers within the first 24 h. CONCLUSION: We found every tenth ACS patient was younger than 45 years of age despite a lesser number of comorbidities such as hypertension and diabetes. Overall, the in-hospital prognosis of young patients was more favorable than that of older patients. The study emphasizes the need for tailored primary prevention programs for ACS, considering the varying risks among different age groups.

"If the food is finished after my brother eats then we (girls) sleep hungry." Food insecurity and dietary diversity among slum-dwelling adolescent girls and boys in Pakistan: A mixed methods study.

To explore gender differences in food insecurity (FI) and minimum dietary diversity (MDD) among adolescent girls and boys in a slum community in Karachi, we employed an explanatory sequential mixed methods study that included a survey of 391 girls and boys of 10-19 years of age and followed by semi-structured interviews of eight purposely selected food insecure adolescents. Survey data was analyzed by Cox proportional algorithm and adjusted prevalence ratios (APR) with 95% confidence intervals (CI) were estimated for associated factors of FI and thematic analysis was undertaken for qualitative work. Meta inferences for mixed methods study were drawn by joint display analysis of survey results juxtaposed to qualitative findings. Overall, FI among adolescents was prevalent (46.5%) which was not different between boys (52.7%) and girls (47.3%) (APR 0.8, (95% CI 0.6, 1.2); p-value-0.4). MDD (5/10 food groups consumed) was achieved by only 23.0% and it was also not different between boys (25.1%) and girls (20.9%) (p-value-0.3). The survey found no significant difference in FI and MDD between boys and girls however, qualitative findings provided insight into the cultural practices at mealtimes that prefer boys. Qualitative results contrasted the survey results and revealed the increased vulnerability of girls towards FI and low MDD compared to boys due to gender norms.

Evaluating the efficacy and safety of empagliflozin addition to insulin and oral antidiabetic medication (OAD) regimen in poorly controlled type 2 diabetes and obese patients.

Insulin resistance complicates diabetes care. Its effectiveness and tolerability as an addition to metformin, DPP4 inhibitor and insulin treatment in type 2 diabetic patients will be examined in this research. Participants with type 2 diabetes from poor socio-economic backgrounds had HbA1c values ≥8.5% when using Insulin+Metformin+DPP-4 inhibitors. They received 10mg Empagliflozin daily for 12 weeks (n=143). The main outcome was change in HbA1c at 12th week from baseline. Secondary outcomes were baseline weight and week 12 FPG. Adjusted mean (SE) HbA1c increases at week 12 were: Mean ± SD 10.38 (6.8-17.0) vs. Mean±SD 9.05±1.77 (5.60-16.0) with empagliflozin 10mg. When added to the regimen, empagliflozin significantly reduced FPG, systolic and diastolic blood pressure. The mean (SE) BMI increases from baseline were 31.28±5.89 (16.0-66.0) and 29.73±5.47 (3.0-46.0) with 10mg empagliflozin. Two individuals experienced urinary tract infections as AEs, but no genital infections. Adding empagliflozin 10mg daily to metformin+DPP4 inhibitor+insulin improved glycemic control, body weight and blood pressure for 12 weeks. The intervention was well-tolerated, highlighting empagliflozin's therapeutic potential.

Highlights of Cardiovascular Disease Prevention Studies Presented at the 2023 European Society of Cardiology Congress.

PURPOSE OF REVIEW: To summarize selected late-breaking science on cardiovascular (CV) disease prevention presented at the 2023 European Society of Cardiology (ESC) congress. RECENT FINDINGS: The NATURE-PARADOX was a naturally randomized trial that used genetic data from the UK Biobank registry to create "cumulative exposure to low-density lipoprotein-cholesterol (LDL-C)" biomarker and evaluate its association with major CV events regardless of plasma LDL-C levels or age. Safety and efficacy data of inclisiran, a PCSK9-interfering mRNA (PCSK9i) administered subcutaneously twice annually, were presented. Data on two new PCSK9is were presented, recaticimab, an oral drug, and lerodalcibep, a subcutaneous drug with a slightly different architecture than currently available PSCK9is. A phase 1 trial on muvalaplin, an oral lipoprotein (a) inhibitor, was presented. An atherosclerotic CV disease (ASCVD) risk prediction algorithm for the Asian population using SCORE2 data was presented. Long-term follow-up of patients enrolled in the CLEAR outcomes trial showed sustained and more significant ASCVD risk reduction with bempedoic acid in high-risk patients. The late-breaking clinical science at the 2023 congress of the ESC extends the known safety and efficacy data of a PCSK9i with the introduction of new drugs in this class. Using cumulative exposure to LDL-C rather than a single value will help clinicians tailor the LDL-C reduction strategy to individual risk and is an important step towards personalized medicine.

Clinical characteristics, management, and 5-year survival compared between no standard modifiable risk factor (SMuRFless) and ≥ 1 SMuRF ACS cases: an analysis of 15,051 cases from Pakistan.

BACKGROUND: There has been an increase in Acute Coronary Syndrome (ACS) patients without standard modifiable risk factors i.e. hypertension, diabetes, dyslipidemia, and tobacco use (SMuRFless) compared to the patients with ≥ 1 SMuRF but this has not been studied in South Asia despite them being a high-risk population. We conducted a comparative analysis of first episodes of ACS cases admitted to a tertiary cardiac center in Pakistan between SMuRFless and ≥ 1 SMuRF patients for clinical presentation, management, in-hospital, and 5-year mortality. METHODS: We undertook a retrospective study and data of 15,051 patients admitted at Tabba Heart Institute (THI) with the first episode of ACS was extracted from Chest Pain-MI™, and the CathPCI Registry® registry affiliated with the National Cardiovascular Data Registry (NCDR®), USA. Logistic regression and Cox proportional algorithm yielded odds ratio (OR) and hazard ratios (HR) with 95% confidence interval (CI) for associated factors of in-patient and 5-year mortality. RESULTS: There were 15% SMuRFless cases and in-hospital mortality was 4.1% in SMuRFless vs. 3.9% in the ≥ 1 SMuRF group (p-0.59), the difference remained insignificant after adjusting for age, gender, Killip class, multivessel disease, type of ACS, percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) (Adjusted OR:1.1 [0.8, 1.3]. Unadjusted 5-year mortality was 40% lower in the SMuRFless group but the difference was insignificant after adjusting for age, gender, disease at presentation, its severity, and management (Adjusted HR 0.7 95% CI[0.5, 1.0]). STEMI, NSTEMI, Killip class, and multivessel disease increased the risk of overall 5-year mortality. CONCLUSION: In-hospital and 5-year mortality was not different between the SMuRFless and ≥ 1 SMuRF group, there is a need to understand mediators of immediate and long-term mortality risk in SMuRFless patients.

Global Cardiovascular Research: Gaps and Opportunities.

PURPOSE OF REVIEW: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. CVDs contribute to a large health and economic burden on a global scale. We aim to describe the current landscape of global cardiovascular research, highlight significant findings, and identify potential opportunities for further studies. RECENT FINDINGS: There has been remarkable research output regarding cardiovascular health in recent decades. Large-scale collaborative studies have made impactful strides in identifying modifiable risk factors and forming evidence-based guidelines to facilitate improved cardiovascular care and outcomes. However, there are significant CVD disparities between high- and low- income countries which require interventions to mitigate these inequalities. Encouraging collaborative partnerships, strengthening research capacity in low-resource settings, and promoting equity in research are fundamental strategic approaches to help improve global cardiovascular research.

Risk factors and Compliance of surviving sepsis campaign: A retrospective cohort study at tertiary care hospital.

BACKGROUND AND OBJECTIVE: Sepsis is one of the leading causes of direct maternal mortality in Pakistan. It is recommended that the first three hours after the presentation are crucial. During this time implementation of surviving sepsis campaign resuscitation bundles reduces maternal mortality. Our objective was to assess the factors contributing to puerperal sepsis and the compliance of "surviving sepsis campaign resuscitation bundles in puerperal sepsis" for the management of puerperal sepsis. METHODS: This was a retrospective record review for five years from January 2011-December 2015. All women who fulfilled the inclusion criteria of puerperal sepsis were included and data from their files were collected and entered in SPSS version 19.0. Mean and standard deviations were calculated for continuous variables while for categorical variable proportion and percentages were used. RESULTS: This retrospective record review in five years showed the 396 patients had P-sepsis, among them 44 patients had severe sepsis with organ dysfunction. The culture was positive in 26(59%) with trend of E-coli in 9(20%) Among them 12(27%) had serum lactate more than ≥4mmol/L. Central venous pressure monitoring with fluid resuscitation was done as per protocol of survival bundle given to all 12(100%), Vasopressin was needed in half of these patients 6(50%). Amid 44 patients of severe sepsis 29(66%) were admitted to special care, while 15(34%) required intensive care admissions. Our 7(16%) patients failed to survive. All of them had multi-organ failure. CONCLUSION: There was moderate adherence of modified surviving sepsis campaign resuscitation bundles. Further improvement in compliance is warranted.

Randomized trial comparing radial hemostasis techniques; catechol conjugated chitosan pad (InnoSEAL) versus pneumatic compression band.

OBJECTIVES: Primary objectives: to compare radial artery occlusion rate (RAO) after cardiac catheterization between catecholamine-chitosan pad (InnoSEAL) and pneumatic compression device (PCD) and to compare difference in hemostasis time and radial monitoring termination time between two arms. Secondary objectives: to compare radial site bleeding and ease of use of two methods by cath-lab technicians. BACKGROUND: Hemostatic pads may be an effective alternative to PCD with lesser chance of access site complications with advantage of shortened compression time. METHODS: Patients (N = 606) undergoing trans-radial, diagnostic or interventional procedures were randomized to either InnoSEAL arm or PCD. RAO was assessed using US Duplex; performed 6-24 hr posthemostatic device removal. Time to hemostasis was recorded as per defined protocols. Ease of use among cath-lab technicians was assessed through 5 point Likert scale. RESULTS: Data of 597 patients was analyzed (299 InnoSEAL, 298 PCD). RAO rate was 8.5% in InnoSEAL and 9.4% in PCD arm (p value >.05). The pooled median hemostasis time and time to termination of radial monitoring was 42 versus 225 min and 50 versus 240 min in InnoSEAL and PCD arms, respectively (p value: <.01). There was no difference in Grade I/II hematoma (InnoSEAL: 1.3% vs. PCD: 3.4%). InnoSEAL was marginally acceptable compared to PCD by technicians. CONCLUSION: Hemostasis time is significantly shorter in InnoSEAL arm with reasonable acceptability to its usage among cath lab staff. RAO and bleeding complications are comparable between the arms. Based on our findings, it seems feasible to include Chitosan based hemostasis pad routinely in cath lab.

Pregnancy after embolization for arteriovenous malformation: An uncommon successful outcome.

Uterine arteriovenous malformation (AVM) is an uncommon but fatal condition and can cause bleeding from abnormal connection between artery and vein. Pregnancy after embolization of uterine AVM is very uncommon, and there are increased risks of spontaneous abortion and growth retardation. We report a case of pregnancy after bilateral uterine artery embolization for AVM and its successful outcome..

Risk factors for postpartum sepsis: a nested case-control study.

BACKGROUND: The Majority (99%) of maternal deaths occur in low and middle-income countries. The three most important causes of maternal deaths in these regions are postpartum hemorrhage, pre-eclampsia and puerperal sepsis. There are several diagnostic criteria used to identify sepsis and one of the commonly used criteria is systematic inflammatory response syndrome (SIRS). However, these criteria require laboratory investigations that may not be feasible in resource-constrained settings. Therefore, this study aimed to develop a model based on risk factors and clinical signs and symptoms that can identify sepsis early among postpartum women. METHODS: A case-control study was nested in an ongoing cohort of 4000 postpartum women who delivered or were admitted to the study hospital. According to standard criteria of SIRS, 100 women with sepsis (cases) and 498 women without sepsis (controls) were recruited from January to July 2017. Information related to the socio-demographic status, antenatal care and use of tobacco were obtained via interview while pregnancy and delivery related information, comorbid and clinical sign and symptoms were retrieved from the ongoing cohort. Multivariable logistic regression was performed and discriminative performance of the model was assessed using area under the curve (AUC) of the receiver operating characteristic (ROC). RESULTS: Multivariable analysis revealed that 1-4 antenatal visits (95% CI 0.01-0.62). , 3 or more vaginal examinations (95% CI 1.21-3.65), home delivery (95% CI 1.72-50.02), preterm delivery, diabetes in pregnancy (95% CI 1.93-20.23), lower abdominal pain (95% CI 1.15-3.42)) vaginal discharge (95% CI 2.97-20.21), SpO2 < 93% (95% CI 4.80-37.10) and blood glucose were significantly associated with sepsis. AUC was 0.84 (95% C.I 0.80-0.89) which indicated that risk factors and clinical sign and symptoms-based model has adequate ability to discriminate women with and without sepsis. CONCLUSION: This study developed a non-invasive tool that can identify postpartum women with sepsis as accurately as SIRS criteria with good discriminative ability. Once validated, this tool has the potential to be scaled up for community use by frontline health care workers.

Pregnancy outcomes amongst adolescents/young adults at tertiary-care hospital in a low-middle-income country: Ten-year retrospective record review.

OBJECTIVE: Adolescent pregnancies are known to be associated with adverse outcomes. Our objective was to compare pregnancy outcomes amongst adolescents (young adolescents YA: 15-17 years; older adolescents OA: 18- 19 years) and young adults (20 to 25 years). METHODS: Study was conducted at the Aga Khan University Hospital, Karachi. Ten-year retrospective record review was done through convenience sampling. Data was collected on predesigned proforma. Participants were 396 primiparous adolescents (15-19 years) with singleton low-risk pregnancy. Reference-group included 410 primiparous, low-risk, young adults. Pregnancies complicated with preexisting diabetes mellitus, chronic hypertension, renal disorders or cardiac diseases were excluded. Maternal /neonatal outcomes were compared amongst groups. RESULTS: Out of 806 charts reviewed, 75 (9.3%) were YA, 321 (39.8%) were OA and 410 (50.9%) were 20-25 years old young adults. Most of the un-booked cases were in young adolescents; 17 (22.7% YA), 41 (12.8% OA) and 33 (8.0% reference -group) (p-value 0.001). This group also booked at a later gestational age; YA (19.6±10.4 weeks), OA (17.2±9.3 weeks) and controls (15.5n±8.8 weeks) (p-value 0.002). Gestational age at delivery was not significantly different among the groups. Adolescents had a decreased likelihood of Caesarian section with youngest group having 29% less chance of Caesarian delivery (OR 95% CI 0.41, 0.2) compared to women of 20-25 years of age. Difference in maternal/neonatal outcomes remained insignificant between groups at univariate and multivariate analysis. CONCLUSIONS: Maternal/neonatal outcomes in adolescents were comparable to young adults. Good antenatal care, evidence-based protocols and strong family backing may reduce risks to mothers/babies in adolescent pregnancies.

Preventive lipid-based nutrient supplements given with complementary foods to infants and young children 6 to 23 months of age for health, nutrition, and developmental outcomes.

BACKGROUND: One nutritional intervention advocated to prevent malnutrition among children is lipid-based nutrient supplements (LNS). LNS provide a range of vitamins and minerals, but unlike most other micronutrient supplements, LNS also provide energy, protein and essential fatty acids. Alternative recipes and formulations to LNS include fortified blended foods (FBF), which are foods fortified with vitamins and minerals, and micronutrient powders (MNP), which are a combination of vitamins and minerals, OBJECTIVES: To assess the effects and safety of preventive LNS given with complementary foods on health, nutrition and developmental outcomes of non-hospitalised infants and children six to 23 months of age, and whether or not they are more effective than other foods (including FBF or MNP).This review did not assess the effects of LNS as supplementary foods or therapeutic foods in the management of moderate and severe acute malnutrition. SEARCH METHODS: In October 2018, we searched CENTRAL, MEDLINE, Embase, 21 other databases and two trials registers for relevant studies. We also checked the reference lists of included studies and relevant reviews and contacted the authors of studies and other experts in the area for any ongoing and unpublished studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs that evaluated the impact of LNS plus complementary foods given at point-of-use (for any dose, frequency, duration) to non-hospitalised infants and young children aged six to 23 months in stable or emergency settings and compared to no intervention, other supplementary foods (i.e. FBF), nutrition counselling or multiple micronutrient supplements or powders for point-of-use fortification of complementary foods. DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies for relevance and, for those studies included in the review, extracted data, assessed risk of bias and rated the quality of the evidence using the GRADE approach. We carried out statistical analysis using Review Manager software. We used a random-effects meta-analysis for combining data as the interventions differed significantly. We set out the main findings of the review in 'Summary of findings' tables,. MAIN RESULTS: Our search identified a total of 8124 records, from which we included 17 studies (54 papers) with 23,200 children in the review. The included studies reported on one or more of the pre-specified primary outcomes, and five studies included multiple comparison groups.Overall, the majority of trials were at low risk of bias for random sequence generation, allocation concealment, blinding of outcome assessment, incomplete outcome data, selective reporting and other sources of bias, but at high risk of bias for blinding of participants and personnel due to the nature of the intervention. Using the GRADE approach, we judged the quality of the evidence for most outcomes as low or moderate.LNS+complementary feeding compared with no intervention Thirteen studies compared LNS plus complementary feeding with no intervention. LNS plus complementary feeding reduced the prevalence of moderate stunting by 7% (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.88 to 0.98; nine studies, 13,372 participants; moderate-quality evidence), severe stunting by 15% (RR 0.85, 95% CI 0.74 to 0.98; five studies, 6151 participants; moderate-quality evidence), moderate wasting by 18% (RR 0.82, 95% CI 0.74 to 0.91; eight studies; 13,172 participants; moderate-quality evidence), moderate underweight by 15% (RR 0.85, 95% CI 0.80 to 0.91; eight studies, 13,073 participants; moderate-quality evidence), and anaemia by 21% (RR 0.79, 95% CI 0.69 to 0.90; five studies, 2332 participants; low-quality evidence). There was no impact of LNS plus complementary feeding on severe wasting (RR 1.27, 95% CI 0.66 to 2.46; three studies, 2329 participants) and severe underweight (RR 0.78, 95%CI 0.54 to 1.13; two studies, 1729 participants). Adverse effects did not differ between the groups (RR 0.86, 95% CI 0.74 to 1.01; three studies, 3382 participants).LNS+complementary feeding compared with FBF Five studies compared LNS plus complementary feeding with other FBF, including corn soy blend and UNIMIX. We pooled four of the five studies in meta-analyses and found that, when compared to other FBF, LNS plus complementary feeding significantly reduced the prevalence of moderate stunting (RR 0.89, 95% CI 0.82 to 0.97; three studies, 2828 participants; moderate-quality evidence), moderate wasting (RR 0.79, 95% CI 0.65 to 0.97; two studies, 2290 participants; moderate-quality evidence), and moderate underweight (RR 0.81, 95% CI 0.73 to 0.91; two studies, 2280 participants; moderate-quality evidence). We found no difference between LNS plus complementary feeding and FBF for severe stunting (RR 0.41, 95% CI 0.12 to 1.42; two studies, 729 participants; low-quality evidence), severe wasting (RR 0.64, 95% CI 0.19 to 2.81; two studies, 735 participants; moderate-quality evidence), and severe underweight (RR 1.23, 95% CI 0.67 to 2.25; one study, 173 participants; low-quality evidence).LNS+complementary feeding compared with MNP Four studies compared LNS plus complementary feeding with MNP. We pooled data from three of the four studies in meta-analyses and found that compared to MNP, LNS plus complementary feeding significantly reduced the prevalence of moderate underweight (RR 0.88, 95% CI 0.78 to 0.99; two studies, 2004 participants; moderate-quality evidence) and anaemia (RR 0.38, 95% CI 0.21 to 0.68; two studies, 557 participants; low-quality evidence). There was no difference between LNS plus complementary feeding and MNP for moderate stunting (RR 0.92, 95% CI 0.82 to 1.02; three studies, 2365 participants) and moderate wasting (RR 0.97, 95% CI 0.77 to 1.23; two studies, 2004 participants). AUTHORS' CONCLUSIONS: The findings of this review suggest that LNS plus complementary feeding compared to no intervention is effective at improving growth outcomes and anaemia without adverse effects among children aged six to 23 months in low- and middle-income countries (LMIC) in Asia and Africa, and more effective if provided over a longer duration of time (over 12 months). Limited evidence also suggests that LNS plus complementary feeding is more effective than FBF and MNP at improving growth outcomes.

Dust exposure risk from stone crushing to workers and locally grown plant species in Quetta, Pakistan.

The aim of this study was to assess the effects of stone crushing dust pollution on three commonly cultivated fruit plant species (Vitis vinifera L., Morus alba L., and Prunus armeniaca L.) and on the health of workers working at crushing plants. The trial was carried out on fruit plant species grown close to the stone crushing units located near the northwestern (Brewery) bypass of Quetta city, Pakistan, near National Highway NH-25. Plant materials were collected from three polluted sites at a distance of 500, 1000, and 1500 m, respectively, away from the stone crushing units and one locality of comparatively clean air considered a control at 4000 m away from these crushing components. To know the status of air disorder near the experimental sites, the suspended particulate matters and both oxides of sulfur and nitrogen were also noted during operating hours. Consequences of the study indicated that during the crushing process, a fine aerosol of stone dust is often generated which could cause a significant health hazard to workers and also affect plant productivity due to the smothering of plant stomata. Environmental data designated that the average highest evaluated total suspended particulate matter (TSPM), NOx, and SOx were 7400 µg/m3, 803.7 µg/m3, and 216 µg/m3, respectively, at 500-m distance which gradually decreases as the distance increases-all of these pose a health risk to operators. The maximum deposit dust washed from the plant leaf surface under study was found to be 8.2, 4.6, and 4.4 at the distance of 500 m in all the investigated plant species which was highly significantly higher than that of the control site (4000 m). Among the plant species, the maximum dust fall was noted on the leaves of Vitis vinifera L., and minimum was on the leaves of Prunus armeniaca. The locations affected by more stone dust pollution (500 m) were leading to a reduction in the yield and quality of fruits. The studied stone crushing units had high percentages of closed stomata both on the upper sides (Us) and lower sides (Ls) of leaves at 500-m distance from stone crushing installations. Data regarding workers' health indicated the maximum age distribution among the workers was between the age groups of 20-35 years (46.15%). Results also showed that stone crushing workers suffered from symptoms of respiratory diseases (82.17%), allergies (72.13%), headaches (75.09%), coughing (78.36%), and tiredness (92.31%).

Implementation of warning tool to improve maternal newborn health outcomes in a developing country.

OBJECTIVE: To improve health outcomes through the implementation of national early warning sign tool for babies delivered through emergency caesarean section in off-work hours. METHODS: This comparative clinical study was conducted at the Aga Khan Hospital for Women and Children, Karachi, from April to August 2014, and comprised women who had an emergency caesarean section. Maternal and perinatal outcomes were compared of patients in Group A and Group B which represented individuals before and after the implementation of the national early warning score respectively. RESULTS: Of the 200 participants, there were 100(50%) in each group. The overall mean age was 26.79±5.10 years. The mean age was 26.3±5 years in Group A, and 27.2±5 years in Group B (p=0.25). The two groups were also comparable in terms of parity (p=0.77) and co-morbidities (p =0.51). There was no stillbirth or maternal death, but decline in complications due to post-partum haemorrhage (p=0.00) was observed due to early recognition and timely management. None of the women required referral to higher facility. CONCLUSIONS: National early warning score was found to be a practical early warning tool for obstetric population.

Community's perceptions of pre-eclampsia and eclampsia in Sindh Pakistan: a qualitative study.

BACKGROUND: Maternal mortality is of global public health concern and >99 % of maternal deaths occur in less developed countries. The common causes of direct maternal death are hemorrhage, sepsis and pre-eclampsia/eclampsia. In Pakistan, pre-eclampsia/eclampsia deaths represents one-third of maternal deaths reported at the tertiary care hospital settings. This study explored community perceptions, and traditional management practices about pre-eclampsia/eclampsia. METHODS: A qualitative study was conducted in Sindh Province of Pakistan from February to July 2012. Twenty-six focus groups were conducted, 19 with women of reproductive age/mothers-in-law (N = 173); and 7 with husbands/fathers-in-law (N = 65). The data were transcribed verbatim in Sindhi and Urdu, then analyzed for emerging themes and sub-themes using NVivo version 10 software. RESULTS: Pre-eclampsia in pregnancy was not recognized as a disease and there was no name in the local languages to describe this. Women however, knew about high blood pressure and were aware they can develop it during pregnancy. It was widely believed that stress and weakness caused high blood pressure in pregnancy and it caused symptoms of headache. The perception of high blood pressure was not based on measurement but on symptoms. Self-medication was often used for headaches associated with high blood pressure. They were also awareness that severely high blood pressure could result in death. CONCLUSIONS: Community-based participatory health education strategies are recommended to dispel myths and misperceptions regarding pre-eclampsia and eclampsia. The educational initiatives should include information on the presentation, progression of illness, danger signs associated with pregnancy, and appropriate treatment.

Health care seeking behaviours in pregnancy in rural Sindh, Pakistan: a qualitative study.

BACKGROUND: Pakistan has alarmingly high numbers of maternal mortality along with suboptimal care-seeking behaviour. It is essential to identify the barriers and facilitators that women and families encounter, when deciding to seek maternal care services. This study aimed to understand health-seeking patterns of pregnant women in rural Sindh, Pakistan. METHODS: A qualitative study was undertaken in rural Sindh, Pakistan as part of a large multi-country study in 2012. Thirty three focus group discussions and 26 in-depth interviews were conducted with mothers [n = 173], male decision-makers [n = 64], Lady Health Workers [n = 64], Lady Health Supervisors [n = 10], Women Medical Officers [n = 9] and Traditional Birth Attendants [n = 7] in the study communities. A set of a priori themes regarding care-seeking during pregnancy and its complications as well as additional themes as they emerged from the data were used for analysis. Qualitative analysis was done using NVivo version 10. RESULTS: Women stated they usually visited health facilities if they experienced pregnancy complications or danger signs, such as heavy bleeding or headache. Findings revealed the importance of husbands and mothers-in-law as decision makers regarding health care utilization. Participants expressed that poor availability of transport, financial constraints and the unavailability of chaperones were important barriers to seeking care. In addition, private facilities were often preferred due to the perceived superior quality of services. CONCLUSION: Maternal care utilization was influenced by social, economic and cultural factors in rural Pakistani communities. The perceived poor quality care at public hospitals was a significant barrier for many women in accessing health services. If maternal lives are to be saved, policy makers need to develop processes to overcome these barriers and ensure easily accessible high-quality care for women in rural communities. TRIAL REGISTRATION: NCT01911494.

Health care provider knowledge and routine management of pre-eclampsia in Pakistan.

BACKGROUND: Maternal mortality ratio is 276 per 100,000 live births in Pakistan. Eclampsia is responsible for one in every ten maternal deaths despite the fact that management of this disease is inexpensive and has been available for decades. Many studies have shown that health care providers in low and middle-income countries have limited training to manage patients with eclampsia. Hence, we aimed to explore the knowledge of different cadres of health care providers regarding aetiology, diagnosis and treatment of pre-eclampsia and eclampsia and current management practices. METHODS: We conducted a mixed method study in the districts of Hyderabad and Matiari in Sindh province, Pakistan. Focus group discussions and interviews were conducted with community health care providers, which included Lady Health Workers and their supervisors; traditional birth attendants and facility care providers. In total seven focus groups and 26 interviews were conducted. NVivo 10 was used for analysis and emerging themes and sub-themes were drawn. RESULTS: All participants were providing care for pregnant women for more than a decade except one traditional birth attendant and two doctors. The most common cause of pre-eclampsia mentioned by community health care providers was stress of daily life: the burden of care giving, physical workload, short birth spacing and financial constraints. All health care provider groups except traditional birth attendants correctly identified the signs, symptoms, and complications of pre-eclampsia and eclampsia and were referring such women to tertiary health facilities. Only doctors were aware that magnesium sulphate is recommended for eclampsia management and prevention; however, they expressed fears regarding its use at first and secondary level health facilities. CONCLUSION: This study found several gaps in knowledge regarding aetiology, diagnosis and treatment of pre-eclampsia among health care providers in Sindh. Findings suggest that lesser knowledge regarding management of pre-eclampsia is due to lack of refresher trainings and written guidelines for management of pre-eclampsia and presentation of fewer pre-eclamptic patients at first and secondary level health care facilities. We suggest to include management of pre-eclampsia in regular trainings of health care providers and to provide management protocols at all health facilities. TRIAL REGISTRATION: NCT01911494.

Potential for task-sharing to Lady Health Workers for identification and emergency management of pre-eclampsia at community level in Pakistan.

BACKGROUND: An estimated 276 Pakistani women die for every 100,000 live births; with eclampsia accounting for about 10 % of these deaths. Community health workers contribute to the existing health system in Pakistan under the banner of the Lady Health Worker (LHW) Programme and are responsible to provide a comprehensive package of antenatal services. However, there is a need to increase focus on early identification and prompt diagnosis of pre-eclampsia in community settings, since women with mild pre-eclampsia often present without symptoms. This study aims to explore the potential for task-sharing to LHWs for the community-level management of pre-eclampsia and eclampsia in Pakistan. METHODS: A qualitative exploratory study was undertaken February-July 2012 in two districts, Hyderabad and Matiari, in the southern province of Sindh, Pakistan. Altogether 33 focus group discussions (FGDs) were conducted and the LHW curriculum and training materials were also reviewed. The data was audio-recorded, then transcribed verbatim for thematic analysis using QSR NVivo-version10. RESULTS: Findings from the review of the LHW curriculum and training program describe that in the existing community delivery system, LHWs are responsible for identification of pregnant women, screening women for danger signs and referrals for antenatal care. They are the first point of contact for women in pregnancy and provide nutritional counselling along with distribution of iron and folic acid supplements. Findings from FGDs suggest that LHWs do not carry a blood pressure device or antihypertensive medications; they refer to the nearest public facility in the event of a pregnancy complication. Currently, they provide tetanus toxoid in pregnancy. The health advice provided by lady health workers is highly valued and accepted by pregnant women and their families. Many Supervisors of LHWs recognized the need for increased training regarding pre-eclampsia and eclampsia, with a focus on identifying women at high risk. The entire budget of the existing lady health worker Programme is provided by the Government of Pakistan, indicating a strong support by policy makers and the government for the tasks undertaken by these providers. CONCLUSION: There is a potential for training and task-sharing to LHWs for providing comprehensive antenatal care; specifically for the identification and management of pre-eclampsia in Pakistan. However, the implementation needs to be combined with appropriate training, equipment availability and supervision. TRIAL REGISTRATION: ClinicalTrial.gov, NCT01911494.