Selective screening for organic acidurias and amino acidopathies in Pakistani children

Objective: To determine the frequency of organic acidurais (OA) and amino acidopathies (AA) in selected high-risk patients screened in two years.Study Design: Retrospective Observational study.Place and Duration of Study: The Aga Khan University Hospital (AKUH), Karachi, from January 2013 to December 2014.Methodology: Patients with OA and AA were included in the study and patients with IMDs other than OA and AA were excluded. Amino acids and organic acids were analyzed on high performance liquid chromatography and gas chromatography-mass spectrometry respectively. Clinical data and chromatograms of patients screened for IMDs were reviewed by chemical pathologist and metabolic physician.Results: Eighty-eight cases (4.7%) were diagnosed including 41 OA (46.5%), 28 AA (31.8%) and 19 others (21.5%) from 1,866 specimens analyzed. Median age of the patients was 1.1 years, with high consanguinity rate (64.8%). Among OA, methyl CoA mutase deficiency was diagnosed in 9 (10.2%) and was suspected in 2 (2.3%) cases. Five (5.7%) cases of MHBD (2-methyl-3-hydroxybutyryl-CoA), 4 (4.5%) each of PPA (propionic aciduria) and HMG-CoA lyase deficiency, 3 (3.4%) cases each of IVA (isovaleric aciduria), multiple carboxylase deficiency, fructose-1, 6-biphosphatase deficiency, fumarase deficiency, GA-1 (glutaric aciduria type 1) and 2 (2.3%) cases of EMA (ethyl-malonic aciduria). AA included 8 (9.1%) cases of MSUD (maple syrup urine disease), 6 (6.8%) cases of CBS (cystathionine beta-synthetase) and UCDs (urea cycle disorders) each, 5 (5.7%) cases of hyperphenylalaninemia and 3 (3.4%) cases of hyperprolinemia were reported. Other inherited metabolic disorders included: 9 (10.2%) cases of intracellular cobalamin defects, 2 (2.3%) cases each of alkaptonuria, Canavan\u27s disease, SUCL (succinate CoA ligase) deficiency, and 1 (1.1%) case each of DPD (dihydropyrimidine) deficiency, GA-2, NKH (non-ketotic hyperglycinemia), AADC (aromatic amino acid decarboxylase) deficiency.Conclusion: This study presents frequency of OA and AA in the high-risk Pakistani pediatric population analyzed locally

Diabetes Mellitus and Mortality after Acute Coronary Syndrome as a First or Recurrent Cardiovascular Event

Diabetes Mellitus (DM) is associated with adverse cardiovascular prognosis. However, the risk associated with DM may vary between individuals according to their overall cardiovascular risk burden. Therefore, we aimed to determine whether DM is associated with poor outcome in patients presenting with Acute Coronary Syndrome (ACS) according to the index episode being a first or recurrent cardiovascular event.We conducted a retrospective analysis of a prospective cohort study involving 2499 consecutively admitted patients with confirmed ACS in 11 UK hospitals during 2003. Usual care was provided for all participants. Demographic factors, co-morbidity and treatment (during admission and at discharge) factors were recorded. The primary outcome was all cause mortality (median 2 year follow up), compared for cohorts with and without DM according to their prior cardiovascular disease (CVD) disease status. Adjusted analyses were performed with Cox proportional hazards regression analysis. Within the entire cohort, DM was associated with an unadjusted 45% increase in mortality. However, in patients free of a history of CVD, mortality of those with and without DM was similar (18.8% and 19.7% respectively; p = 0.74). In the group with CVD, mortality of patients with DM was significantly higher than those without DM (46.7% and 33.2% respectively; p<0.001). The age and sex adjusted interaction between DM and CVD in predicting mortality was highly significant (p = 0.002) and persisted after accounting for comorbidities and treatment factors (p = 0.006). Of patients free of CVD, DM was associated with smaller elevation of Troponin I (p<0.001). However in patients with pre-existing CVD Troponin I was similar (p = 0.992).DM is only associated with worse outcome after ACS in patients with a pre-existing history of CVD. Differences in the severity of myocyte necrosis may account for this. Further investigation is required, though our findings suggest that aggressive primary prevention of CVD in patients with DM may have beneficially modified their first presentation with (and mortality after) ACS

Assessment of Wind Energy Potential for the Production of Renewable Hydrogen in Sindh Province of Pakistan

In this study, we developed a new hybrid mathematical model that combines wind-speed range with the log law to derive the wind energy potential for wind-generated hydrogen production in Pakistan. In addition, we electrolyzed wind-generated power in order to assess the generation capacity of wind-generated renewable hydrogen. The advantage of the Weibull model is that it more accurately reflects power generation potential (i.e., the capacity factor). When applied to selected sites, we have found commercially viable hydrogen production capacity in all locations. All sites considered had the potential to produce an excess amount of wind-generated renewable hydrogen. If the total national capacity of wind-generated was used, Pakistan could conceivably produce 51,917,000.39 kg per day of renewable hydrogen. Based on our results, we suggest that cars and other forms of transport could be fueled with hydrogen to conserve oil and gas resources, which can reduce the energy shortfall and contribute to the fight against climate change and global warming. Also, hydrogen could be used to supplement urban energy needs (e.g., for Sindh province Pakistan), again reducing energy shortage effects and supporting green city programs

Cohort characteristics.

*<p>Log-rank test.</p>**<p>Mann-Whitney test.</p><p>BP = Blood Pressure.</p

Cohort mortality.

<p>Kaplan-Meier curves illustrating mortality of the 4 study cohorts according to pre-existing CVD and DM status.</p

Adjusted analyses.

<p>Hazard ratios (with 95% confidence intervals) for the risk attributable to DM within cohorts with and without prior CVD are displayed for the 3 adjusted analyses performed. HR = Hazard Ratio.</p