Anthracycline-induced cardiotoxicity: prospective cohort study from Pakistan

Objectives: To identify anthracycline-induced acute (within 1 month) and early-onset chronic progressive (within 1 year) cardiotoxicity in children younger than 16 years of age with childhood malignancies at a tertiary care centre of Pakistan. Design: Prospective cohort study. Setting: Aga Khan University, Karachi, Pakistan. Participants: 110 children (aged 1 month–16 years). Intervention: Anthracycline (doxorubicin and/or daunorubicin). Outcome measurements: All children who received anthracycline as chemotherapy and three echocardiographic evaluations (baseline, 1 month and 1 year) between July 2010 and June 2012 were prospectively analysed for cardiac dysfunction. Statistical analysis including systolic and diastolic functions at baseline, 1 month and 1 year was carried out by repeated measures analysis of variance. Results: Mean age was 74±44 months and 75 (68.2%) were males. Acute lymphoblastic leukaemia was seen in 70 (64%) patients. Doxorubicin alone was used in 59 (54%) and combination therapy was used in 35 (32%). A cumulative dose of anthracycline /m2was used in 95 (86%). Fifteen (14%) children developed cardiac dysfunction within a month and 28 (25%) children within a year. Of these 10/15 (66.6%) and 12/28 (43%) had isolated diastolic dysfunction, respectively, while 5/15 (33.3%) and 16/28 (57%) had combined systolic and diastolic dysfunction. Seven (6.4%) patients expired due to severe cardiac dysfunction. Eight of 59 (13.5%) children showed dose-related cardiotoxicity (p= Conclusions: Incidence of anthracycline-induced cardiotoxicity is high. Long-term follow-up is essential to diagnose its late manifestations

Formulation design and evaluation of Cefuroxime axetil 125 mg immediate release tablets using different concentration of sodium lauryl sulphate as solubility enhancer

Formularam-se comprimidos de liberação imediata à base de cefuroxima axetil, pelo método de compressão direta, com diferentes percentagens de lauril sulfato de sódio (LSS), tais como 0,5, 1,0, 1,5, e também sem SLS. Os lotes resultantes dos comprimidos foram avaliados por ambos os métodos da farmacopeia e não farmacopeicos para determinar as propriedades físico-mecânicas. O teste de dissolução foi realizado em meios diferentes, como HCl 0,07 M, água destilada, HCl 0,1 M com pH 1,2 e os tampões fosfato (pH 4,5 e 6,8) para observar a liberação do fármaco contra a correspondente concentração de LSS utilizado. Em seguida, as formulações de teste foram comparadas por fatores f1 (dissimilaridade) e f2 (similaridade), utilizando uma marca de referência de cefuroxima axetil. Diferenças significativas (pCefuroxime axetil immediate release tablets were formulated by direct compression method with different percentages of sodium lauryl sulphate (SLS) such as 0.5, 1.0, 1.5 and also without SLS. Resulting batches of tablets were evaluated by both pharmacopeial and non-pharmacopeial methods to ascertain the physico-mechanical properties. Dissolution test were carried out in different medium like 0.07 M HCl, distilled water, 0.1M HCl of pH 1.2 and phosphate buffers at pH 4.5 and 6.8 to observe the drug release against the respective concentration of SLS used. Later, test formulations were compared by f1 (dissimilarity) and f2 (similarity) factors using a reference brand of cefuroxime axetil. Significant differences (

DIRECT COST OF TREATMENT OF DIABETES MELLITUS TYPE 2 IN PAKISTAN

Objective: Diabetes is a serious illness. It is a key and growing threat to the health of the global world. The prime concern of this research was to estimate the cost-of-illness of type 2 diabetes in Karachi, a major metropolitan city of Pakistan. This study was performed on the basis a community perspective to calculate the economic burden of diabetes mellitus type 2 in Pakistan. Methods: This study was conducted in all districts of Karachi, the patients were taken from all economic segment of society from low income group, average revenue and high revenue group. A preliminary test questionnaire was used to collect the data directly from patients and in some locations conducted interviews with patients due to lack of understanding and un-educated patients. The total of 885diabetes patients was selected with convenient random sampling. Results: The average direct cost of all these expense bear by diabetic patient in Pakistan is Pak Rupees Rs.5542 per month. The cost range starts from Rs. 650/month to 20000 per month on the basis of patient economic condition and disease state. The average appointment fee of a physician, laboratory test and medicines came to Rs. 700/visit, 400/test, and 1100/visit precisely. The average travel and food spent was Rs.200/visit and 1000/month. Medicine accounted for largest cost followed by consultation with the physician. Conclusion: This is clearly indicated by this study that considerable cost is amounted by diabetes, it is suggested that a huge amount of resources could be prevented by taking care, initial understanding of the disease and a decrease in diabetes co-morbidities and complications through better diabetes mellitus treatment. Very extensive and cost-effective programs should be started to maximize health benefits and to diminish the prevalence of this epidemic

SURVEY BASE STUDY ON CURRENT TREND OF TREATMENT OF COMMUNITY-ACQUIRED PNEUMONIA IN KARACHI

Objective: Community-acquired pneumonia (CAP) is a potentially serious infection that results in various general physicians (GP) visits and hospital admission every year. The prime objective of this research was to find the current trend of treatment of community-acquired pneumonia in Karachi.Methods: It was a prospective survey conducted in all districts of Karachi. A Questionnaire was filled by distinctive specialities of doctors in an outpatient setting in Karachi. A preliminary test questionnaire was used to collect the data directly from distinctive specialities of doctors in outpatient setting in Karachi. Total 500 doctors were selected from distinct districts of Karachi with convenient random sampling.Results: Majority (33.8%) of the respondents recommended complete blood count and chest x-ray for diagnosis of community-acquired pneumonia in an outpatient setting. Most (76%) of the respondents recommended nebulization for the management of community-acquired pneumonia in an outpatient setting. 31% and 25.4% of the physicians recommended clarithromycin as 1st line antibiotic therapy in adults and children for the management of a community-acquired pneumonia patients in outpatient setting.55.6% of the physicians recommended two-week duration of antibiotic therapy for the management of CAP in outpatient setting.Conclusion: This is clearly indicated by this study that deviation from the standard guideline is observed in the management of community-acquired pneumonia in Karachi. These deviations from the highly recommended guideline can results excess cost and inappropriateness of the management of the disease of community-acquired pneumonia. There is a need that the physician should take a decision of therapy according to the standard guidelines for the treatment of CAP in an outpatient setting.Â

Biallelic Variants in Seven Different Genes Associated with Clinically Suspected Bardet-Biedl Syndrome

Bardet-Biedl syndrome (BBS) is a rare clinically and genetically heterogeneous autosomal recessive multi-systemic disorder with 22 known genes. The primary clinical and diagnostic features include six different hallmarks, such as rod-cone dystrophy, learning difficulties, renal abnormalities, male hypogonadism, post-axial polydactyly, and obesity. Here, we report nine consanguineous families and a non-consanguineous family with several affected individuals presenting typical clinical features of BBS. In the present study, 10 BBS Pakistani families were subjected to whole exome sequencing (WES), which revealed novel/recurrent gene variants, including a homozygous nonsense mutation (c.94C>T; p.Gln32Ter) in the IFT27 (NM_006860.5) gene in family A, a homozygous nonsense mutation (c.160A>T; p.Lys54Ter) in the BBIP1 (NM_001195306.1) gene in family B, a homozygous nonsense variant (c.720C>A; p.Cys240Ter) in the WDPCP (NM_015910.7) in family C, a homozygous nonsense variant (c.505A>T; p.Lys169Ter) in the LZTFL1 (NM_020347.4) in family D, pathogenic homozygous 1 bp deletion (c.775delA; p.Thr259Leufs*21) in the MKKS/BBS5 (NM_170784.3) gene in family E, a pathogenic homozygous missense variant (c.1339G>A; p.Ala447Thr) in BBS1 (NM_024649.4) in families F and G, a pathogenic homozygous donor splice site variant (c.951+1G>A; p?) in BBS1 (NM_024649.4) in family H, a pathogenic bi-allelic nonsense variant in MKKS (NM_170784.3) (c.119C>G; p.Ser40*) in family I, and homozygous pathogenic frameshift variants (c.196delA; p.Arg66Glufs*12) in BBS5 (NM_152384.3) in family J. Our findings extend the mutation and phenotypic spectrum of four different types of ciliopathies causing BBS and also support the importance of these genes in the development of multi-systemic human genetic disorders

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection