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venous thromboembolism is a complication among admitted medical and surgical patients. International guidelines recommend patients are assessed upon admission and appropriate thromboprophylaxis should be initiated. However, studies have shown that thromboprophylaxis for patients at risk of venous thromboembolism is underutilized.this was a retrospective study conducted on hospitalized medical and surgical patients at Aga Khan Hospital Dar es salaam from January to June 2019. Patient's medical records were reviewed and data was collected for analysis of venous thromboembolism assessment and compliance with Caprini risk assessment model. The data was entered into statistical package for the social sciences (SPSS) 25 and categorized into risk groups, frequency of patients' demographic and clinical characteristics data was calculated and the main study outcomes were analyzed with Fisher´s exact test or Pearson chi-square test for categorical variables and student t-test for continuous variables. Regression analyses were done to identify significant risk factors where by P ≤ 0.05 was considered statistically significant.compliance of venous thromboembolism assessment among medical and surgical patients was similar at 78% and 80%, respectively, with a baseline 22% of all admitted patients considered at risk of venous thromboembolism, hence needing thromboprophylaxis following the Caprini risk assessment modelscore. Thromboprophylaxis practices was identified at just 25% of at-risk individuals received pharmacological prophylaxis with enoxaparin; the most commonly used agent (92%). Identified risk factors for venous thromboembolism were advancing age (60 years), history of prior major surgery, Major surgery lasting60 minutes, obesity, and immobilization.risk assessment for venous thromboembolism should be emphasized upon admission of both surgical and medical patients. Adequate thromboprophylaxis should be prescribed upon identification of patients at risk.

Among the well-known Health care-associated infections (HAIs), surgical site infections (SSIs) contribute to considerable high mortality and morbidity rate, substantial prolongation in hospitalization period and extra expenses in terms of treatment cost. This study was aimed to evaluate the predictive variables associated with surgical site infections, and their clinical consequences. This was a prospective, cross sectional study conducted in the surgical department of tertiary care setting in Karachi, Pakistan. Each patient was followed up from the time of admission until time of the discharge postoperatively for 30 days. A total of 554 surgical procedures were performed and 81 SSIs were identified. The predictor variable/risk factors significantly associated with the presence of SSI were age, gender, BMI, ASA score, co-morbid condition, surgical wound class, emergency surgeries, duration of surgery, type of anesthesia, prosthetic implant, pre operative length of stay and pre operative blood transfusion. Outcomes of such studies may be utilized in the design of a multi factorial practice to get better patient's safety and clinical outcomes.

Objectives Our aim was to determine the frequency of restless leg syndrome (RLS) in rheumatoid arthritis (RA) patients from a low socioeconomic area of Pakistan and compare results with a control group to evaluate the effect of variables on RLS patients. Methods A clinical observational study was carried out on 240 RA patients form low socioeconomic group. Controls (n = 210) were frequency-matched by age group to the RA patients. We evaluated the presence of RLS and collected information on characteristics believed to be correlated with RLS in the general population. Multiple logistic regression models were used to study the association between RLS and other risk factors such as age, smoking status, and obesity. Results Among all rheumatic patients seen at our rheumatology clinic, 70.8 % were women. Our study shows that 20 % of RA patients were suffering from RLS compared with 10 % of the control group with other rheumatic diseases. Multivariate logistic regression adjusted for age, obesity, and smoking also showed that women with RA were more likely to have RLS than control patients. RLS was also significantly associated with increasing age, high body mass index, and smoking status. Conclusions Approximately 20 % of RA patients were suffering from RLS. Hence, there is need of increase awareness of RLS among rheumatologists to enhance early RLS diagnosis and appropriate management of this treatable condition.

Background: serum level of amino-terminal pro-B-type natriuretic peptide, a cardiac hormone produced by the heart, is elevated in patients with left ventricular dysfunction. The purpose of this study was to compare the abilities of serum and pericardial fluid levels of amino-terminal pro-B-type natriuretic peptide to detect the left ventricular systolic dysfunction determined by echocardiography. Methods: 50 patients undergoing coronary artery bypass grafting were included in this study. Left ventricular systolic function was assessed using echocardiography before coronary artery bypass grafting. The samples of serum and pericardial fluid were collected during surgery, and amino-terminal pro-B-type natriuretic peptide levels were assessed by an electrochemiluminescence immunoassay. The log value of amino-terminal pro-B-type natriuretic peptide concentrations was calculated. Results: the pericardial fluid levels of log amino-terminal pro-B-type natriuretic peptide were significantly elevated compared to the serum levels in patients with impaired left ventricular systolic function. Both serum and pericardial fluid levels of log amino-terminal pro-B-type natriuretic peptide correlated significantly with left ventricular ejection fraction and end-diastolic and end-systolic volume indices. Furthermore, a paired comparison of receiver operating characteristic curves showed a similar performance of amino-terminal pro-B-type natriuretic peptide levels both in serum and pericardial fluid to discriminate left ventricular systolic dysfunction. Conclusion: serum amino-terminal pro-B-type natriuretic peptide levels have comparable diagnostic value for left ventricular systolic dysfunction with its pericardial fluid levels in patients undergoing CABG.

Interactions of killer cell immunoglobulin-like receptors (KIRs) with major histocompatibility complex (MHC) class I ligands diversify natural killer cell responses to infection. By analyzing sequence variation in diverse human populations, we show that the KIR3DL1/S1 locus encodes two lineages of polymorphic inhibitory KIR3DL1 allotypes that recognize Bw4 epitopes of protein">HLA-A and HLA-B and one lineage of conserved activating KIR3DS1 allotypes, also implicated in Bw4 recognition. Balancing selection has maintained these three lineages for over 3 million years. Variation was selected at D1 and D2 domain residues that contact HLA class I and at two sites on D0, the domain that enhances the binding of KIR3D to HLA class I. HLA-B variants that gained Bw4 through interallelic microconversion are also products of selection. A worldwide comparison uncovers unusual KIR3DL1/S1 evolution in modern sub-Saharan Africans. Balancing selection is weak and confined to D0, KIR3DS1 is rare and KIR3DL1 allotypes with similar binding sites predominate. Natural killer cells express the dominant KIR3DL1 at a high frequency and with high surface density, providing strong responses to cells perturbed in Bw4 expression.

Role of vitamin D in the health of bones has been well established for over decades; It was known that its deficiency caused rickets in children and osteomalacia in adults. Later it was discovered that these can be corrected by giving vitamin D. Researchers discovered that vitamin D can be synthesized by exposure to sun. Hence it was also named "the sunshine vitamin". As time passed it was observed that low levels of vitamin D were associated with multiple diseases. This sparked the interest of the scientific community to further the research on vitamin D which led to the studies that started associating vitamin D with various diseases like cancers (prostate, colon and breast), autoimmune diseases (rheumatoid arthritis), infectious diseases (tuberculosis, hepatitis B, hepatitis C, HIV), cardiovascular diseases, mental illnesses (schizophrenia), diabetes mellitus (type 1, type 2 and gestational) and allergic conditions like asthma. With time, more studies were carried out relating levels of vitamin D to development of asthma, asthma exacerbations and risk factors leading to development of asthma like respiratory tract infections with positive associations. A number of studies were carried out which tried to explain the possible molecular mechanisms relating deficiency of vitamin D in pathogenesis of asthma. This review summarizes the role of vitamin D in development of asthma and probable mechanisms relating vitamin D to the pathogenesis of asthma.

Web servers at the National Library of Medicine (NLM) displayed images of ten skin lesions to practicing dermatologists and provided an online form for capturing text they used to describe the pictures. The terms were submitted to the UMLS Metathesaurus (Meta). Concepts retrieved, their semantic types, definitions and synonyms, were returned to each subject in a second web-based form. Subjects rated the concepts against their own descriptive terms. They submitted 825 terms, 346 of which were unique and 300 mapped to UMLS concepts. The dermatologists rated 295 concepts as 'Exact Match' and they accomplished both tasks in about 30 min.

Natural killer (NK) and some T cells express killer cell immunoglobulin-like receptors (KIRs), which interact with HLA class I expressed by target cells and consequently regulate cytolytic activity. The number of KIR loci can vary and so a range of genetic profiles is observed. We have determined the KIR genetic profiles from one African (n = 62) and two South Asian (n = 108, n = 78) populations. Several of the KIRs are present at significantly different frequencies between the two major ethnic groups (eg KIR2DS4 gene frequency 0.82 African, 0.47 S Asian. Pc < 1 × 10−6) and this is due to uneven distribution of two KIR haplotype families ‘A’ and ‘B’. All three populations described here displayed a greater degree of diversity of KIR genetic profiles than other populations investigated, which indicates further complexity of underlying haplotypes; in this respect we describe two individuals who appear homozygous for a large deletion including the previously ubiquitous 2DL4. We have also reanalysed three populations that we studied previously, for the presence of a KIR which is now known to be an indicator of the ‘B’ haplotype. South Asians had the highest overall frequencies of all KIR loci characteristic of ‘B’ haplotypes (Pc < 0.0001 to < 0.004). Furthermore, gene frequency independent deviances in the linkage disequilibrium were apparent between populations.

Several studies have demonstrated differences between ethnic groups in the severity and pattern of rheumatoid arthritis (RA) and osteoarthritis (OA). The current investigation compared RA and OA in Pakistani and British White Caucasian out-patients in two teaching hospitals. There were 88 RA patients in each setting, matched for age, gender and disease duration. The pattern of OA was sought by recording the details of 44 consecutive new referrals to each clinic. Amongst the RA patients, joint deformity and tenderness were similar, but disability was more severe, ESR higher, anaemia more pronounced and RA latex more often positive amongst the Pakistani patients. X-ray damage was more pronounced amongst the British patients, especially in the feet. The British were also more likely to have rheumatoid nodules and to have undergone disease-modifying treatment or joint surgery. The paradox of more severe indices of disease activity and disability with less X-ray erosion in hands and feet might be explained by the impact of treatment on joint inflammation and the beneficial influence of surgery on disability in the British. The worse X-ray scores in the White Caucasians might indicate a genetic predisposition to radiologically more severe disease. The age of the British OA patients was significantly higher, but this is unlikely to have influenced the striking disparity in the frequency of isolated knee OA, which was significantly greater in the Pakistani patients. Comparison with age- and sex-matched healthy Pakistani subjects suggested that susceptibility to knee OA was strongly associated with body weight, but not with knee bending at prayer or with joint laxity. Amongst the Pakistanis, Heberden nodes, hip involvement and evidence of generalized OA were significantly less, but these observations may have been due to their younger age. The study confirmed differences in the clinical presentation of both RA and OA amongst patients in Pakistan compared with White Caucasians in Britain. Several confounding factors, such as patient recruitment, culture, treatment and age, may have influenced the results, but it remains likely that genetic factors are important.

Using previously applied methods a survey of joint symptoms was undertaken among 4232 adults, evenly distributed between affluent and poor areas of Karachi, Pakistan. Only six cases of definite rheumatoid arthritis (RA) (1958 ARA criteria) were identified in the 245 persons who complained of joint problems of at least 4 weeks duration. The prevalence was 0.9 [confidence interval (CI) 0.21-3.61] and 1.98 (CI 0.55-5.1) per thousand in the poor and affluent districts, respectively. These were substantially less than prevalence rates reported in the West but were similar to figures derived from other developing countries. There was no obvious impact of current living standards on the findings. The relative paucity of older female subjects in both the affluent and poor communities may account at least in part for the low rates observed. The infrequency of rheumatoid nodules in Southern Asians with RA illustrates the difficulty of applying existing diagnostic criteria to this community.

An indicator for emergency room performance is the ability to establish the correct diagnosis within the emergency room over the years. The authors chose to examine the non-congruence of Emergency Room diagnoses to that established after hospital stay for three selected years. A total of 8488 records were reviewed and all disparate diagnosis were recorded and categorized. Retrospective chart reviews were done from July 2008 to February 2009 at the Aga Khan University Hospital, Karachi. A substantial reduction in the percentage of disparate diagnoses was seen over the years from 41% in the initial year to 14% in the last year evaluated. It was concluded that over the years there has been an improvement in the reliability of Emergency Room diagnoses at the Aga Khan University Hospital, Karachi.

In order to compare the efficacy and toxicity of methotrexate and leflunomide for the treatment of rheumatoid arthritis, a double-blind randomized clinical trial was carried out at the Department of Medicine, Jinnah Medical College Hospital, Korangi, Karachi. The sample size was 240 patients and the duration of the study was 1 year. The patients enrolled were randomly divided into two groups (methotrexate and leflunomide). RA activity was clinically assessed by noting changes in the four primary (tender joint count, swollen joint count, physician and patient global assessment score) and three secondary (morning stiffness, pain intensity, HAQ) clinical efficacy end-points. Data were expressed as the mean ± SD. A P value of

Natural killer (NK) cells contribute to the essential functions of innate immunity and reproduction. Various genes encode NK cell receptors that recognize the major histocompatibility complex (MHC) Class I molecules expressed by other cells. For primate NK cells, the killer-cell immunoglobulin-like receptors (KIR) are a variable and rapidly evolving family of MHC Class I receptors. Studied here isKIR3DL1/S1, which encodes receptors for highly polymorphic human HLA-A and -B and comprises three ancient allelic lineages that have been preserved by balancing selection throughout human evolution. While the 3DS1 lineage of activating receptors has been conserved, the two 3DL1 lineages of inhibitory receptors were diversified through inter-lineage recombination with each other and with 3DS1. Prominent targets for recombination were D0-domain polymorphisms, which modulate enhancer function, and dimorphism at position 283 in the D2 domain, which influences inhibitory function. In African populations, unequal crossing over between the3DL1and3DL2genes produced a deletedKIRhaplotype in which the telomeric “half” was reduced to a single fusion gene with functional properties distinct from its3DL1and3DL2parents. Conversely, in Eurasian populations, duplication of theKIR3DL1/S1locus by unequal crossing over has enabled individuals to carry and express alleles of all threeKIR3DL1/S1lineages. These results demonstrate how meiotic recombination combines with an ancient, preserved diversity to create new KIR phenotypes upon which natural selection acts. A consequence of such recombination is to blur the distinction between alleles and loci in the rapidly evolving humanKIRgene family.

To study the burden of anxiety and depression as a comorbid among patients of chronic rheumatological disorders and to investigate possible determinants of depression and anxiety.It was a cross-sectional study conducted at the rheumatology clinic of The Aga Khan University Hospital (AKUH) Karachi, Pakistan. With convenient sampling, 111 patients who fulfilled inclusion/exclusion criteria were screened for anxiety and depression with help of Aga Khan University Anxiety and Depression Scale (AKUADS). The data was entered and analyzed by Statistical Package for Social Sciences (Version 10.0).The population consisted mainly of middle aged (mean age 41) females (80.2%). The most common diagnosis was rheumatoid arthritis 57% followed by systemic lupus erythmatosis 17% and systemic sclerosis 9%. The permanent joint deformity was present in 33.3% patients and 36.9% patients were suffering from active disease with pain and inflammation. The frequency of anxiety and depression was 65.8%. Educational qualification, permanent joint deformity, active inflammation and time elapsed since diagnosis had significant association with anxiety and depression. Marital Status, gender, economic activity and monthly family income had no effect on the frequency of anxiety and depression.Almost two third of patients with chronic rheumatological disorders, also suffered from a concomitant mood disorder. Systematic evaluation of all patients for mood disorders and psychological distress in rheumatology clinics is highly recommended.

The human leukocyte receptor complex (LRC) of Chromosome 19q13.4 encodes polymorphic and highly homologous genes that are expressed by cells of the immune system and regulate their function. There is an enormous diversity at the LRC, most particularly the variable number of killer cell immunoglobulin-like receptor (KIR) genes. KIR have been associated with several disease processes due to their interaction with polymorphic human leukocyte antigen class I molecules. We have assessed haplotype compositions, linkage disequilibrium patterns and allele frequencies in two Caucasoid population samples (n=54, n=100), using a composite of single-nucleotide polymorphism (SNP) markers and high-resolution, allele-specific molecular genotyping. Particular KIR loci segregated with SNP and other markers, forming two blocks that were separated by a region with a greater history of recombination. The KIR haplotype composition and allele frequency distributions were consistent with KIR having been subject to balancing selection (Watterson's F: P=0.001). In contrast, there was a high inter-population heterogeneity measure for the LRC-encoded leukocyte immunoglobulin-like receptor A3 (LILRA3), indicating pathogen-driven disruptive selection (Wright's FST=0.32). An assessment of seven populations representative of African, Asian and Caucasoid ethnic groups (total n=593) provided little evidence for long-range LRC haplotypes. The different natural selection pressures acting on each locus may have contributed to a lack of linkage disequilibrium between them.

To describe the etiology and outcome in patients with ventricular tachycardia in our patient population.A descriptive study.The study was conducted at the Aga Khan University Hospital from November 2002 to October 2003.We enrolled 58 patients who presented to the emergency room with clinical and electrocardiographic evidence of ventricular tachycardia (VT) and/or who developed it during the inpatient stay at the Aga Khan University Hospital. Medical records were retrieved through the computerized data retrieval system. Patients above 18 years of age were included. Those with a pacemaker or who developed VT during electrophysiological testing were excluded. A pre-designed proforma was filled for all patients who fulfilled the inclusion criteria. All patients were worked up for etiological causes of ventricular tachycardia. Outcomes in the form of death or discharge were recorded.There were 58 patients who suffered ventricular tachycardias during the study period. These included 70.7 %( 42) males and 29.3 %( 16) females. Mean age of the patients was 57.06+/-11.84 years. Emergency room admissions accounted for 55.2% and ventricular tachycardia was seen in 44.8% during the inpatient stay. Unresponsiveness was the presenting symptom in 25.9%, chest pain in 24.1%, palpitations in 13.8% and ghabrahat in 12.1% patients. Myocardial ischemia was seen in 43.5% of the patients while 23.2% had cardiomyopathy, followed by 33.3% miscellaneous. Out of the patients who had myocardial ischemia (43.5%), 76.6% had non-ST elevation myocardial infarction, 20 % patients had ST elevation myocardial infarction and 3.3% had unstable angina. Hemodynamic instability was noted in 50%, who subsequently required defibrillation. The mortality among these patients with VT was 13.7%.Myocardial ischemia was most commonly seen in patients with ventricular tachycardia in our group of patients. Ventricular tachycardia is associated with a significant mortality of 13.7%.

To estimate the frequency of acute coronary syndrome (ACS) at 30 days in patients less than 40 years of age reporting with acute chest pain in Emergency Department (ED).Prospective cohort study.Emergency Department (ED) of Aga Khan University Hospital, Karachi between July to December 2002.One hundred young patients with chest pain in whom an electrocardiogram (ECG) was performed. A standardized data collection form was completed. Physical examination included initial vital signs and presence or absence of jugular venous pressure (JVP), rales, or fourth heart sound. Outcome variables were seen in the patients admitted or discharged within 30 days of reporting to the ED.Out of one hundred young patients in the study, 24 had an ACS. Of those, 22 (91.66%) were males and their mean age was 35 years. Most of these patients had cardiac risk factors on physical findings. The final diagnosis of patients consisted of 47 patients with atypical chest pain, 20 with acute myocardial infarction (AMI), 16 with musculoskeletal chest pain, 7 with psychogenic chest pain, 4 with angina, 4 with others and 2 with gastritis.Young patients, presenting to ED with chest pain, had a greater likelihood of suffering from ACS if they were male and between 30 to 40 years of age. People of any age group, presenting to ED with chest pain should not be disregarded in the presence of cardiac risk factors and positive physical findings.

SUMMARY The association of particular HLA-DR alleles and the shared epitope with rheumatoid arthritis (RA) is now well established. The strength of these links varies between races. Furthermore, the proposition that the presence of the shared epitope is indicative of severe disease has been more diAcult to sustain in non-Europeans. This study examines the frequency of HLA-DR and HLA-DRB1 amongst Pakistanis for the first time. Using the polymerase chain reaction (PCR) and sequencespecific oligonucleotide probes (PCR-SSOP) and primers (PCR-SSP), HLA-DR phenotype and genotype frequencies were ascertained in 86 RA hospital out-patients and 79 healthy controls matched for age, gender and ethnicity. HLA-DR1 and HLA-DR4 frequency was similar in patients and controls. HLA-DR10 occurred in 26 instances (15%) in RA and in eight (5%) controls (Pcorr = 0.048). HLA-DR2 was also increased in patients (P = 0.053) and its major subtype DR15 was significantly increased (Pcorr = 0.03). HLA-DR5 frequency was 5% in patients and 19% in controls (Pcorr = 0.002). The HLA- DR4 alleles possessing the shared epitope were more common in RA (Pcorr = 0.03) and this diAerence was enhanced by inclusion of other alleles possessing the shared epitope (Pcorr = 0.002). Shared epitope alleles were observed in 43 (50%) patients and 17 (22%) controls (Pcorr = 0.003). The shared epitope did not distinguish patients with more severe disease, as reflected by pain, joint deformities, disability, rheumatoid factor or X-ray damage. The distribution of HLA-DR alleles in Pakistanis with RA supports the shared epitope hypothesis. In common with other non-European racial groups, HLA-DR4 was not associated with RA. Unlike other groups, there was a weak link of RA with HLA-DR2. A protective eAect of HLA-DR5 was apparent. In accord with some other studies, the shared epitope in this hospital out-patient population was not a marker for more severe disease.

The impact of environmental factors on the causation of rheumatoid arthritis (RA) is thought to be considerable. We explored this by comparing the prevalence of RA amongst Pakistanis living in England, where it is relatively high amongst ethnic English, and in Pakistan. The frequency of other rheumatic diseases was also compared. Information on 2056 adult Pakistanis in England and 4232 in Pakistan was obtained by house-to-house surveys using identical protocols. Positive respondents were examined by the same two clinicians in both countries. Rheumatic complaints increased with age and were more common in females in both communities. The standardized morbidity ratio (SMR) (95% CI) of RA in England was 2.1 (1.1-3.1) compared with Pakistan, a difference that was entirely attributable to females. The SMR (95% CI) for women was 3.0 (0.4-5.6) and for men 0.86 (-0.84 to 2.56). In Pakistan, there was a trend to more reporting of some but not all rheumatic complaints amongst the affluent segment of the population. This was increasingly apparent amongst those resident in England and the possibility of an impact of easier ascertainment amongst the more educated cannot be discounted. Low back pain was significantly more common in England. Furthermore, the colder climate was frequently invoked as a cause of more symptoms in England. Thus, several factors may have influenced the observation that RA is more common amongst Pakistanis in England compared with Pakistan. An environmental factor cannot be excluded. However, the frequency of non-specific musculoskeletal pain was similar. The regions of Pakistan from which the two populations were derived were also different and immunogenetic heterogeneity might also have contributed to the difference in RA prevalence.

The high frequency of diabetes mellitus and coronary artery disease among people of South Asian extraction living in the West is well established. The prevalence of these disorders in Southern Asia is less certain. No previous attempt has been made to estimate their occurrence in Pakistan. In order to compare the prevalence of known diabetes mellitus, hypertension and ischaemic heart disease between affluent and poor urban communities in Pakistan, a survey of consecutive households was undertaken in a relatively prosperous and a poor area in Karachi. Information was obtained on 4232 adults evenly distributed between the two areas. Body weight and height were measured in 199 healthy subjects at the two sites. The prevalence of known diabetes in the affluent population was 4.5%, significantly higher than 1.8% in the poor area (p < 0.001). A maximal prevalence of 25% was seen in the affluent community aged 55-64. Diabetes was more common in females in both populations. The overall prevalence of hypertension was similar in the two areas although significantly more frequent in the middle aged and affluent. A history of ischaemic heart disease occurred in 1.9% of the affluent and 0.6% of the poor (p = 0.003). Healthy subjects were heavier and more obese in the richer community. Thus the susceptibility of South Asian populations to diabetes and ischaemic heart disease is also apparent in an affluent segment of Pakistani society. The phenomenon is not attributable simply to urbanization. Obesity is probably an important contributory factor. The economic implications for developing South Asian countries are serious.