Two-year follow-up of 196 interstitial lung disease patients after ICU stay.

OBJECTIVE: Interstitial lung diseases (ILDs) are associated with poor prognosis in the intensive care unit (ICU). We aimed to assess factors associated with hospital mortality in ILD patients admitted to the ICU and to investigate long-term outcome.MATERIAL AND METHODS: This was a retrospective study in a teaching hospital specialised in ILD management. Patients with ILD who were hospitalised in the ICU between 2000 and 2014 were included. Independent predictors of hospital mortality were identified using logistic regression.RESULTS: A total of 196 ILD patients were admitted to the ICU during the study period. Overall hospital mortality was 55%. Two years after ICU admission, 70 (36%) patients were still alive. Of the 196 patients, 108 (55%) required invasive mechanical ventilation, of whom 21 (20%) were discharged alive from hospital. Acute exacerbation of ILD and multi-organ failure were highly associated with hospital mortality (OR 5.4, 95% CI 1.9-15.5 and OR 12.6, 95% CI 4.9-32.5, respectively).CONCLUSION: Hospital mortality among ILD patients hospitalised in the ICU was high, but even where invasive mechanical ventilation was required, a substantial number of patients were discharged alive from hospital. Multi-organ failure could lead to major ethical concerns.

Eligibility and patient barriers to peritoneal dialysis in patients with advanced chronic kidney disease.

INTRODUCTION: The burden of chronic kidney disease (CKD) is increasing in Kenya and is a significant cause of morbidity and mortality. While definitive treatment is renal transplantation, many patients require kidney replacement therapy with haemodialysis (HD) or peritoneal dialysis (PD). The predominant modality utilized in Kenya is currently HD. There is a need to explore why PD remains underutilized and whether patient factors may be contributory to barriers that limit the uptake of PD. METHODS: This was a descriptive cross-sectional study where patients with advanced CKD were assessed by a multidisciplinary team for PD eligibility using a standardized tool. Contraindications and barriers to the modality were recorded as was the presence or absence of support for the provision of PD. Demographic and clinical data were recorded using a standardized questionnaire. The impact of support on PD eligibility was determined. RESULTS: We found that 68.9% patients were eligible for PD. Surgery-related abdominal scarring was the most common contraindication. Barriers to PD were identified in 45.9% and physical barriers were more common than cognitive barriers. Presence of support was associated with a significant increase in PD eligibility (p < 0.001). CONCLUSION: The rate of eligibility for PD in this study was similar to that found in other populations. Surgical-related factors were the most commonly identified contraindication. Physical and cognitive barriers were commonly identified and may be overcome by the presence of support for PD.

Worldwide Network for Blood and Marrow Transplantation (WBMT) recommendations for establishing a hematopoietic stem cell transplantation program in countries with limited resources (Part II): Clinical, technical and socio-economic considerations.

The development of hematopoietic stem cell transplantation (HSCT) programs can face significant challenges in most developing countries because such endeavors must compete with other government health care priorities, including the delivery of basic services. While this is may be a limiting factor, these countries should prioritize development of the needed expertise to offer state of the art treatments including transplantation, by providing financial, technological, legal, ethical and other needed support. This would prove beneficial in providing successful programs customized to the needs of their population, and potentially provide long-term cost-savings by circumventing the need for their citizens to seek care abroad. Costs of establishing HSCT program and the costs of the HSCT procedure itself can be substantial barriers in developing countries. Additionally, socioeconomic factors intrinsic to specific countries can influence access to HSCT, patient eligibility for HSCT and timely utilization of HSCT center capabilities. This report describes recommendations from the Worldwide Network for Blood and Marrow Transplantation (WBMT) for establishing HSCT programs with a specific focus on developing countries, and identifies challenges and opportunities for providing this specialized procedure in the resource constrained setting.

INDEX-db: The Indian Exome Reference Database (Phase I).

Deep sequencing-based genetic mapping has greatly enhanced the ability to catalog variants with plausible disease association. Confirming how these identified variants contribute to specific disease conditions, across human populations, poses the next challenge. Differential selection pressure may impact the frequency of genetic variations, and thus detection of association with disease conditions, across populations. To understand genotype to phenotype correlations, it thus becomes important to first understand the spectrum of genetic variation within a population by creating a reference map. In this study, we report the development of phase I of a new database of genetic variations called INDian EXome database (INDEX-db), from the Indian population, with an aim to establish a centralized database of integrated information. This could be useful for researchers involved in studying disease mechanisms at clinical, genetic, and cellular levels.

Exome sequencing in families with severe mental illness identifies novel and rare variants in genes implicated in Mendelian neuropsychiatric syndromes.

AIM: Severe mental illnesses (SMI), such as bipolar disorder and schizophrenia, are highly heritable, and have a complex pattern of inheritance. Genome-wide association studies detect a part of the heritability, which can be attributed to common genetic variation. Examination of rare variants with next-generation sequencing may add to the understanding of the genetic architecture of SMI. METHODS: We analyzed 32 ill subjects from eight multiplex families and 33 healthy individuals using whole-exome sequencing. Prioritized variants were selected by a three-step filtering process, which included: deleteriousness by five in silico algorithms; sharing within families by affected individuals; rarity in South Asian sample estimated using the Exome Aggregation Consortium data; and complete absence of these variants in control individuals from the same gene pool. RESULTS: We identified 42 rare, non-synonymous deleterious variants (~5 per pedigree) in this study. None of the variants were shared across families, indicating a 'private' mutational profile. Twenty (47.6%) of the variant harboring genes were previously reported to contribute to the risk of diverse neuropsychiatric syndromes, nine (21.4%) of which were of Mendelian inheritance. These included genes carrying novel deleterious variants, such as the GRM1 gene implicated in spinocerebellar ataxia 44 and the NIPBL gene implicated in Cornelia de Lange syndrome. CONCLUSION: Next-generation sequencing approaches in family-based studies are useful to identify novel and rare variants in genes for complex disorders like SMI. The findings of the study suggest a potential phenotypic burden of rare variants in Mendelian disease genes, indicating pleiotropic effects in the etiology of SMI.

Response of Proliferative Lupus Nephritis with Pulse Cyclophosphamide Therapy during Induction Period: A Single Centre Study in Bangladesh.

This prospective study was conducted to assess the response of proliferative lupus nephritis with pulse cyclophosphamide therapy during induction period in the department of Nephrology of Dhaka Medical College, Dhaka, Bangladesh from December 2012 to November 2013. A total of 35 clinically diagnosed SLE patients of class III/IV lupus nephritis were included. But 3 patients were dropped out during follow-up, therefore finally 32 patients (class III = 4, class IV = 28) were studied. The patients were evaluated for response on the basis of proteinuria, serum creatinine & active sediment in urine after 6th cycle of cyclophosphamide and 62.5% patients achieved complete response, 25% patients achieved partial response & 12.5% patients achieved no response. The factors favored complete response was early clinical presentation (7 months duration), proteinuria ≤3gm/day& normal renal function during their initial presentation. And higher anti ds DNA titre was an independent predictor for partial response/no response.

Cytoplasmic p21 Mediates 5-Fluorouracil Resistance by Inhibiting Pro-Apoptotic Chk2.

The oncogenic cytoplasmic p21 contributes to cancer aggressiveness and chemotherapeutic failure. However, the molecular mechanisms remain obscure. Here, we show for the first time that cytoplasmic p21 mediates 5-Fluorouracil (5FU) resistance by shuttling p-Chk2 out of the nucleus to protect the tumor cells from its pro-apoptotic functions. We observed that cytoplasmic p21 levels were up-regulated in 5FU-resistant colorectal cancer cells in vitro and the in vivo Chorioallantoic membrane (CAM) model. Kinase array analysis revealed that p-Chk2 is a key target of cytoplasmic p21. Importantly, cytoplasmic form of p21 mediated by p21T145D transfection diminished p-Chk2-mediated activation of E2F1 and apoptosis induction. Co-immunoprecipitation, immunofluorescence, and proximity ligation assay showed that p21 forms a complex with p-Chk2 under 5FU exposure. Using in silico computer modeling, we suggest that the p21/p-Chk2 interaction hindered the nuclear localization signal of p-Chk2, and therefore, the complex is exported out of the nucleus. These findings unravel a novel mechanism regarding an oncogenic role of p21 in regulation of resistance to 5FU-based chemotherapy. We suggest a possible value of cytoplasmic p21 as a prognosis marker and a therapeutic target in colorectal cancer patients.

First report of pediatric hematopoietic stem cell transplantation activities in the eastern mediterranean region from 1984 to 2011: on behalf of the pediatric cancer working committee of the eastern mediterranean blood and marrow transplantation group.

To describe the hematopoietic stem cell transplantation (HSCT) activities for children in the Eastern Mediterranean (EM) region, data on transplants performed for children less than 18 years of age between 1984 and 2011 in eight EM countries (Egypt, Iran, Jordan, Lebanon, Oman, Pakistan, Saudi Arabia and Tunisia) were collected. A total of 5187 transplants were performed, of which 4513 (87%) were allogeneic and 674 (13%) were autologous. Overall, the indications for transplantation were malignant diseases in 1736 (38.5%) and non-malignant in 2777 (61.5%) patients. A myeloablative conditioning regimen was used in 88% of the allografts. Bone marrow (BM) was the most frequent source of stem cells (56.2%), although an increasing use of PBSC was observed in the last decade. The stem cell source of autologous HSCT has shifted over time from BM to PBSC, and 80.9% of autologous HSCTs were from PBSCs. The donors for allogeneic transplants were matched-related in 94.5% of the cases, and unrelated transplants, mainly cord blood (99%) in 239 (5.5%) cases. This is the first report to describe the pediatric HSCT activities in EM countries. Non-malignant disorders are the main indication for allogeneic transplantation. Frequency of alternate donor transplantation is low.

A modified indirect mathematical model for evaluation of ethanol production efficiency in industrial-scale continuous fermentation processes.

AIMS: To calculate fermentation efficiency in a continuous ethanol production process, we aimed to develop a robust mathematical method based on the analysis of metabolic by-product formation. METHODS AND RESULTS: This method is in contrast to the traditional way of calculating ethanol fermentation efficiency, where the ratio between the ethanol produced and the sugar consumed is expressed as a percentage of the theoretical conversion yield. Comparison between the two methods, at industrial scale and in sensitivity studies, showed that the indirect method was more robust and gave slightly higher fermentation efficiency values, although fermentation efficiency of the industrial process was found to be low (~75%). CONCLUSIONS: The traditional calculation method is simpler than the indirect method as it only requires a few chemical determinations in samples collected. However, a minor error in any measured parameter will have an important impact on the calculated efficiency. In contrast, the indirect method of calculation requires a greater number of determinations but is much more robust since an error in any parameter will only have a minor effect on the fermentation efficiency value. SIGNIFICANCE AND IMPACT OF THE STUDY: The application of the indirect calculation methodology in order to evaluate the real situation of the process and to reach an optimum fermentation yield for an industrial-scale ethanol production is recommended. Once a high fermentation yield has been reached the traditional method should be used to maintain the control of the process. Upon detection of lower yields in an optimized process the indirect method should be employed as it permits a more accurate diagnosis of causes of yield losses in order to correct the problem rapidly. The low fermentation efficiency obtained in this study shows an urgent need for industrial process optimization where the indirect calculation methodology will be an important tool to determine process losses.

Presentation and Treatment Outcomes of 100 Lupus Nephritis Patients: Single Center Study.

Over a period of 3 years (January 2011 to December 2013) 100 cases of Lupus nephritis patients admitted in nephrology department of Bangabandhu Sheikh Mujib Medical University (BSMMU) were evaluated. Their clinical characteristics, biochemical parameters, renal histology according to WHO classification were categorized and their treatment modalities and outcome was observed. Among 100 patients, 84 were female and 16 were male, with F:M ratio 5:1. Mean age of female were 23±4 years and male were 29±4 years, mean BP in male was systolic 135±8 mmHg, diastolic 80±9mmHg and in female systolic was 130±7mmHg, diastolic 75±6 mmHg, mean Serum Creatinine for male was 180±12µmol/L and mean serum creatinine in female was 170±20µmol/L. Sixty five percent (65%) patient showed extra renal manifestation. All patients presented with proteinuria, among them 45% were nephrotic presentation, 25% patients presented with acute nephritic illness, 15% were nephritic nephrotic, 10% patients had rapidly progressing glomerulonephritis (RPGN), and 5% were with asymptomatic proteinuria. Renal biopsy of 100 patient according to WHO classification showed class I - 5%, class II - 20%, class III - 26%, class IV - 35%, class V - 8%, class VI - 6%. Immunosuppressive protocol used was prednisolone and cyclophorphamide in the majority of patients in class III to class VI LN patients. Few patients received prednisolone and mycophenolate mofetil. Twenty four percent (24%) patients were in complete remission during this study period and 12% developed end stage renal disease (ESRD). Seventy six percent (76%) patients passed through various stages of CKD, majority of them were in CKD stage IV and stage III, and few were in CKD stage I and stage II. About 70% of the participants had suffered from one or more complications, where majority were infections. Infections and renal failure were the leading cause of death in our study.

Assessment of Quality of Life among Children with Bronchial Asthma and their Caregivers at the National Hospital Abuja; Nigeria

Background: The global disease burden associated with bronchial asthma has continued to increase particularly among children. Asthma-related quality of life is a health related assessment of disease impact on patient and care givers.Aim: To determine the perceived quality of life (QOL) among children with bronchial asthma and their caregivers as well as the related factors.Subjects and methods: This was a prospective study of children diagnosed with bronchial asthma and the caregivers attending the Respiratory Clinic of the National hospital Abuja; Nigeria. Using the Paediatric Asthma Quality of Life Questionnaire (PAQLQ) and the Paediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ) information from the various domains was obtained. The PAQLQ 23 questions assessed the child physical domain (5); emotional (8) and social behaviors (10); and the PACQLQ 13 questions assessed the caregivers' activity limitation domain (4) and emotional function (9).Mean QOL scores from each domain and overall scores were calculated based on a seven-point scale. A QOL score of 7 was reported as best with no impairment; score one as least and severest impairment; score 4 as mid point in the range from 2-6 of moderate degree impairment. Other information on the demographic biodata and clinical information from child and caregivers was also obtained.Results: Forty-three children and 43 caregivers each were enrolled; from August to December 2014. Patients were aged 7-15years; 25(58.1%) males; 18(41.9%) females; while caregiver's were males 23(53.5%); females 20(46.5%); age range 21- 48years. 25(58.1%) caregivers were of middle- lower socio-economic status; 20(46.5%) children had persistent asthma; 22(51.2%) well controlled; 21(48.8%) partly controlled. Medication use were; none; 17 (39.5%); long acting beta2 agonist/ inhaled corticosteroids (LABA/ ICS); 13(30.2%); antihistamine; 8 (18.6%); leukotriene receptor antagonist (LTRA);5(11.6%). Overall mean QOL was 4.89(4.54- 5.24;95% CI) for the children and 4.6 (3.91- 4.82; 95% CI) for caregivers; correlation (R) 0.438 p=0.003. Multiple regression showed that females gender had significant impairment in mean QOL scores in the activity domain (p= 0.022); and those with poor control and severe asthma also had significant impairment in mean QOL (p 0.05).Conclusion: Asthma impacted QOL of both the asthmatic children and caregivers with female gender in the activity domain; severe and not well controlled disease as independent predictors of quality of life

Review of childhood measles admissions at the National Hospital, Abuja.

BACKGROUND: The global disease burden from measles as a vaccine preventable disease remains high despite decades of interventions by various organs and agencies. OBJECTIVES: To determine the prevalence and outcome of childhood cases of measles admitted into the children's emergency ward of the National hospital and highlight the possible contributing factors. DESIGN: Retrospective. SUBJECTS: A total number of 43 children with measles presenting at the National Hospital Abuja, seen over a 40 months period; January 2002 and April 2005. METHODS: Cases-folders of patients seen at the Emergency Paediatric Unit (EPU) of the National Hospital Abuja during the period under review with the clinical diagnosis of measles were reviewed. RESULTS: The children were aged between seven to 12months, with 25 (58.1%) age 24months and below. Twenty three (53.5%) of the subjects had received prior measles vaccination. History of contact with cases of acute measles was present in 26 (60.5%). Associated protein energy malnutrition (PEM) was found in 30 (69.8%) with 28 (65.1 %) parents of these children being of lower social economic classes (III, IV &V). Recorded complications included gastroenteritis, bronchopneumonia, laryngo-tracheo-bronchitis as part of croup syndrome, tuberculosis, and otitis media. Three fatalities (7.0%) were record in this review, all in association with bronchopneumonia. CONCLUSION: Measles with its complications still present as a fatal illness even among vaccinated children.

Review of Childhood Measles Admissions at the National Hospital, Abuja

Background: The global disease burden from measles as a vaccine preventable disease remains high despite decades of interventions by various organs and agencies. Objectives: To determine the prevalence and outcome of childhood cases of measles admitted into the children's emergency ward of the National hospital and highlight the possible contributing factors. Design: Retrospective. Subjects : A total number of 43 children with measles presenting at the National Hospital Abuja; seen over a 40 months period; January 2002 and April 2005. Methods: Cases-folders of patients seen at the Emergency Paediatric Unit (EPU) of the National Hospital Abuja during the period under review with the clinical diagnosis of measles were reviewed. Results: The children were aged between seven to 12months; with 25 (58.1) age 24 months and below. Twenty three (53.5) of the subjects had received prior measles vaccination. History of contact with cases of acute measles was present in 26 (60.5). Associated protein energy malnutrition (PEM) was found in 30 (69.8) with 28 (65.1) parents of these children being of lower social economic classes (III; IV etV). Recorded complications included gastroenteritis; bronchopneumonia; laryngo-tracheo-bronchitis as part of croup syndrome; tuberculosis; and otitis media. Three fatalities (7.0) were record in this review; all in association with bronchopneumonia. Conclusion : Measles with its complications still present as a fatal illness even among vaccinated children

Examining the effectiveness of a peer-led education programme for Type 2 diabetes and cardiovascular disease in a Bangladeshi population.

AIMS: The aim of this study was to assess an adapted version of the X-PERT Programme for Type 2 diabetes within a Bangladeshi population. METHODS: Bangladeshi adults, living in the UK, with Type 2 diabetes participated in a diabetes educational session based on an adapted version of the X-PERT Programme. Participants attended a session, led by a trained peer educator and carried out in Sylheti. All participants who registered on the course were telephoned or visited in person the day before the course as a reminder. RESULTS: Registration to attend the course was excellent. However, actual attendance rates were 58% (42/72) out of those registered. Once participants attended, overall they enjoyed attending the sessions and felt they benefited as they understood more about how to better self-manage their condition. Those aspects of the sessions that were most enjoyed were group discussions and interactive posters to explain diabetes. Participants requested a home-based exercise guide, which was developed by the research team. The study was underpowered to show behaviour change, but did demonstrate a trend to improvement in self-care activities. All participants reported recommending the course to others. CONCLUSIONS: There was an excellent response in terms of registration for the course. However, the time to attend the course appeared to be a barrier to participants. Nevertheless, for those attending the course, responses were very positive. The amended X-PERT Programme could be used as a component of a package to improve outcome and self-management for people with diabetes in the Bangladeshi community.

Intervention, recruitment and evaluation challenges in the Bangladeshi community: experience from a peer lead educational course.

BACKGROUND: The incidence of Type 2 diabetes is increasing worldwide and diabetes is four times more common among ethnic minority groups than among the general Caucasian population. This study reflects on the specific issues of engaging people and evaluating interventions through written questionnaires within older ethnic minority groups. METHODS: The original protocol set out to evaluate an adapted version of the X-PERT patient program http://www.xpert-diabetes.org.uk/ using questionnaires and interviews. RESULTS: Questionnaires, even verbally completed, were unsuccessful and difficult to administer as participants found the questionnaire structure and design difficult to follow and did not perceive any benefit to completing the questionnaires. The benefits of attending the course were also poorly understood by participants and in many cases people participated in coming to the course as a favour to the researcher. Engaging participants required word of mouth and the involvement of active members of the community. CONCLUSION: Peer led courses and their evaluation in older ethnic minority communities needs a very different approach for that in younger Caucasian patients. A structured approached to evaluation (favoured by western educational system) is inappropriate. Engaging participants is difficult and the employment of local well known people is essential.

Allogeneic stem cell transplantation in hematological disorders: single center experience from Pakistan.

One hundred and fifty-four patients received allogeneic stem cell transplantations from HLA-matched siblings for various hematological disorders from July 2001 to September 2006. Indications for transplantation included aplastic anemia (n=66), beta-thalassemia major (n=40), CML (n=33), acute leukemia (n=8), and miscellaneous disorders (n=7). One hundred and twenty patients were males and 34 were females. Median patient age was 14 years (range, 1(1/4)-54 years). All patients achieved successful engraftment. Median time to engraftment (ANC>0.5x10(9)/L) was 14 days. Posttransplant complications encountered in our patients included acute graft versus host disease (GvHD) (grade II-IV) 28.5%, chronic GvHD 15.5%, hemorrhagic cystitis 9.7%, VOD liver 5.1%, acute renal failure 3.2%, bacterial infections 51.2%, fungal infections 15.0%, cytomegalovirus (CMV) infection 4%, herpes zoster 4%, tuberculosis 2.6%, Pneumocystis jirovicii infection 0.6%, malaria 0.6% patients, graft rejection 5.2% patients, and relapse in 4% patients. Certain unexpected and rare posttransplant complications were also observed in our patients. These included Hickman catheter embolization, Guillain-Barré (GB) syndrome, deep vein thrombosis, hemorrhagic pericarditis with clots leading to cardiac tamponade, idiopathic polycythemia, dengue fever, and cyclosporine-induced neurotoxicity. Mortality was observed in 27.2% patients. Major causes of mortality were GvHD, VOD, disease relapse, intracranial hemorrhage, acute renal failure, pseudomonas septicemia, tuberculosis, disseminated aspergillosis, and CMV infection. At 5 years, overall survival (OS) and disease-free survival (DFS) rates were 72.5% and 70.7%, respectively.

Allogeneic bone marrow transplantation in beta-thalassaemia--single centre study.

OBJECTIVE: To evaluate outcome of allogeneic BMT in beta-Thalassaemia at the Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan from August 2001 to November 2003. METHODS: Nineteen patients with beta-Thalassaemia underwent allogeneic BMT/PBSC transplantation from HLA identical sibling donors. Patients were classified in three groups according to Pesaro (Italy) risk classification. Class-I (n = 9) and Class-II (n = 7) patients received conditioning with busulphan/cyclophosphamide, whereas Class-III (n = 3) patient received conditioning with hydroxyurea, azathioprine, fludarabine, along with Bu14 / Cy 200. Cyclosporine, prednisolone and methotrexate were given for GvHD prophylaxis. Stem cells dose infused was >4.0 x 10(8)/kg body weight of the patient. RESULTS: Engraftment was achieved in all Class-I patients, whereas in Class-II and Class-III , graft rejection was observed in one patient from each class. Median time to achieve absolute neutrophil recovery (> 0.5 x 10(9)/l) was 13 days, platelet count (> 20 x 10(9)/1) was 15 days and reticulocyte count (>0.5%) was 15 days. Acute GvHD was observed in 15 patients. One patient developed grade IV GvHD (liver and skin) and died within 30 days post BMT. Post transplant infectious complications were pseudomonas septicemia, disseminated fungal infection, CMV pneumonia and tuberculosis. Three patients died of these complications during post transplant period (31-90 days). Median stay in hospital was 25 days. CONCLUSION: Allogeneic BMT is the only curative therapy for beta-Thalassaemia patients, however the success rate can be increased if the patients are selected carefully and transplanted at an early age.