Deaths due to dengue fever at a tertiary care hospital in Lahore, Pakistan.

OBJECTIVE: We conducted this study to review deaths due to dengue fever (DF) during a large outbreak of DF in Lahore, Pakistan. METHODS: We reviewed deaths due to DF at Jinnah Hospital Lahore between August and November 2011. Clinical and laboratory data were abstracted. The 2011 World Health Organization Regional Office for South-East Asia (WHO SEARO) guidelines were used to classify the disease. RESULTS: Out of 128,634 probable DF patients who visited the outpatient department, 2313 patients were hospitalized; 1699 (73.3%) were male. RT-PCR was positive in 92 of 114 hospitalized patients (DENV-2 in 91 patients and DENV-3 in 1 patient). Sixty dengue-related deaths were reported; 41 (68.3%) were male. The mean age (± standard deviation) was 44 (± 20.5) y. The diagnosis at the time of presentation was DF in 5 (8.3%), dengue haemorrhagic fever without shock in 16 (26.6%), dengue shock syndrome in 20 (33%), and expanded dengue syndrome in 19 (31.7%) patients. Expanded dengue syndrome included encephalopathy in 12 (20%) patients, intracerebral bleed in 3 (5%), multiorgan failure in 3 (5%), and Guillain-Barré syndrome in 1 (1.6%). Twenty-nine (48.3%) patients had at least 1 comorbidity. CONCLUSION: Dengue shock syndrome and expanded dengue syndrome were the most common causes of death.

Effectiveness of platelet transfusion in dengue Fever: a randomized controlled trial.

BACKGROUND: Scientific data regarding effects of platelet transfusion on platelet count in dengue-related thrombocytopenia is scanty. METHODS: A single center, randomized non-blinded trial was conducted on adult patients with dengue fever and platelet counts less than 30,000/µl. Patients were randomized to treatment and control group. Treatment group received single donor platelets. Patients with post-transfusion platelet increment (PPI) ≥10,000/µl and/or corrected count increment (CCI) ≥5,000/µl 1 h post-transfusion were considered responders. Primary outcome was platelet count increments at 24 and 72 h. RESULTS: 87 patients were enrolled, and 43 (48.2%) received platelet transfusion. Mean PPI and CCI at 1 h post-transfusion in the treatment group were 18,800/µl and 7,000/µl respectively. 22 (53.6%) patients in the treatment group were non-responders. Mean platelet increments at 24 and 72 h were higher in the treatment group as compared to the control group. Responders showed significantly higher increments when compared to non-responders and the control group at 24 h (p = 0.004 and p ≤ 0.001, respectively) and 72 h (p = 0.001 and p ≤ 0.001, respectively). Significant differences were found between non-responders and the control group at 24 h (p ≤ 0.001), but not at 72 h (p = 0.104). Patients with lower baseline platelet count were more likely to be non-responders. Platelet transfusion neither prevented development of severe bleeding nor shortened time to cessation of bleeding. Three severe transfusion reactions and two deaths occurred in treatment group. CONCLUSION: In this trial, almost half the patients showed no response to a high-dose platelet transfusion. Platelet transfusion did not prevent development of severe bleeding or shorten time to cessation of bleeding and was associated with significant side effects. Therefore, platelet transfusion should not be routinely done in the management of dengue fever.

Nicotinic Acid as a Phosphate-lowering Agent in Patients with End-stage Renal Disease on Maintenance Hemodialysis: A Single-center Prospective Study.

Background Hyperphosphatemia increases the risk of mortality and morbidity in patients with end-stage renal disease (ESRD). In addition to dietary restriction and renal replacement therapy, phosphorus-binding agents are the mainstay of treatment. While the use of calcium-containing binders has certain limitations, non-calcium-based binders are expensive and not readily available in developing countries. Previous studies on nicotinic acid as a phosphorus-lowering agent have limited data. In this study, we evaluated the efficacy of nicotinic acid in patients with ESRD on hemodialysis (HD) in Pakistan. Methods Forty-five patients with ESRD on maintenance HD having serum phosphorus levels >5.5 mg/dL were recruited. Nicotinic acid 250 mg was administered with food for four weeks. All patients with serum phosphorus levels <8 mg/dL were placed on a twice-daily regimen while the rest received it three times a day with meals. Patients were assessed at the beginning and end of the study with serum phosphorus levels. Results Mean age of the sample population was 44.6 ± 13.9 years and 57.8% of participants were male. Serum phosphorus level before treatment ranged from 5.6 to 10.8 mg/dL (mean, 6.91 ± 1.33). After nicotinic acid therapy, it ranged from 2.60 to 8.70 mg/dL (mean, 5.82 ± 1.40). Mean decrease in serum phosphorus levels with nicotinic acid after one month of treatment was 1.08 ± 1.16 mg/dL (p-value <0.001). Conclusion Nicotinic acid is effective in lowering serum phosphorus levels in patients with ESRD who are under renal replacement therapy with maintenance HD.

Characteristics and Outcome of Obstetric Acute Kidney Injury in Pakistan: A Single-center Prospective Observational Study.

Introduction Acute kidney injury (AKI) continues to be a cause of increased morbidity and mortality in pregnant women. While studies have been conducted on the incidence and etiology of this complication, the outcomes of obstetric AKI have not been extensively investigated. The primary focus of this prospective observational study was to analyze the risk factors, etiologies as well as maternal and fetal outcomes of AKI in pregnant females in Pakistan. Methods A total of 56 patients with obstetric AKI were recruited. Patients were followed for a period of three months postpartum. The diagnosis and staging of AKI were based on the classification of the Acute Kidney Injury Network (AKIN). Results Fifteen patients were lost to follow-up and were excluded from the study. The mean age of the remaining 41 patients was 26±6 years. Twenty-two (54%) patients were multigravida, and 19 (46%) were primigravida. Twenty (48%) patients did not receive any antenatal care, 13 (31%) were visited by a traditional birth attendant, and only eight (19%) had adequate antenatal care by a gynecologist. Out of 41 patients, seven (17%) presented before 28 weeks, and 34 (83%) patients presented after 28 weeks of gestation. Four (10%) patients were found to be in stage I, four (10%) in stage II, and 33 (80%) patients in stage III AKI during hospitalization. The causes of AKI included sepsis in 32 (78%), intrauterine death in 24 (60%), postpartum hemorrhage in 17 (41%), shock in 15 (36%), pre-eclampsia/eclampsia in seven (17%), and coagulopathy in three (7%) patients. Twenty-eight (68.3%) patients received hemodialysis during the hospital stay. Three-month follow-up showed complete resolution of AKI in 14 (34.2%) patients, partial resolution in seven (17%), end-stage renal disease in 10 (24.4%), and death in 10 (24.4%) patients. Conclusion The present study indicates that a vast majority of patients with obstetric AKI require dialysis. Residual renal dysfunction and end-stage renal disease were common at the three-month follow-up. Incidentally, sepsis and intrauterine death were the leading causes in this study population. Increased awareness and appropriate obstetrical care may have a significantly positive impact on decreasing the morbidity and mortality in these patients.

The development of malnutrition is not dependent on its traditional contributing factors in patients on maintenance hemodialysis in developing countries.

Malnutrition in dialysis population is associated with significant morbidity and mortality. Nutritional assessment is a neglected area in hemodialysis (HD) patients in developing countries. The aim of the study was to find out whether any traditional parameters have statistically significant correlation with malnutrition. All 58 end-stage renal disease patients on maintenance HD in our dialysis unit were enrolled in this cross-sectional study. The nutritional status was assessed by a predesigned questionnaire including subjective global assessment (SGA). Anthropometric measurements, peripheral neuropathy, and pertinent laboratory parameters were checked. The duration of HD ranged between three months to 10 years (mean 4 ± 1.5 years). Of these 49 patients, 26 (53%) were males with a median age 45 (25-76) years. Fifteen patients (31%) were well nourished and 34 (69%) were undernourished including nine (19%) patients classified as severely malnourished according to SGA. Malnutrition appeared more prevalent in males, however, statistically not significant (P = 0.063). On univariate and multivariate analysis, no significance was found across well-nourished and malnourished patients in terms of age, body mass index, calorie count, duration and frequency of dialysis, dry weight, interdialytic weight loss or gain in the past six months, body fat percentage, serum albumin, blood pressure, intradialytic hypotension, urea reduction ration, Kt/Vurea, peripheral neuropathy, and comorbidities. Psychosocial factors were identified in 24 (49%) patients with 19 (79%) having some degrees of malnutrition, but the finding did not reach the statistical significance. Surprisingly, the traditional factors studied in previous trials have not shown any significant association to malnutrition in our study based on the statistical analysis.

Cardiovascular Autonomic Neuropathy and its Association with Cardiovascular and All-cause Mortality in Patients with End-stage Renal Disease.

Background End-stage renal disease frequently leads to increased cardiovascular mortality. Cardiovascular autonomic neuropathy (CAN) may be predictive of cardiac arrhythmias and sudden cardiac death in patients with end-stage renal disease. Methods A total of 70 patients with end-stage renal disease were included in the study. The assessment of cardiac dysautonomia was based on the four standardized tests performed at the baseline and, again, at the end of the study. The criteria for CAN included at least two abnormal test results. Results Fifty of 70 patients completed the study and were followed-up after one year. Out of the 50 patients, 44 (88%) had CAN at baseline. Twelve (24%) patients died at the one-year follow-up. Sudden cardiac death was reported in seven out of 12 (58%) patients. All seven patients who died had high dysautonomia scores (three abnormal tests) at the baseline. There was a significantly higher percentage of patients with all four abnormal tests amongst patients who died of any cause (56% vs. 17%; RR 6.07, 95% CI 1.29-28.49; p-value 0.02) or due to sudden cardiac death (43% vs. 10.5%; RR 6.37, 95% CI 1.03-39.36; p-value 0.04). All five patients who did not have CAN at the baseline developed this abnormality on repeat testing after one year. Conclusion The prevalence of CAN in patients with end-stage renal disease on maintenance hemodialysis was significantly higher. CAN was an independent predictor of all-cause and cardiovascular mortality, which highlights it as a risk stratification tool in patients with end-stage renal disease.

Concurrent dengue and malaria infection in Lahore, Pakistan during the 2012 dengue outbreak.

INTRODUCTION: We conducted this study to determine the frequency of malaria and dengue-malaria co-infection in patients admitted to our hospital as 'probable' cases of dengue fever during the 2012 outbreak of dengue, and to ascertain whether dengue-malaria co-infection was more severe than either infection alone. METHODS: This cross-sectional observational study was conducted at Jinnah Hospital Lahore, Pakistan between August and November 2012. Patients with 2-10 days of fever and with two or more of the following: myalgia, arthralgia, retro-orbital pain, headache, skin rash, and hemorrhagic manifestations plus thrombocytopenia and leukopenia, were classified as probable cases of dengue fever and were subjected to reverse transcriptase (RT)-PCR and/or dengue-specific IgM by ELISA. The diagnosis of malaria was established on thick and thin blood film microscopy. Severe disease was defined by the presence of an altered level of consciousness, World Health Organization grade ≥2 bleeding, jaundice, circulatory shock, hemoglobin <50g/l, platelet count <50×10(9)/l, serum creatinine >265µmol/l, or death. RESULTS: There were 85 probable cases of dengue fever. Sixty-four (75%) were male and the median age was 22 years (range 12-90 years). Of 52 patients for whom results of diagnostic tests for both dengue and malaria were available, five (10%) had isolated dengue infection, 18 (35%) isolated Plasmodium infection, and 17 (33%) dengue-malaria co-infection. Thirty-five out of 52 (67%) probable cases had malaria and 17 out of 22 (77%) dengue-specific IgM reactive patients had concurrent malaria. Patients with isolated malaria had significantly lower median hemoglobin concentrations (124.5g/l vs. 144.0 g/l, p = 0.04) and median hematocrit (36.0 vs. 41.7, p=0.02) at presentation than cases of isolated dengue. Patients with dengue-malaria co-infection had a significantly lower rate of jaundice than those with isolated dengue (0% vs. 40%, p = 0.04). The frequency of severe disease was comparable amongst the three groups; this was seen in five (100%) cases of isolated dengue, 17 (94%) cases of isolated malaria, and 16 (94%) cases of dengue-malaria co-infection. CONCLUSIONS: The rate of isolated malaria and dengue-malaria co-infection was high in probable cases of dengue fever in our study. Except for jaundice, we could not find any significant between-group differences in the severity of the disease.

An outbreak of pyrimethamine toxicity in patients with ischaemic heart disease in Pakistan.

We investigated an outbreak of darkening of skin, bleeding from multiple sites, leucopenia and thrombocytopenia in ischaemic heart disease patients. Case patients were defined as patients who had received medicines from the pharmacy of Punjab Institute of Cardiology between 1 December 2011 and 12 January 2012 and who developed any one of the following: darkening of skin, bleeding from any site, thrombocytopenia and leucopenia. Clinical and drug-related data were abstracted. All 664 case patients had received iso-sorbide-mono-nitrate contaminated with about 50 mg of pyrimethamine, and 151 (23%) died. The median age of 117 patients admitted at Jinnah Hospital Lahore was 57 years (range, 37-100) and 92 (79%) were male. The median time from intake of medicine to presentation was 37 days (range 13-72). Symptoms and signs included bleeding (in 95% of the patients), skin hyperpigmentation (in 61%), diarrhoea (in 53%) and abdominal pain (in 48%). At presentation, the median white cell count was 2.3 × 10(9) /L (range, 0.1 × 10(9) -16.0 × 10(9) ), the median hemoglobin concentration was 109 g/L (range 58-169) and the median platelet count was 18 × 10(9) /L (range, 0 × 10(9) -318 × 10(9) ). Bone marrow examination revealed trileneage dysplasia and severe megaloblastosis. The predictors of mortality included presentation prior to 15 January 2012, age more than 57 years, hypotension and leukocyte count less than 1.5 × 10(9) /L. None of the patients who died received Calcium folinate because all deaths occurred prior to contaminant identification. We describe an outbreak of pyrimethamine toxicity in ischaemic heart disease patients receiving medicines from a single pharmacy due to accidental contamination of iso-sorbide mono-nitrate tablets at industrial level. Late recognition of illness resulted in high mortality.