Single Center In Pakistan Research Articles

Clinicopathological features and medium-term outcomes of histologic variants of primary focal segmental glomerulosclerosis in adults: A retrospective study.

The Columbia classification identified five histological variants of focal segmental glomerulosclerosis (FSGS). The prognostic significance of these variants remains controversial. To evaluate the relative frequency, clinicopathologic characteristics, and medium-term outcomes of FSGS variants at a single center in Pakistan. This retrospective study was conducted at the Department of Nephrology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan on all consecutive adults (≥ 16 years) with biopsy-proven primary FSGS from January 1995 to December 2017. Studied subjects were treated with steroids as a first-line therapy. The response rates, doubling of serum creatinine, and kidney failure (KF) with replacement therapy were compared between histological variants using ANOVA or Kruskal Wallis, and Chi-square tests as appropriate. Data were analyzed by SPSS version 22.0. P-value ≤ 0.05 was considered significant. A total of 401 patients were diagnosed with primary FSGS during the study period. Among these, 352 (87.7%) had a designated histological variant. The not otherwise specified (NOS) variant was the commonest, being found in 185 (53.9%) patients, followed by the tip variant in 100 (29.1%) patients. Collapsing (COL), cellular (CEL), and perihilar (PHI) variants were seen in 58 (16.9%), 6 (1.5%), and 3 (0.7%) patients, respectively. CEL and PHI variants were excluded from further analysis due to small patient numbers. The mean follow-up period was 36.5 ± 29.2 months. Regarding response rates of variants, patients with TIP lesions achieved remission more frequently (59.5%) than patients with NOS (41.8%) and COL (24.52%) variants (P < 0.001). The hazard ratio of complete response among patients with the COL variant was 0.163 [95% confidence interval (CI): 0.039-0.67] as compared to patients with NOS. The TIP variant showed a hazard ratio of 2.5 (95%CI: 1.61-3.89) for complete remission compared to the NOS variant. Overall, progressive KF was observed more frequently in patients with the COL variant, 43.4% (P < 0.001). Among these, 24.53% of patients required kidney replacement therapy (P < 0.001). The hazard ratio of doubling of serum creatinine among patients with the COL variant was 14.57 (95%CI: 1.87-113.49) as compared to patients with the TIP variant. In conclusion, histological variants of FSGS are predictive of response to treatment with immunosuppressants and progressive KF in adults in our setup.

A randomized, double-blind, positive-controlled, Phase-II clinical trial to evaluate efficacy and safety of Fuke Qianjin capsule in Pakistani patients with pelvic inflammatory disease.

Ethnopharmacological relevance: Pelvic inflammatory disease (PID) is a frequently occurring gynecological disorder mainly caused by the inflammation of a woman's upper genital tract. Generally, antibiotics are used for treating PID, but prolonged use poses potential risks of gut bacterial imbalance, bacterial resistance, super bacteria production, and associated adverse reactions. Traditional Chinese medicine (TCM) has shown unique advantages in various ailments and has received widespread clinical research attention. Fuke Qianjin (FUKE) capsule is an approved National Medical Products Administration (NMPA License No. Z20020024) Chinese herbal prescription that has been widely used individually or in combination with other Western medicines for the treatment of various gynecological inflammatory diseases, including chronic cervicitis, endometritis, and chronic PID. Aim: This clinical trial was designed to assess the safety and efficacy of FUKE capsule in mild-to-moderate symptomatic PID patients. Materials and methods: This phase 2, randomized, double-blind, positive controlled clinical trial was conducted in mild-to-moderate symptomatic PID patients at a single center in Pakistan from 21 September 2021 to 11 March 2022. Eligible female participants were randomly assigned to a test and a control group with a ratio of 1:1. The test group subjects received two metronidazole (METRO) tablets and one doxycycline hyclate (DOXY) simulant at a time, twice daily for 14 days, and two Fuke Qianjin (FUKE) capsules, three times a day after a meal for 28 days. Subjects in the control group received two METRO tablets and one DOXY tablet at a time, twice daily for 14 days, and two FUKE simulant capsules, three times a day after meal for 28 days. The primary efficacy outcome was an improvement in pelvic pain symptoms assessed through a visual analog scale (VAS). The secondary outcomes were the improvement in secondary efficacy symptoms like local physical signs, clinical assessment of leucorrhea and cervical secretions through laboratory examination, and improvement in the maximum area of pelvic effusion assessed through gynecological ultrasound after the treatment. The safety outcomes were assessed through vital signs, laboratory tests, electrocardiogram findings, and adverse events/serious adverse events. Results: A total of 198 subjects with active PID were randomly assigned to a test group (n = 99) and a control group (n = 99). The baseline characteristics of the subjects in the two groups were similar. In the intention-to-treat analysis, the primary efficacy was 84.9% for the test group and 71.6% for the control group, with a statistically significant difference (p = 0.0370; 95% CI -0.2568 to -0.0088). The secondary clinical efficacy was 88.4% for the test group and 82.7% for the control group, with no significant difference (p = 0.2977; 95% CI -0.1632 to 0.0501). The improvement in local physical signs was 95.8% for the test group and 76.9% for the control group, with no significant difference (p = 0.0542; 95% CI -0.3697 to -0.0085). The inter-group non-inferiority comparison showed that the upper limit of the 95% CI was less than 0.15 and thus met the non-inferiority requirements of the test group to the control group. The results of clinical signs of leucorrhea and cervical secretions showed that there was no difference in the rate of improvement between the test and control groups, indicating that FUKE was non-inferior to DOXY. A total of 14 adverse events in eight subjects were observed in the trial, with an incidence rate of 4.7%. Four subjects in each group experienced seven adverse events with 4.5% and 4.8% incidence rates of adverse reactions in the test and control groups, with no statistically significant differences (p = 0.2001). No serious adverse events occurred in the trial. Conclusion: The results of this trial indicate that the test drug (Fuke Qianjin capsule) is non-inferior to the control drug (doxycycline hyclate tablet) in treating mild-to-moderate PID patients with comparable efficacy, safety, and tolerability to the control drug. Clinical Trial Registration: www.clinicaltrials.gov, identifier NCT04723069.

Clinical Characteristics and Cytogenetics of Childhood Acute Lymphoblastic Leukemia in a Single Center in Pakistan.

Objectives. This study aimed to find the association between clinical characteristics, cytogenetics, and post-induction outcomes of childhood acute lymphoblastic leukemia. Methods. The study was conducted at the Indus Hospital in Karachi. Initial total leukocyte count (TLC), cytogenetics, CNS status, and post-induction remission status were recorded. Results. Out of 108 children diagnosed with ALL, 66 (61.1%) were male and 42 (38.9%) were female. The majority 90 (83.3%) had B-ALL. CNS1 status was observed in 76 (84.4%) B-ALL and 18 (88.9%) T-ALL. All T-ALL and 89 (98.8%) B-ALL achieved remission post-induction. In B-ALL, 50 (55.5%) had a normal diploid karyotype, and 22 (24.4%) had numerical abnormalities. No typical gene rearrangement was observed in 66 (73.3%), 11 (12.2%) had BCR::ABL1, 10 (11.1%) had ETV6::RUNX1 and 3 (3.3%) KMT2A on FISH. No significant difference was observed between cytogenetics and clinical characteristics (P > .05). Conclusion. The study provides valuable data on childhood acute lymphoblastic leukemia in the Pakistani population.

1090. Factors effecting mortality among Covid-19 patients in Renal Transplant Recipients from a single center in Pakistan

Abstract Background Corona virus disease-19 (Covid-19) has significantly affected organ transplantation with concerns regarding severe infection and mortality. Data on Covid-19 in renal transplant recipients (RTRs) is scarce from Pakistan. The aim of this study is find out the factors effecting mortality among Covid-19 patients in renal transplant recipients from the largest transplant center of Pakistan. Methods All RTRs &amp;gt;18 years, with positive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) polymerase chain reaction (PCR) and diagnosed as severe disease, between April to December 2020 were retrospectively reviewed. The severe disease was defined as O2 saturation &amp;lt; 94% at room air on admission. Survivors and non- survivors were compared. Demographics, immunosuppression, comorbid conditions, clinical features, laboratory investigations and graft function were noted. Results A total of 95 RTRs had severe disease. There was no difference in mortality between age, gender and co-morbid conditions among survivors and non-survivors. Both groups received similar immunosuppressive regimen. Intensive care unit (ICU) admission [16.5% vs 68.8% p&amp;lt; 0.001 OR 11.17 95% CI (3.3-37.6)] and high D-dimers &amp;gt;1.5µg/ml (p=0.052) at the time of admission were significantly associated with mortality. There was no association of graft function with mortality. Treatment with methyl-prednisolone was found to be significantly associated with survival [83% vs 43% P=0.02 OR 0.15 95% CI (0.05-0.49)]. (Table 1) WHO grading of the disease is shown in figure 1, there was a 100% mortality among patients on mechanical ventilator. Figure 1:WHO clinical grading of severe diseaseTable 2:Comparison between survivors and non-survivors among patients with severe disease Conclusion ICU admission and high D-dimers at the time of admission are the significant risk factors for mortality in patients with Covid-19 infection. There was no association of graft dysfunction with mortality. Steroids use has significantly improved survival in renal transplant recipients with severe Covid-19 infection. Disclosures All Authors: No reported disclosures.

314.6: Factors Effecting Mortality Among COVID-19 Patients in Renal Transplant Recipients From a Single Center in Pakistan

Introduction: Corona virus disease-19 (Covid-19) has significantly affected organ transplantation with concerns regarding severe infection and mortality. Data on Covid-19 in renal transplant recipients (RTRs) is scarce from Pakistan. The aim of this study is find out the factors effecting mortality among Covid-19 patients in renal transplant recipients from the largest transplant center of Pakistan. Methods: All RTRs >18 years, with positive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) polymerase chain reaction (PCR) and diagnosed as severe disease, between April to December 2020 were retrospectively reviewed. The severe disease was defined as O2 saturation <94% at room air on admission. Survivors and non-survivors were compared. Demographics, immunosuppression, comorbid conditions, clinical features, laboratory investigations, and graft function were noted. Results: A total of 95 RTRs had severe disease. There was no difference in mortality between age, gender, and co-morbid conditions among survivors and non-survivors. Both groups received a similar immunosuppressive regimen. Intensive care unit (ICU) admission [16.5% vs 68.8% p<0.001 OR 11.17 95% CI (3.3-37.6)] and high D-dimers >1.5µg/ml (p=0.052) at the time of admission were significantly associated with mortality. There was no association of graft function with mortality. Treatment with methyl-prednisolone was found to be significantly associated with survival [83% vs 43% P=0.02 OR 0.15 95% CI (0.05-0.49)]. (Table 1) WHO grading of the disease is shown in figure 1, there was a 100% mortality among patients on a mechanical ventilator.Conclusion: ICU admission and high D-dimers at the time of admission are the significant risk factors for mortality in patients with Covid-19 infection. There was no association of graft dysfunction with mortality. Steroids use has significantly improved survival in renal transplant recipients with severe Covid-19 infection.

Tocilizumab and Cytokine Release Syndrome in COVID-19 Pneumonia: Experience From a Single Center in Pakistan.

BackgroundTocilizumab (TCZ), an interleukin-6 (IL-6) receptor blocker, emerged as a treatment for cytokine release syndrome (CRS) in patients with severe COVID-19 pneumonia. The main objective of the study is to discuss the treatment response of TCZ in severe and critically ill patients with COVID-19 pneumonia. Patient demographics, laboratory parameters before and after TCZ therapy, and clinical outcomes in 20 patients in a single center were prospectively reviewed.ResultsOut of 120 patients, 96 (80%) were males and 24 (20%) were females. Only eight (10%) patients did not have any previously known comorbidity. There were 78 (65%) patients with severe disease, while 42 (35%) have critically severe disease. Of the 120 patients, only 36 required a second dose of TCZ in our study based on clinical background. Neutrophils and C-reactive protein (CRP) levels were observed to be raised in all patients, while lymphopenia was observed in 114/120, and D-dimer levels were elevated in 102 (85%) patients. After the second dose of tocilizumab, 102 (85%) patients reduced oxygen requirement within four days, and 14 patients were removed on the second dose of tocilizumab on clinical grounds. Of these 120 patients, in two weeks, 30 (25%) were discharged. Within three weeks, 60 of them were discharged, while 12 were discharged after three weeks, and 18 patients died in our study despite treatment.ConclusionTCZ appeared to be a good treatment option in patients with CRS and severe and critical pneumonia, and for patients with raised IL-6 levels despite single TCZ therapy, a repeat dose is recommended.

Bridging the gaps in secondary fracture prevention at a single center in Pakistan—compliance with the IOF best practice framework

The International Osteoporosis Foundation (IOF) formulated a set of best practice framework as an international benchmark for secondary fracture prevention (SFP) and fracture liaison services (FLS), delineating essential elements of service delivery. The aim of this audit was to assess compliance with the IOF standards for patients ≥ 50years presenting with fragility hip fractures at a tertiary care center in Pakistan. A retrospective sample of hip fracture cases from Jan 2019 to Dec 2019, treated at the section of Orthopedic Surgery, Aga Khan University, Karachi, was conducted. After excluding high energy trauma cases and patients younger than 50years of age, medical records were audited, using a pre-structured Performa based on IOF standards. Compliance level of 0, 1, 2, and 3 was recorded as defined by IOF. Microsoft excel was used for data analysis. A compliance level of 3 was recorded for patient identification and fall prevention services, whereas level 1 was attained for database maintenance for 25 (100%) cases. For medication initiation, level 0 was recorded for all the cases; however, 8 (32%) cases were prescribed calcium and vitamin D supplements. For the standards, including post-fracture assessment timing, evaluation of secondary causes of osteoporosis, multifaceted assessment, medication review, communication strategy, and long-term management, a level 0 was noted for 25 (100%) cases. Moreover, no recommended assessment guidelines were followed uniformly. The care gaps identified require substantial efforts to ensure adequate implementation of the overall best practice standards for SFP, necessitating the need for FLS initiation and establishment of fracture care pathway.

Influence of Rifampicin Pre-treatment on the In vivo Pharmacokinetics of Metoclopramide in Pakistani Healthy Volunteers Following Concurrent Oral Administration.

Metoclopramide is metabolized by various cytochrome P450 (CYP) enzymes such as CYP3A4, CYP1A2, CYP2D6, CYP2C9, and CYP2C19. Rifampicin is a non-selective inducer of P-glycoprotein (P-gp) and CYP enzymes such as CYP3A4 and others. This study was aimed at the evaluation of rifampicin's enzyme induction effect on the pharmacokinetic parameters of orally administered metoclopramide. This randomized, single-blind, two-phase cross-over pharmacokinetic study separated by a 4-week washout period was conducted at a single center in Pakistan. It involved twelve Pakistani healthy male volunteers (nonsmokers) divided into two groups. In the reference phase, each volunteer received a single oral dose of 20 mg metoclopramide (Maxolon 10 mg, GlaxoSmithKline, Pakistan), while in the rifampicin-treated phase, each volunteer received 600 mg rifampicin once daily for 6 days through oral route. On day 6, metoclopramide (20 mg) was administered 2 hours after the last pretreatment dose of rifampicin. The serial blood samples were collected on predetermined time points (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, and 18 h) and analyzed using a validated HPLC method for the determination of pharmacokinetic parameters, i.e. Cmax, Tmax, and AUC0-∞ of metoclopramide. The whole study was monitored by an unblinded clinician for the purpose of volunteer's health safety. All the volunteers participated in the study until the end. Twelve healthy Pakistani males having mean age 26.0 (range 20.6-34.1) years and body mass index 25.1 (range 16.2-31.5) kg/m2 were included in this study after taking written informed consent. Rifampicin significantly (P<0.05) decreased the mean Cmax, AUC0-∞ and T1/2 of metoclopramide by 35%, 68%, and 44%, respectively. The laboratory tests did not reveal any significant change in the biochemical, physical, hematological, or urinalytical values before and after metoclopramide treatment. None of the volunteers complained of any discomfort during the study. Rifampicin noticeably decreased the concentration of plasma metoclopramide. These results give in vivo confirmation of the CYP3A4 involvement in the metoclopramide metabolism, in addition to CYP2D6. Therefore, metoclopramide pharmacokinetics may be clinically affected by rifampicin and other potent enzyme inducers.

Clinical spectrum and factors impacting outcome of Candida auris: a single center study from Pakistan

BackgroundAn outbreak of Candida auris began globally in 2014 including Pakistan and since then it has emerged as a nosocomial multi-drug resistant pathogen. The aim of this study was to assess the clinical spectrum and outcome of patients, from a single center in Pakistan, in whom C. auris was isolated.MethodsA retrospective study was conducted on 92 patients; ≥16 years with at least one culture positive for C. auris, at the Aga Khan University Hospital Karachi, Pakistan from Sept 2014-Mar 2017.Demographics, clinical history, management and outcome were studied. A logistic regression model was used to identify the risk factors for mortality.ResultsWe identified 92 patients with C. auris (193 isolates), of whom 52.2% were males. Mean age was 54.14 ± 20.4 years. Positive cultures were obtained after a median hospital stay of 14 days. Most patients had a history of surgery (57.6%), antibiotic use (95.6%), ICU stay (44.6%), indwelling lines (88.04%) and isolation of another multi-resistant organism (52.2%).Most patients were symptomatic (70.7%). Amongst these, 38 had candidemia while 27 had non-candidemia infections. Sites of infection included central lines (35), urinary tract (19), peritonitis (4), nosocomial ventriculitis (1), empyema (1), fungal keratitis (1) otitis externa (1) and surgical site (1). Fluconazole resistance was 100% while 28.5 and 7.9% were Voriconazole and Amphotericin resistant respectively. Overall crude mortality was 42.4% while 14-day mortality was 31.5%. Both infected and colonized cases shared similar mortality (46.2% vs 33.3%; p-value = 0.25). Among infected cases mortality was high in candidemia compared to non-candidemia (60.5% vs 25.9%) in which deaths related to C. auris were 34.2% vs 22.2% respectively. On multivariate analysis candidemia (AOR 4.2, 95% CI: 1.09–16.49; p-value = 0.037) was associated with greater mortality with source control being the only protective factor for mortality (AOR 0.22, 95% CI: 0.05–0.92; p-value0.038] while ICU stay, rapidity of blood culture clearance, DM, malignancy and MDR co-infection had no impact.ConclusionPatients with C.auris from a single center in Pakistan have a wide clinical spectrum with line associated infection being the predominant site of infection. Candidemia leads to high mortality while source control improves outcome.

Acute tubulointerstitial nephritis/drug induced acute kidney injury; an experience from a single center in Pakistan.

Introduction: There is no information in literature specifically on the prevalence and clinicopathological characteristics of acute tubulointerstitial nephritis/drug induced acute kidney injury (AKI) from Pakistan. Objectives: We aim to report a series of cases from patients developing AKI after exposure to some medications or finding of interstitial nephritis on histopathology. Patients and Methods: This is an observational study of patients identified as having AKI after exposure to medications. AKI was defined according to RIFLE criteria and all patients fell from risk to loss category on arrival. On ultrasonography, all patients had normal size non-obstructed kidneys. Renal biopsy findings were consistent with tubule interstitial nephritis. Results: Mean age of patients was 36.41 ± 17.40 years. Among total of 155, 80 were male and 75 female. Regarding drugs, most common was exposure to aminoglycoside in 34 (22%) followed by use of non-steroidal anti-inflammatory analgesics in 28, contrast induced agents in 11. Renal biopsy was performed in 58 patients. In half of these, insulting agent was not known and in rest either multiple medications were ingested or there was denial to substance use or recovery was delayed despite discontinuation of responsible medication. Renal replacement therapy was required on arrival in 119/155 (hemodialysis = 115, peritoneal dialysis = 4) cases. Complete renal recovery was observed in 71%, while 7.7% expired during acute phase, partial renal recovery was seen in 15% and 5% disappeared after first discharge from the hospital. Conclusion: Tubulointerstitial nephritis may occur with many drugs of common use. Early and intensive efforts must be made to consider and then timely correct the injury to the kidney.

Pediatric Hodgkin’s Lymphoma: 5-Year Experience at Single Center in Pakistan

OBJECTIVES:To review patients’ characteristics and treatment outcome pattern of pediatric hodgkinlympoma in a well funded center in developing countryMATERIALS & METHOD: This was retrospective review of data of 301 pediatric hodgkin lymphoma patients up to 18 years of age treated in Shaukat Khanum Memeorial Cancer Hospital & Research Center, Lahore, Pakistan, during 2009 to 2013.RESULTS:Total No. of patients was 301, 81% were male. The median age of studied data was 9 years; ranging from 2 to 18 years. B symptoms in the form of fever, weight loss and night sweats were found in 51%, 29% and 34%, respectively. Median stage was 3 with neck bulky disease in 28% and Medistinal widening in 18% of patients. Trend of histopathology was mixed cellualrity at 56.5%. Most common treatment regime was ChlVPP/ABVD (59.5%); 30.6% of these 301 patient also got radiotherapy. At the end of treatment complete response was reported in 76.5%; 11.3% of these were relapsed afterward.CONCLUSION:Our data shows excellent outcome of pediatric hodgkin lympoma and results are comparable to that of developed countries. DisclosuresNo relevant conflicts of interest to declare.

Prevalence of cryptosporidiosis in renal transplant recipients presenting with acute diarrhea at a single center in Pakistan.

Background: Cryptosporidium is an intracellular protozoan organism which causes diarrhea, both in immunocompetent and immunocompromised hosts. Renal transplant recipients are prone to develop a variety of infections including protozoal infections. Objectives: The aim of this study was to determine the prevalence of cryptosporidiosis in our renal transplant recipients presenting with acute diarrhea. Patients and Methods: During six months of the study, 644 renal transplant recipients presented with acute diarrhea. Single stool sample was obtained for detailed analysis including gross and microscopic examination for red blood cells, pus cells, ova, cysts, and protozoa. The modified Ziehl-Neelsen (ZN) staining was done to identify the oocysts of cryptosporidia. Results: Out of 644 renal transplant patients, oocysts of cryptosporidia were identified in 343 patients (53%). Detailed stool analysis of these patients showed the presence of numerous pus cells in 27 (7.9%) patients, co-infection with giardia intestinalis cysts in 15 (4.3%), and entamoeba histolytica cysts in 10 (2.9%). In all, out of 343 patients, 43 (12.5%) had dual infection with bacteria and protozoa in addition to cryptosporidiosis. Conclusions: Cryptosporidium is an important pathogen causing acute diarrhea in renal transplant recipients in our set up. Stool examination is usually negative for pus cells. It is recommended that in all transplant recipients presenting with acute diarrhea modified ZN staining should be done to rule out cryptosporidiosis in highly endemic areas like Pakistan.

Posttransplant Malignancies in Renal Transplant Recipients: 22-years Experience from a Single Center in Pakistan

To study the incidence, types and distribution pattern of malignant tumors in renal transplant recipients at a single center in Pakistan. This retrospective study was conducted at Sindh Institute of Urology and Transplantation (SIUT) and included all transplant patients on regular follow-up from November 1986 to December 2008. The original biopsy reports and case files of all patients who developed posttransplant malignancies were reviewed and relevant demographic, clinical, radiological, and histopathological data were retrieved and analyzed. SPSS version 10.0 was used for statistical analysis. Over 22 years of study period, 1816 renal transplants were carried out at our center. Among these, 44 patients developed malignancies constituting an overall incidence rate of 2.4%. All patients in this study were males with a mean age of 34.9±9.5 years (range: 9 to 60 years). The most common type of malignancy was lymphoma (27 patients, 61.4%), followed by Kaposi's sarcoma (11 patients, 25%) and skin malignancies (3 patients, 6.8%). One case each of adenocarcinoma of the gallbladder, acute myeloid leukemia (AML), conjunctival carcinoma-in-situ and seminoma were also diagnosed. Posttransplant malignancies occurring in our renal transplant recipients show different incidence rates and patterns as compared with western studies.

Comment on "Ten-year experience of pediatric renal biopsies from a single center in Pakistan"

Comment on "Ten-year experience of pediatric renal biopsies from a single center in Pakistan"

The Spectrum of Histopathological Lesions in Children Presenting with Steroid-Resistant Nephrotic Syndrome at a Single Center in Pakistan

Steroid-resistant nephrotic syndrome (SRNS) is a common problem in pediatric nephrology practice. There is currently little information in the literature on the spectrum of histopathologic lesions in children presenting with SRNS in Pakistan. This study was designed to determine the histopathologic lesions in children presenting with SRNS at our center. The study was conducted at the Histopathology Department, Sindh Institute of Urology and Transplantation (SIUT) from January 2009 to August 2011. All children (≤16 years) presenting with SRNS, in whom renal biopsies were performed, were included. Their demographic, clinical, laboratory, and histopathological data were retrieved from files and original renal biopsy forms. The results were analyzed by SPSS version 10.0. A total of 147 children were included. Of these, 91 (61.9%) were males and 56 (38.1%) females, with male-to-female ratio of 1.6 : 1. The mean age was 7.03 ± 4.0 years (range: 6 months–16 years). The histopathological lesions seen on renal biopsies comprised of focal segmental glomerulosclerosis (FSGS) (38.5%), followed by minimal change disease (MCD) (23.2%), IgM nephropathy (IgMN) (13.6%), idiopathic mesangial proliferative GN (10.2%), membranous GN (8.2%), and mesangiocapillary GN (4.8%). Our results indicate that FSGS is the predominant lesion in children with SRNS, followed by MCD and IgMN.

Outcome of In-Hospital Pediatric Cardiopulmonary Arrest from a Single Center in Pakistan

To review the incidence and outcome of in-hospital pediatric cardiopulmonary arrest (CPA). This retrospective six-year case series was carried out at the PICU and Pediatric Units of Aga Khan University Hospital (AKUH). All children aged 1 month to 14 years who underwent cardiopulmonary resuscitation from January 2001 through December 2006 were included. Data were recorded according to the Utstein style. The outcome variables were sustained return of spontaneous circulation (initial survival) and hospital discharge (final survival). Factors associated with survival were evaluated using logistic regression analysis. The incidence of CPA was 0.4% of all the admissions. Most of the CPR attempts took place in pediatric intensive care unit (53%) and the most frequent etiology was shock (78%). After initial CPR, the sustained return of spontaneous circulation was achieved in 58 patients (55%). Only 12 patients (11%) were discharged alive from the hospital. The most common initial documented rhythm was bradycardia (78%). Multivariate logistic regression analysis revealed that prolonged duration of CPR (>20 min) was the best predictor of initial and final mortality (p < 0.001). The survival rate of in-hospital pediatric cardiopulmonary arrest in the present report is low.

Comparative bioavailability and pharmacokinetics of investigational enteric- and film-coated formulations of flurbiprofen 100-mg tablets: A single-dose, randomized, open-label, two-period, two-way crossover study in healthy Pakistani male volunteers

Background: Flurbiprofen, a chiral, 2-arylpropionic acid NSAID with analgesic and antipyretic properties, has been associated with important gastrointestinal adverse events, including peptic ulcer and gastrointestinal perforation. An investigational enteric-coated tablet formulation of flurbiprofen was produced to evaluate whether it would improve the gastric tolerability of flurbiprofen. Objective: This study compared the pharmacokinetic parameters and bioavailability of flurbiprofen from the investigational enteric-coated tablet (test) and from a film-coated immediate-release tablet compounded for the purposes of this study (reference). Methods: This was a randomized, open-label, 2-period, 2-way crossover study conducted in healthy male volunteers at a single center in Pakistan. Small batches of the test and reference tablets were manufactured and evaluated according to US Pharmacopoeia criteria. Each volunteer received a single 100-mg tablet of the test and reference formulations, separated by a 14-day washout period. Tablets were administered after an overnight fast. Blood samples were obtained before dosing (0) and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, 12, and 24 hours after drug administration. Safety monitoring was performed by an unblinded physician and included adverse events, biochemistry and hematology tests, urinalysis, and ECGs. Plasma concentrations of the 2 formulations were determined, and pharmacokinetic parameters were compared using noncompartmental analysis. The 2 formulations were considered bioequivalent if the 90% CI for the ratios (test:reference) of log-transformed C max, AUC 0−t, and AUC 0–∞ were between 0.80 and 1.25. Results: Of the 23 healthy male subjects originally recruited, 2 withdrew before commencement of the study. Twenty-one subjects (mean [SD] age, 25.4 [2.7] years [range, 20–30 years]; weight, 63.4 [7.2] kg [range, 56–78 kg]) were enrolled in and completed the study. There were significant differences in C max, AUC 0−t, and AUC 0–∞ between the test and reference formulations (all, P < 0.001). The 90% CIs for the geometric mean ratios of log-transformed C max, AUC 0−t, and AUC 0–∞ (49.78–55.22, 57.51–64.42, and 58.48–65.30, respectively) were not within the predetermined bioequivalence range. There were no clinically meaningful changes in hematology, biochemistry, urinalysis, or physical variables with either formulation over the course of the study. Mild headache was reported in 2 volunteers who received the reference formulation during the first study period; this was not considered related to study drug. Conclusions: In this small study in healthy Pakistani male subjects, there were significant differences in the bioavailability and pharmacokinetic parameters of the enteric- and film-coated tablet formulations of flurbiprofen. Thus, the 2 formulations could not be considered bioequivalent. Both formulations were well tolerated.

Ten year experience of pediatric kidney biopsies from a single center in Pakistan

There are many established registries of kidney biopsies around the world. In addition, there are several reports available in literature from many countries on pediatric kidney biopsy. This study was done to determine the indications and pathological patterns of kidney biopsies of children referred to our hospital, and compare our data with the data available from other countries. This is a cross-sectional study of pediatric kidney biopsies over a 10-year period, from January 1997 to December 2006. All biopsies were done in Aga Khan University Hospital, Karachi, Pakistan. Age range was from 1 to 14 years. Data were analyzed for indications and histopathological diagnosis. A total of 54 kidney biopsies were included in the initial analysis. Here 13 samples were excluded and final analysis was done on the remaining 41 samples. The most common indication of kidney biopsy was nephrotic syndrome in 25 samples (61%). The most common histopathology was minimal change disease in 15 (37%), followed by focal segmental glomerulosclerosis in 5 (12%) of the biopsies.