Nauman Tarif

Diabetes complications in 1952 type 2 diabetes mellitus patients managed in a single institution

BACKGROUND AND OBJECTIVES Because there is no recent update on the state of diabetes and its concomitant complications in Saudi Arabia, we undertook a study of the prevalence of health complications in patients with type 2 diabetes mellitus admitted to our institution. METHODS We conducted a retrospective review of medical records of adult Saudi patients with type 2 diabetes who were seen in clinics or admitted to the Security Forces Hospital, Riyadh, Saudi Arabia, between January 1989 and January 2004. RESULTS Of 1952 patients, 943 (48.3%) were males. For the whole study population the mean age at enrollment was 58.4±14.2 years, the mean age at onset of diabetes was 48.1±12.8 years, the mean duration of diabetes was 10.4±7.5 years, and the mean duration of follow-up was 7.9±4.6 years. Nephropathy was the most prevalent complication, occurring in 626 patients (32.1%). Acute coronary syndrome occurred in 451 (23.1%), cataracts in 447 (22.9%), retinopathy in 326 (16.7%), and myocardial infarction in 279 (14.3%), Doubling of serum creatinine was seen in 250 (12.8%) and 79 (4.0%) went into dialysis. Hypertension was present in 1524 (78.1%) and dyslipidemia in 764 (39.1%). Overall mortality was 8.2%. Multiple complications were frequent. Males had higher prevalence of complications than females (P<.05). Mortality was significantly higher in males 92 (9.8%) than females 69 (6.8%) (P=.024). The prevalence of complications significantly increased with duration of diabetes and age (P<.05). CONCLUSION Among Saudis, the prevalence of concomitant diabetic complications is high, with cardiovascular and renal complications the most frequent. Many patients had multiple complications. Early and frequent screenings in the patients with type 2 diabetes are desirable to identify patients at high risk for concomitant complications and to prevent disabilities.

Effect of Chronic Viral Hepatitis on Graft Survival in Saudi Renal Transplant Patients

Background: In Saudi Arabia the prevalence of hepatitis C among hemodialysis patients is very high ranging from 60 to 80%. A large number of these dialysis patients go for renal transplant, resulting into a higher prevalence of hepatitis C virus (HCV) infection in renal transplant patients. Yet no current systematic report is available on the influence of hepatitis C status on patient and graft survival. The present study was therefore undertaken to address this objective. Methods: Retrospective analysis of data of 448 renal transplantation subjects was undertaken. The mean follow-up period was 5.85 ± 2.7 (median 5.3) years. The factors associated with renal graft survival were reviewed and these include: age, sex, and type of donor, immunosuppressive medication, episodes of infection, blood pressure, serum creatinine, and status of hepatitis. The primary end-points were renal graft function and patient survival. Logistic regression, COX regression analysis, and Kaplan-Meier survival estimates were used to evaluate the influence of hepatitis C on the above parameters. Results: Among 448 recipients of first kidney transplant patients, 286 (63.8%) were positive for HCV infection. In the HCV-positive group, 204 (71.32%) were males. Kaplan-Meier survival analysis showed a significantly better graft survival for HCV-negative patients than HCV-positive patients (p < 0.001; log-rank test). Logistic regression analysis and COX regression analysis have shown different grades of graft dysfunction were present in HCV-positive patients after adjustment for covariates: age, sex, blood pressure, type of donor, and immunosuppressive medication; the presence of HCV was a major predictor of bad outcome and significantly influenced graft survival (odds ratio = 4.37; 95% Cl = 1.81–4.77). Significant deterioration of liver function was noted in HCV-positive patients at the last follow-up, taking ALT as a marker (ALT level 80.6 ± 5.8 U/l at the last follow-up versus 49.5 ± 32 U/l at baseline p ≤ 0.0001). Sixteen patients had a chronic active course and 1 patient developed biopsy-proven liver cirrhosis and portal hypertension. A serious and significantly greater incidence of fatal chest infections was seen in HCV-positive patients. Although mortality was greater in HCV-positive versus HCV-negative patients (20 vs. 7), the difference did not attain statistical significance (p = 0.23) and none of the patients died as a result of hepatic failure. Conclusion: The presence of HCV infection greatly influenced graft survival in renal transplant patients and a higher proportion of infected patients had renal and hepatic dysfunction. A significant increase in fatal chest infections was noted in HCV-positive patients. Overall mortality was higher in HCV-positive patients, but it was not statistically significant. All measures should be taken to prevent HCV transmission in the dialysis population. Renal transplant recipients with HCV infection need close monitoring for both graft and liver function.

Role of Interferon-α in the treatment of primary glomerulonephritis

Interferon-alpha (IFN-alpha) is a naturally occurring cytokine. It was the first cytokine used with clinical benefit in the treatment of viral hepatitis and malignancies. Patients with viral hepatitis B or C may have complications with glomerulonephritis (GN). Improvement in proteinuria with or without clearing of viral markers after IFN-alpha therapy has been reported. This encouraged us to offer IFN-alpha therapy to four patients with GN. These patients refused treatment with steroids and/or cyclophosphamide because of concerns about side effects. One patient with membranous GN and two patients with mesangial GN (MesGN) had a remission of nephrotic syndrome. In one patient with type II diabetes and MesGN, renal insufficiency and proteinuria did not subside; however, renal function remained stable. The mechanism of action of IFN-alpha is discussed, with its possible role in the treatment of primary GN.

Six-Month Clinical Outcome of Cyclosporine Microemulsion Formulation (Sigmasporin Microral) in Stable Renal Transplant Patients Previously Maintained on Sandimmun Neoral

The trial objective was to investigate the feasibility and safety of conversion to a generic microemulsion cyclosporine in stable renal transplant patients premaintained on Neoral. We enrolled 75 patients from seven centers in five Middle Eastern countries monitored them for 6 months after conversion to Sigmasporin Microral. Readings at 0, 0.5, 1, 2, 3, 4.5, and 6 months included cyclosporine blood level, serum creatinine, liver enzymes, lipid profile, blood sugar, blood pressure and adverse events. Patients included 54 men and 21 women of mean age 38.9 +/- 10.7 years at 30.3 +/- 29.3 months post-transplantation maintained on Sigmasporin Microral dose of 2.8 +/- 1.0 mg/kg per day; they were observed to be stable throughout the study period as reflected by the therapeutic blood C0 level of 181.6 +/- 102.1 and C2 of 759.2 +/- 384.4. Their absorption profile as represented by C2/C0 was 4.9 +/- 2.8, and C2/cyclosporine dose of 282.3 +/- 128.8. An average serum creatinine level of 116.1 +/- 29.5 micromol/L denoted stable graft function and their liver enzymes did not change during the study. No new-onset cases of hypertension, diabetes mellitus, or hyperlipidemia were reported among the patients. Graft function was stable for all patients, except for two incidences of mild acute rejection and two of mild cyclosporine nephrotoxicity; graft and patient survival rates were both 100%. Results of this 6-month study showed that Sigmasporin Microral was effective to maintain stable renal function in kidney transplant patients converted from Neoral with similar safety and tolerability profiles as those reported in the literature.

Therapeutic Equivalence and mg:mg Switch Ability of a Generic Cyclosporine Microemulsion Formulation (Sigmasporin Microral) in Stable Renal Transplant Patients Maintained on Sandimmun Neoral

We tested a hypothesized pharmacokinetic difference between the reference (Sandimmun Neoral) and test (Sigmasporin Microral) products to prove therapeutic equivalence in an open, multiple fixed dose, one-way crossover, multicenter, and multinational study over a period of 29 days. Forty two stable renal transplant recipients maintained on Sandimmun Neoral were enrolled. Whole blood was collected at day 14 of the study at 0, 0.5, 1.0, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after reference dosing and the same schedule was repeated at day 29 after switching on an mg:mg basis to the test product at day 15 of the study. Analysis of variance was performed for the pharmacokinetic parameters (area under the curve [AUC]0-12, maximum concentration [Cmax]) of cyclosporine using log-transformed values. Tolerability was assessed by vital signs, adverse events, and laboratory investigations. The 90% confidence interval (CI) test for the Ln-transformed, pharmacokinetic parameters was all within the US Food and Drug Administration acceptable range of 80% to 125%, as Ln area under the steady-state curve (AUCss) was within the range of 92.56 to 103.55 and Ln Cmax was within the range of 85.73 to 103.58; the same also applied for AUC0-4, which may be considered the area of greatest inter- and intra-patient variability. Furthermore, in line with the newly adopted recommendations of the Expert Advisory Committee on Bioavailability and Bioequivalence of Health Canada, the 90% CI for AUCss was within the narrow range of 90% to 112%. No significant difference in tolerability was recorded between the two products. Sigmasporin Microral (Julphar) was found to be bioequivalent and clinically interchangeable on an mg:mg basis with Sandimmun Neoral (Novartis).

Invasive aspergillosis of pulmonary hydatid cyst.

Ann Saudi Med 29(1) January-February 2009 www.saudiannals.net 53 Pulmonary aspergillosis frequently complicates existing pulmonary cavity, which is commonly due to tuberculosis.1-6 Pulmonary aspergillosis has also been reported, though rarely, in pulmonary cavities as a consequence of the removal of a hydatid cyst.7-9 We report a case with active pulmonary hydatid disease that was co-infected with aspergillosis.