Drug use evaluation of cefepime at Khartoum North Teaching Hospital in Sudan.

BACKGROUND: Cefepime is essentially used for life-threatening infections. Although overutilisation of antibiotics is strongly discouraged around the world, they are still overused in developing countries including Sudan. OBJECTIVES: This study aims to evaluate the rational use of cefepime at Khartoum North Teaching Hospital-Sudan. METHODS: A retrospective cross-sectional, hospital-based study was conducted in the internal medicine ward at Khartoum North Teaching Hospital from August/2018 to April/2019. The study covered medical records of adult patients receiving cefepime during the study period. Patient's data were analysed using simple descriptive statistics (frequency and percentage) and inferential statistics (logistic regression) to describe the relationship between dependent and independent variables. P ≤ .05 was considered statistically significant. RESULTS: Out of 90 patients, only 16.7% of patients were tested for antibiotic sensitivity. Cefepime was prescribed to 50% and 23.3% of patients for the treatment of UTIs/post-dialysis and sepsis, respectively. Although the majority of patients (72.2%) received cefepime with appropriate indication, only 21.1% and 15.6% received the drug with appropriate dose and duration, respectively. Cefepime had been prescribed appropriately in a correct dose, duration, and indications for only 7.8% of patients. The vast majority of patients tested for kidney functions had elevated creatinine levels (96.1%); however, cefepime dose had been adjusted for only 4.1% of them. CONCLUSION: This study highlighted the irrational use of cefepime regarding inappropriate dose, duration, and inadequate antibiotic sensitivity tests. A lack of attention to dosage adjustment in patients with renal impairment had been observed. Positive clinical outcome was significantly associated with antibiotic sensitivity test.

Acne Vulgaris Relapse in Sudanese Patients Treated with Oral Isotretinoin: Rate and Predictive Factors.

Purpose: Acne vulgaris is a skin disorder primarily affecting teenagers and young adults. Acne relapse is the main drawback of oral isotretinoin (OI), which is the golden therapy for severe acne. This study aimed to assess the rate and predictive factors of acne relapse among Sudanese patients using OI. Patients and Methods: A cross-sectional study was conducted in a dermatology and venereology clinic-Sudan, using a self-administered questionnaire and data collection sheet. Patients using OI for acne treatment were enrolled in the study. Chi-square test and logistic regression analysis were used to evaluate the association between variables. P-value <0.05 was considered statistically significant. Results: 225 acne patients (mean age: 26.0±4.2 years, females: 88.9%) were included in this study. OI daily dose ranged from 0.25 to 1 mg/kg/day, with frequent daily doses of 40-49 mg (57.3%) over 3-6 months (81.8%). Around one-third of patients (36%) received maintenance therapy after completion of OI course. At a 2-year follow-up, approximately 36% of patients experienced acne relapse that commonly occurred within 6-18 months after the last OI therapy. Early discontinuation of OI was a positive predictor of acne relapse which was 3.99 times greater in patients who had early discontinued OI than those completing the planned OI course (OR=3.99; p=0.002). OI cumulative doses of 120-139 mg/kg and 140-159 mg/kg were negative predictors of acne relapse (OR=0.23; p=0.001 and OR=0.15; p=0.02, respectively). Most patients (94.2%) received prescription OI, and 76.4% of women were advised to use contraceptives. About 69% of patients practiced skin care. Conclusion: About one-third of patients experienced acne relapse. Early discontinuation and low cumulative doses of OI are the main risk factors for acne relapse. Long-term therapy of OI, with cumulative doses of 120-159 mg/kg, would be beneficial to reduce acne relapse.

Letrozole vs clomiphene citrate in Sudanese patients with infertility secondary to polycystic ovary syndrome.

PCOS is a cluster of metabolic, hormonal, and environmental factors coupled with infertility in patients within reproductive age. This cross-sectional study compared letrozole (LTZ) vs Clomiphene citrate (CC) as ovulation inducers in infertile Sudanese patients with PCOS. Follicles ≥18 mm and pregnancy tests were used for comparison. SPSS version 23 was used for analysis. Significance was calculated with Chi-square, t-test, and logistic regression. P ≤ 0.05 was considered significant.Our results showed 49% of the patients were 20-30 years old, 60% had secondary infertility 98.4% were secondary to PCOS and 64% had a family history of infertility. Comparable results on positive pregnancy tests of 26% (P ≤ 0.017) and 17% (P ≤ 0.027) were observed for LTZ vs CC respectively. Similar strengths (P ≤ 0.000) in compacting the ovarian cysts were recorded. LTZ showed less activity (P ≤ 0.013) on follicles size maturation compared to (P ≤ 0.000) with CC. The endometrial thickness was increased with LTZ (51.87%) but reduced with CC (25.54%). The positive pregnancy test was associated with age and BMI. Conclusion: Letrozole 20 mg single dose showed comparable results on positive pregnancy tests but less significance on follicle maturation compared to CC100mg. Both drugs compacted the ovarian cysts' sizes. letrozole significantly increased the endometrial lining thickness.

Mycetoma management and clinical outcomes: the Mycetoma Research Center experience.

BACKGROUND: Mycetoma is a chronic granulomatous inflammatory disease that affects the cutaneous and subcutaneous tissues, leading to gruesome complications if not treated early. As a neglected disease, it has received scant attention in developing curable drugs. Mycetoma treatment is still based on expert opinions in the absence of guidelines. METHODS: This descriptive, cross-sectional, hospital-based study aimed to determine and assess the disease treatment outcomes observed at Mycetoma Research Center, Sudan. RESULTS: In this study, 75% of patients had eumycetoma, all of whom were treated with itraconazole and 37.4% underwent surgical excision, while 25% of the patients had actinomycetoma, 99.2% of whom were treated with a combination of cotrimoxazole and amoxicillin-clavulanate. The cure rate was 12.7% and 14.3% for patients with eumycetoma and actinomycetoma, respectively. Only 6.1% of eumycetoma patients underwent amputation. Remarkably, no patient with actinomycetoma underwent an amputation. Small lesions (OR=10.09, p<0.001) and good follow-up (OR=6.81, p=0.002) were positive predictors of complete cure. In terms of amputation, history of surgical recurrence at presentation (OR=3.67, p=0.020) and presence of grains (OR=7.13, p=0.012) were positive predictors, whereas small lesions were negative predictors (OR=0.06, p=0.009). CONCLUSIONS: Treatment of mycetoma was suboptimal, with a low cure rate despite a long treatment duration. Complete cure has a significant association with small lesions and good follow-up.

Pediatric Sickle Cell Disease in Sudan: Complications and Management.

BACKGROUND: Sickle cell disease (SCD) is a life-threatening genetic disorder due to the formation of sickle hemoglobin molecule (HbS) that polymerizes in hypoxic conditions leading to SCD-related complications. Different approaches have been used in the management of SCD including symptomatic management, supportive management, and preventive management. OBJECTIVES: To assess the management of SCD in pediatric patients in Gaafar Ibnauf Referral Hospital in Khartoum locality, Sudan. METHOD: A descriptive, retrospective, hospital-based study was conducted in Gaafar Ibnauf Hospital using a data collection sheet. The study included all medical files of pediatric patients with SCD attending the hospital during the period from the first of April 2018 to the first of July 2018. The data were analyzed using descriptive statistics and the chi-square test. P < 0.05 was considered statistically significant. RESULTS: Out of 207 pediatric patients, 53.1% were females (mean age of 7.5 ± 3.1 years), with a 1.1 : 1 female:male ratio and low socioeconomic status. Only 4.3% of participants had health insurance. The Messeryia tribe in western Sudan had the highest prevalence of the disease among the Sudanese tribes (11.1%). Vaso-occlusive crisis (33.3%), infections (13.5%), and neurological complications (10.6%) were the most frequent complications reported during routine visits. After initiation of management, only 3.4% of pediatric patients had hemolytic crises, and 1.4% of the anemic patients had splenomegaly. 100% of patients received folic acid, 73.9% used hydroxyurea, and 69.6% underwent blood transfusion for the management of SCD. Prophylactic penicillin was prescribed for 15% of patients, and 41.1% were immunized with pneumococcal vaccine (PPSV23). Most patients had been scheduled for planned follow-up visits every 3-6 months (93.2%). Hydroxyurea and blood transfusion significantly reduced fever and vaso-occlusive crisis. CONCLUSION: The SCD treatment protocol in Gaafar Ibnauf Children's Hospital, involving preventive and symptomatic therapy, is consistent with the internationally implemented protocols for SCD management. However, immunization and prophylactic penicillin approaches are deficient.

Therapeutic outcomes evaluation of adjuvant hyperbaric oxygen therapy for non-healing diabetic foot ulcers among sudanese patients.

BACKGROUND AND AIMS: Diabetic foot ulcers (DFUs) are common complications of diabetes that frequently lead to amputation and disability. Despite some promising results in using hyperbaric oxygen therapy (HBOT) for DFUs treatment, its efficacy is still debatable. The aim of this study was to evaluate the therapeutic outcomes of adjuvant HBOT in non-healing DFUs treatment. METHODS: A descriptive, retrospective, hospital-based study was conducted at Al-Mo'alem Medical City-Khartoum, Sudan from August to December 2018. Medical records of Type 2 diabetic patients, treated with HBOT plus standard wound care for DFUs, were included in the study. Data were analyzed by simple descriptive statistics and logistic regression. P ≤ 0.05 was considered statistically significant. RESULTS: The study results showed that 51.7% of patients had Wagner grade-3 ulcers and 28.3% had complete loss of protective sensation. Almost 61% of patients achieved complete ulcer healing while 16.7% underwent amputation. Twenty percent of patients treated with HBOT experienced ear barotraumas as adverse effects. Protective sensation (OR = 6.00, 95% CI = 1.79-20.16, p = 0.004) and more sessions of HBOT (OR = 17.35, 95% CI = 4.51-66.73, p = 0.000) were positive predictors of complete ulcer healing. Loss of protective sensation (OR = 0.17, 95% CI = 0.05-0.63, p = 0.007) was an indicator of amputation. CONCLUSIONS: Treatment with adjuvant HBOT enhanced ulcer healing and reduced amputation rate in patients with non-healing DFUs. HBOT could be considered a relatively safe intervention.

The incidence, risk factors, and outcomes of acute kidney injury in the intensive care unit in Sudan.

Background There is a paucity of studies in acute kidney injury in the intensive care unit, particularly in Sudan. Objectives The current study has estimated the incidence; risk factors and outcomes of subjects with acute kidney injury developed during admission to the intensive care unit at Fedail Hospital, Khartoum, Sudan. Methodology This was a cross-sectional study conducted in the intensive care unit during the period from July 2018 to June 2019. The data was collected from the clinical profiles of all adult subjects' who have met the published criteria for acute kidney injury. Analysis of association (Chi square test χ2) and multivariate logistic regression were used to analyze data. Main outcome measure The development of acute kidney injury during the subjects' stay in the intensive care unit, length of hospital stay and death. Results From a total of 187 subjects admitted to the intensive care unit; only (105, 56.2%) have met the inclusion criteria (mean age was 61 ± 3.5 years). The main finding of the study was the high incidence of acute kidney injury 39%. The major significant predictors for the development of acute kidney injury with respective odds ratio (OR) were: sepsis (OR 7.5 [95% CI 3-19.7]; P .001); hypovolemia (OR 5.1 [95% CI 2-15.7]; P .001); chronic cardiovascular diseases (OR 3.4 [95% CI 1.2-9.4]; P .017); age > 60 years (OR 2.7 [95% CI 1.2-6.3]; P .018); diabetes mellitus (OR 2.6 [95% CI 1.2-6]; P .02); hypertension (OR 2.4 [95% CI 1.2-5.4]; P .028); and renal replacement therapy (OR 0.2 [95% CI 0.15-0.3]; P .001). The length of hospital stay within the AKI cohort was (6.7 ± 3.8; [range 2-17]) and the mortality rate was (36, 87.8%). Conclusion The major significant predictors for the development of acute kidney injury in the intensive care unit were: sepsis; hypovolemia; chronic cardiovascular diseases; age > 60 years; diabetes mellitus; hypertension; and renal replacement therapy. Sepsis and hypovolemia were common etiologies for acute kidney injury post-admission to the intensive care unit. Acute kidney injury was associated with increased length of hospital stay and a very high absolute mortality rate.

Ameliorative activity of Adansonia digitata fruit on high sugar/high fat diet-simulated Metabolic Syndrome model in male Wistar rats.

Metabolic syndrome is a complex of metabolic disorders characterized by oxidative stress which compromises cell functions and entails multiple organs pathologies. We investigated the therapeutic and protective potential of Adansonia digitata fruit -a potent antioxidant- in high sugar/high fat diet-simulated metabolic syndrome in Wistar rats. 42 male rats (140-200 g) were randomly divided into 7 groups. G1 was kept on standard laboratory diet (SLD) for all 9 weeks (negative control). 5 groups were fed high Sugar/high fat diet for 6 weeks then switched to SLD for another 3 weeks + oral treatment as follows: G2+ no treatment (positive control), G3-G5 + 200, 400 and 800 mg/kg/day aqueous A. digitata fruit respectively, G6 + 10 mg/kg/day Simvastatin. G7 + HS/HFD + 400 mg/kg/day A. digitata fruit simultaneously and was terminated at W6. Our results showed that G2-G6 develops dyslipidemia, hyperglycaemia, weight gain, elevated hepatic biomarkers, elevated creatinine and urea plus pathological derangements in the heart, liver and kidney tissues compared to negative control at W6. 200 mg/kg/day A. digitata fruit significantly ameliorated the induced dyslipidemia (P ≤ 0.001), hyperglycaemia (P ≤ 0.001) with a significant reduction in the Atherogenic Index of Plasma (P ≤ 0.000) after 3 weeks treatment. The fruit normalized the elevated hepatic biomarkers as well as creatinine and urea. A dose dependent partial reduction in lesion intensity was observed in the hepatic tissue while the heart and kidney showed mostly reversed to normal histology. The inflammatory infiltration was eliminated. Relevant results were observed for the two higher doses. The simultaneous treatment showed significant lower levels in all biomarkers investigated compared to positive control which could be interpreted as protective activity. A reduction of 4-11% in whole body weight was achieved. CONCLUSION: MetS was successfully simulated with a HS/HFD formula in male Wistar rats. Treatment with aqueous A. digitata fruit showed anti-Metabolic Syndrome potential reflected by weight loss, anti-inflammatory, hypolipidemic, hypoglycaemic, renal, hepatic and cardio-protective activities.

Isolation and Characterization of Four Terpenoidal Compounds with Potential Antimicrobial Activity from Tarconanthus camphorantus L. (Asteraceae).

OBJECTIVES: The objective of this study is to describe the isolation, characterization, and antimicrobial activity of isolated compounds from Tarconanthus camphorantus. MATERIALS AND METHODS: Bioactive compounds such as trifloculoside, parthenolide (sesquiterpene lactones), lupeol, and erythrodiol (pentacyclic triterpens) were isolated from n-hexane extract of T. camphoratus, and their antimicrobial activity against Candida albicans, Escherichia coli, Psuedomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus, and Mycobacterium smegmatis was evaluated. The compounds were characterized using chromatographic and spectroscopic techniques. RESULTS: Trifloculoside, lupeol, and erythrodiol are being reported for the first time from T. camphoratus. The isolated compounds sesquiterpens and lupeol exhibited prodigious antimicrobial activity against B. subtilis and S. aureus with minimum inhibitory concentration values in the range of 25-1000 µg/mL but no activity was observed against other tested organisms, and erythrodiol showed no antimicrobial activity against any of the tested organisms. CONCLUSION: The findings of this study revealed that the new compounds trifloculoside, parthenolide, and lupeol isolated from T. camphoratus exhibited effective antimicrobial potential. It was inferred that T. camphoratus can be effectively used in traditional medicine.

Impact of clinical pharmacist intervention in anticoagulation clinic in Sudan.

Background Many trials have compared anticoagulation management provided by a pharmacist led anticoagulation clinic versus usual physician care showing the role for clinical pharmacist in the management of anticoagulant therapy, and demonstrating excellent outcomes. In Sudan, there is no published research evaluating the role of pharmacist in providing pharmaceutical care for patients taking warfarin. Objective The objective of the study is to assess the role of clinical pharmacist intervention in warfarin patients compared to usual medical care. Setting This study was conducted in Ahmed Gasim cardiac surgery and renal transplant center warfarin clinic. Methods One hundred thirty-five patients were randomly selected from adult patients on warfarin therapy The history of INR records, and adverse effects for the past year, were recorded. Then patients' warfarin dose adjustments according to INR, was done by the clinical pharmacist for one year. Patients received continuous verbal education and written information about warfarin. Main outcome measure The primary outcome for this study was the INR control, while the secondary outcomes were the bleeding events and hospitalization due to warfarin. Results After the clinical pharmacist intervention there was significant (P < 0.01) improvement in INR control and a significant (P < 0.05) reduction in incidence of bleeding after clinical pharmacist intervention. Hospitalization due to warfarin related complications (bleeding, high INR, low INR) was also significantly (P < 0.001) reduced. Conclusion Clinical pharmacists intervention in warfarin therapy improve INR control, reduce bleeding and hospitalization due to warfarin complications.

Prophylactic ceftizoxime for elective cesarean delivery at Soba Hospital, Sudan.

BACKGROUND: A prophylactic antibiotic is recommended to reduce infection-related complication following cesarean delivery. There is a current debate on the time of prophylactic antibiotic in cesarean delivery. METHODS: An opened randomized, controlled clinical trial was conducted at Soba hospital, Sudan to investigate the timing (pre-incision or after clamping of the umbilical cord) of ceftizoxime for elective cesarean delivery. The outcome measures were; the incidence of post-cesarean febrile and infection-related morbidity and neonatal outcomes between the two groups. RESULTS: Hundred -eighty women (90 women in each arm of the study) received intravenous injection of 1 g of ceftizoxime as single dose either at pre-incision or after clamping of the umbilical cord. None of the women in either group had endometritis. One woman in the pre-incision group had chest infection. There was no significant difference in the incidence of wound infection between the two groups, 8 (6.7%) vs. 3 (3.3%); P = 0.2. Two babies in the pre-incision group (P = 0.497) had a low Apgar score (< 8) at 1 min. Similar number of neonate (15 in each arm) was admitted to nursery. There were no significant difference in the neonatal jaundice between the two groups, 5 (5.5%) vs. 4 (4.4%), P = 0.2. There was no perinatal death. CONCLUSIONS: There was no difference in the two regimens (pre-incision or post-clamping of the umbilical cord) of ceftizoxime as prophylactic for elective cesarean delivery. TRIAL REGISTRATION: NCT01347593.

Cyclosporin A and tacrolimus induce renal Erk1/2 pathway via ROS-induced and metalloproteinase-dependent EGF-receptor signaling.

We previously demonstrated that the widely used immunosuppressive drugs cyclosporin A (CsA) and tacrolimus (FK506), independent of immunophilin binding, can activate profibrogenic transforming growth factor ß (TGFß)/Smad signaling cascades in rat renal mesangial cells (MC). Here we report that both peptidyl-prolyl cis/trans isomerase (PPIase) inhibitors activate the extracellular-signaling regulated kinase (ERK) a member of the mitogen activated protein kinase (MAPK) and induce a rapid and transient increase in ERK phosphorylation. The MEK inhibitor U0126, the reactive oxygen species (ROS) scavenger N-acetyl-cysteine (NAC), a cell-permeant superoxide dismutase (SOD) and stigmatellin, an inhibitor of mitochondrial cytochrome bc1 complex strongly attenuated the increase in ERK1/2 phosphorylation triggered by PPIase inhibitors. Moreover, neutralizing antibodies against heparin binding-epidermal growth factor (HB-EGF), and inhibition of the EGF receptor by either small interfering (si)RNA or AG1478, demonstrate that ERK activation by both PPIase inhibitors is mediated via HB-EGF-induced EGF receptor (EGFR) tyrosine kinase activation. The strong inhibitory effects achieved by GM6001 and TAPI-2 furthermore implicate the involvement of a desintegrin and metalloproteinase 17 (ADAM17). Concomitantly, the PPIase inhibitor-induced ADAM17 secretase activity was significantly reduced by SOD and stigmatellin thus suggesting that mitochondrial ROS play a primary role in PPIase inhibitor-induced and ADAM17-mediated HB-EGF shedding. Functionally, both immunosuppressants caused a strong increase in MC proliferation which was similarly impeded when cells were treated in the presence of NAC, TAPI-2 or AG1478, respectively. Our data suggest that CsA and FK506, via ROS-dependent and ADAM17-catalyzed HB-EGF shedding induce the mitogenic ERK1/2 signaling cascade in renal MC.

Differential modulation of the cytokine-induced MMP-9/TIMP-1 protease-antiprotease system by the mTOR inhibitor rapamycin.

The mTOR-inhibitor rapamycin is a potent drug used in many immunosuppressive and antiinflammatory therapeutic regimes. In renal transplantation despite its beneficial roles rapamycin in some cases can promote renal fibrosis in the kidney but the underlying mechanisms are unknown. In this study, we tested for possible modulatory effects of rapamycin on the cytokine-triggered matrix metalloproteinase 9 (MMP-9)/tissue inhibitor of metalloproteinase (TIMP)-1 protease-antiprotease system which is critically involved in renal inflammation and fibrosis. Treatment of rat mesangial cells (MC) with rapamycin dose-dependently reduced the interleukin 1ß (IL-1ß)-triggered increase in gelatinolytic levels as demonstrated by zymography. The reduction in the extracellular MMP-9 content by rapamycin coincided with an attenuation in cytokine-induced steady-state MMP-9 mRNA levels. Conversely, rapamycin caused a dose-dependent increase in cytokine-evoked TIMP-1 expression in a Smad binding element (SBE)-dependent manner. Surprisingly, the attenuation of MMP-9 mRNA levels by rapamycin is accompanied by a potentiation of IL-1ß-induced MMP-9 promoter activity in which the stimulatory effects by rapamycin are mainly attributed to a proximal AP-1 binding site. Furthermore, the rapamycin-dependent potentiation of MMP-9 expression is accompanied by an amplification of cytokine-triggered activities of nuclear factor κB (NF-κB) and activator protein 1 (AP-1) transcription factors. Importantly, rapamycin-triggered increase in MMP-9 promoter activity is fully impaired when we used a MMP-9 reporter construct which is under the additional control of the 3' untranslated region (3'-UTR) of MMP-9. Collectively, these data imply that rapamycin inhibits the cytokine-induced MMP-9 mainly through posttranscriptional events and thereby exerts profibrotic activities.

Rapamycin induces the TGFbeta1/Smad signaling cascade in renal mesangial cells upstream of mTOR.

The mTOR kinase inhibitor rapamycin (sirolimus) is a drug with potent immunosuppressive and antiproliferative properties. We found that rapamycin induces the TGFbeta/Smad signaling cascade in rat mesangial cells (MC) as depicted by the nuclear translocation of phospho-Smads 2, -3 and Smad-4, respectively. Concomitantly, rapamycin increases the nuclear DNA binding of receptor (R)- and co-Smad proteins to a cognate Smad-binding element (SBE) which in turn causes an increase in profibrotic gene expression as exemplified by the connective tissue growth factor (CTGF) and plasminogen activator inhibitor 1 (PAI-1). Using small interfering (si)RNA we demonstrate that Smad 2/3 activation by rapamycin depends on its endogenous receptor FK binding protein 12 (FKBP12). Mechanistically, Smad induction by rapamycin is initiated by an increase in active TGFbeta(1) as shown by ELISA and by the inhibitory effects of a neutralizing TGFbeta antibody. Using an activin receptor-like kinase (ALK)-5 inhibitor and by siRNA against the TGFbeta type II receptor (TGFbeta-RII) we furthermore demonstrate a functional involvement of both types of TGFbeta receptors. However, rapamycin did not compete with TGFbeta for TGFbeta-receptor binding as found in radioligand-binding assay. Besides SB203580, a specific inhibitor of the p38 MAPK, the reactive oxygen species (ROS) scavenger N-acetyl-cysteine (NAC) and a cell-permeable superoxide dismutase (SOD) mimetic strongly abrogated the stimulatory effects of rapamycin on Smad 2 and 3 phosphorylation. Furthermore, the rapid increase in dichlorofluorescein (DCF) formation implies that rapamycin mainly acts through ROS. In conclusion, activation of the profibrotic TGFbeta/Smad signaling cascade accompanies the immunosuppressive and antiproliferative actions of rapamycin.