25-Hydroxyvitamin-D deficiency in chronic kidney disease stages III, IV, and V in South Asian population: a retrospective cohort.

Objective: Vitamin D deficiency in Chronic Kidney Disease is a known fact, but the data regarding the prevalence and extent of vitamin D deficiency in different stages of Chronic Kidney Disease is scarce. This leads to a delay in addressing this issue. We conducted this study to assess vitamin-D deficiency in different stages of Chronic Kidney Disease to improve the evidence available to Physicians and Nephrologists which can help them better address this common finding in Chronic Kidney Disease. Methods: This retrospective study from a tertiary care hospital in Karachi, Pakistan, included adult Chronic Kidney Disease patients who had their serum 25 Hydroxy vitamin D levels done. The patients were classified according to stages of Chronic Kidney Disease using Estimated Glomerular Filtration Rate values. Appropriate statistical tests were performed to find a correlation between the severity of vitamin D deficiency in different stages of Chronic Kidney Disease with a statistically significant p value of <0.05 and a 95% confidence interval. Results: In total, 148 patients were included in the study. All patients had serum 25 Hydroxy vitamin D levels less than 30 ng/ml. The severity of vitamin D deficiency was observed to increase progressively from stage 3A Chronic Kidney Disease through stage 5. Vitamin D levels in Chronic Kidney Disease stage 3 were significantly greater than in Chronic Kidney Disease stages 4 and 5 (p value < 0.001), and stage 5 patients had the lowest vitamin D levels in our study. Similar, statistically significant findings were observed for serum phosphate levels, too, with stage 5 Chronic Kidney Disease patients having a greater serum phosphate concentration than stages 3A and 3B (p value = 0.002, 0.006). Conclusion: All Chronic Kidney Disease patients in our study either had vitamin D insufficiency or deficiency. In addition, we observed a significant decrease in vitamin D levels from Chronic Kidney Disease stage 3 to stage 5. Greater serum phosphate levels were detected in stage 5 compared to stages 3A and 3B.

Renal Stromal Expression of Oestrogen and Progesterone Receptors in Chronic Pyelonephritis as Compared to Normal Kidneys.

OBJECTIVE:  To determine and compare the distribution of oestrogen and progesterone receptors (ER and PR) expression between normal kidneys and chronic pyelonephritis. STUDY DESIGN: Comparative-descriptive study. PLACE AND DURATION OF STUDY: King Faisal Specialist Hospital and Research Centre, and Alfaisal University, Riyadh, Saudi Arabia, between January 2017 and December 2018.  Methodology: Renal specimens, including 41 chronic pyelonephritis, and 21 healthy specimens were examined. ER/PR expression was determined immunohistochemically, termed focal if <50% of nuclei stained positively, and diffuse when >50%. The intensity of staining was labelled weak (pale), moderate or strong. RESULTS: Majority of samples showed presence of diffuse ER (82.9% diseased; 71.4% healthy) and focal PR (53.7% diseased; 76.2% healthy), mostly with strong intensity. ER and PR distribution whether focal or diffuse, correlated with each other in 41.9%. All proportions comparisons showed p values greater than 0.05. CONCLUSION: There was a trend of diffuse renal stromal expression of ER and PR in chronic pyelonephritis as compared to healthy specimens. However, the difference did not reach statistical significance. Key Words: Oestrogen receptor, Progesterone receptor, Chronic pyelonephritis, Renal cancer, Renal stroma.

Learning clinical skills through audiovisual aids embedded in electronic-PBL sessions in undergraduate medical curriculum: perception and performance.

Learning clinical skills in a large group of undergraduate medical students is challenging. Innovative technology-based modalities are being evaluated to complement limited hospital rotations. We determined the effectiveness of clinical skills-related audiovisual (AV) aids embedded in electronic-problem-based learning (PBL) sessions, in terms of students' feedback and formative Objective Structured Clinical Examinations (OSCE) grades. This mixed-method study was conducted during the Cardiovascular System module in year 3 of the Bachelor of Medicine, Bachelor of Surgery program. The AV aids, mainly consisting of abnormal chest auscultation sounds, were linked to the cases for the intervention group. The control group received only a description of clinical signs. Sessions were conducted using an intranet platform. At the end of the module, feedback was obtained from intervention group students and faculty using a self-administered questionnaire. The learning was compared between intervention and control groups through an OSCE. Finally, focus group interviews were conducted to explore factors underlying deviation from the expected results. Out of 110 intervention group students, 86 (78%) responded. The students appreciated the inclusion of AV aids, as suggested by a high average satisfaction score of 4.2 (SD 0.8). They agreed that, apart from being appropriate and relevant, the aids improved the learning environment and engagement in the process. The tutors also gave a similar feedback. However, no difference in the OSCE scores was found between control and intervention groups. The study indicates that inclusion of AV aids improved students' engagement and classroom environment in electronic-PBL sessions, but did not improve diagnostic abilities based on the learned clinical skills.

Implications of genetic variation of common Drug Metabolizing Enzymes and ABC Transporters among the Pakistani Population.

Genetic polymorphism of drug metabolizing enzymes and transporters may influence drug response. The frequency varies substantially between ethnicities thus having implications on appropriate selection and dosage of various drugs in different populations. The distribution of genetic polymorphisms in healthy Pakistanis has so far not been described. In this study, 155 healthy adults (98 females) were included from all districts of Karachi. DNA was extracted from saliva and genotyped for relevant SNVs in CYP1A1, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4 and CYP3A5 as well as ALDH3A1, GSTA1, ABCB1 and ABCC2. About 64% of the participants were born to parents who were unrelated to each other. There was generally a higher prevalence (p < 0.05) of variant alleles of CYP450 1A2, 2B6, 2C19, 3A5, ALDH3A1, GSTM1 as well as ABCB1 and ABCC2 in this study cohort than in other ethnicities reported in the HapMap database. In contrast, the prevalence of variant alleles was lower in GSTA1. Therefore, in the Pakistani population sample from Karachi a significantly different prevalence of variant drug metabolizing enzymes and ABC transporters was observed as compared to other ethnicities, which could have putative clinical consequences on drug efficacy and safety.

Lung resistance-related protein (LRP) predicts favorable therapeutic outcome in Acute Myeloid Leukemia.

There is conflicting evidence that MDR1, MRP2 and LRP expression is responsible for chemotherapy resistance. We conducted this study to explore their role in AML therapy outcomes. Bone marrow and peripheral blood samples of 90 AML patients, receiving chemotherapy, were analyzed by real time PCR. Gene expression was calculated by the 2-ΔΔCt method. The patients who had a persistent remission were labelled 'Good Responder' (GRes) whereas, those with relapse or drug resistance were labelled 'Poor Responders' (PRes). Higher LRP expression in bone marrow, but not in peripheral blood, was positively associated with persistent remission (p = 0.001), GRes (p = 0.002), 1-year overall as well as disease-free survival (p = 0.02 and p = 0.007, respectively). Marrow and blood MDR1 and MRP2 expression did not differ significantly between the above groups. Logistic regression analysis showed that only a diagnosis of acute promyelocytic leukemia (APL; M3) or high marrow LRP expression significantly predicted a favorable therapeutic outcome. This is the first report showing that high bone marrow LRP expression predicts significant favorable therapeutic outcome. Peripheral blood LRP expression as well as marrow and blood MDR1 and MRP2 expression have no predictive value in AML patients treated with standard dose cytarabine and daunorubicin 3+7 regimen.

Gene expression of hENT1, dCK, CDA, dCMPD and topoisomerase IIα as an indicator of chemotherapy response in AML treated with cytarabine and daunorubicin.

PURPOSE: Acute myeloid leukemia patients are commonly treated with cytarabine (Ara-C) and anthracyclines but the sustained remission rate is not very promising. We explored the role of drug-metabolizing enzymes and transporters in the therapeutic response. PATIENTS AND METHODS: Bone marrow and peripheral blood samples of 90 newly diagnosed acute myeloid leukemia patients treated with standard 3+7 regimen were analyzed through real-time PCR for expression of human equilibrative nucleoside transporter 1, deoxycytidine kinase, cytidine deaminase (CDA), deoxycytidine monophosphate deaminase (dCMPD) and topoisomerase IIα (Topo-IIa). The expression of these markers was studied in relationship with good (persistent remission) and poor therapeutic response (relapse/resistance). RESULTS: High Topo-IIa expression in peripheral blood was associated with good response (P=0.006). Relapse was higher among low expressors of Topo-IIa in peripheral blood (OR: 26.25). Bone marrow Topo-IIa expression followed a similar trend but did not reach statistical significance. In contrast, patients with high bone marrow dCMPD expression had poor response (OR: 3; P=0.043). One-year disease-free survival (DFS) was better among those with high bone marrow Topo-IIa (P=0.04) or CDA (P=0.03) expression. High bone marrow Topo-IIa expression also had better DFS at 6 months (P=0.04) and at 12 months (P=0.04). CONCLUSION: High expression of Topo-IIa in peripheral blood is a favorable indicator of persistent remission, good therapeutic response and DFS. High dCMPD and low CDA expression in bone marrow is associated with poor therapeutic outcome.

Bax, Bcl-2, and Bax/Bcl-2 as prognostic markers in acute myeloid leukemia: are we ready for Bcl-2-directed therapy?

PURPOSE: Many anticancer drugs induce apoptosis in malignant cells, and resistance to apoptosis could lead to suboptimal or no therapeutic benefit. Two cytoplasmic proteins, B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax) and Bcl-2, act as a promoter and an inhibitor of apoptosis, respectively. Both Bax and Bcl-2 as well as their ratio have been regarded as prognostic markers in various cancers. However, conflicting results have been reported. A clear understanding of apoptosis has also become crucial due to reports about anti-Bcl-2 chemotherapy. We explored the relationship of Bax and Bcl-2 gene expression and their ratio with the therapeutic response in acute myeloid leukemia (AML) patients. PATIENTS AND METHODS: Bone marrow and/or blood samples from 90 AML patients treated with cytarabine and daunorubicin were included. Expression of Bax and Bcl-2 was determined through real-time polymerase chain reaction by using ΔΔCt method of relative expression. RESULTS: Bax and Bcl-2 expression among marrow and blood samples correlated with each other (rs=0.5, p<0.01). Although bone marrow expression of Bax and Bcl-2 tended to remain higher among responders (median 1.01 and 0.29, respectively) as compared to non-responders (median 0.66 and 0.24, respectively), the difference failed to reach statistical significance (U=784.5 and 733; p=0.68 and 0.28, respectively). Conversely, Bax/Bcl-2 ratio was higher among poor responders (median 3.07 vs 1.78), though again failed to reach statistical significance (U=698.5, p=0.07). CONCLUSION: Expression of Bax and Bcl-2 does not differ significantly among AML patients treated with cytarabine and daunorubicin in terms of remission, relapse, resistance, overall survival, and disease-free survival, thus questioning the utility of emerging anti-Bcl-2 therapy.

Evaluation of effectiveness of a paediatric simulation course in procedural skills for paediatric residents - A pilot study.

OBJECTIVE: To explore the effects of simulation training on paediatric residents' confidence and skills in managing advanced skills in critical care. METHODS: The study was conducted at Alfaisal University, Riyadh, Saudi Arabia, from March to June 2016, and comprised junior residents in paediatrics. All paediatric residents (years 1 and 2) were recruited into two workshops, held one week apart. The first workshop covered lumbar puncture/ cerebrospinal fluid interpretation, oral intubation, bone marrow aspiration, and critical airway management. The second workshop covered chest tube insertion, pleural tap, insertion of central line, and arthrocentesis. The participants were surveyed using a 5-point Likert scale survey pre- and post-course, assessing their confidence. Their practical skills were assessed using a pre-objective structured clinical examination on the same day and post-course objective structured clinical examination a week later on selected skills. The outcome measures were: (1) pre-/post-course confidence rating, and (2) pre-/post-course objective structured clinical examination results. Data was analysed using SPSS 20. RESULTS: Of the 16 participants, 8(50%) were boys and 8(50%) girls. Besides, 13(81%) residents were in year-1 and 3(19%) in year-2. Median post-course confidence level ranks for all the skills were higher (p<0.05). There was no improvement in mean pre-objective structured clinical examination scores (2.31±2.66/ 7.46±3.02) and post- objective structured clinical examination scores (22.54±4.39/ 31.85±6.90) in Year 1 residents (p<0.001). CONCLUSIONS: Simulation course was significantly successful in improving residents' clinical skills and confidence in performing critical tasks.

Objectivity in subjectivity: do students' self and peer assessments correlate with examiners' subjective and objective assessment in clinical skills? A prospective study.

OBJECTIVES: The qualitative subjective assessment has been exercised either by self-reflection (self-assessment (SA)) or by an observer (peer assessment (PA)) and is considered to play an important role in students' development. The objectivity of PA and SA by students as well as those by faculty examiners has remained debated. This matters most when it comes to a high-stakes examination. We explored the degree of objectivity in PA, SA, as well as the global rating by examiners being Examiners' Subjective Assessment (ESA) compared with Objective Structured Clinical Examinations (OSCE). DESIGN: Prospective cohort study. SETTING: Undergraduate medical students at Alfaisal University, Riyadh. PARTICIPANTS: All second-year medical students (n=164) of genders, taking a course to learn clinical history taking and general physical examination. MAIN OUTCOME MEASURES: A Likert scale questionnaire was distributed among the participants during selected clinical skills sessions. Each student was evaluated randomly by peers (PA) as well as by himself/herself (SA). Two OSCEs were conducted where students were assessed by an examiner objectively as well as subjectively (ESA) for a global rating of confidence and well-preparedness. OSCE-1 had fewer topics and stations, whereas OSCE-2 was terminal and full scale. RESULTS: OSCE-1 (B=0.10) and ESA (B=8.16) predicted OSCE-2 scores. 'No nervousness' in PA (r=0.185, p=0.018) and 'confidence' in SA (r=0.207, p=0.008) correlated with 'confidence' in ESA. In 'well-preparedness', SA correlated with ESA (r=0.234, p=0.003). CONCLUSIONS: OSCE-1 and ESA predicted students' performance in the OSCE-2, a high-stakes evaluation, indicating practical 'objectivity' in ESA, whereas SA and PA had minimal predictive role. Certain components of SA and PA correlated with ESA, suggesting partial objectivity given the limited objectiveness of ESA. Such difference in 'qualitative' objectivity probably reflects experience. Thus, subjective assessment can be used with some degree of objectivity for continuous assessment.

Evaluation of a combined approach of clinical skills training utilizing near-peers, in-campus faculty and clinicians: An innovative integrated model.

INTRODUCTION: Training clinical skills is essential in medicine. Different models of clinical skills courses have been previously suggested. Here, we report an innovative approach adopted to train junior medical students in clinical skills in a multimodal fashion by near-peers, basic scientists with clinical background and senior clinicians. METHODS: This quasi-experimental study was conducted at Alfaisal University College of Medicine at Riyadh. An electronic survey was conducted among year-2 and year-3 medical students seeking their perception about the (a) organization, (b) delivery, (c&d) self- and peer-assessment in clinical skills courses. Total 298 male and female medical students (91%), consisting of 164 from year 2 and 134 from year 3, participated by filling out a questionnaire (Cronbach's alpha 0.93). RESULTS: Out of maximum five, the average ratings for the course were 3.81, 3.72, 3.67 and 3.73 in organization, delivery, self-evaluation and peer-assessment respectively, with no significant difference between both subgroups. The in-campus sessions rated higher than hospital sessions (p < 0.001). As tutors, interns were rated higher than clinicians (p < 0.001). The qualitative analysis suggested high satisfaction. CONCLUSIONS: The clinical skills course that was conducted in a multimodal fashion utilizing diverse tutors showed a positive attitude of students toward the organization and delivery of the course.

Stress, anxiety, and depression among medical students in a multiethnic setting.

BACKGROUND: Contemporary literature suggests that medical education might adversely affect students' mental health. Alfaisal University in Riyadh, Saudi Arabia is a developing institution; hence, there has been a concern regarding the mental well-being of the students. OBJECTIVES: This study was designed to assess the traits of depression, anxiety, and stress among students in relation to potential underlying reasons. METHODS: All 575 medical students across the 5 years of study participated by filling out the Depression, Anxiety, and Stress Scale-21 (DASS-21) questionnaire anonymously twice. Firstly, 2-3 weeks before a major examination (pre-examination), and secondly, during regular classes (post-examination). Correlation was sought regarding sex, year of scholarship, attendance of a premedical university preparatory program (UPP), housing, and smoking. Subjective comments from students were also obtained. RESULTS: A total of 76.8% and 74.9% of students participated in pre-and post-examination groups, respectively. The majority were the children of expatriate workers in Saudi Arabia, and included Arabs, South Asians, and North Americans. Prevalence of depression, anxiety, and stress was high (43%, 63%, and 41%, respectively) which reduced (to 30%, 47%, and 30%, respectively) to some extent after examinations. Saudis and those who had attended UPP had higher DASS-21 scores. Smoking and female sex predicted higher levels of "baseline" depression, anxiety, or stress. The students perceived the curriculum and schedule to be the primary causes of their high DASS-21 scores. CONCLUSION: The students had high "baseline" traits of depression, anxiety, and stress, and these were higher if an examination was near, especially among Saudis and those who had attended UPP. Smoking and female sex predicted higher levels of "baseline" depression, anxiety, or stress. Students suggested that study burden and a busy schedule were the major reasons for their high DASS-21 scores.

Relationship of drug metabolizing enzyme genotype to plasma levels as well as myelotoxicity of cyclophosphamide in breast cancer patients.

PURPOSE: The cytotoxic drug cyclophosphamide (CP) is bioactivated into 4-hydroxy-cyclophosphamide (4-OH-CP) through cytochrome P450 enzymes and cleared through aldehyde dehydrogenase and glutathione S-transferase. This prospective study analyzes the influence of drug metabolizing enzyme genotype on (1) plasma 4-OH-CP:CP ratio and (2) myelotoxicity in breast cancer patients on 500 mg/m(2) cyclophosphamide. METHODS: Sixty-eight female breast cancer patients on FAC (fluorouracil, adriamycin, cyclophosphamide) were included. Genotyping of cytochrome P450 enzymes CYP2B6, CYP2C9, CYP2C19, CYP3A5, aldehyde dehydrogenase (ALDH3A1), and glutathione S-transferase (GSTA1) was done either through RFLP or pyrosequencing. Plasma CP and 4-OH-CP were measured immediately and 1 and 2 h after the end of infusion through LC-MS. The leukocyte count was determined on day 10 and 20 after chemotherapy. RESULTS: At CP dose of 500 mg/m(2), the 4-OH-CP:CP ratio was negatively affected by CYP2C19*2 genotype (p = 0.039) showing a gene-dose effect. Moreover ALDH3A1*2 genotype increased 4-OH-CP:CP ratio (p = 0.037). These effects did not remain significant in a univariate analysis of variance including all genotypes. GSTA1*B carriers were at increased risk of severe leucopenia (OR 6.94; 95% CI 1.75-27.6, p = 0.006). CONCLUSION: The myelotoxicity in patients receiving FAC is related to the activity of the phase-II enzyme GSTA1 but is independent of the formation of 4-OH-CP.

Breast cancer pattern and chemotherapy response--an institutional study in Pakistan.

BACKGROUND: This study was planned to audit female breast cancers and their chemotherapy in a busy public sector institution. As a case-study, Pakistan provides an opportunity to explore the issue in a low-GDP, low-literacy, populous developing country. METHOD: Retrospective analysis of the records at Karachi Institute of Radiotherapy and Nuclear Medicine. RESULTS: A total of 3,431 female breast cancer patients presented during 2001-2008, half being <45 years, mostly suffering from infiltrating ductal carcinoma of breast. Further analyzing a subgroup of 183 consecutive patients over six months revealed that only 1.6% were at stage-I, whereas 75% had node-positive disease, including 19.1% with distant metastases. Some 41.6% were either high grade or poorly differentiated. The low grade tumors showed a two-fold likelihood of ER and PR positivity as compared to high grade lesions. 5-Flourouracil, doxorubicin and cyclophosphamide (FAC) constituted the most common chemotherapy. Earlier diagnosis was associated with complete remission. Overall, 33% developed myelotoxicity, more often if age ≥ 45 years (p=0.012), out of which 60% needed active correction. All those patients who did not experience a drop in total leukocyte count (TLC) below 4 x 109/L did not show complete remission. CONCLUSIONS: Infiltrating ductal carcinoma of the breast is the most common type. FAC is the most common chemotherapy. Tendency for late diagnosis, metastatic disease, treatment failure as well as leukopenia especially in ≥ 45 years is present. Failure to show leukopenia is suggestive of poor therapeutic outcome.

Genotype frequencies of selected drug metabolizing enzymes and ABC drug transporters among breast cancer patients on FAC chemotherapy.

Polymorphic genes of drug metabolizing enzymes and transporters may influence drug response. With some exemptions, single nucleotide polymorphisms in such genes, however, are not known to be susceptibility factors for breast cancer. This study explored genotype profiles for the breast cancer patients on fluorouracil, doxorubicin and cyclophosphamide (FAC) in a Pakistani set of population and their comparison with HapMap data. Sixty-eight female breast cancer patients were included. All received FAC chemotherapy. Relevant genotyping was done either through restriction fragment length polymorphism or pyrosequencing. The variant allele frequencies were: 5.1% for CYP2C9*2 (430C>T), 15.4% for CYP2C9*3 (1075A>C), 27.2% for CYP2C19*2 (681G>A), 33.1% for GSTA1*B (-69C>T, -52G>A), 62.5% for ALDH3A1*2 (985C>G), 58.8% and 4.4% for ABCB1 (2677 G>T/A), 64.7% for ABCB1 3435 C>T, and 15.4%, 33.1% and 39.7% for ABCC2 (-24 C>T, 1249 G>A and 3972 C>T). In comparison with HapMap, this first exploration in Pakistani samples shows higher frequency of (i) CYP2C9*3 carriers (p < 0.05) than in Hispanic, Chinese, Japanese and African samples, (ii) ALDH3A1*2 carriers (p < 0.01) than Caucasian, Hispanic, Chinese, Japanese and African samples. For ABC transporters, a higher frequency of variant allele was observed in (iii) ABCB1 2677 G>T/A (p < 0.01) than Caucasian, Hispanic and African, (iv) ABCB1 3435 C>T (p < 0.05) than Chinese, Japanese and African, (v) ABCC2 1249 G>A (p < 0.01) than Hispanic, Chinese and Japanese samples. In conclusion, cyclophosphamide activation and detoxification of reactive intermediates may be altered in the Pakistani. Though carriers of CYP2C19*2 were higher than in Caucasian and Hispanics, they did not reach statistical significance (p = 0.05).

Effect of low dose oral pill on haemostatic parameters in a set of Pakistani population.

OBJECTIVE: To observe the adverse effects of low dose combination contraceptive pills on blood coagulation in a set of local population. METHODS: Between December 2002 to December 2003 a comparative cross-sectional study was conducted at the Department of Pharmacology, Ziauddin Medical University, Karachi and Aga Khan University Hospital, Karachi. Fifty women of reproductive age were divided in two equal groups; one being the users of combination oral contraceptive pills (ethinyl estradiol and levonorgestrel) and the other being matching controls not taking any hormonal contraceptives. We studied, CBC, PT and INR, APTT, BT and platelet aggregation against ADP, collagen, epinephrine and ristocetin. RESULTS: PT, INR, and platelet aggregation response to ADP, collagen, epinephrine, and ristocetin were not significantly different among the groups. However, APTT was shortened in users of contraceptives (p = 0.003). CONCLUSION: The referred oral contraceptive is associated with enhanced activity of intrinsic pathway of secondary haemostasis.

Effect of a 'progestin only' contraceptive on platelet aggregation in a Pakistani set of population.

BACKGROUND: Safe use of progestin-only hormonal preparations has remained quite controversial though they are being employed in various disorders very commonly. These hormones result in a number of adverse effects in the body, the most drastic being predisposition to higher risk of thromboembolism with reports of involvement of platelets. Despite a large number of studies, no definite inference had been derived regarding the effects of these agents on blood coagulation. It has been reported that the response in various ethnic groups may vary. Therefore this study is designed to observe the effects of progestin-only hormonal contraceptives regarding primary hemostasis in our population. METHODS: We carried out this study on 50 women divided into two equal groups of 25 each, namely, a group of users of Progestin-only injectable hormonal contraceptive Norethisterone oenanthate 200 mg used as a 2-monthly injection and a control group and studied platelet aggregation against ADP, Collagen, Epinephrine and Ristocetin. RESULTS: There was no statistical difference regarding the platelet aggregation studies against ADP, collagen, epinephrine and ristocetin between users and nonusers of progestin-only injectable contraceptive. The menstrual irregularities were found to be more frequent in users of injectable hormonal contraceptives than in non-users, especially amenorrhea and irregularities of menstrual flow. In users of injectable hormnonal contraceptives, hemoglobin and hematocrit were slightly better maintained as compared to non-users. CONCLUSION: This suggests that Norethisterone oenanthate at currently used doses does not increase the platelet aggregation against ADP, collagen, epinephrine and ristocetin in our population.

Use of norethisterone oenanthate and predisposition to thrombosis.

OBJECTIVE: To observe the effects of progestin-only hormonal contraceptives in our population. DESIGN: Cohort study. PLACE AND DURATION OF STUDY: Department of Pharmacology, Ziauddin Medical University, Karachi and Department of Pathology, Faculty of Health Sciences, The Aga Khan University, Karachi from October 2002 to September 2003. PATIENTS AND METHODS: The study comprised of 50 women of reproductive age group, divided into two equal and matched groups of 25 each, namely, a group of users of progestin-only injectable hormonal contraceptive Norethisterone oenanthate [NET EN] 200 mg used as a 2-monthly injection and a control group not using any hormonal contraception. Complete blood counts, prothrombin time (PT) and international normalized ratio (INR) as well as activated partial thromboplastin time (APTT) were monitored. RESULTS: APTT and prothrombin time were not significantly different in both the groups. Menstrual irregularities were found out by more frequent in users of injectable hormonal contraceptives than in non-users (p= 0.001). Hemoglobin (p= 0.029) and hematocrit were slightly better preserved in the same group. CONCLUSION: Use of Norethisterone oenanthate does not predispose to thrombogenesis in current dose for contraception.