A Survey of Traumatic Brain Injuries from Road Traffic Collisions in a Lower Middle-Income Country.

The burden of traumatic brain injury (TBI) from road traffic collisions (RTCs) is great in low-and middle-income countries (LMICs) due to shortfalls in preventative measures, and the lack of relevant, accurate data collection. To address this gap, we sought to study the epidemiology of TBI from RTCs in two LMIC neurosurgical centres in order to identify factors amenable to preventative strategies. A prospective survey of all adult and paediatric cases of TBI from RTCs admitted to Northwest General Hospital (NWGH) and Hayatabad Medical Complex (HMC) over a four-week period was carried out. Data on patient demographics, risk factors, injury details, pre-hospitalisation details, admission details and post-acute care was collected and analysed. A total of 68 patients were included in the study. 18 (26%) of the patients were male and in the 30 to 39 age group. Fifty-two percent were two-wheeler riders and/or passengers. 51 (75%) of the RTCs occurred between 12 noon and 12 midnight and in rural areas (66.2%). The most commonly documented risk factor that led to the RTC was speeding (35.3%). Pre-hospital care was either absent or undocumented. Up to two-thirds of patients were not direct transfers, and most were transported in private vehicles (48.5%) arriving later than an hour after injury (94.1%). Less than half with documented disabilities were referred for rehabilitation (38.5%). There are still gaps in the prevention of TBI from RTCs and in relevant data collection. Data collection systems must be strengthened, and further exploratory research carried out in order to improve the prevention of TBI from RTCs.

Association of candidate genes (ALR2, RAGE, and VEGF) polymorphisms with diabetic retinopathy in type 2 diabetic patients of Khyber Pakhtunkhwa, Pakistan.

AIM: To evaluate the aldose reductase (ALR2, rs759853), receptor for advanced glycation end products (RAGE, rs2070600), and vascular endothelial growth factor (VEGF, rs833061) association with diabetic retinopathy in type 2 diabetic patients of Khyber Pakhtunkhwa population. METHODS: A case-control study was conducted on a total of 550 subjects consisting of 186 with diabetic retinopathy (DR) having type 2 diabetes, 180 had type 2 diabetes (T2DM), and 184 healthy controls (HC). All the samples were subjected to DNA isolation using salting-out method followed by SNP genotyping through Tetra-ARMS PCR. Chi square and Exact Fischer tests were used for alleles and genotypes distribution. Odd ratio and confidence interval values were found out by online software Medcalc Odd ratio Calculator. RESULTS: Multiple parameters such as random blood sugar (RBS) (p < 0.001), fasting blood sugar (FBS) (p < 0.001), HbA1c (p < 0.001), total cholesterol (p < 0.001), LDL (p < 0.001), HDL (p < 0.001), BMI (p < 0.001) and hypertension (p = 0.018) exhibited strong association with DR as compared to DM and HC. Our results displayed that the VEGF-rs833061 and RAGE- rs2070600 exhibited significant association (p < 0.05) with an increased DR risk, when compared with T2DM. In contrast, ALR2 didn't display association with DR (p > 0.05) when compared with T2DM, but showed association (p < 0.05) when compared with HC. CONCLUSION: Statistically significant association was observed in VEGF-rs833061 and RAGE-rs2070600 with DR in type 2 diabetic patients. While, ALR2- rs759853 didn't exhibit significant association with DR. This is the first study to report the association of candidate genes (ALR2, VEGF and RAGE) with DR in type 2 diabetes of Khyber Pakhtunkhwa population. More similar research studies are recommended with larger data sets in other ethnicities both national and international.

Synthesis, anticancer evaluation and molecular docking studies of methotrexate's novel Schiff base derivatives against malignant glioma cell lines.

Recent years have witnessed advancement in cancer research that has led to the development of improved cytotoxic therapies with reduced side effects. Methotrexate (MTX) is a commonly used anticancer drug having robust activity, but with serious side effects. Several derivatives of MTX have been reported by modification at different sites to reduce its side effects and enhance efficacy. The current work describes the development of active MTX Schiff base derivatives by treating MTX with several aldehydes viz 2-chlorobenzaldehyde, 3-nitrobenzaldehyde, 5-chloro-2-hydroxybenz-aldehyde, 2-hydroxy-5-nitrobenzaldehyde, 2-thiocarboxyaldehyde, trans-2-pentenal and glutaraldehyde. Newly synthesized derivatives were evaluated for their anticancer potential against human malignant glioma U87 (MG-U87) cell lines at different concentrations of 200 µM, 100 µM, 50 µM, 25 µM, 12.5 µm, 6.25 µm and 0 µM. MTX derivatives with 2-Chlorobenzaldehyde (IC50 ∼100 µM), 2-Thiocarboxyaldehyde (IC50 <200 µM) and 2- Pentenal (IC50 ∼250 µM) showed much better activity at 100 µM compared to 400 µM concentration of MTX. Molecular docking studies were performed that showed a good correlation with the results obtained from in vitro experiments. The excellent agreement between molecular modeling and growth inhibition assay shows that the binding mode hypothesis is justly close to the experimentally biological values, therefore, may prove helpful for further lead optimization and clinical trials.Communicated by Ramaswamy H. Sarma.

Role of ATP-Binding Cassette Transporter Proteins in CNS Tumors: Resistance- Based Perspectives and Clinical Updates.

Despite gigantic advances in medical research and development, chemotherapeutic resistance remains a major challenge in complete remission of CNS tumors. The failure of complete eradication of CNS tumors has been correlated with the existence of several factors including overexpression of transporter proteins. To date, 49 ABC-transporter proteins (ABC-TPs) have been reported in humans, and the evidence of their strong association with chemotherapeutics' influx, dissemination, and efflux in CNS tumors, is growing. Research studies on CNS tumors are implicating ABC-TPs as diagnostic, prognostic and therapeutic biomarkers that may be utilised in preclinical and clinical studies. With the current advancements in cell biology, molecular analysis of genomic and transcriptomic interplay, and protein homology-based drug-transporters interaction, our research approaches are streamlining the roles of ABC-TPs in cancer and multidrug resistance. Potential inhibitors of ABC-TP for better clinical outcomes in CNS tumors have emerged. Elacridar has shown to enhance the chemo-sensitivity of Dasatanib and Imatinib in various glioma models. Tariquidar has improved the effectiveness of Temozolomide's in CNS tumors. Although these inhibitors have been effective in preclinical settings, their clinical outcomes have not been as significant in clinical trials. Thus, to have a better understanding of the molecular evaluations of ABC-TPs, as well as drug-interactions, further research is being pursued in research labs. Our lab aims to better comprehend the biological mechanisms involved in drug resistance and to explore novel strategies to increase the clinical effectiveness of anticancer chemotherapeutics, which will ultimately improve clinical outcomes.

CLINICAL FEATURES AND OUTCOME ANALYSIS OF INTRACRANIAL HYDATID CYSTS.

BACKGROUND: Hydatid cyst of the brain is serious zoonotic parasitic infections which have profound health consequences if left untreated. The surgical excisions of the cysts are rewarding for both the patient the neurosurgeon. METHODS: The study was conducted prospectively at Department of Neurosurgery Hayatabad Medical Complex Peshawar from January 2013 to December 2014. Patients with a diagnosis of intracranial hydatid cysts were included, clinical and radiological features recorded, intervention and postoperative outcome were analysed. RESULTS: Eleven patients with a male to female ratio of 1.7:1. Mean age was 12.4 (SD ± 6.5) years with median GCS on arrival of 10 (SD ± 2.5). Clinical features were headache (81.8%), vomiting (90.9%), seizures (36.4%), focal deficits (54.5%) and papilloedema (72.7%). The median GCS on discharge was 13 (SD ± 1.1) while GOS at 1 month follow up was 4 (SD ± 0.7). The bivariate analysis showed inverse correlation (R² = -0.68; p = 0.02) between duration of symptoms and outcome while GCS on admission was positively correlated (r(s) = 0.75; p = 0.007) with the outcome. There was no mortality. CONCLUSION: Despite its rarity the clinical features are non-specific while radiological features help in establishing diagnosis. Earlier diagnosis and prompt intervention is the key to favourable outcome.

Feasibility, relevance and effectiveness of teaching and assessment of ethical status and communication skills as attributes of professionalism.

OBJECTIVE: To examine the feasibility and effectiveness of teaching and assessing professionalism in a developing country. METHODS: The pre-intervention and post-intervention study was conducted from January to August 2012 and comprised 7 workshops of three days each that were held at four teaching hospitals of Khyber Pakhtunkhwa province in Pakistan. Overall, there were 10 Objective Structured Clinical Examination stations and 10 written scenarios. After the pre-test, workshop was held on various aspects of professionalism which was considered 'intervention', and it was followed by a post-test similar to the pre-test at the end of day 3. Stata 12 was used for all statistical analyses. RESULTS: There were 136 postgraduate residents in the study. The correlation between Objective Structured Clinical Examination stations and written exam for pre-test was 0.42 (p<0.001), while for post-test the correlation was 0.17(p=0.046). Correlation between pre-test written and post-test Objective Structured Clinical Examination stations was 0.23 (p=0.001), but the correlation between pre-test Objective Structured Clinical Examination stations and post-test written was not significant (p>0.05).The standardised effect size for the adjusted regression was 0.37 for both comparisons (p<0.001).Mean pre-test scores were 38.13+/-13.13% vs. 76.50+/-14.4%for the post-test score (p<0.001). CONCLUSIONS: Although post-test scores increased significantly both for the Objective Structured Clinical Examination stations and the written scenarios, the former has shown a higher reliability compared to the written test. Furthermore, teaching and assessment of professionalism was found relevant, effective and feasible in resource-constrained countries. Teaching and assessment of professionalism has become globally relevant and is recommended to be included in the curricula of medical institutions.

Survey on perceptions and skills amongst postgraduate residents regarding breaking bad news at teaching hospitals in Peshawar, Pakistan.

OBJECTIVE: To assess the perception, skills and comfort level of postgraduate residents with respect to breaking bad news. METHODS: Five workshops were conducted on communication skills, including the task of breaking bad news, at three teaching hospitals of Peshawar, Pakistan. Teaching methods included interactive lectures, video presentations, role play and small group discussions. Pre- and post-workshop data was collected from all the 97 participants to assess their previous training, comfort level and perceptions regarding the subject and any improvement after attending the workshop. RESULTS: Of the total participants, 92 (95%) residents had not received any training in communication skills at the undergraduate level. Only 64 (66%) residents had witnessed bad news being broken by a consultant. Before the workshop, 83 (85%) residents felt either not comfortable or somewhat comfortable while breaking bad news compared to 36% post-workshop (p < 0.0000). Besides, 64 (66%) residents reported breaking bad news to be extremely stressful or very stressful before the workshop versus 25% post-workshop (p < 0.0000). Before the workshop, 18 (19%) residents said they would withhold the information from the patient on family's insistence despite the patient's wish to be informed, compared to 6% post-workshop (p < 0.007). Regarding the utility of the workshop, 91 (94%) residents said it had changed their perceptions to a major extent, while 92 (95%) residents rated the workshop as extremely useful or very useful. CONCLUSION: Formal structured training in breaking bad news is lacking both at undergraduate and postgraduate levels in Pakistan. Structured training programmes for residents can do the task effectively.

Per-operative findings of blocked ventriculoperitoneal shunt: a study of 72 cases.

BACKGROUND: Most patients with hydrocephalus are treated with ventriculo-peritoneal (VP) shunt placement; however, malfunction is common and is usually caused by mechanical failure. The aim of this study was to evaluate the per-operative findings accompanying presumed VP shunt malfunction. METHODS: This is a descriptive study of 72 patients operated for shunt malfunction in the Department of Neurosurgery, Postgraduate Medical Institute, Lady Reading Hospital, Peshawar from January to December 2008. Presenting symptoms and signs, clinical shunt function, operative findings and outcome were recorded. RESULTS: Common presenting features were vomiting, irritability and general toxic look of patients. Male to female ratio was 3:1. Upper end block was observed in 39 patients while lower end and reservoir block was noted in 13 and 2 patients respectively. Choroids plexus was found in 29.2% of cases with upper end block, shunt revision was performed in most of cases (80.6%). CONCLUSION: The importance of clinical features cannot be overlooked in a patient with shunt malfunction. Upper end block due to choroids plexus is common operative finding.

Surgical outcome of transpedicular fixation in thoracolumber fractures.

BACKGROUND: Development of transpedicular screw fixation techniques and instrumentation systems has brought short-segment instrumentation (fixation of one normal vertebra above and below an injured segment) into general clinical practice. The purpose of this study is to report the surgical outcome of thoracolumber fractures treated with short-segment pedicle instrumentation. METHODS: A retrospective review of all surgically managed thoracolumbar fractures during two years was performed. The 84 surgically managed patients were instrumented by the short-segment technique. Patients charts, operation notes, preoperative and postoperative radiographs, computed tomographic scans, magnetic resonance imaging (MRI) was done. Neurological findings (Frankel functional classification), and follow-up records up to 6 months were reviewed. RESULTS: Transpedicular fixation was performed in 84 cases including 52 male and 32 female with male to female ratio 1.6:1. Mean +/- SD of age was 40 +/- 13.75 years (range 15-60). The level of injuries was different in different age groups. Outcome was assessed on Frankle grading. No patient showed an increase in neurological deficit. Most of the patients showed improvement to the next grade. Screw breakage occurred in 8 cases, bed sores in 16 cases and deep vein thrombosis in 3 cases. Misplaced screw in 5 cases. Eight cases got wound infection. CONCLUSION: Although long- term follow-up evaluation needs to verified, the short-term follow-up results suggest a favourable outcome for short-segment instrumentation.

Computerized stereotactic brain biopsies: an experience of 15 patients at Ayub Teaching Hospital.

BACKGROUND: Deep seated lesions of the brain cannot be approached by conventional neurosurgical approach stereotactic system offers minimally invasive and accurate approach to such lesions. This study was carried out with an objective to determine the safety, efficacy and diagnostic yield of stereotactic biopsies of brain lesions using Brown-Roberts-Wells (BRW) system. METHODS: This study was carried out in patients with intracranial lesions at Ayub teaching hospital Abbottabad from September 1999 to October 2003. Suitable patients with intra cranial lesions underwent computerized stereo tactic biopsy with BRW system. Tissue specimens were analyzed in histopathology department of the Ayub Medical College and results were obtained. Data was analyzed via computer software SPSS 8.0 version for windows. RESULTS: Fifteen patients were selected for stereotactic brain biopsy. Age ranged from 15 years to 54 years. Among them 09 (60%) were male and 06 (40%) were female patients. Out come of the procedure was highly promising in terms of safety and positive diagnostic yield in 14 patients (93.3%), and histopathalogical validity of results (93.3%). Only one patient suffered mild neurological deficit (6.7%), one patient had inconclusive tissue diagnosis and invalid result (6.7%). biopsy proven lesion was astrocytoma in 04 patients (26.7%), anaplastic astrocytoma in 04 (26.7%), gliomatosis in 02 (13.3%), tuberculomas in 03 (20.0%). metastatic adenocarcinomas in 01 (6.7%) and lymphoma in 01(6.7%). CONCLUSIONS: We conclude that computerized stereotactic brain biopsy is safe and effective procedure with a high diagnostic yield at our center.