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Background: Poly(ADP-ribose) polymerase (PARP) inhibitors may synergize with programmed cell death receptor-1 (PD-1) inhibitors to enhance adaptive and innate antitumor immune responses. In the phase 2 JASPER study (NCT04475939), the PARP inhibitor niraparib was evaluated in combination with the PD-1 inhibitor pembrolizumab in patients with metastatic and/or locally advanced non-small cell lung cancer (NSCLC)., Methods: Patients whose tumors had programmed cell death ligand 1 (PD-L1) tumor proportion scores (TPS) ≥50% (cohort 1) or 1%-49% (cohort 2) received first-line niraparib (200 mg once daily) plus pembrolizumab (200 mg every 3 weeks). The primary end point was investigator-assessed objective response rate (ORR). Secondary end points included duration of response (DoR), progression-free survival (PFS), overall survival (OS), safety, and pharmacokinetics., Results: Thirty-eight patients were enrolled in cohorts 1 and 2. In cohort 1, ORR (95% confidence interval [CI]) was 56.3% (9 of 16 patients; 29.9%-80.2%); 2 of 16 patients had complete responses and 7 of 16 had partial responses (PRs). In cohort 2, ORR was 20.0% (5.7%-43.7%) with 4 of 20 PRs. In cohorts 1 and 2, the median DoR was 19.7 months (95% CI, 4.2 months to not estimable [NE]) and 9.4 months (95% CI, 4.2 months to NE), the median PFS was 8.4 months (95% CI, 3.9-22.1 months) and 4.2 months (95% CI, 2.0-6.2 months), and the median OS was NE (95% CI, 6.0 months to NE) and 7.7 months (95% CI, 4.0-12.5 months), respectively. Grade ≥3 treatment-emergent adverse events occurred in 88.2% and 85.7% of patients in cohorts 1 and 2, respectively. Safety was consistent with known profiles of single-agent niraparib and pembrolizumab., Conclusions: Niraparib plus pembrolizumab showed clinical activity in patients with advanced and/or metastatic NSCLC., Lay Summary: The JASPER clinical trial studied a new combination treatment for advanced or metastatic non-small cell lung cancer (NSCLC). Pembrolizumab, a drug approved for NSCLC, was given with niraparib. Previous research showed that these 2 drugs together might work better than either drug alone. This study found that more than half of patients with high levels of a tumor marker responded to the combination, and one-fifth of patients with lower levels of the marker responded. The types of side effects from the combination were similar to side effects from both drugs alone. These results support more research on this combination., (© 2021 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: We have conducted this study to examine the clinical and morphological pattern of brain arteriovenous malformations (BAVMs) along with their treatment and short term outcome in a tertiary care hospital in Bangladesh. This retrospective chart review was carried out from the records of neuro-endovascular division at Department of Neurology, Dhaka Medical College Hospital (DMCH) from January 2010 to June 2013. A total 60 patients were evaluated. All the necessary information regarding the demographic, clinical, morphologic and treatment profile was gathered through a predesigned questionnaire. To our knowledge, we have the largest cohort of BAVM patients in Bangladesh and this is the first of this kind of study done in Bangladesh., Results: The mean age at diagnosis was 30.3 years with a standard deviation of ±14.3 and the majority was teenagers (30%). Intracerebral hemorrhage was the commonest (70%) type of presentation at diagnosis, followed by headache (50%), altered consciousness (50%), vomiting (40%) and seizure (40%). Majority of the AVMs had feeders from anterior circulation (50%) and most of the AVMs (73.3%) were supplied from the main feeders, whereas the rest from distal vessels. Regarding venous drainage, AVMs drained mostly either to superficial (43.3%) or deep (40%) venous system. AVMs frequently had larger (40%) nidus size and a slow to medium flow (60%), through the nidus. An eloquent AVM location was found in 50% of the patients. Intranidal aneurysm was found in 10% AVM and angiopathic AVM in 13.3%. Patients were treated by endovascular embolization (31) or surgical excision (11) or conservative approach. There was one event of death, both in embolization group and surgically treated group before discharge. The patients were followed up for 1.3 ± 0.8 years. The rate of rebleed was 6.6, 30 and 60% during follow up in endovascular, surgical and conservatively treated group. Though five patients in conservative group died during this time, no deaths reported in intervention group (endovascular or surgery)., Conclusion: Intracerebral hemorrhages, headache, altered consciousness and seizure are common clinical presentations of AVM at diagnosis. The remarkable morphologic features are larger AVM size at eloquent location, medium to slow flow with frequent feeders from main vessels of anterior circulation and drainage to superficial venous systems. Endovascular embolization or surgical excision of AVM are relatively safe and effective and provides better short term outcome than conservative approach.

To evaluate comprehensively the distribution of established risk factors of stroke among Bangladeshi patients. This is an observational study. It involved 8400 stroke patients from different hospitals in Bangladesh over a period of sixteen years. Common established risk factors of stroke e.g. age, sex, family history, hypertension, diabetes, ischemic heart disease, smoking, obesity, dyslipidaemia, alcoholism, use of oral contraceptive pill, lack of fresh fruit consumption etc. were evaluated in these patients through a preformed questionnaire and data were analyzed. Majority of the stroke events occurred after the age of forty (82.3%) and the ischemic stroke (72%) is the most common. Apart from non modifiable risk factors (advancing age, sex, Family history of stroke) hypertension was the most common modifiable risk factor found in stroke patients (57.6%) followed by smoking (44.6%), tobacco use (24.3%), OCP use in female (40% of female stroke), diabetes (23%), ischemic heart disease (17.1%), obesity (10.6%) and dyslipidaemia (5.3%). Lack of fresh fruit consumption and alcoholism were found in some of the patients. Stroke is common after the age of forty. Ischemic events are commonest type of stroke. Hypertension, smoking, tobacco use, diabetes and ischemic heart disease were five most common risk factors of stroke. Outlining the common stroke risk factors in our settings, may help the physicians and care givers in managing this disabling disease properly.

Background: Epilepsy is a common health problem which carries a huge medical social psychological and economic impact for a developing country. The aim of this hospital-based study was to get an insight into the effectiveness and tolerability of low cost antiepileptic drugs (AEDs) in Bangladeshi people with epilepsy., Methods: This retrospective chart review was done from hospital records in weekly Epilepsy outdoor clinic of Department of Neurology, Dhaka Medical College Hospital (DMCH) from October 1998 to February 2013. A total of 854 epilepsy patients met the eligibility criteria (had a complete record of two years of follow up data) from hospital database. A checklist was used to take demographics (age and gender), epilepsy treatment and adverse event related data. At least two years of follow up data were considered for analysis., Results: Out of 854 patients selected, majority of the patients attending outdoor clinic were >11-30 years age group (55.2%) with a mean age of 20.3 ± 9 years and with a male (53%) predominance. Focal epilepsy were more common (53%), among whom secondary generalized epilepsy was the most frequent diagnosis (67%) followed by complex partial seizure (21%). Among those with Idiopathic Generalized Epilepsy (46%), generalized tonic clonic seizure was encountered in 74% and absence seizure was observed in 13%. The number of patients on monotherapy and dual AED therapy were 67% and 24% respectively and polytherapy (i.e. >3 AEDs) was used only in 9%. CBZ (67%) was the most frequently prescribed AED, followed by VPA (43%), PHB (17%), and PHT (8%). CBZ was prescribed in 37% patients as monotherapy followed by VPA in 21% and PHB in 8% patients. Newer generation drugs eg lemotrigine and topiramate were used only as add on therapy in combination with CBZ and VPA in only 2% patients. The treatment retention rates over the follow up period for the AEDs in monotherapy varied between 86 and 91% and were highest for CBZ, followed by VPA. Most of the combination regimens had a treatment retention rate of 100%. The effectiveness of AED in terms of reduction of seizure frequency was highest for PHT (100%) and PHB (98%) followed by CBZ (96%) and VPA (95%). PHB and PHT were the cheapest of all AEDs (42 I$ and 56 I$/ year respectively). The costs of VPA and CBZ were two times and LTG and TOP were six to eight times higher. Adverse drug reaction (ADR) were observed among 140 (24.5%) of those with monotherapy. PHT (64%) was the most common drug to cause ADR, CBZ was at the bottom of the list to cause adverse effect (11.6%). VPA and PHB caused weight gain commonly. Adjustment of drug dose or withdrawal due to ADRs was necessary in 39% with PHT and 26% with PHB., Conclusion: Though PHT and PHB are cheapest and efficacious among all, CBZ and VPA are less costly, effective and well tolerated drug for seizure control in context of Bangladesh.

Objective: To determine the pattern of headache and its associated symptoms in school going children., Methods: The data of all the school going children attending the Headache Clinic in the Dept. of Neurology, Dhaka Medical College Hospital were retrospectively reviewed. A total of 1021 patients from October 1996 to September 2011 were selected. Data were collected through a predesigned questionnaire containing information on age, sex, social status, clinical features, opthalmoscopic findings, management, and in selected cases imaging results., Result: The mean age of headache in school children was 12.6±1.08 years with relatively older age of presentation among girls. The sex ratio was 1.64:1 in favor of girls at older age. Tension type headache (71.1%) was the most common form of headache, followed by migraine (18.4%) and mixed headache (6.7%). Though the girls had more frequent headache of both tension type (59.4%) and migraine (68.1%) variety, the latter was significantly associated in girls (p<0.001). Headache was of moderate severity in 53.3%, whereas severe headache was experienced by 19.9% of the children. The children commonly had nausea and/or vomiting (47.2%), as well as photophobia (24.7%) with headache. Mental stress (34%) and sunlight (30.9%) were common triggering factors whereas a sound sleep relieved headache in the majority (59.4%). Paracetamol (83.3%) and nortryptyline (62.8%) were the most commonly prescribed drug taken by them., Conclusion: Headache is a major health problem in school children, apart from other common health issues at this age. With increasing age, the girls more commonly suffer not only from migraine but also with other chronic headache. The direct causal association is yet to be determined.

Number of elderly persons gradually increased in Bangladesh due to improved health awareness and health care. Age is the single most important risk factor for stroke. This study aims at finding the prevalence of stroke in a Bangladeshi population aged forty years and above. The cases of stroke were ascertained in two phases of door-to-door survey. In phase-I, trained interviewers performed face-to-face interview with subjects for the detection stroke cases using the World Health Organization (WHO) screening protocol for neurological diseases. In phase-II, subjects suspected to have a stroke underwent a clinical evaluation for diagnosis or exclusion of stroke by a neurological team. The study involved 15627 participants aged 40 years and above. A total of 47 participants found to have stroke, expressing an overall prevalence rate of 3.00 per 1000 (95% CI 0.95 to 2.45). Prevalence of stroke were 2.0, 3.0, 2.0, 10.0, and 10.0 per 1000 within age groups of 40-49 years, 50-59 years, 60-69 years, 70-79 years and 80 years and above age group respectively. Prevalence of stroke in people with age range 70-79 years compared to 40-49 years age range is 4.988 (95% CI 2.309 to 10.77) times and people with age range ≥80 years compared to 40-49 years age range is 4.798 (95% CI 1.597 to14.416) times. Prevalence was higher among men in comparison with women. The male: female ratio is 3.44:2.41 per 1000 respectively. Bangladeshi male populations in rural areas are found to have stroke more than urban people. A large community based study should be undertaken to further confirm the result of this present study.

Epilepsy occurs in 30 to 40% of individuals with autism spectrum disorder (ASD). However the association of epilepsy or abnormal electroencephalogram is not known in our population. This study addresses the incidence of epilepsy and or abnormal electroencephalogram in Bangladeshi children with autism spectrum disorder. The clinical history and electroencephalogram of 18 children diagnosed with autism spectrum disorder were retrospectively reviewed. Forty four percent were diagnosed with epilepsy or abnormal electroencephalogram. This abnormal electroencephalogram or epilepsy occurred at significantly higher rates in children with more impaired range of autism spectrum disorder. These finding suggest that the use of neurological investigative technique such as electroencephalogram (EEG) should be considered routinely in children with autism spectrum disorder especially in more impaired individuals.

Prevention of rejection and prolongation of graft survival are critical to achieving successful islet cell transplantation. Various techniques have been utilized to prolong graft survival. Recently, protection of pancreatic islets from host immune mechanisms by isolating the islets in artificial membranes has emerged as an attractive alternative to the use of immunosuppression. In this Rapid Communication, we describe a novel method for macroencapsulation of rat islets in hydrophilic macrobeads made with various combinations of agarose, collagen, and Gelfoam. Encapsulated xenotypic islets were placed intraperitoneally in mice in which diabetes was induced by streptozotocin. The encapsulated xenografts maintained normoglycemia > 170 days. Recipients mice had normal glucose tolerance tests, which indicates that the islets in the macrobeads were functioning as they would in an intact pancreas. Macrobeads retrieved up to 103 days after transplantation showed no evidence of tissue reaction or local inflammation. These retrieved macrobeads could also be retransplanted and replaced. Our studies indicate that the agarose-collagen/Gelfoam macrobeads we have developed serve both to protect islet xenografts from rejection and to provide a microenvironment in which the islets maintain and support their normal function in vivo. Because they may be retrieved after implantation and replaced, these macrobeads may be suitable for human clinical islet cell xenotransplantation.