A randomised controlled trial to examine the effectiveness of group cognitive behavioural therapy for the treatment of unipolar depression in Malaysia

Malaysia has been experiencing a dearth in mental health resources. Group Cognitive Behavioural Therapy (GCBT) has been an established form of treatment for unipolar depression. The objectives of the current study were to examine the effectiveness of using GCBT for the treatment of depression in Malaysia. A total of 174 participants suffering from unipolar depression were recruited and randomly allocated to one of GCBT+Treatment as Usual (TAU), Relaxation training+TAU, or TAU only treatment groups. The participants were between 18-60 years of age. The participants in the GCBT+TAU group received eight Group CBT sessions of over a span of two months. The participants receiving Relaxation+TAU treatment received eight relaxation training sessions over a span of two months. The participants in the TAU only treatment group received treatment as usual from their psychiatrists. The BDI-M, ATQ-M, ATQP-M and DAS-M were administered at pre-treatment, mid-treatment (week 4) and post-treatment. Repeated Measures MANOVA showed a significant interaction effect between treatment group and time for BDI-M, ATQ-M, ATQP-M and DAS-M. Results showed that GCBT+TAU was able to significantly reduce depressive symptoms, negative cognitions and beliefs. Moderate effect sizes for the BDI-M scores, as well as significantly reliable and clinical change, were also found. The current study was limited by geographical boundaries, where only hospitals in and around the greater Klang Valley area were sampled. Results from the current study suggest that GCBT is effective in reducing the symptoms of depression in a Malaysian setting

Cost-utility model of brivaracetam in the adjunctive treatment of patients with epilepsy in Spain

[EN] Objective This study aims to assess the cost utility of Brivaracetam compared with the third-generation anti-epileptic drugs used as standard care. Methods A cost utility analysis of Brivaracetam was carried out with other third-generation comparators. The treatment pathway of a hypothetical cohort over a period of 2 years was simulated using the Markov model. Data for effectiveness and the QALYs of each health status for epilepsy, as well as for the disutilities of adverse events of treatments, were analyzed through a studies review. The cost of the anti-epileptics and the use of medical resources linked to the different health statuses were taken into consideration. A probabilistic sensitivity analysis was performed using a Monte Carlo simulation. Results Brivaracetam was shown to be the dominant alternative, with Incremental Cost Utility Ratio (ICUR) values from -11,318 for Lacosamide to -128,482 for Zonisamide. The probabilistic sensitivity analysis validates these results. The ICUR sensitivity is greater for increases in the price of Brivaracetam than for decreases, and for Eslicarbizapine over the other adjunctives considered in the analysis. Conclusions Treatment with Brivaracetam resulted in cost effective and incremental quality adjusted life years come at an acceptable cost.Barrachina Martínez, I.; Vivas-Consuelo, D.; Reyes-Santias, F. (2020). Cost-utility model of brivaracetam in the adjunctive treatment of patients with epilepsy in Spain. Expert review of pharmacoeconomics & outcomes research (Online). 1-10. https://doi.org/10.1080/14737167.2021.1838899S110WHO | Epilepsy: aISBN public health imperative. ISBN 978-92-4-151593-1. World Health Organization. 2019. Printed in Thailand.Ngugi, A. K., Kariuki, S. M., Bottomley, C., Kleinschmidt, I., Sander, J. W., & Newton, C. R. (2011). Incidence of epilepsy: A systematic review and meta-analysis. Neurology, 77(10), 1005-1012. doi:10.1212/wnl.0b013e31822cfc90Henning, O., Landmark, C. J., Henning, D., Nakken, K. O., & Lossius, M. I. (2019). Challenges in epilepsy—The perspective of Norwegian epilepsy patients. Acta Neurologica Scandinavica, 140(1), 40-47. doi:10.1111/ane.13098Brodie, M. J. (2005). Diagnosing and predicting refractory epilepsy. Acta Neurologica Scandinavica, 112(s181), 36-39. doi:10.1111/j.1600-0404.2005.00507.xGarcía-Ramos, R., Pastor, A. G., Masjuan, J., Sánchez, C., & Gil, A. (2011). FEEN: Informe sociosantario FEEN sobre la epilepsia en España. Neurología, 26(9), 548-555. doi:10.1016/j.nrl.2011.04.002Kwan, P., & Brodie, M. J. (2000). Early Identification of Refractory Epilepsy. New England Journal of Medicine, 342(5), 314-319. doi:10.1056/nejm200002033420503Brodie, M. J. (2008). Epilepsy: randomised trials and genetic tribulations. The Lancet Neurology, 7(1), 7-8. doi:10.1016/s1474-4422(07)70301-0French, J. A. (2006). Refractory Epilepsy: One Size Does Not Fit All. Epilepsy Currents, 6(6), 177-180. doi:10.1111/j.1535-7511.2006.00137.xLaxer, K. D., Trinka, E., Hirsch, L. J., Cendes, F., Langfitt, J., Delanty, N., … Benbadis, S. R. (2014). The consequences of refractory epilepsy and its treatment. Epilepsy & Behavior, 37, 59-70. doi:10.1016/j.yebeh.2014.05.031Giordano, C., Marchiò, M., Timofeeva, E., & Biagini, G. (2014). Neuroactive Peptides as Putative Mediators of Antiepileptic Ketogenic Diets. Frontiers in Neurology, 5. doi:10.3389/fneur.2014.00063European Medicines Agency. Committee for Medicinal Products for Human Use (CHMP). Briviact brivaracetam. Assessment Report EMA/CHMP/822086/2015 Nov.Markham, A. (2016). Brivaracetam: First Global Approval. Drugs, 76(4), 517-522. doi:10.1007/s40265-016-0555-6Willems, L. M., Bauer, S., Rosenow, F., & Strzelczyk, A. (2019). Recent advances in the pharmacotherapy of epilepsy: brivaracetam and perampanel as broad-spectrum antiseizure drugs for the treatment of epilepsies and status epilepticus. Expert Opinion on Pharmacotherapy, 20(14), 1755-1765. doi:10.1080/14656566.2019.1637420Craig, D., Rice, S., Paton, F., Fox, D., & Woolacott, N. (2013). Retigabine for the Adjunctive Treatment of Adults with Partial-Onset Seizures in Epilepsy with and without Secondary Generalization. PharmacoEconomics, 31(2), 101-110. doi:10.1007/s40273-012-0018-1Charokopou, M., Harvey, R., Srivastava, K., Brandt, C., & Borghs, S. (2019). Relative performance of brivaracetam as adjunctive treatment of focal seizures in adults: a network meta-analysis. Current Medical Research and Opinion, 35(8), 1345-1354. doi:10.1080/03007995.2019.1584501Chhatwal J. Changing cycle lengths in state-transition models: doing it the right way; [cited 2018 Jan 23]. Available from: https://www.ispor.org/News/Connections_methodology_state-transition-models.PDFMulhern, B., Rowen, D., Snape, D., Jacoby, A., Marson, T., Hughes, D., … Brazier, J. (2014). Valuations of epilepsy-specific health states: a comparison of patients with epilepsy and the general population. Epilepsy & Behavior, 36, 12-17. doi:10.1016/j.yebeh.2014.04.011Kristian, B., Wachtmeister, K., Stefan, F., & Forsgren, L. (2013). Retigabine as add-on treatment of refractory epilepsy - a cost-utility study in a Swedish setting. Acta Neurologica Scandinavica, 127(6), 419-426. doi:10.1111/ane.12077Vera-Llonch, M., Brandenburg, N. A., & Oster, G. (2008). Cost-effectiveness of Add-on Therapy with Pregabalin in Patients with Refractory Partial Epilepsy. Epilepsia, 49(3), 431-437. doi:10.1111/j.1528-1167.2007.01279.xSimoens, S. (2010). Pharmacoeconomics of anti-epileptic drugs as adjunctive therapy for refractory epilepsy. Expert Review of Pharmacoeconomics & Outcomes Research, 10(3), 309-315. doi:10.1586/erp.10.18Wijnen, B. F. M., van Mastrigt, G. A. P. G., Evers, S. M. A. A., Gershuni, O., Lambrechts, D. A. J. E., Majoie, M. H. J. M., … de Kinderen, R. J. A. (2017). A systematic review of economic evaluations of treatments for patients with epilepsy. Epilepsia, 58(5), 706-726. doi:10.1111/epi.13655Boeck, J. D., Verpoorten, K., Luyten, K., & Coninx, K. (2007). A Comparison between Decision Trees and Markov Models to Support Proactive Interfaces. 18th International Conference on Database and Expert Systems Applications (DEXA 2007). doi:10.1109/dexa.2007.94Zhang, Y., Wu, H., Denton, B. T., Wilson, J. R., & Lobo, J. M. (2017). Probabilistic sensitivity analysis on Markov models with uncertain transition probabilities: an application in evaluating treatment decisions for type 2 diabetes. Health Care Management Science, 22(1), 34-52. doi:10.1007/s10729-017-9420-8Swallow, E., Fang, A., Signorovitch, J., Plumb, J., & Borghs, S. (2017). Can Matching-Adjusted Indirect Comparison Methods Mitigate Placebo Response Differences Among Patient Populations in Adjunctive Trials of Brivaracetam and Levetiracetam? CNS Drugs, 31(10), 899-910. doi:10.1007/s40263-017-0462-8Malyshkina NV, Mannering FL. Markov switching multinomial logit model: an application to accident injury severities; 2008 [cited 2019 Sep 25]. Available from: http://arxiv.org/abs/0811.3644Hawkins, N., Epstein, D., Drummond, M., Wilby, J., Kainth, A., Chadwick, D., & Sculpher, M. (2005). Assessing the Cost-Effectiveness of New Pharmaceuticals in Epilepsy in Adults: The Results of a Probabilistic Decision Model. Medical Decision Making, 25(5), 493-510. doi:10.1177/0272989x05280559Agencia Española del Medicamento. Utilización de medicamentos antiepilépticos en España durante el periodo 2008–2016 [Internet]; 2017 [cited 2019 Sep 25]. Available from: https://www.aemps.gob.es/medicamentosUsoHumano/observatorio/docs/antiepilepticos-periodo-2008-2016.pdfMegiddo, I., Colson, A., Chisholm, D., Dua, T., Nandi, A., & Laxminarayan, R. (2016). Health and economic benefits of public financing of epilepsy treatment in India: An agent‐based simulation model. Epilepsia, 57(3), 464-474. doi:10.1111/epi.13294De Andrés-Nogales, F., Oyagüez, I., Álvarez-Sala, L. A., García-Bragado, F., Navarro, A., González, P., … Soto, J. (2017). Análisis coste-efectividad y coste-utilidad de apixaban frente a dabigatrán y rivaroxaban en el tratamiento y prevención secundaria del tromboembolismo venoso. PharmacoEconomics Spanish Research Articles, 14(1), 7-18. doi:10.1007/s40277-016-0064-8Fricke-Galindo, I., Jung-Cook, H., LLerena, A., & López-López, M. (2018). Farmacogenética de reacciones adversas a fármacos antiepilépticos. Neurología, 33(3), 165-176. doi:10.1016/j.nrl.2015.03.005Steinhoff, B. J., Bacher, M., Bucurenciu, I., Hillenbrand, B., Intravooth, T., Kornmeier, R., … Staack, A. M. (2017). Real-life experience with brivaracetam in 101 patients with difficult-to-treat epilepsy—A monocenter survey. 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Nature, prevalence and factors associated with depression among the elderly in a rural south Indian community

Background: Depression in old age is an important public health problem causing considerable morbidity and disability worldwide. There is a dearth of community studies from India investigating geriatric depression and its associated risk factors. This study aimed to establish the nature, prevalence and factors associated with geriatric depression in a rural south Indian community

Prevalence and correlates of physical disability and functional limitation among community dwelling older people in rural Malaysia, a middle income country

<p>Abstract</p> <p>Background</p> <p>The prevalence and correlates of physical disability and functional limitation among older people have been studied in many developed countries but not in a middle income country such as Malaysia. The present study investigated the epidemiology of physical disability and functional limitation among older people in Malaysia and compares findings to other countries.</p> <p>Methods</p> <p>A population-based cross sectional study was conducted in Alor Gajah, Malacca. Seven hundred and sixty five older people aged 60 years and above underwent tests of functional limitation (Tinetti Performance Oriented Mobility Assessment Tool). Data were also collected for self reported activities of daily living (ADL) using the Barthel Index (ten items). To compare prevalence with other studies, ADL disability was also defined using six basic ADL's (eating, bathing, dressing, transferring, toileting and walking) and five basic ADL's (eating, bathing, dressing, transferring and toileting).</p> <p>Results</p> <p>Ten, six and five basic ADL disability was reported by 24.7% (95% CI 21.6-27.9), 14.4% (95% CI 11.9-17.2) and 10.6% (95% CI 8.5-13.1), respectively. Functional limitation was found in 19.5% (95% CI 16.8-22.5) of participants. Variables independently associated with 10 item ADL disability physical disability, were advanced age (≥ 75 years: prevalence ratio (PR) 7.9; 95% CI 4.8-12.9), presence of diabetes (PR 1.8; 95% CI 1.4-2.3), stroke (PR 1.5; 95% CI 1.1-2.2), depressive symptomology (PR 1.3; 95% CI 1.1-1.8) and visual impairment (blind: PR 2.0; 95% CI 1.1-3.6). Advancing age (≥ 75 years: PR 3.0; 95% CI 1.7-5.2) being female (PR 2.7; 95% CI 1.2-6.1), presence of arthritis (PR 1.6; 95% CI 1.2-2.1) and depressive symptomology (PR 2.0; 95% CI 1.5-2.7) were significantly associated with functional limitation.</p> <p>Conclusions</p> <p>The prevalence of physical disability and functional limitation among older Malaysians appears to be much higher than in developed countries but is comparable to developing countries. Associations with socio-demographic and other health related variables were consistent with other studies.</p

Large family with both parents affected by distinct BRCA1 mutations: implications for genetic testing

Although the probability of both parents being affected by BRCA1 mutations is not negligible, such families have not been systematically described in the literature. Here we present a large breast-ovarian cancer family, where 3 sisters and 1 half-sister inherited maternal BRCA1 5382insC mutation while the remaining 2 sisters carried paternal BRCA1 1629delC allele. No BRCA1 homozygous mutations has been detected, that is consistent with the data on lethality of BRCA1 knockout mice. This report exemplifies that the identification of a single cancer-predisposing mutation within the index patient may not be sufficient in some circumstances. Ideally, all family members affected by breast or ovarian tumor disease have to be subjected to the DNA testing, and failure to detect the mutation in any of them calls for the search of the second cancer-associated allele

Prevalence of Mistreatment or Belittlement among Medical Students – A Cross Sectional Survey at a Private Medical School in Karachi, Pakistan

Background: Mistreatment or belittlement of medical students either by faculty or fellow students has often been reported. Perception of mistreatment has also been associated with increased degree of psychological morbidity. There is a lack of such studies being conducted amongst the medical students of Pakistan. The aim of this study was to determine the prevalence and forms of perceived mistreatment and presence of mental health morbidity in a private medical school in Pakistan. Also, any association between mental health morbidity and mistreatment was to be identified. Methods: A cross sectional study was carried out on medical students from Aga Khan University Hospital, Karachi, Pakistan during the period of June-September 2007. A self administered questionnaire, adapted from Frank et al and Baldwin et al was distributed to a total of 350 students. The questionnaire consisted of three parts: the first dealing with the demographics of the population, the second concerning the various forms of mistreatment, while the third assessed the mental health of students using the General Health Questionnaire 12(GHQ12). Descriptive statistics were performed. The Chi-square test and Fisher\u27s exact tests were applied. Results: A total of 350 students were approached out of which 232 completed the questionnaire giving a response rate of 66.2%. Mistreatment was reported by 62.5% (145/232) of the respondents. Of these, 69.7% (83/145) were males and 54.9% (62/145) were females. There was a significant relationship between gender, year division, stress at medical school and possible use of drugs/alcohol and reported mistreatment but no statistical relationship was seen with psychiatric morbidity. The overall prevalence of psychological morbidity was 34.8% (77/221). Conclusion: This study suggests high prevalence of perceived mistreatment and psychological morbidity among Pakistani medical students. However, no association was found between these two aspects of medical student education. There is a need to bring about changes to make the medical education environment conducive to learning. Increased student feedback, support systems and guidance about progress throughout the year and the provision of adequate learning resources may provide help with resolving both of these issues

High frequency of BRCA1, but not CHEK2 or NBS1 (NBN), founder mutations in Russian ovarian cancer patients

<p>Abstract</p> <p>Background</p> <p>A significant portion of ovarian cancer (OC) cases is caused by germ-line mutations in BRCA1 or BRCA2 genes. BRCA testing is cheap in populations with founder effect and therefore recommended for all patients with OC diagnosis. Recurrent mutations constitute the vast majority of BRCA defects in Russia, however their impact in OC morbidity has not been yet systematically studied. Furthermore, Russian population is characterized by a relatively high frequency of CHEK2 and NBS1 (NBN) heterozygotes, but it remains unclear whether these two genes contribute to the OC risk.</p> <p>Methods</p> <p>The study included 354 OC patients from 2 distinct, geographically remote regions (290 from North-Western Russia (St.-Petersburg) and 64 from the south of the country (Krasnodar)). DNA samples were tested by allele-specific PCR for the presence of 8 founder mutations (BRCA1 5382insC, BRCA1 4153delA, BRCA1 185delAG, BRCA1 300T>G, BRCA2 6174delT, CHEK2 1100delC, CHEK2 IVS2+1G>A, NBS1 657del5). In addition, literature data on the occurrence of BRCA1, BRCA2, CHEK2 and NBS1 mutations in non-selected ovarian cancer patients were reviewed.</p> <p>Results</p> <p>BRCA1 5382insC allele was detected in 28/290 (9.7%) OC cases from the North-West and 11/64 (17.2%) OC patients from the South of Russia. In addition, 4 BRCA1 185delAG, 2 BRCA1 4153delA, 1 BRCA2 6174delT, 2 CHEK2 1100delC and 1 NBS1 657del5 mutation were detected. 1 patient from Krasnodar was heterozygous for both BRCA1 5382insC and NBS1 657del5 variants.</p> <p>Conclusion</p> <p>Founder BRCA1 mutations, especially BRCA1 5382insC variant, are responsible for substantial share of OC morbidity in Russia, therefore DNA testing has to be considered for every OC patient of Russian origin. Taken together with literature data, this study does not support the contribution of CHEK2 in OC risk, while the role of NBS1 heterozygosity may require further clarification.</p