Neha Dahiya

Drug treatment of obesity: current status and future prospects.

Obesity is a growing epidemic and a major contributor to the global burden of disease. Obesity strains the healthcare systems and has profound economic and psychosocial consequences. Historically, pharmacotherapy for obesity has witnessed the rise and fall of several promising drug candidates that had to be eventually withdrawn due to unacceptable safety concerns. Currently four drugs are approved for chronic weight management in obese adults: orlistat, lorcaserin, phentermine/topiramate extended release and naltrexone/bupropion extended release. While lorcaserin and phentermine/topiramate were approved by US Food and Drug Administration (FDA) in 2012, after a gap of 13 years following the licensing of orlistat, naltrexone/bupropion has been recently approved in 2014. This review provides a brief overview of these current therapeutic interventions available for management of obesity along with the evidence of their safety and efficacy. Additionally, several novel monotherapies as well as combination products are undergoing evaluation in various stages of clinical development. These therapies if proven successful will strengthen the existing armamentarium of antiobesity drugs and will be critical to combat the global public health crisis of obesity and its associated co-morbidities.

Bedaquiline for the treatment of resistant tuberculosis: Promises and pitfalls

Treatment of multidrug-resistant tuberculosis (MDR-TB) is hindered by limited efficacy and significant toxicity of second-line drugs. The need for new therapeutic options is critical to combat the global MDR-TB epidemic. Bedaquiline is a novel oral diarylquinoline approved by Food and Drug administration (FDA) for the treatment of adults with pulmonary MDR-TB on the basis of Phase IIb trial data under the provisions of the accelerated approval regulations for serious or life-threatening conditions. The FDA advisory committee members voted unanimously on efficacy data based on surrogate measures, however they were split on the issues of safety of bedaquiline. Main safety concerns include QT interval prolongation, hepatic related adverse events, and excess mortality in bedaquiline treated patients. While bedaquiline approval is a story of many firsts and certainly a welcome addition to the existing arsenal of anti-TB agents, a cautiously optimistic approach is required to assess the risk benefit profile of the drug. Acceleration of further Phase III trials and clinical studies is imperative, as is timely analysis of emerging data on the real world use of the drug. This mini review outlines the clinical pharmacology of bedaquiline highlighting the potential promises and challenges that implicate the risk benefit profile of drug.

Management of Parkinson׳s disease: Current and future pharmacotherapy

Parkinson׳s disease (PD) is chronic progressive neurodegenerative disorder characterized by profound loss of dopaminergic neurons in the nigrostriatal pathway. It is recognized by the cardinal clinical features of bradykinesia, rigidity, tremor and postural instability. Current therapeutic options are primarily dopamine replacement strategies that only provide symptomatic improvement without affecting progressive neuronal loss. These treatments often fail to provide sustained clinical benefit and most patients develop motor fluctuations and dyskinesias as the disease progresses. Additionally, non-motor symptoms such as autonomic disturbances, sensory alterations, olfactory dysfunction, mood disorders, sleep disturbances and cognitive impairment cause considerable functional disability in these patients and these features often fail to respond to standard dopaminergic treatments. This mini review outlines the current pharmacotherapeutic options for PD and highlights the emerging experimental therapies in various phases of clinical development.

The evolving drug development landscape: from blockbusters to niche busters in the orphan drug space.

Strategy, Management and Health Policy

Current Issues With the Use of Bedaquiline

TO THE EDITOR: We read with interest the article by Chahine et al. The authors have reviewed the clinical pharmacology, safety, and efficacy of bedaquiline, a welcome addition to the existing arsenal of antitubercular drugs. However, we believe a cautiously optimistic approach is required to assess the risk benefit profile of this agent in the present scenario. Most of drug approvals are based on robust clinical trial data where thousands of patients have been exposed to test drug and actual clinical outcomes have been evaluated. However, Food and Drug Administration (FDA) approval of bedaquiline was based on sputum culture conversion, a surrogate endpoint evaluated in a small number of patients. The currently available clinical studies with bedaquiline have several other limitations, namely, low-quality evidence on background treatment regimens, use of modified intention to treat analysis, and low cure rates observed in the placebo group when compared with those reported by recent reviews. Also, FDA approval committee members may have been unanimous on efficacy data; however, they were split on the issues of drug safety and excess mortality. In the pivotal clinical study, the number of deaths in bedaquiline group was 5 times as compared with those in the control group. Concerns have been raised about evidence of QT prolongation and raised liver transaminase levels. Evidence base for the use of bedaquiline needs to be strengthened through well-designed large phase III clinical studies based on actual outcomes such as cure rates and studies investigating efficacy, safety, and pharmacokinetics in special populations, including children, the elderly, pregnant women, HIV patients, alcohol users, and patients with extrapulmonary tuberculosis. Because of its likelihood to be involved in drug interactions, dedicated studies exploring effects of its co-administration with other antitubercular and antiretroviral regimens and identification of optimal dose and duration of such therapies are needed. In addition, reliable drug susceptibility tests for bedaquiline need to be developed. Cost-effectiveness and patient acceptability also needs to be ascertained especially in settings where it is considered for inclusion in nationwide tuberculosis control programs. Another issue plaguing the usefulness of bedaquiline is its potential unregulated use in high multidrug-resistant tuberculosis burden countries. Such misuse in the absence of clear-cut national prescribing guidelines can rapidly limit its usefulness and promote emergence of resistance. Regimens containing bedaquiline need to be cautiously designed to avoid an extended period of exposure to low levels of bedaquiline as the sole drug. To address these concerns, both the World Health Organization and the Centers for Disease Control and Prevention have issued provisional guidelines on the use of bedaquiline in the treatment of multidrug-resistant tuberculosis. The possible benefits of using bedaquiline outweigh the potential risks in select group of patients. However, its precise role in various clinical settings will remain unclear until further efficacy and safety data are obtained through well-designed phase III studies and a timely analysis of data on its real-world use.

Knowledge and Practices Related to Screening for Breast Cancer among Women in Delhi, India

Background: Breast cancer is a major public health problem globally. The ongoing epidemiological, socio-cultural and demographic transition by accentuating the associated risk factors has disproportionately increased the incidence of breast cancer cases and resulting mortality in developing countries like India. Early diagnosis with rapid initiation of treatment reduces breast cancer mortality. Therefore awareness of breast cancer risk and a willingness to undergo screening are essential. The objective of the present study was to assess the knowledge and practices relating to screening for breast cancer among women in Delhi. Methods: Data were obtained from 222 adult women using a pretested self-administered questionnaire. Results: Rates for knowledge of known risk factors of breast cancer were: family history of breast cancer, 59.5%; smoking, 57.7%; old age, 56.3%; lack of physical exercise, 51.9%; lack of breastfeeding, 48.2%; late menopause, 37.4%; and early menarche, 34.7%. Women who were aged < 30 and those who were unmarried registered significantly higher knowledge scores (p ≤ 0.01). Breast self-examination (BSE) was regularly practiced at-least once a month by 41.4% of the participants. Some 48% knew mammography has a role in the early detection of breast cancer. Since almost three-fourths of the participants believed BSE could help in early diagnosis of breast cancer, which is not supported by evidence, future studies should explore the consequences of promoting BSE at the potential expense of screening mammography. Conclusion: Our findings highlight the need for awareness generation among adult women regarding risk factors and methods for early detection of breast cancer.

Factors affecting choice of future specialty among medical students

Dear Editor, We read with interest the article by Kumar et al., where the authors have evaluated the future career interests and factors that influence undergraduate medical students’ choice of specialty.[1] A medical specialization encompasses transition from an undifferentiated medical graduate to the fully differentiated professional who is usually restricted to one specialized field of medical work. The medical specialty chosen by the medical student has important implications for both the practitioner as well as the national community. It is critical in determining the future supply of doctors in different specialties and the planning of the workforce for the healthcare services. In the present study, some interesting trends can be seen. Although the male students were interested in only internal medicine or surgery, the females preferred obstetrics and gynecology the most. The most alarming finding being that none of the students in China, Sri Lanka, India, and Nepal preferred pediatrics. Also while the questionnaire used in the study had an option for public health and social medicine, apparently none of the students opted for them. This problem has been highlighted time and again and underlines the issues in achieving health equity and limits the access of people living in rural and underserved areas to trained health manpower. Although nearly one half of world population resides in rural areas, they are served by less than a quarter of available physician workforce. The World Health Organization (WHO) has suggested principles and evidence-based recommendations to improve rural retention of doctors.[2] The educational recommendations include the use of favorable admission policies for students with rural background, location of medical schools and campuses outside of major cities, exposing undergraduates to rural community postings, inclusion of rural health topics in undergraduate and postgraduate curricula, and planning of continuing medical education and professional development programs that address the needs of rural health workers. The current bias of study sample in favor of urban students is one of the possible reasons for none of the students opting for public health as specialty of choice. The study also involves only specific medical schools in these five countries and may not be generalized to South Asian Association for Regional Cooperation (SAARC) nations as a whole. However, the study highlights the need for these developing countries to reassess their existing policies and introduce and/or reinforce the suggested reforms to ensure a stronger workforce in the rural areas. Also the basic medical sciences were neglected as a choice of specialization by all students across the five study settings. We also feel that students in first year Bachelor of Medicine and Bachelor of Surgery (MBBS) program have limited exposure to the clinics and thus their career choices are likely to be influenced at later stages of their education by various factors like perceived academic and career opportunities, societal/family expectations, effects of role models among supervisors, faculty and residents, work-related hazards, opportunities to perform procedures and urgent interventions, prospects of working in an urban setting, difficulty level of training, number of practice work hours per week, opportunities to work independently in the specialty, type of problems and patients encountered, and likely patient outcomes.-[3,4,5] In addition, a previous study has shown that students in their clinical phase of study are more likely to decide a future medical specialization than students in their basic sciences phase of medical education.[3] The range of career options available to a medical graduate has become even broader as a result of the emergence of several new subspecialties within the traditional specialties. The fact that none of the students opted for prestige, respect, and status is discordant with previously reported studies.[3,5,6] There are individual differences in the medical curriculum among these countries that might have affected the study results, e.g. the first year MBBS students in India have little exposure to paraclinical subjects like pathology, microbiology, and pharmacology. This might be one of the reasons for their lack of awareness and inclination toward these basic medical sciences. Possible ways of enabling undergraduate medical students to make informed choices regarding postgraduate specialities need to be explored. Efforts should also be made to enhance the attractiveness of medical specialities facing considerable manpower shortages to address the current and future healthcare needs of the nation. The medical schools in developing countries can introduce medical laboratory internships and modules based on research and laboratory medicine that can help to inculcate students interest in research and basic medical sciences. Another intervention includes introduction of mentoring programs and formal career counseling. Such mentoring programs during undergraduate training can positively influence students interest in careers in public health and basic medical specialities.