Drugs for cardiovascular disease in India: perspectives of pharmaceutical executives and government officials on access and development-a qualitative analysis

Background: India shoulders the greatest global burden of cardiovascular diseases (CVDs), which are the leading cause of mortality worldwide. Drugs are the bedrock of treatment and prevention of CVD. India’s pharmaceutical industry is the third largest, by volume, globally, but access to CVD drugs in India is poor. There is a lack of qualitative data from government and pharmaceutical sectors regarding CVD drug development and access in India. Methods: By purposive sampling, we recruited either Indian government officials, or pharmaceutical company executives. We conducted a stakeholder analysis via semi-structured, face-to-face interviews in India. Topic guides allow for the exploration of key issues across multiple interviews, along with affording the interviewer the flexibility to examine matters arising from the discussions themselves. After transcription, interviews underwent inductive thematic analysis. Results: Ten participants were interviewed (Government Officials: n = 5, and Pharmaceutical Executives: n= 5). Two themes emerged: i) ‘Policy-derived Factors’; ii) ‘Patient- derived Factors’ with three findings. First, both government and pharmaceutical participants felt that the focus of Indian pharma is shifting to more complex, high-quality generics and to new drug development, but production of generic drugs rather than new molecular entities will remain a major activity. Second, current trial regulations in India may restrict India’s potential role in the future development of CVD drugs. Third, it is likely that the Indian government will tighten its intellectual property regime in future, with potentially far-reaching implications on CVD drug development and access. Conclusions: Our stakeholder analysis provides some support for present patent regulations, whilst suggesting areas for further research in order to inform future policy decisions regarding CVD drug development and availability. Whilst interviewees suggested government policy plays an important role in shaping the industry, a significant force for change was ascribed to patient-derived factors. This suggests a potential role for Indian initiatives that market the unique advantages of its patient population for drug research in influencing national and multinational pharmaceutical companies to undertake CVD drug development in India, rather than simply IP policy-directed factors

Two Cheers For Diversity: An Experimental Study Of Micro-level Heterogeneity In Problemistic Search

In this paper, we argue for an expanded view of problemistic search. Recent behavioral theory research suggests that individual search preferences influence problemistic search. We draw on this to challenge the view of problemistic search as a centrally directed organizational process that proceeds sequentially from local to distant search. We argue that search activities in organizations are heterogeneous – some individuals will first engage in local search while others may move directly to distant search. We propose that problemistic search at the macroorganizational level is therefore the result of a mix of local and distant search activities at the micro-level that shifts towards distant search in response to negative performance evaluation. We test this idea in a laboratory experiment using a repetitive task and performance feedback

Validating self-reported strokes in a longitudinal UK cohort study (Whitehall II): Extracting information from hospital medical records versus the Hospital Episode Statistics database

Background: Valuable information on the determinants of non-fatal stroke can be obtained from longitudinal observational cohort studies. Such studies often rely on self-reported stroke events, which are best validated with external medical evidence. The aim of this paper is to compare the information on incident non-fatal stroke events arising from different sources.Methods: We carried out a validation of self-reported stoke events among participants in the Whitehall II Study, a large UK based cohort study (baseline sample size 10,308 men and women).Results: 106 stroke events were self-reported in three self-administered questionnaires between 2002 and 2009. Eight (7.5%) of these events were discarded as false positives after medical review, 66 were validated by information from the NHS Hospital Episode Statistics (HES) database in England, 16 by manual searches of hospital records alone, and 12 by letters from general practitioners alone. HES provided information on an additional (i.e. not self-reported) 47 events coded as stroke during the period 2002 to 2009 in hospitals in England among the original baseline participants. Of these, 43 participants were no longer active in the study and 4 had completed questionnaires but not reported a stroke event.Conclusions: Validating self-reported strokes in cohort studies with information from the NHS HES database was efficient and provided information on probable non-fatal stroke events among cohort members no longer in active follow-up. Manual extraction from hospital notes can provide supplementary information beyond that available in the HES discharge summary and was used to sub-type some strokes. However, the process was labour intensive. Multiple sources are needed to capture maximum information on stroke events but increasingly with hospitalisation in the acute phase of stroke, HES has an important role. Further development of HES is required to assure validity and coverage.</p

Living with offshoring: The impact of offshoring on the evolution of organizational configurations

Offshoring allows firms to pursue greater flexibility at lower costs, but it also presents major structural and managerial challenges. Adopting the activity configuration perspective, we argue that offshoring creates tensions between benefits to the competitive position of the firm, and potential disruption to the cohesion and consistency of the organization's internal activity configuration. We further argue that both benefits and risks increase as organizations move from offshoring low to offshoring high value-creating activities, and as they seek tight as opposed to loose couplings among offshored and onshored value-creating activities. Our research site is the UK operations of Tiscali, a European telecommunications firm. We examine how Tiscali uses offshoring as it grows and expands its service offerings from single, to double, and then triple play, and also analyze how Tiscali addresses the ensuing disruption to its activity configuration. We conclude with implications of our study to future research on offshoring

Trends in prevalence of acute stroke impairments:A population-based cohort study using the South London Stroke Register

Background Acute stroke impairments often result in poor long-term outcome for stroke survivors. The aim of this study was to estimate the trends over time in the prevalence of these acute stroke impairments. Methods and findings All first-ever stroke patients recorded in the South London Stroke Register (SLSR) between 2001 and 2018 were included in this cohort study. Multivariable Poisson regression models with robust error variance were used to estimate the adjusted prevalence of 8 acute impairments, across six 3-year time cohorts. Prevalence ratios comparing impairments over time were also calculated, stratified by age, sex, ethnicity, and aetiological classification (Trial of Org 10172 in Acute Stroke Treatment [TOAST]). A total of 4,683 patients had a stroke between 2001 and 2018. Mean age was 68.9 years, 48% were female, and 64% were White. After adjustment for demographic factors, pre-stroke risk factors, and stroke subtype, the prevalence of 3 out of the 8 acute impairments declined during the 18-year period, including limb motor deficit (from 77% [95% CI 74%–81%] to 62% [56%–68%], p &lt; 0.001), dysphagia (37% [33%–41%] to 15% [12%–20%], p &lt; 0.001), and urinary incontinence (43% [39%–47%) to 29% [24%–35%], p &lt; 0.001). Declines in limb impairment over time were 2 times greater in men than women (prevalence ratio 0.73 [95% CI 0.64–0.84] and 0.87 [95% CI 0.77–0.98], respectively). Declines also tended to be greater in younger patients. Stratified by TOAST classification, the prevalence of all impairments was high for large artery atherosclerosis (LAA), cardioembolism (CE), and stroke of undetermined aetiology. Conversely, small vessel occlusions (SVOs) had low levels of all impairments except for limb motor impairment and dysarthria. While we have assessed 8 key acute stroke impairments, this study is limited by a focus on physical impairments, although cognitive impairments are equally important to understand. In addition, this is an inner-city cohort, which has unique characteristics compared to other populations. Conclusions In this study, we found that stroke patients in the SLSR had a complexity of acute impairments, of which limb motor deficit, dysphagia, and incontinence have declined between 2001 and 2018. These reductions have not been uniform across all patient groups, with women and the older population, in particular, seeing fewer reductions.</p

Visual Field Mapping by Tangent Screen and Humphrey Perimetry: A Comparative Study

Background and Objectives: (a) To compare manual tangent screen perimetry and automated Humphrey perimetry for visual field testing, and (b) to analyze whether manual tangent screen perimetry still has a role or it should be replaced by computerized automated Humphrey perimetry in physiology labs and clinical diagnostic settings.Methods: Study was done on 45 patients between 18 and 65 years of age that included 30 eyes of patients suffering from glaucoma/ other eye diseases giving rise to visual field defects, 5 eyes of patients suffering from neurological diseases and 10 eyes of normal subjects.All patients underwent perimetry examination by tangent screen at 1 meter distance (and 2 meter distance, if required) and automated Humphrey perimetry by Humphrey visual field analyzer (HFA) using 30-2 ‘white on white’ full threshold strategy. Tangent screen consists of black screen 2 meter square or 1 meter square. Accordingly, patient is seated at a distance of 2 meter or 1 meter respectively. A patient with organically constricted visual fields will show an increase in the size of the visual field when moved to a farther distance while a patient with functional visual field loss will often report the same absolute size of the field (tubular or gun-barrel field) to be consistent with their first field. This is clear evidence of functional visual field impairment.Results: Out of 45 patients, 29 were male and 16 were female. The age cases in the study ranged from 40-79 years with mean age of 60.70 years. Tangent screen perimetry was able to detect about 5 patients with early field defects and 15 patients with moderate/ advanced field defects. On the other hand, Humphrey automated perimetry was able to detect 10 patients with early field defects and 18 patients with moderate/ advanced field defects. While only 13.33% technicians preferred tangent screen perimetry, around three-fourths of the technicians found Humphrey automated perimetry more preferable. 91.11% technicians found HVF to be technically easier because the automated perimeter eliminates observer bias, is easier to perform and also overcomes the tedium of manual perimetry. Moreover, automated perimetry also uses quantified parameters while manual perimetry does not. On evaluating sensitivity and specificity of manual tangent screen perimeter using the Humphrey automated perimeter as the standard, the tests showed that the tangent screen perimeter had 75.75% sensitivity and 88.88% specificity. Since the mean time taken was more in automated perimetry: 474.5 sec, 474 sec and 459.9 sec versus 340.5 sec, 339.1 sec, and 339.1 sec in glaucoma, neurological and normal patients respectively; more patients-66% preferred tangent screen perimetry.Interpretation and Conclusions: Our results suggest that visual field testing with automated perimetry is superior to visual field testing with tangent screen perimetry. The automated perimeter picked up visual field defects in a larger number of eyes than the tangent screen perimeter. Visual field defects were more extensive on automated perimetry compared to tangent screen perimetry.The advantage of the HVF analyzer also lies in its ability to make use of quantified parameters like mean deviation and corrected pattern standard deviation to detect subtle worsening of visual field defect, with statistical level of confidence

Developing a novel peer support intervention to promote resilience after stroke

Stroke can lead to physical, mental and social long-term consequences, with the incidence of stroke increasing with age. However, there is a lack of evidence of how to improve long-term outcomes for people with stroke. Resilience, the ability to ‘bounce back’, flourish or thrive in the face of adversity improves mental health and quality of life in older adults. However, the role of resilience in adjustment after stroke has been little investigated. The purpose of this study is to report on the development and preliminary evaluation of a novel intervention to promote resilience after stroke. We applied the first two phases of the revised UK Medical Research Council (UKMRC) framework for the development and evaluation of complex interventions: intervention development (phase 1) and feasibility testing (phase 2). Methods involved reviewing existing evidence and theory, interviews with 22 older stroke survivors and 5 carers, and focus groups and interviews with 38 professionals to investigate their understandings of resilience and its role in adjustment after stroke. We used stakeholder consultation to co-design the intervention and returned to the literature to develop its theoretical foundations. We developed a 6-week group-based peer support intervention to promote resilience after stroke. Theoretical mechanisms of peer support targeted were social learning, meaning-making, helping others and social comparison. Preliminary evaluation with 11 older stroke survivors in a local community setting found that it was feasible to deliver the intervention, and acceptable to stroke survivors, peer facilitators, and professionals in stroke care and research. This study demonstrates the application of the revised UKMRC framework to systematically develop an empirically and theoretically robust intervention to promote resilience after stroke. A future randomised feasibility study is needed to determine whether a full trial is feasible with a larger sample and wider age range of people with stroke

Does Admission to Hospital Affect Trends in Survival and Dependency after Stroke Using the South London Stroke Register?

Background and Purpose—Despite guidelines for specialist assessment in hospital for stroke, it is important to identify patient characteristics, trends, and outcome in patients not admitted to hospital compared with patients admitted to hospital. Methods—Population-based stroke register of first in a life time strokes between 1995 and 2012 were examined. Baseline data included admission or nonadmission, case mix, stroke subtype, and risk factors before stroke. Survival curves were estimated with Kaplan–Meier methods. Logistic regression was used to determine factors associated with poor outcome (dead and dependency: Barthel index, &lt;15) at 3 months and 1 year. Results—Three thousand four hundred sixty-four patients were admitted to hospital for stroke. Patients admitted were more likely have more severe impairments (P&lt;0.001). There was a significant trend for increasing admission over time; 1995 to 2000 (82%), 2001 to 2006 (90%), and 2007 to 2012 (94%); P&lt;0.001. When survival analysis was stratified according to Barthel index ≥15 at day 7, there were no significant differences in survival curves between admission and nonadmission groups in 1995 to 2000 (P=0.15) or 2001 to 2006 (P=0.06), but there was a significant trend for higher survival rates for nonadmission in the 2007 to 2012 cohort (P=0.025). Admission to hospital (stroke unit) compared with nonadmission was also associated with poor outcome in the 2001 to 2006 time period (odds ratio, 2.66; confidence interval, 1.17–6.04) and the 2007 to 2012 time period (odds ratio, 5.26; confidence interval, 1.27–21.81). Conclusion—There is a survival advantage from 2007 onward and lower levels of dependency from 2001 onward after adjusting for case mix for those patients who are not admitted to hospital, which requires further explanation

A systematic review of qualitative studies on adjusting after stroke:lessons for the study of resilience

Purpose: To synthesize qualitative studies on adjusting after stroke, from stroke survivors’ and carers’ perspectives, and to outline their potential contribution to an understanding of resilience. Methods: A systematic review of qualitative studies in peer reviewed journals from 1990 to 2011 was undertaken. Findings from selected studies were summarized and synthesized and then considered alongside studies of resilience. Results: Forty studies were identified as suitable. These suggested that the impact of stroke was felt on many dimensions of experience, and that the boundaries between these were permeable. Nor was stroke as an adverse “event” temporally bounded. Adjustment was often marked by setbacks and new challenges over time. Participants identified personal characteristics as key, but also employed practical and mental strategies in their efforts to adjust. Relationships and structural factors also influenced adjustment after stroke. Conclusions: The impacts of stroke and the processes of adjusting to it unfold over time. This presents a new challenge for resilience research. Processes of adjustment, like resilience, draw on personal, inter-personal and structural resources. But the reviewed studies point to the importance of an emic perspective on adversity, social support, and what constitutes a “good” outcome when researching resilience, and to a greater focus on embodiment

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy