Role of patient-reported outcomes and other efficacy endpoints in the drug approval process in Europe (2008-2012)

The present study aimed at systematically reviewing the role and extent of patient-reported outcomes (PROs) usage within the package of scientific evidence considered for marketing authorization (MA). All regulatory information published by the European Medicines Agency (EMA) for products authorized between January 2008 and December 2012 and appearing in the European Public Assessment Report (EPAR) database was examined for efficacy endpoints. The endpoints here considered included: PROs, clinician reported outcomes (CROs), and laboratory reported outcomes (LROs). LROs were the most frequently reported endpoints. Out of the 180 products here selected, 99 (55%), 67 (37%), and 30 (17%), respectively, used LROs, CROs and PROs as primary endpoints (PEs). PROs as any endpoints were used in 82 (46%) products. Out of these, PROs were documented as PE in 30 (37%), with 27 (33%) products having used PROs both as primary and non-PEs. PRO usage was most frequently identified with nervous system and antineoplastic agents. During the study period, the use of all the three types of endpoints appeared to be static. Both the regulatory bodies and the industry should ensure complete and clear reporting of all endpoints used, including PROs, to improve transparency.Peer reviewedFinal Published versio

High Prevalence of Neuropathic Pain Component in Patients with Low Back Pain : Evidence from Meta-Analysis

BACKGROUND: Low back pain (LBP) is a complex syndrome which includes a nociceptive (NcP) component, a neuropathic (NeP) component, or a mixture of components (mixed pain). The NeP component (NePC) in LBP is defined as the presence of NeP with or without an NcP. OBJECTIVE: This meta-analysis aimed at assessing the pooled prevalence of NePC in patients with LBP and at identifying the factors causing significant heterogeneity in reported prevalence. STUDY DESIGN: Meta-analysis. METHODS: A systematic literature search was carried out, with inclusion of all epidemiological studies describing the NeP prevalence levels in LBP patients while using standard diagnostic methods. The "pooled prevalence rate (PPR)" of NePC, either on its own or in combination with NcP, was calculated. A pre-specified subgroup analysis was carried out, considering LBP duration, presence of leg pain, diagnostic method(s), and questionnaire(s) used. RESULTS: The meta-analysis included 20 studies relating to a total of 14,269 LBP patients, of whom 7,969 patients (55.8%) were identified as presenting with NePC. The pooled PR (95% CI) of NePC in patients with LBP was 0.47 (0.40 - 0.54), while the pooled PR of NcP was 0.56 (0.48 - 0.63). Higher NePC pooled PR values were identified in LBP with leg pain as compared to uncomplicated LBP (respectively: 0.60; 0.47 - 0.73 vs 0.27; 0.23 - 0.31; Pinteraction < 0.01). LIMITATIONS: The quality of the included studies was assessed using ad-hoc criteria. Due to the limited number of available studies, one may need to be cautious in reaching conclusions about the impact of disease duration on NePC prevalence values. We pooled studies which used a range of different diagnostic methods, with putatively different sensitivity/specificity diagnosing levels. CONCLUSIONS: Overall, high NePC prevalence levels were here identified in LBP patients. As the pain is a subjective phenomenon and there is no gold standard for the diagnosis of NePC, there is the possibility that the pooled effect estimate may alter depending upon the diagnostic method used. KEY WORDS: Neuropathic pain, nociceptive pain, low back pain, symptom-based questionnaire, chronicity.Peer reviewedFinal Published versio

Cost Effectiveness and Budget Impact of Siponimod Compared to Interferon Beta-1a in the Treatment of Adult Patients with Secondary Progressive Multiple Sclerosis with Active Disease in Switzerland

OBJECTIVE The study aim was to evaluate the cost effectiveness and budget impact of siponimod compared to interferon beta-1a for adult patients with secondary progressive multiple sclerosis (SPMS) with active disease, from a Swiss health insurance perspective. METHODS We conducted an analysis using a Markov cohort model with a cycle length of 1 year, life-long time horizon, and discount rate of 3% for cost and health outcomes. We used a matching-adjusted indirect comparison to estimate clinical outcomes using data from the EXPAND randomised controlled trial of siponimod vs placebo and the Nordic SPMS randomised controlled trial of interferon beta-1a vs placebo as the basis for estimates of disability progression and relapse outcomes. We used 6-month confirmed disability progression results to estimate disability progression in the base-case analysis. We calculated quality-adjusted life-years (QALYs) based on an external study that administered the EQ-5D-3L questionnaire to European patients with multiple sclerosis. We included costs (Swiss Franc (CHF), year 2020) of drug acquisition/administration, adverse events and disease management. We also performed a budget impact analysis to estimate the cost over the first 3 years of introducing siponimod. RESULTS For the base case, siponimod resulted in mean incremental costs of CHF 84,901 (siponimod: CHF 567,838, interferon beta-1a: CHF 482,937) and mean incremental QALYs of 1.591 (siponimod: 7.495, interferon beta-1a: 5.905), leading to an incremental cost-effectiveness ratio of CHF 53,364 per QALY gained. In the probabilistic sensitivity analysis, the probability of the cost effectiveness of siponimod assuming a willingness-to-pay threshold of CHF 100,000 per QALY gained was 90%. Siponimod was projected to result in drug administration costs for siponimod of CHF 23,817,856 in the first 3 years after introduction, accompanied by large cost offsets in drug acquisition of other multiple sclerosis drugs. Considering drug administration, monitoring and adverse event management costs, it was estimated to result in additional healthcare costs in Switzerland of CHF 2,177,021. CONCLUSIONS In the base-case analysis, we found that siponimod may be cost effective for treating Swiss adult patients with SPMS with active disease. The results of the cost-effectiveness analyses are valid under the assumption that the efficacy of siponimod and the comparators on disability progression for the overall SPMS population would be the same in the active SPMS population. CLINICAL TRIAL IDENTIFIER NCT01665144. This economic evaluation was based on the EXPAND trial

Surface roughness of acrylic denture base resins polished with different abrasive agents: an in vitro study

Background: Excessive surface roughness on the denture base can adversely impact the oral health of the patient. Therefore, it is necessary to polish the denture before they are delivered to the patient. The abrasive and polishing agents should provide a smoother surface without affecting the physical and mechanical properties of denture bases. Aim: This study aims to examine and understand the potential of different polishing materials on surface roughness of acrylic denture base resins. Materials and methods: A total of 60 Heat-cure acrylic specimens (acrylic bars) were made and grouped into six groups. Control (no abrasive), Pumice (Micro-white), Eggshell powder, Seashell powder, Black sand powder, White sand powder are used as abrasive materials for polishing these specimens. These polished specimens were subjected to profilometer surface roughness analysis. Results: The acrylic specimens polished with eggshell powder on acrylic specimens showed the least surface roughness followed by black sand, white sand, pumice and seashell powders. Tukey HSD showed significant differences (p=0.000) between unpolished and polished specimens. Conclusion: Eggshell powder effectively reduced the surface roughness of denture base resin material. However, the surface roughness demonstrated by all the abrasive materials used was within the threshold limit (2 µm). Therefore, all the materials can be used as abrasives

DESIGN AND IMPLEMENT OF WIRELESS SENSOR STREET LIGHT CONTROL AND MONITORING STRATEGY ALONG WITH GUI

As of late improving the lattice unwavering quality amid the top moment is picked up a great deal of considerations. Also, utilizing renewable vitality frameworks to nourish remote regions which are not wanted to be encouraged from the utility since they are a long way from it is an another objective of numerous scientists. One out of these heaps is the road lighting particularly. In this manner, this paper proposes a standalone sunlight based vitality free framework for road lighting as there is no force requested from the matrix. The proposed framework comprises of a PV board, stockpiling framework, LED light, control molding framework (PCS) and the controller which can deal with the force bearing and framework operation. Utilizing LED as a part of lighting applications has numerous focal points contrasted with other light. It is extremely proficient (high productivity lighting source) and financially savvy (the life time is long contrast with different lights). In augmentations to, it needs low dc voltage source to be worked. The capacity framework will be charged amid the day time utilizing the accessible daylight. Then again, amid the evening time the controller will give a sign to the framework to associate the LED light to be prepared for use. Subsequent to the LED needs a low dc voltage to be worked, so a basic dc-dc converter will be sufficient for this framework bringing about diminishing the expense of the general framework. Chosen of recreation results have been given to approve the proposed framework

Patient and Provider Perspectives on Medication Non-adherence Among Patients with Depression and/or Diabetes in Diverse Community Settings - A Qualitative Analysis.

BACKGROUND: Diabetes and depression affect a significant percentage of the world\u27s total population, and the management of these conditions is critical for reducing the global burden of disease. Medication adherence is crucial for improving diabetes and depression outcomes, and research is needed to elucidate barriers to medication adherence, including the intentionality of non-adherence, to intervene effectively. The purpose of this study was to explore the perspectives of patients and health care providers on intentional and unintentional medication adherence among patients with depression and diabetes through a series of focus groups conducted across clinical settings in a large urban area. METHODS: This qualitative study utilized a grounded theory approach to thematically analyze qualitative data using the framework method. Four focus groups in total were conducted, two with patients and two with providers, over a one-year period using a semi-structured facilitation instrument containing open-ended questions about experiences, perceptions and beliefs about medication adherence. RESULTS: Across the focus groups, communication difficulties between patients and providers resulting in medication non-adherence was a primary theme that emerged. Concerns about medication side effects and beliefs about medication effectiveness were identified as perceptual barriers related to intentional medication non-adherence. Practical barriers to medication adherence, including medication costs, forgetting to take medications and polypharmacy, emerged as themes related to unintentional medication non-adherence. CONCLUSION: The study findings contribute to a growing body of research suggesting health system changes are needed to improve provider education and implement multicomponent interventions to improve medication adherence among patients with depression and/or diabetes, both chronic illnesses accounting for significant disease burden globally

Validity and reliability of Arabic version of the ID Pain screening questionnaire in the assessment of neuropathic pain

Diagnosis of neuropathic pain (NP) can be challenging. The ID Pain (ID-P) questionnaire, a screening tool for NP, has been used widely both in the original version and translated forms. The aim of this study was to develop an Arabic version of ID-P and assess its validity and reliability in detecting neuropathic pain. The original ID-P was translated in Arabic language and administered to the study population. Reliability of the Arabic version was evaluated by percentage observed agreement, and Cohen’s kappa; and validity by sensitivity, specificity, correctly classified, and receiver operating characteristic (ROC) curve. Physician diagnosis was considered as the gold standard for comparing the diagnostic accuracy. The study included 375 adult patients (153 [40.8%] with NP; 222 [59.2%] with nociceptive pain). Overall observed percentage agreement and Cohen’s kappa were >90% and >0.80, respectively. Median (range) score of ID-P scale was 3 (2–4) and 1 (0–2) in the NP group and NocP group, respectively (p<0.001). Area under the ROC curve was 0.808 (95% CI, 0.764–0.851). For the cut-off value of ≥2, sensitivity was 84.3%, specificity was 66.7%, and correct classification was 73.9%. Thus, the Arabic version of ID-P showed moderate reliability and validity as a pain assessment tool. This article presents the psychometric properties of the Arabic version of ID Pain questionnaire. This Arabic version may serve as a simple yet important screening tool, and help in appropriate management of neuropathic pain, specifically in primary care centers in the Kingdom of Saudi Arabia

Impacts of overweight and obesity in older age on the risk of dementia: A systematic literature review and a meta-analysis

Background: It is unclear whether overweight and obesity in older age reduces or increases the risk of incident dementia. Objective: To assess the impacts of overweight and obesity in older age on incident dementia. Methods: We searched cohort studies reporting body weight measured in older age and dementia through PubMed, Embase, Medline, PyschInfo, and Cochrane library until July 2016. Sixteen articles were identified for the review. We pooled data from them and a new unpublished study from China, to calculate relative risk (RR) of incident dementia in relation to body mass index (BMI) and waist circumference (WC). Results: All 16 cohort studies were undertaken in high income countries, with follow-up periods ranging between 3 to 18 years. Thirteen studies showed an inverse association between BMI and dementia, and three studies demonstrated a positive association. Pooled RR of dementia in relation to continuous BMI from 14 studied populations, including the new Chinese data was 0.97 (95% CI 0.95–1.00); in those with followed up <9 years was 0.95 (0.93–0.96) while in ≥9 years follow-up was 1.03 (0.96–1.11). In five studied populations examining categorical BMI, RR of dementia in older people classified as overweight and obese was 0.98 (0.54–1.77) and 1.17 (0.65–2.10) respectively, in comparison with other weights. The pooled WC data showed no association between increased WC and reduced risk of dementia. Conclusion: The current evidence did not support a paradox on beneficial impacts of overweight and obesity in older age on incident dementia. More studies with long term follow up are needed to clarify the association of body weight in older age with dementia risk

Insulin in the nervous system and the mind: Functions in metabolism, memory, and mood

Background: Insulin, a pleotrophic hormone, has diverse effects in the body. Recent work has highlighted the important role of insulin's action in the nervous system on glucose and energy homeostasis, memory, and mood. Scope of review: Here we review experimental and clinical work that has broadened the understanding of insulin's diverse functions in the central and peripheral nervous systems, including glucose and body weight homeostasis, memory and mood, with particular emphasis on intranasal insulin. Major conclusions: Implications for the treatment of obesity, type 2 diabetes, dementia, and mood disorders are discussed in the context of brain insulin action. Intranasal insulin may have potential in the treatment of central nervous system-related metabolic disorders. Keywords: Insulin, Intranasal insulin, Memory, Metabolism, Moo