Neuropathic Pain Assessment with the PainDETECT Questionnaire: Cross-Cultural Adaptation and Psychometric Evaluation to Hindi.

OBJECTIVE: The contribution of neuropathic pain (NeP) in chronic pain conditions is increasingly emphasized with the development of multiple questionnaire-based measurement scales. The painDETECT questionnaire (PDQ) is a frequently used self-reported outcome measure to assess NeP in patients with chronic pain conditions in research and regular clinical practice. The aim of the study was to translate and cross-culturally adapt the PDQ into Hindi (Hi-PDQ) for use in India and to investigate its psychometric properties. METHODS: PainDETECT questionnaire translation into the Hindi language was carried out according to standard guidelines. Patients suffering from chronic pain attending a pain clinic were recruited. Patients completed the Hi-PDQ at baseline and were retested was conducted after 3 days Exploratory factor analysis (EFA) was carried out to assess the factor structure of the Hi-PDQ. Measurement properties, including floor and ceiling effects, discriminative validity, and psychometric properties, were also assessed. RESULTS: A total of 160 patients with chronic pain were recruited, including 80 in each NeP and non-NeP group. The retest was completed in 82 patients. Mean Hi-PDQ scores were significantly higher in the NeP group compared with the non-NeP group (20.7 [SD 5.9] vs. 9.9 [SD 5.9]; P < 0.01). EFA revealed a 2-factor structure explaining 56.9% variance. The Hi-PDQ was found to have adequate internal consistency (Cronbach's alpha = 0.83), test-retest reliability (intraclass correlation coefficient = 0.94), and excellent discriminant validity (area under the curve = 0.88), with an optimal cutoff value of > 18 (sensitivity and specificity of 82.5% and 91.2%, respectively). CONCLUSION: The PDQ was successfully translated into the Hindi language. The Hi-PDQ showed good discriminative validity and psychometric properties. The Hi-PDQ is a reliable instrument to assess NeP in chronic pain conditions.

Translation, Adaptation, and Validation of Hindi Version of the Pain Catastrophizing Scale in Patients with Chronic Low Back Pain for Use in India.

OBJECTIVES : This study translates the Pain Catastrophizing Scale (PCS) into Hindi and examines the psychometric properties of the translated version (Hindi PCS [Hi-PCS]) in patients with chronic low back pain (CLBP). METHODS : Forward and backward translations were performed from English to Hindi according to standard methodology. A final version was evaluated by a committee of clinical experts and Hi-PCS was then pilot-tested in 10 patients with CLBP. Cross-cultural validation of the resulting adapted Hi-PCS was done by administering Hi-PCS at baseline to 100 patients with CLBP (≥ 12 weeks pain) who were able to read and write in Hindi, and re-administering Hi-PCS after 3 days. Construct validity was assessed using factor analysis. Psychometric properties including internal consistency; test-retest reliability; and convergent validity with pain severity, functional disability, and health-related quality of life (HRQoL) were also assessed. RESULTS : Principal component analysis observed a three-factor structure, which explained 58% of the variance. Confirmatory factor analysis elicited the best fit as judged by the model fit indices. Hi-PCS as a whole was deemed to be internally consistent (Cronbach's α = 0.76). Intraclass correlation coefficient for the Hi-PCS is 0.923 (95% CI: 0.875-0.953). Hi-PCS was moderately correlated with pain intensity (r = 0.651) and functional disability (r = 0.352), and negatively correlated with QoL (r = -0.380). CONCLUSIONS : PCS translation and cross-cultural adaptation to Hindi demonstrated good factor structure along adequate psychometric properties and could be recommended for use in CLBP research in India.

Evaluating the impact of early vs delayed ofatumumab initiation and estimating the long-term outcomes of ofatumumab vs teriflunomide in relapsing multiple sclerosis patients in Spain.

OBJECTIVES: To evaluate the impact of early (at first-line) vs delayed (3-year delay) ofatumumab initiation and long-term clinical, societal, and economic outcomes of ofatumumab vs teriflunomide in relapsing multiple sclerosis (RMS) patients from a Spanish societal perspective. METHODS: A cost-consequence analysis was conducted using an Expanded Disability Status Scale (EDSS)-based Markov model. Inputs were sourced from ASCLEPIOS I and II trials and published literature. RESULTS: At the end of 10 years, compared with first-line teriflunomide treatment, early first-line ofatumumab initiation was projected to result in 35.6% fewer patients progressing to EDSS ≥ 7 and 27.8% fewer relapses. The ofatumumab cohort required 7.3% reduced informal care time and had 19% fewer disability-adjusted life years (DALYs) than the teriflunomide cohort. A 3-year delay in ofatumumab treatment (3-year teriflunomide + 7-year ofatumumab) was projected to result in 32.2% more patients progressing to EDSS ≥ 7, 20.2% more relapses, 5.4% increased informal care time, and 16.6% more DALYs compared with early ofatumumab initiation. Early ofatumumab initiation was associated with total annual cost savings (excluding disease-modifying-therapies' acquisition costs) of €35,328 ($34,549; conversion factor 1€= $1.02255) and €24,373 ($23,836) per patient vs teriflunomide and 3-year delayed ofatumumab initiation, respectively. CONCLUSIONS: This study highlights the benefits of early initiation of high-efficacy therapy such as ofatumumab vs its delayed initiation for improving the outcomes in RMS patients (having characteristics similar to those of patients included in the ASCLEPIOS trials). Ofatumumab treatment was projected to provide improved long-term clinical, societal, and economic outcomes vs teriflunomide treatment in RMS patients from a Spanish societal perspective.

The therapeutic benefits of ofatumumab in relapsing multiple sclerosis (RMS) patients have been reported in the ASCLEPIOS I and II trials. Using an Expanded Disability Status Scale-based Markov model, this study aimed to assess the impact of early (i.e. at first-line, as the first treatment after diagnosis) vs delayed (i.e. 3-year delay) ofatumumab initiation in RMS patients from a Spanish societal perspective. In addition, the long-term clinical, societal, and economic outcomes of ofatumumab vs teriflunomide treatment were assessed. Evidence from this study suggests that early initiation of a high-efficacy therapy such as ofatumumab, compared with its delayed initiation, is an effective and cost-saving strategy for improving outcomes in RMS patients. Furthermore, patients receiving ofatumumab for 10 years are projected to experience comparatively better outcomes (clinical, societal, and economic) than those receiving teriflunomide.

Cost-consequence analysis of ofatumumab for the treatment of relapsing-remitting multiple sclerosis in Canada.

Aim: The costs and consequences of initial and delayed ofatumumab treatment were evaluated in relapsing-remitting multiple sclerosis with active disease in Canada. Materials & methods: A Markov cohort model was used (10-year horizon, annual cycle length, 1.5% discounting). Scenario analyses examined ofatumumab as first-line treatment versus 3 and 5 years following switch from commonly used first-line therapies. Results: Ofatumumab resulted in improvements in clinical outcomes (relapses and disease progression) and productivity (employment and full-time work), and reduction of economic burden (administration, monitoring and non-drug costs) that were comparable to other high-efficacy therapies (ocrelizumab, cladribine and natalizumab). Switching to ofatumumab earlier in the disease course may improve these outcomes. Conclusion: Results highlight the value of a high-efficacy therapy such as ofatumumab as initial treatment (i.e., first-line) in newly diagnosed relapsing-remitting multiple sclerosis patients with active disease.

Comparing the long-term clinical and economic impact of ofatumumab versus dimethyl fumarate and glatiramer acetate in patients with relapsing multiple sclerosis: A cost-consequence analysis from a societal perspective in Germany.

Background: Evidence suggests that early highly efficacious therapy in relapsing multiple sclerosis is superior to escalation strategies. Objective: A cost-consequence analysis simulated different treatment scenarios with ofatumumab (OMB), dimethyl fumarate (DMF) and glatiramer acetate (GA): immediate OMB initiation as first treatment, early switch to OMB after 1 year on DMF/GA, late switch after 5 years or no switch. Methods: An EDSS-based Markov model with a 10-year time horizon was applied. Cycle transitions included EDSS progression, improvement or stabilization, treatment discontinuation, relapse or death. Input data were extracted from OMB trials, a network meta-analysis, published literature, and publicly available sources. Results: The late switch compared to the immediate OMB scenario resulted in a lower proportion of patients with EDSS 0-3 (Δ - 7.5% DMF; Δ - 10.3% GA), more relapses (Δ + 0.72 DMF; Δ + 1.23 GA) and lower employment rates (Δ - 4.0% DMF; Δ - 5.6% GA). The same applies to late versus early switches. No switch scenarios resulted in worse outcomes. Higher drug acquisition costs in the immediate OMB and early switch scenarios were almost compensated by lower costs for patient care and productivity loss. Conclusion: Immediate OMB treatment and an early switch improves clinical and productivity outcomes while remaining almost cost neutral compared to late or no switches.

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.

Development, validation and evaluation of a novel self-instructional module in patients with chronic non-specific low back pain.

BACKGROUND: Low back pain (LBP) is ranked highest in terms of disability-adjusted life-years lived. Patient education and self-management have shown to play a crucial role in the overall pain management. However, the literature on the same with respect to Indian context is still lacking. The study was aimed to develop, validate and assess the acceptability and effectiveness of self-instructional educational module among Indian chronic LBP (CLBP) patients. METHODS: A prospective single-arm open-label study was conducted in a pain clinic of a tertiary care public hospital in North India with 'Backcare booklet-self-instructional module (SIM)' as an intervention in patients with CLBP. SIM was developed with the intent to provide up-to-date evidence-based information in an easy understanding way to patients with CLBP. 132 patients were administered SIM with a single session of verbal explanation. Pain intensity (numeric rating scale [NRS]), disability, fear-avoidance belief Questionnaire (FABQ), quality of life (EQ5D) and knowledge level were assessed at baseline and after 3 months of intervention. Student's paired t-test and Chi-square test were used. Data were analysed using SPSS version 15.0. RESULTS: 120 patients successfully completed the 3 months' follow-up. Significant reductions were observed in pain intensity (76[12] vs 55 [15, P < 0.01); disability (51[14] vs 43 [10], P < 0.01); FABQ (46[12] vs 41 [10], P < 0.01); EQ5D (0.35 [0.27] vs 0.18 [0.26], P < 0.01). CONCLUSION: Backcare booklet as an intervention, along with usual pharmacological care is a cost-effective educational medium to promote self-management of CLBP in the clinical outpatient settings.

Hindi version of short form of douleur neuropathique 4 (S-DN4) questionnaire for assessment of neuropathic pain component: a cross-cultural validation study.

BACKGROUND: Pain with neuropathic characteristics is generally more severe and associated with a lower quality of life compared to nociceptive pain (NcP). Short form of the Douleur Neuropathique en 4 Questions (S-DN4) is one of the most used and reliable screening questionnaires and is reported to have good diagnostic properties. This study was aimed to cross-culturally validate the Hindi version of the S-DN4 in patients with various chronic pain conditions. METHODS: The S-DN4 is already translated into the Hindi language by Mapi Research Trust. This study assessed the psychometric properties of the Hindi version of the S-DN4 including internal consistency and test-retest reliability after 3 days' post-baseline assessment. Diagnostic performance was also assessed. RESULTS: One hundred sixty patients with chronic pain, 80 each in the neuropathic pain (NeP) present and NeP absent groups, were recruited. Patients with NeP present reported significantly higher S-DN4 scores in comparison to patients in the NeP absent group (mean (SD), 4.7 (1.7) vs. 1.8 (1.6), P < 0.01). The S-DN4 was found to have an AUC of 0.88 with adequate internal consistency (Cronbach's α = 0.80) and a test-retest reliability (ICC = 0.92) with an optimal cut-off value of 3 (Youden's index = 0.66, sensitivity and specificity of 88.7% and 77.5%). The diagnostic concordance rate between clinician diagnosis and the S-DN4 questionnaire was 83.1% (kappa = 0.66). CONCLUSIONS: Overall, the Hindi version of the S-DN4 has good internal consistency and test-retest reliability along with good diagnostic accuracy.

Usefulness of four commonly used neuropathic pain screening questionnaires in patients with chronic low back pain: a cross-sectional study.

BACKGROUND: Recently symptoms-based screening questionnaires have gained attention for screening for a neuropathic pain component (NePC) in various chronic pain conditions. The present study assessed the usefulness of four commonly used NePC screening questionnaires including the Self-completed douleur neuropathique 4 (S-DN4), the ID Pain, the painDETECT questionnaire (PDQ), and the Self-completed Leeds Assessment of neuropathic Symptoms and Signs (S-LANSS) questionnaire in patients with chronic low back pain (CLBP) to assess the presence of NePC. METHODS: This is a single-center cross-sectional study where patients with CLBP, with or without leg pain, were included. Participants were initially screened for NePC presence by a physician according to the regular practice, and later assessed using screening questionnaires. The diagnostic accuracy of these questionnaires was compared assuming the physician-made diagnosis as the gold standard. RESULTS: A total of 215 patients with CLBP of which 164 (76.3%, 95% CI, 70.2-81.5) had a NePC were included. S-DN4, ID Pain, and PDQ have an area under the curve (AUC) > 0.8 indicating excellent discrimination. However, S-LANSS has an AUC of 0.69 (0.62-0.75), indicating low discrimination. S-DN4 has a significantly higher AUC as compared to ID Pain (d(AUC) = 0.063, P < 0.01) and S-LANSS (d(AUC) = 0.197, P < 0.01). But the AUC of S-DN4 does not significantly differ from that of PDQ (d(AUC) = 0.013, P = 0.62). CONCLUSIONS: S-DN4, ID Pain, and PDQ, but not S-LANSS, have good discriminant validity to screen for NePCs in patients with CLBP. Despite using all the tests, 20-30% of patients with an NePC were missed. Thus, these questionnaires can only be used as an initial clue in screening for NePCs, but do not replace clinical judgment.

Predictors of health related quality of life in childhood epilepsy and comparison with healthy children: findings from an Indian study.

BACKGROUND/AIM: Children with epilepsy have reduced health-related quality of life (HRQOL) due to disease and medications. We aimed to assess child-reported HRQOL in Indian children with epilepsy and compare it with that in healthy children. MATERIALS AND METHODS: A cross-sectional study of 256 children with epilepsy aged between 5 and 18 years on antiepileptic drug (AED) treatment for at least 3 months was performed and 125 age and sex matched healthy children were included. A generic version of the Pediatric Quality of Life (PedsQL version 4) scale was used to assess HRQOL. RESULTS: Children with epilepsy had diminished scores in total score and all subdomains of PedsQL as compared to healthy children. Children with epilepsy on polytherapy had diminished HRQOL compared with those on monotherapy. Children with generalized seizures or with symptomatic epilepsy had diminished HRQOL. Significant predictors of poor HRQOL were adverse drug reactions (ADRs) to AED, polytherapy, longer duration of epilepsy, shorter seizure-free interval, and seizure frequency. CONCLUSION: Children with epilepsy have diminished HRQOL than healthy children in all subdomains of PedsQL. Significant predictors are ADRs to AED, polytherapy, longer duration of epilepsy, shorter seizure-free interval, and seizure frequency. Comprehensive management of children with epilepsy must go beyond seizure control.

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.

Vitamin D Supplementation in Patients with Chronic Low Back Pain: An Open Label, Single Arm Clinical Trial.

BACKGROUND: Vitamin-D deficiency may possibly be related to chronic low back pain (CLBP). OBJECTIVE: The study is aimed to assess the impact of vitamin-D supplementation on pain intensity, functional disability, and vitamin-D levels in patients with CLBP. STUDY DESIGN: Single arm open-label study. SETTING: Outpatient pain clinic of a tertiary care hospital. METHODS: Sixty-eight eligible patients (CLBP for = 3 months, pain score = 50 on visual analogue scale (VAS) and plasma 25-Hydroxyvitamin D3 levels < 30 ng/mL) were enrolled. Patients were supplemented with 60,000 IU of oral vitamin-D3 given every week for 8 weeks. Efficacy parameters included pain intensity and functional disability measured by VAS and modified Oswestry disability questionnaire (MODQ) scores at baseline, 2, 3, and 6 months post-supplementation. Plasma 25(OH) D3 levels were measured at baseline and 8 weeks. RESULTS: Baseline mean (SD) vitamin-D levels were 12.8 (5.73) ng/mL and increased to 36.07 (12.51) post supplementation (P < 0.01). Forty-five (66%) patients attained normal levels (> 29 ng/mL) post supplementation. Significant reduction in VAS was observed at 2, 3, and 6 months [61 (19), 45 (19), 36 (18)] as compared to 81 (19) at baseline (P = 0.001 at all-time intervals). A significant improvement in the functional ability was also observed at 2, 3, and 6 months [36 (12), 31 (13), and 26 (10)] as compared to baseline 45 (16) (P = 0.001 at all-time intervals). CONCLUSION: Vitamin-D supplementation in deficient CLBP patients may lead to improvement in pain intensity and functional ability apart from normalization of the levels. Future controlled clinical trials are required to confirm the hypothesis.Key words: Vitamin D, deficiency, screening, low back pain, chronic, supplementation.

Risk of Parkinson's Disease in the Users of Antihypertensive Agents: An Evidence from the Meta-Analysis of Observational Studies.

Background. Antihypertensive agents have been shown to inhibit oxidative stress and inflammatory response and thus neuroprotection in Parkinson's disease (PD). Epidemiological evidence suggests inconsistency between use of antihypertensives and risk of PD. This study is aimed to examine the association between antihypertensive use and risk of PD. Methods. Literature search in PubMed, EMBASE, and PsycINFO database was undertaken through February 2012 looking for observational studies evaluating the association between antihypertensive drug use and risk of PD. Before meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using random-effects model (DerSimonian and Laird method). Subgroup analyses and sensitivity analysis were also performed. Results. Seven relevant studies including a total of 28,32,991 subjects were included. Pooled RR of overall use of antihypertensive agents was found to be 0.95 (95% CI 0.84-1.05). A significant reduction in the risk of PD was observed among users of calcium channel blockers (RR 0.82, 95% CI 0.71-0.93). Significant heterogeneity (I (2) = 76.2%) but no publication bias was observed. Conclusions. Overall use of antihypertensive agents showed no significant association with the risk of PD. CCBs provided significant protective role. However, studies with large sample size and dose relationships are required to strengthen our hypothesis.

Reduced Risk of Parkinson's Disease in Users of Calcium Channel Blockers: A Meta-Analysis.

Aim. To pool the data currently available to determine the association between calcium channel blockers (CCBs) and risk of Parkinson's disease (PD). Methods. Literature search in PubMed, EBSCO, and Cochrane library was undertaken through March 2014, looking for observational studies evaluating the association between CCBs use and PD. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using random-effects model. Subgroup analyses, sensitivity Analysis, and cumulative meta-analysis were also performed. Results. Six studies were included in our meta-analysis according to the selection criteria, including three cohort studies and three case-control studies involving 27,67,990 subjects including 11,941 PD cases. We found CCBs use was associated with significant decreased risk of PD, compared with not using CCBs (random effects model pooled RR, 0.81 (95% CI, 0.69-0.95)); a significant heterogeneity was found between studies (P = 0.031; I (2) 54.6%). Both the classes of CCB, that is, dihydropyridine calcium channel blockers (DiCCB) (0.80 (95% CI, 0.65-0.98) P = 0.032) and non-DiCCB (0.70 (95% CI, 0.53-0.92) P = 0.013), were found to be reducing the risk of PD. Conclusion. In our analysis, we found that CCBs use was associated with a Significantly decreased risk of PD compared with non-CCB use.

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.

Agreement between Framingham Risk Score and United Kingdom Prospective Diabetes Study Risk Engine in Identifying High Coronary Heart Disease Risk in North Indian Population.

BACKGROUND: The aim of the study is to evaluate the concurrence between Framingham Risk score (FRS) and United Kingdom Prospective Diabetes Study (UKPDS) risk engine in identifying coronary heart disease (CHD) risk in newly detected diabetes mellitus patients and to explore the characteristics associated with the discrepancy between them. METHODS: A cross-sectional study involving 489 subjects newly diagnosed with type 2 diabetes mellitus was conducted. Agreement between FRS and UKPDS in classifying patients as high risk was calculated using kappa statistic. Subjects with discrepant scores between two algorithms were identified and associated variables were determined. RESULTS: The FRS identified 20.9% subjects (range, 17.5 to 24.7) as high-risk while UKPDS identified 21.75% (range, 18.3 to 25.5) as high-risk. Discrepancy was observed in 17.9% (range, 14.7 to 21.7) subjects. About 9.4% had high risk by UKPDS but not FRS, and 8.6% had high risk by FRS but not UKPDS. The best agreement was observed at high-risk threshold of 20% for both (κ=0.463). Analysis showed that subjects having high risk on FRS but not UKPDS were elderly females having raised systolic and diastolic blood pressure. Patients with high risk on UKPDS but not FRS were males and have high glycosylated hemoglobin. CONCLUSION: The FRS and UKPDS (threshold 20%) identified different populations as being at high risk, though the agreement between them was fairly good. The concurrence of a number of factors (e.g., male sex, low high density lipoprotein cholesterol, and smoking) in both algorithms should be regarded as increasing the CHD risk. However, longitudinal follow-up is required to form firm conclusions.

Prevalence and risk factors of development of peripheral diabetic neuropathy in type 2 diabetes mellitus in a tertiary care setting.

AIMS/INTRODUCTION: The study was carried out to assess the prevalence of diabetic peripheral neuropathy (DPN), compare the prevalence between known diabetes mellitus (KDM) and newly detected diabetes mellitus (NDDM), identify risk factors associated, its prevalence pattern and to assess if any sex-specific differences are present. MATERIALS AND METHODS: A cross-sectional study was carried out in a tertiary care hospital. Patients with duration of diabetes ≤6 months were considered to be NDDM. DPN was diagnosed by the combination of more than one abnormal result of 10-g monofilament, pinprick sensations and ankle reflexes, and categorized according to the severity level using vibration perception threshold. The study included 1,637 KDM and 369 NDDM patients. RESULTS: A total of 586 participants were found to have DPN, accounting for 29.2% (95% confidence interval [CI] 27.2-31.2) prevalence. The higher prevalence was observed in KDM compared with NDDM 33.7% (95% CI 31.42-36.01) vs 9.2% (95% CI 6.3-12.2; P < 0.001). Prevalence of mild, moderate, and severe neuropathies was 8.06, 14.55 and 6.63%, respectively. Regression analysis showed age (P < 0.001), duration of diabetes (P < 0.001), dyslipidemia (P = 0.03), glycated hemoglobin (P < 0.001), the presence of other microvascular complications (P < 0.001), macrovascular complications (P = 0.003) and alcoholic status (P < 0.033) to be associated. No sex-specific differences were observed in the mean age at diagnosis of diabetes, mean age at the diagnosis of neuropathy, and duration taken for the DPN development among females and males. CONCLUSIONS: The study showed a high prevalence (29.2%) of DPN among north Indian type 2 diabetes mellitus patients. Thus, timely screening with earlier detection and intervention would be useful in preventing the progression of neuropathy.

Microvascular Complications and Their Associated Risk Factors in Newly Diagnosed Type 2 Diabetes Mellitus Patients.

The study was aimed at assessing the prevalence of microvascular complications and associated risk factors in newly diagnosed type 2 diabetes mellitus patients. A cross-sectional study was conducted in a public tertiary care hospital. All the recruited patients underwent extensive examination for the presence of microvascular complications like neuropathy, retinopathy, and nephropathy. Prevalence of any complication was 18.04%. Prevalence of neuropathy, retinopathy, and nephropathy was found to be 8.2%, 9.5%, and 2.8%, respectively. Triglycerides (OR, 1.01; P = 0.011) and old age (OR, 1.06; P ≤ 0.01) were significantly associated with any complication. Triglycerides were significantly associated with neuropathy (OR, 1.01; P = 0.05) and retinopathy (OR, 1.01; P = 0.02). Being male posed high risk for nephropathy (OR, 0.06; P = 0.01). These results are suggesting need of regular screening for microvascular complications.

Role of serum cholesterol in Parkinson's disease: a meta-analysis of evidence.

BACKGROUND: Results from several epidemiological studies found a potential role of cholesterol metabolism in Parkinson's disease (PD) pathogenesis. Further several studies assessed relation between dietary intake of cholesterol and risk of PD, although these studies showed varied results but give a clue of association between serum cholesterol and PD. OBJECTIVE: We therefore examined the association between serum cholesterol and risk of PD. METHODS: PubMed database and bibliographies of retrieved articles were searched for observational studies (published up to January 2013) investigating the relationship between serum cholesterol and PD. Pooled risk ratio (RR) was calculated using random-effects model. Subgroup, sensitivity analysis and publication bias were also done. RESULTS: Eight relevant studies were identified, consisting of 4 each case-control and cohort studies involving a total of 246,112 subjects including 5,488 PD cases. Because of significant heterogeneity (P(heterogeneity) < 0.001, I2 = 70.34%) was observed, a random-effects model was chosen over a fixed-effects model. A combined analysis of 8 studies found no significant association between serum cholesterol and risk of PD (RR 0.87, 95% CI 0.67-1.13; p = 0.41). CONCLUSIONS: We observed no probable association between serum cholesterol and risk of PD.