Back to the Future: A Report From the 16th International Forum for Back and Neck Pain Research in Primary Care and Updated Research Agenda.

STUDY DESIGN: The 16th meeting of the International Forum for Back and Neck Pain Research in Primary Care was held in Québec City in July 2019 under the theme of innovation. This paper addresses the state of research in the field. OBJECTIVE: To ascertain the evolution of knowledge and clinical application in back and neck pain and identify shifting research priorities. MATERIALS AND METHODS: After a brief presentation of the Forum and its history, the current state of the field was depicted from the scientific program and the recordings of the plenary and parallel oral and poster communications of Forum XVI. Research agendas established in 1995 and 1997 were updated from a survey of a multidisciplinary group of experts in the field. A discussion of the progress made and challenges ahead follows. RESULTS: While much progress has been made at improving knowledge at managing back pain in the past 25 years, most research priorities from earlier decades are still pertinent. The need for integration of physical and psychological interventions represents a key challenge, as is the need to better understand the biological mechanisms underlying back and neck pain to develop more effective interventions. Stemming the tide of back and neck pain in low and middle-income countries and avoiding the adoption of low-value interventions appear particularly important. The Lancet Low Back Pain Series initiative, arising from the previous fora, and thoughts on implementing best practices were extensively discussed, recognizing the challenges to evidence-based knowledge and practice given competing interests and incentives. CONCLUSION: With the quantity and quality of research on back and neck pain increasing over the years, an update of research priorities helped to identify key issues in primary care.

Dronedarone, amiodarone and other antiarrhythmic drugs, and acute liver injuries: a case-referent study.

BACKGROUND: Spontaneous reports of acute liver injuries (ALI) in patients taking dronedarone triggered an EMA alert in 2011. This study aimed to assess the risk of ALI for class III antiarrhythmic drugs controlling for the use of other potential ALI-inducing drugs. METHODS: Between 2010 and 2014, consecutive ALI cases (≥50 years-old) were identified across Germany. ALI was defined as a new increase in at least one of the transaminases ≥3 times the upper limit of normal (ULN) or ≥2 ULN if alkaline phosphatase, with ("definite" case) or without ("biochemical" case) suggestive signs/symptoms of ALI, excluding other liver diseases. Recruited community controls were matched to cases on gender, age and inclusion date. Exposure to antiarrhythmic drugs and co-medication up to 2 years before ALI onset was informed by patients and confirmed by physicians' prescriptions. Adjusted Odds Ratios (aOR) were obtained from conditional multivariable logistic regressions, adjusted for a multivariate disease risk score and co-medication. RESULTS: 252 cases and 1081 matched controls were included (59.1% females; mean age: 64 years). Exposure to class III antiarrhythmic drugs was 4.0% in cases and 1.5% in controls, aOR = 3.6 (95% CI: 1.6-8.4). Associations with exposure to dronedarone and amiodarone were respectively 3.1 (95% CI: 0.7-14. 8) and 5.90 (1.7-20.0). Restricting the analysis to definite or severe ALI cases did not change these results. CONCLUSIONS: Class III antiarrhythmic drugs were associated with ALI, amiodarone displaying the highest risk, and results were robust to case definitions. Continued vigilance is needed for patients taking these drugs.

What are private sector physiotherapists' perceptions regarding interprofessional and intraprofessional work for managing low back pain?

In the last decades, interactions between health professionals have mostly been discussed in the context of interprofessional teamwork where professionals work closely together and share a team identity. Comparatively, little work has been done to explore interactions that occur between professionals in contexts where traditionally formal structures have been less supporting the implementation of interprofessional teamwork, such as in the private healthcare sector. The objective of this study was to identify private sector physiotherapists' perceptions of interprofessional and intraprofessional work regarding interventions for adults with low back pain. This was a cross-sectional survey of 327 randomly-selected physiotherapists. Data were analysed using descriptive statistics. A majority of physiotherapists reported positive effects of interprofessional work for their clients, themselves and their workplaces. Proximity of physiotherapists with other professionals, clinical workloads, and client's financial situation were perceived as important factors influencing the implementation of interprofessional work. Low back pain is a highly prevalent and disabling condition. The results of this study indicate that integrating interprofessional work in the management of low back pain in the private sector is warranted. Furthermore, the implementation of interprofessional work is viewed by practicing physiotherapists as dependent upon certain client-, professional- and organizational-level factors.

Number of patients needed to prescribe statins in primary cardiovascular prevention: mirage and reality.

Background: Number of patients needed to treat (NNT) with a statin in primary prevention of coronary heart disease (CHD) is often misinterpreted because this single statistic averages results from heterogeneous studies. Objective: To provide estimates of the number of individuals needed to be prescribed a statin to prevent one CHD event accounting for their level of CHD risk and for persistence to treatment. Methods: A post hoc analysis was conducted based on a Cochrane review on statins for the primary prevention of cardiovascular diseases. Five-year NNTs were calculated separately from randomized clinical trials (RCTs), including 'lower' and 'higher' risk populations (CHD mean event rates of 3.7 and 14.4 per 1000 person-years, respectively). NNTs were adjusted for 5-year persistence to treatment using a value of 65%. Results: Persistence-adjusted 5-year NNTs to prevent one CHD for the lower and higher CHD risk categories were 146 [95% confidence interval (CI): 117-211] and 53 (95% CI: 39-88) respectively, values 25% and 15% higher than their unadjusted counterpart (117, 95% CI: 94-167 and 46, 95% CI: 34-78). Conclusions: Five-year NNTs for statins to prevent a first CHD is almost three times higher in those at lower versus higher risk populations. Reporting combined results from RCTs including subjects at different cardiovascular risks should be avoided. Individualizing the risk of CHD should orient family physicians and their patients in their choice of preventive approaches and generate more realistic expectations about compliance and outcomes.

Proteomics analysis of Medicago truncatula response to infection by the phytopathogenic bacterium Ralstonia solanacearum points to jasmonate and salicylate defence pathways.

The infection of the model legume Medicago truncatula with Ralstonia solanacearum GMI1000 gives rise to bacterial wilt disease via colonisation of roots. The root and leaf responses to early infection (1 and 3 days post infection) were characterised to investigate the molecular mechanisms of plant resistance or susceptibility. A proteomics approach based on pools of susceptible and resistant recombinant inbred lines was used to specifically target the mechanisms for tolerance. Differential abundances were evidenced for proteins involved in defence (e.g., PR5, PR10, or Kunitz protease inhibitors) and signalling pathways (such as cyclophilin). R. solanacearum inoculation modifies expression levels of those genes, either in both genotypes (AOS1, LOX4, and proteinase inhibitors) or specifically in the resistant line (PR proteins). Exogenous application of salicylic acid (SA) enhanced tolerance to the bacteria, whereas methyl jasmonate (MeJA) enhanced short-term tolerance then promoted disease in the susceptible ecotype, suggesting that they may mediate defence responses. Conversely, proteomics-identified genes were also shown to be SA or MeJA responsive. This is the first description of differential response to R. solanacearum in M. truncatula. Our results suggest that root basal defence is activated at 1 dpi, together with the JA pathway. Specific resistance is then evidenced at three dpi, with the up-regulation of SA-dependent PR proteins.

Initiation of DNA replication requires actin dynamics and formin activity.

Nuclear actin regulates transcriptional programmes in a manner dependent on its levels and polymerisation state. This dynamics is determined by the balance of nucleocytoplasmic shuttling, formin- and redox-dependent filament polymerisation. Here, using Xenopus egg extracts and human somatic cells, we show that actin dynamics and formins are essential for DNA replication. In proliferating cells, formin inhibition abolishes nuclear transport and initiation of DNA replication, as well as general transcription. In replicating nuclei from transcriptionally silent Xenopus egg extracts, we identified numerous actin regulators, and disruption of actin dynamics abrogates nuclear transport, preventing NLS (nuclear localisation signal)-cargo release from RanGTP-importin complexes. Nuclear formin activity is further required to promote loading of cyclin-dependent kinase (CDK) and proliferating cell nuclear antigen (PCNA) onto chromatin, as well as initiation and elongation of DNA replication. Therefore, actin dynamics and formins control DNA replication by multiple direct and indirect mechanisms.

Effect of an Institutional Medication Adherence Program for Long-Acting Injectable Risperidone on Adherence and Psychiatric Hospitalizations: Evidence from a Prospective Cohort Study.

BACKGROUND: Long-acting injectable (LAI) atypical antipsychotics are associated with improved adherence and reduced relapse rates in schizophrenia but reminder-based interventions may further improve outcomes. OBJECTIVES: To assess an institutional medication adherence program's (IMAP) effectiveness on adherence and psychiatric hospitalizations among schizophrenia patients taking risperidone LAI (RLAI). METHODS: Between 2009 and 2010, we recruited patients meeting DSM-IV criteria for schizophrenia treated with RLAI receiving outpatient care from psychiatric centres in France. The IMAP consisted of calling patients 48 hours prior to their scheduled RLAI injections and within 3 days of a missed appointment. Centres applying the IMAP to ≥50% of scheduled patient injections were deemed compliant. Patients were followed up to one year for adherence (≥80% of scheduled RLAI injections received within 5 days of the scheduled date) and psychiatric hospitalizations. RESULTS: Among 506 patients recruited from 36 centres, the hospitalization rate was 32.5 per 100 person-years. 15 centres treating 243 patients were IMAP compliant and 21 centres treating 263 patients were not. IMAP compliance was associated with lower psychiatric hospitalization rates (crude RR: 0.64 [95% CI: 0.44-0.93]; adjusted RR: 0.78 [95% CI: 0.47-1.27]). Nearly 75% of patients were adherent to RLAI. While patient adherence had little impact on hospitalization rates (adjusted RR: 0.92 [95% CI: 0.59-1.44]), IMAP compliance was more effective among non-adherent (adjusted RR: 0.45 [95% CI: 0.16-1.28]) than adherent (adjusted RR: 0.88 [95% CI: 0.51-1.53]) patients. CONCLUSIONS: IMAPs may improve patient adherence and reduce psychiatric hospitalizations, particularly among patients with difficulties adhering to LAI antipsychotics.

Risk of autoimmune diseases and human papilloma virus (HPV) vaccines: Six years of case-referent surveillance.

BACKGROUND: Safety of HPV vaccines is still in question due to reports of autoimmune diseases (ADs) following HPV immunization. OBJECTIVES: To assess the risk of ADs associated with HPV vaccination of female adolescents/young adults in France. METHODS: Systematic prospective case-referent study conducted to assess the risks associated with real-life use of HPV vaccines. Cases were female 11-25 years old with incident ADs [central demyelination/multiple sclerosis (CD/MS), connective tissue disease (CTD), Guillain-Barré syndrome (GBS), type-1 diabetes (T1D), autoimmune thyroiditis (AT), and idiopathic thrombocytopenic purpura (ITP)]. Cases were consecutively and prospectively identified at specialized centers across France (2008-2014) and individually matched by age and place of residence to referents recruited in general practice. Risk was computed using multivariate conditional logistic regression models adjusted for family history of ADs, living in France (north/south), co-medications and co-vaccinations. RESULTS: With a total of 478 definite cases matched to 1869 referents, all ADs combined were negatively associated to HPV vaccination with an adjusted odds ratio of 0.58 (95% confidence interval: 0.41-0.83). Similar results were obtained for CD/MS, AT, CT, and T1D, the last two not reaching statistical significance. No association was found for ITP and GBS. Sensitivity analyses combining definite and possible cases with secondary time window showed similar results. CONCLUSION: Exposure to HPV vaccines was not associated with an increased risk of ADs within the time period studied. Results were robust to case definitions and time windows of exposure. Continued active surveillance is needed to confirm this finding for individual ADs.

Antiepileptic drugs and risk of suicide attempts: a case-control study exploring the impact of underlying medical conditions.

PURPOSE: Randomized-controlled trials and claims databases suggest that antiepileptic drug (AED) use may increase the risk of suicide attempts (SA). The present case-control study explores the impact of underlying indications on this potential association. METHODS: Physicians collected the medical history; prior 12-month drug use was obtained from standardized telephone interviews with patients. The association between AED use and SA was explored using multivariate conditional logistic regression. The analyses were replicated after stratification on depression and neurological disorders (epilepsy, migraine, and chronic neuropathic pain). RESULTS: Between 2008 and 2012, 506 adults with an incident SA were recruited in suicide treatment centers from across France and socio-demographically matched to 2829 controls from primary care settings. The association between AED use and odds of SA was not significant overall (odds ratio [OR], 1.5; 95% confidence interval [CI], 0.9-2.4). No association was observed for patients with neurological disorders (OR, 1.1; 95%CI, 0.5-2.4) as opposed to patients with depression (OR, 1.6; 95%CI, 1.0-2.5), but unmeasured confounding was suspected. CONCLUSIONS: Our results suggest that the association observed between AED use and increased odds of non-fatal SA in patients with either a lifetime history of depression or no neurological disorder may be explained by the presence of an underlying psychiatric disorder. Accounting for underlying indications is crucial in drug safety studies, as these can cause a reported association (or lack thereof) to be misleading. This may require the prospective collection of medical data at a patient level. Copyright © 2017 John Wiley & Sons, Ltd.

The University-Public Health Partnership for Public Health Research Training in Quebec, Canada.

Enhancing effective preventive interventions to address contemporary public health problems requires improved capacity for applied public health research. A particular need has been recognized for capacity development in population health intervention research to address the complex multidisciplinary challenges of developing, implementing, and evaluating public health practices, intervention programs, and policies. Research training programs need to adapt to these new realities. We have presented an example of a 2003 to 2015 training program in transdisciplinary research on public health interventions that embedded doctoral and postdoctoral trainees in public health organizations in Quebec, Canada. This university-public health partnership for research training is an example of how to link science and practice to meet emerging needs in public health.

Model-observational bridging study on the effectiveness of ezetimibe on cardiovascular morbidity and mortality in France: A population-based study.

BACKGROUND: To evaluate the real-life impact of ezetimibe on cardiovascular (CV) morbidity and mortality in France. OBJECTIVE: To estimate the number of non-fatal and fatal CV events that could be prevented and corresponding number of patients needed to treat (NNT) with ezetimibe to prevent one CV event over 5 years. METHODS: Non-interventional 48-month follow-up cohort conducted in hypercholesterolemic patients starting on ezetimibe <3 months at study entry, either as monotherapy or combined with statins. Prediction modeling using discrete event simulation with calibrated Framingham CV risk equations was applied to data from pivotal clinical trials on ezetimibe and real-life data derived from the cohort. RESULTS: A total of 3215 patients in the cohort accumulated 9314 person-years of follow-up for an average of 2.9 years. Mean age was 61.5 (standard deviation [SD] = 10.7), 54.6% were males, and 27.0% had a history of CV disease. Baseline LDL-cholesterol averaged 4.1 mmol/L (159 mg/dL; SD = 1.0) and HDL-C 1.6 mmol/L (62 mg/dL; SD = 0.5). LDL-C decreased in the first 12 months in ezetimibe-LLT (lipid-lowering therapy) initiators, switchers (monotherapy), and combination therapy with a statin by respectively 21.3%, 6.4%, and 29.1%. The corresponding predicted rate reductions of CV events (non-fatal and fatal) compared to no treatment or to a statin (combination therapy) were respectively 8, 2, and 12 per 1000 patients treated over 5 years, with a global NNT of 143 patients over 5 years. CONCLUSION: These results, accounting for observed CV event rates, risk factors evolution over time and adherence to treatment in real life, were consistent with those from clinical trials.

Inter-Professional Practices of Private-Sector Physiotherapists for Low Back Pain Management: Who, How, and When?

Purpose: Although there have been increasing demands for health care providers to take part in inter-professional practices in recent years, very little attention has been paid to the actualization of such practices in the private sector. This study describes private-sector physiotherapists' inter-professional practices regarding low back pain (LBP) management and identifies organizational and provider-level variables associated with the intensity of such practices. Method: A total of 327 randomly selected physiotherapists were surveyed in the province of Quebec. Data were analyzed using descriptive and multiple regression analyses. Results: Physiotherapists reported frequent interactions with other physiotherapists (daily/weekly for 52.6%), family physicians (51.0%), and physiotherapy (PT) assistants (45.2%), but infrequent interactions with psychologists (3.6%), neurosurgeons (0.9%), and chiropractors (0.3%). Frequently reported means of interactions were written and oral messages sent through clients (55.1% and 24.1%, respectively), face-to-face unplanned discussions (41.9%), and faxed or mailed letters (23.2%). Variables associated with the intensity of inter-professional practices (mean of 6.7 [SD 1.7] out of 10 on the Intensity of Interprofessional Practices Questionnaire for Private Sector Physiotherapists) were related to physiotherapists' clientele, social activities with other providers, and perceptions of inter-professional practices as well as organizational models, vision, and provision of PT training. Conclusions: There is room to improve inter-professional practices with private-sector physiotherapists involved in managing LBP. Targets for action include physiotherapists and their workplaces.

Objectif : la collaboration entre intervenants a été fortement encouragée au cours des dernières décennies. À ce jour, on en sait toutefois peu sur les pratiques interprofessionnelles des physiothérapeutes du secteur privé. Cette étude décrit les pratiques interprofessionnelles des physiothérapeutes œuvrant dans le secteur privé auprès de personnes présentant de la douleur lombaire et identifie les variables organisationnelles et professionnelles associées à l'intensité de ces pratiques. Méthode : une enquête a été réalisée auprès de 327 physiothérapeutes du Québec sélectionnés de façon aléatoire. Les données ont été soumises à des analyses descriptives et de régression multiple. Résultats : les physiothérapeutes avaient des interactions fréquentes avec d'autres physiothérapeutes (quotidiennement ou hebdomadairement pour 52,6 % d'entre eux), des omnipraticiens (51,0 %) et des thérapeutes en réadaptation physique (45,2 %), alors qu'elles étaient peu fréquentes avec des psychologues (3,6 %), neurochirurgiens (0,9 %) et chiropraticiens (0,3 %). Ces interactions prenaient le plus souvent la forme de messages écrits ou oraux transmis par le client (55,1 % et 24,1 % respectivement), de discussions non planifiées (41,9 %) et de lettres postées ou télécopiées (23,2 %). Les variables associées à l'intensité des pratiques interprofessionnelles (scores moyens de 6,7/10 au Questionnaire d'intensité des pratiques interprofessionnelles des physiothérapeutes du secteur privé; écart type de 1,7) étaient liées à la clientèle des physiothérapeutes, à leurs activités sociales avec d'autres intervenants et à leurs perceptions des pratiques interprofessionnelles, ainsi qu'aux modèles organisationnels, à la vision de l'organisation et à l'offre de stages en physiothérapie. Conclusions : il est possible de faire mieux sur le plan des pratiques interprofessionnelles des physiothérapeutes œuvrant dans le secteur privé auprès de personnes présentant de la douleur lombaire. Des cibles d'action se situeraient au niveau des physiothérapeutes eux-mêmes et de leur milieu de travail.

Homeopathic medical practice for anxiety and depression in primary care: the EPI3 cohort study.

BACKGROUND: The purpose of the study was to compare utilization of conventional psychotropic drugs among patients seeking care for anxiety and depression disorders (ADDs) from general practitioners (GPs) who strictly prescribe conventional medicines (GP-CM), regularly prescribe homeopathy in a mixed practice (GP-Mx), or are certified homeopathic GPs (GP-Ho). METHODS: This was one of three epidemiological cohort studies (EPI3) on general practice in France, which included GPs and their patients consulting for ADDs (scoring 9 or more in the Hospital Anxiety and Depression Scale, HADS). Information on all medication utilization was obtained by a standardised telephone interview at inclusion, 1, 3 and 12 months. RESULTS: Of 1562 eligible patients consulting for ADDs, 710 (45.5 %) agreed to participate. Adjusted multivariate analyses showed that GP-Ho and GP-Mx patients were less likely to use psychotropic drugs over 12 months, with Odds ratio (OR) = 0.29; 95 % confidence interval (CI): 0.19 to 0.44, and OR = 0.62; 95 % CI: 0.41 to 0.94 respectively, compared to GP-CM patients. The rate of clinical improvement (HADS <9) was marginally superior for the GP-Ho group as compared to the GP-CM group (OR = 1.70; 95 % CI: 1.00 to 2.87), but not for the GP-Mx group (OR = 1.49; 95 % CI: 0.89 to 2.50). CONCLUSIONS: Patients with ADD, who chose to consult GPs prescribing homeopathy reported less use of psychotropic drugs, and were marginally more likely to experience clinical improvement, than patients managed with conventional care. Results may reflect differences in physicians' management and patients' preferences as well as statistical regression to the mean.

Comparative shotgun proteomic analysis of wild and domesticated Opuntia spp. species shows a metabolic adaptation through domestication.

UNLABELLED: The Opuntia genus is widely distributed in America, but the highest richness of wild species are found in Mexico, as well as the most domesticated Opuntia ficus-indica, which is the most domesticated species and an important crop in agricultural economies of arid and semiarid areas worldwide. During domestication process, the Opuntia morphological characteristics were favored, such as less and smaller spines in cladodes and less seeds in fruits, but changes at molecular level are almost unknown. To obtain more insights about the Opuntia molecular changes through domestication, a shotgun proteomic analysis and database-dependent searches by homology was carried out. >1000 protein species were identified and by using a label-free quantitation method, the Opuntia proteomes were compared in order to identify differentially accumulated proteins among wild and domesticated species. Most of the changes were observed in glucose, secondary, and 1C metabolism, which correlate with the observed protein, fiber and phenolic compounds accumulation in Opuntia cladodes. Regulatory proteins, ribosomal proteins, and proteins related with response to stress were also observed in differential accumulation. These results provide new valuable data that will help to the understanding of the molecular changes of Opuntia species through domestication. BIOLOGICAL SIGNIFICANCE: Opuntia species are well adapted to dry and warm conditions in arid and semiarid regions worldwide, and they are highly productive plants showing considerable promises as an alternative food source. However, there is a gap regarding Opuntia molecular mechanisms that enable them to grow in extreme environmental conditions and how the domestication processes has changed them. In the present study, a shotgun analysis was carried out to characterize the proteomes of five Opuntia species selected by its domestication degree. Our results will help to a better understanding of proteomic features underlying the selection and specialization under evolution and domestication of Opuntia and will provide a platform for basic biology research and gene discovery.

Validation of a New Tool to Measure Physiotherapists' Interprofessional Practices.

Interprofessional collaboration is recommended in health systems everywhere, but research on its measurement is needed. This psychometric study assessed the construct validity, internal consistency, and test-retest reliability of the Intensity of Interprofessional Practices Questionnaire for Private-Sector Physiotherapists (IIPQ-PT). A random sample of 303 physiotherapists (PTs) completed the 12-item questionnaire, and a subsample of 103 completed it a second time 2 weeks later. Exploratory factor analyses revealed a one-factor solution for the instrument. IIPQ-PT scores showed respectively fair and moderate relationships with the percentage of low back pain clients for whom PTs reported interactions with other professionals (0.30; 95% CI 0.19-0.40; p<0.001) and perceived degree of interactions (0.58; 95% CI 0.50-0.65; p<0.001). The IIPQ-PT had high internal consistency (Cronbach's a= 0.86; 95% CI 0.83-0.88) and good test-retest reliability (ICC=0.69; 95% CI 0.57-0.78). The minimum detectable difference for a 95% CI was 2.52. Although further study of this instrument is warranted, our results are promising for its future use. The IIPQ-PT may prove useful to evaluate the effectiveness of interventions aiming to improve interprofessional practices and to measure the effects of such practices on service users, providers, and the health system.

Dietary cladode powder from wild type and domesticated Opuntia species reduces atherogenesis in apoE knock-out mice

Dietary intake of Opuntia species may prevent the development of cardiovascular diseases. The present study was designed to characterize the biological antioxidant and anti-inflammatory properties of Opuntia species and to investigate whether Opuntia cladodes prevent the development of atherosclerosis in vivo, in apoE−KO mice. The effects of the two Opuntia species, the wild Opuntia streptacantha and the domesticated Opuntia ficus-indica, were tested on the generation of intra- and extracellular reactive oxygen species (ROS) production and kinetics of the LDL oxidation by murine CRL2181 endothelial cells and on the subsequent inflammatory signaling leading to the adhesion of monocytes on the activated endothelium and the formation of foam cells. Opuntia species blocked the extracellular ROS (superoxide anion) generation and LDL oxidation by CRL2181, as well as the intracellular ROS rise and signaling evoked by the oxidized LDL, including the nuclear translocation of the transcription factor NFκB, the expression of ICAM-1 and VCAM-1 adhesion molecules, and the adhesion of monocytes to CRL2181. In vivo, Opuntia significantly reduced the formation of atherosclerotic lesions and the accumulation of 4-hydroxynonenal adducts in the vascular wall of apoE-KO mice, indicating that Opuntia cladodes prevent lipid oxidation in the vascular wall. In conclusion, wild and domesticated Opuntia species exhibit antioxidant, anti-inflammatory, and antiatherogenic properties which emphasize their nutritional benefit for preventing cardiovascular diseases (AU)

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Calcium channel blockers and cancer: a risk analysis using the UK Clinical Practice Research Datalink (CPRD).

OBJECTIVE: The evidence of an association between calcium channel blockers (CCBs) and cancer is conflicting. The objective of the present study was to evaluate the risk of cancer (all, breast, prostate and colon cancers) in association with exposure to CCB. METHODS: This is a population-based cohort study in patients exposed to CCBs from across the UK, using two comparison cohorts: (1) patients with no exposure to CCB (non-CCB) matched on age and gender and (2) unmatched patients unexposed to CCB and at least one other antihypertensive (AHT) prescription. Cancer incidence rates computed in the exposed and the two unexposed groups were compared using HRs and 95% CIs obtained from multivariate Cox regression analyses. RESULTS: Overall, 150,750, 557,931 and 156,966 patients were included, respectively, in the CCB, non-CCB and AHT cohorts. Crude cancer incidence rates per 1000 person-years were 16.51, 15.75 and 10.62 for the three cohorts, respectively. Adjusted HRs (CI) for all cancers comparing CCB, non-CCB and AHT cohorts were 0.88 (0.86 to 0.89) and 1.01 (0.98 to 1.04), respectively. Compared to the AHT cohort, adjusted HRs (CI) for breast, prostate and colon cancer for the CCB cohort were 0.95 (0.87 to 1.04), 1.07 (0.98 to 1.16) and 0.89 (0.81 to 0.98), respectively. Analyses by duration of exposure to CCB did not show excess risk. CONCLUSIONS: This large population-based study provides strong evidence that CCB use is not associated with an increased risk of cancer. The analyses yielded robust results across all types of cancer and different durations of exposure to CCBs.

The "Efficacy-Effectiveness Gap": Historical Background and Current Conceptualization.

BACKGROUND: The concept of the "efficacy-effectiveness gap" (EEG) has started to challenge confidence in decisions made for drugs when based on randomized controlled trials alone. Launched by the Innovative Medicines Initiative, the GetReal project aims to improve understanding of how to reconcile evidence to support efficacy and effectiveness and at proposing operational solutions. OBJECTIVES: The objectives of the present narrative review were 1) to understand the historical background in which the concept of the EEG has emerged and 2) to describe the conceptualization of EEG. METHODS: A focused literature review was conducted across the gray literature and articles published in English reporting insights on the EEG concept. The identification of different "paradigms" was performed by simple inductive analysis of the documents' content. RESULTS: The literature on the EEG falls into three major paradigms, in which EEG is related to 1) real-life characteristics of the health care system; 2) the method used to measure the drug's effect; and 3) a complex interaction between the drug's biological effect and contextual factors. CONCLUSIONS: The third paradigm provides an opportunity to look beyond any dichotomy between "standardized" versus "real-life" characteristics of the health care system and study designs. Namely, future research will determine whether the identification of these contextual factors can help to best design randomized controlled trials that provide better estimates of drugs' effectiveness.

Production of Biologically Active Cecropin A Peptide in Rice Seed Oil Bodies.

Cecropin A is a natural antimicrobial peptide that exhibits fast and potent activity against a broad spectrum of pathogens and neoplastic cells, and that has important biotechnological applications. However, cecropin A exploitation, as for other antimicrobial peptides, is limited by their production and purification costs. Here, we report the efficient production of this bioactive peptide in rice bran using the rice oleosin 18 as a carrier protein. High cecropin A levels were reached in rice seeds driving the expression of the chimeric gene by the strong embryo-specific oleosin 18 own promoter, and targeting the peptide to the oil body organelle as an oleosin 18-cecropin A fusion protein. The accumulation of cecropin A in oil bodies had no deleterious effects on seed viability and seedling growth, as well as on seed yield. We also show that biologically active cecropin A can be easily purified from the transgenic rice seeds by homogenization and simple flotation centrifugation methods. Our results demonstrate that the oleosin fusion technology is suitable for the production of cecropin A in rice seeds, which can potentially be extended to other antimicrobial peptides to assist their exploitation.