Moderate Benefit Research Articles

Benefits and Risks of Nonsteroidal Anti-inflammatory Drugs: Methodologic Limitations Lead to Clinical Uncertainties.

Nonsteroidal anti-inflammatory drugs (NSAIDs) include traditional (tNSAIDs), such as ibuprofen, naproxen, and diclofenac, as well as selective cyclooxygenase-2 inhibitors (COXIBs), principally celecoxib. COXIBs were developed to decrease gastrointestinal side effects. Recently, the US Food and Drug Administration strengthened its warning about the risks of non-aspirin NSAIDs on myocardial infarction and stroke. The Cyclooxygenase 2 and Non-Steroidal Anti-Inflammatory Drug Trialist collaboration conducted a comprehensive worldwide meta-analysis using individual patient data exploring the risks of various COXIBs and NSAIDs on cardiovascular disease (CVD). Recently, the results of the Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen (PRECISION) trial were published that tested risks of COXIBs and NSAIDs on CVD. Generally, data from meta-analyses of trials not designed a priori to test hypotheses are less reliable than large-scale randomized trials to test small to moderate benefits or harm. When the sample size is large, randomization provides control of confounding not possible to achieve in any observational study. Further, observational studies, and especially claims data, have inherent confounding by indication larger than the effects being sought. Nonetheless, trials must be of sufficient size and duration and achieve high compliance and follow-up to avoid bias and confounding. In this regard, PRECISION has high rates of nonadherence and losses to follow-up that may have introduced bias and confounding. At present, therefore, it may be most prudent for clinicians to remain uncertain about benefits and risks of these drugs and make individual clinical judgments for each of their patients.

Lewy body dementia: therapeutic propositions according to evidence based medicine and practice

Lewy body dementia (LBD) may present with two clinical forms: dementia with Lewy bodies (DLB) and Parkinson's disease with dementia. LBD is characterized by a profound deficiency of acetylcholine and a deficiency of dopamine. The cholinergic deficit is implicated in major attention disorders and fluctuations. Acetylcholinesterase inhibitors (donepezil or rivastigmine) were studied in several double-blind placebo-controlled studies. The meta-analyzes show a moderate benefit on the cognitive level and on some psychiatric manifestations including hallucinations. A disabling parkinsonian syndrome can be treated with L-dopa as in Parkinson's disease. However, the results are often limited because the increase in doses is restricted by cognitive and psychobehavioral disorders. Hallucinations may require antipsychotic treatment and the best documented drug is clozapine. Some other antipsychotics were assessed but in few therapeutic trials, and appear less efficacious, and with bad tolerance. Finally, the last of LBD cardinal disorders, REM sleep behavior disorders can be improved by melatonin. Other manifestations of LBD are troublesome. Some therapeutic trials with modafinil were proposed to improve diurnal hypersomnia. Anxiety and depression are often difficult to be treated. For antidepressant drugs, the first choice seems to be selective serotonin receptor inhibitors. Treatment for orthostatic hypotension, constipation, and swallowing dysfunction has also been more or less documented. In each case, non-drug management is considered (cognitive stimulation, physiotherapy, speech therapy, etc.). Finally, a therapeutic strategy is suggested, based on the medical and clinical experience. This strategy underlines the importance to improve cholinergic deficit and sleep disturbances. It also stresses the importance of a careful revision of all drugs administered to the patients with a peculiar attention to the anticholinergic treatment.

Gain adjustment at tinnitus pitch to manage both tinnitus and speech perception in noise

To investigate how much gain variation is required from prescription to effect tinnitus percept, and if this revised prescription affects speech recognition. Twenty participants who experienced catastrophic tinnitus even after fitted with hearing aid were included. Participants were grouped based on their tinnitus pitch and the prescriptive formula used to fit hearing aid. They were evaluated for handicap from tinnitus using Tinnitus Handicap Inventory (THI). Hearing aid was programmed using either NAL- NL2 or DSL (I/o) v5 prescriptive formula and gain at tinnitus pitch was adjusted till the tinnitus get suppressed. SNR 50 was determined soon after fitted with hearing aid and 30 days of hearing aid use. Further, THI and international outcome inventory for hearing aid (IOI-HA) were determined after 30 days of hearing aid use. A significant higher gain adjustment was needed at tinnitus pitch to reduce tinnitus precept using NAL- NL2 than DSL (I/o) v5 prescriptive formula. Further, SNR 50 was not affected by either tinnitus pitch or revised prescription formulas. However, SNR 50 improved after 30 days of hearing aid use. A 76% of the participants’ experienced habituation to perception after 30 days of hearing aid use, 10% had slight, 10% had mild, and 4% had a moderate degree of tinnitus on THI. On IOA-HA, 96% (N=19) of participants have reported satisfactory, and 4% (N=1) reported moderate benefit from hearing aid. Irrespective of prescriptive formula adjusting gain at tinnitus pitch is an efficient method to reduce tinnitus symptoms and improve speech perception.

Contribution of fibrin glue in the surgery of cyanogenic and non-cyanogenic congenital cardiopathies: retrospective cohort study

BackgroundPostoperative bleeding in cardiovascular surgery is a frequent and complicated situation for the surgical team, and may also be responsible for significant hospital expenditures. Fibrin glue are indicated in surgery to improve hemostasis when conventional techniques such as compression, sutures or electrocoagulation are insufficient. Through this study, we tried to study the contribution of fibrin glue to the improvement of the clinical parameters (volume of postoperative bleeding, length of stay in intensive care, volume of blood transfusion ...) in two populations having undergone cardiac surgery, one in which we used the fibrin glue and one without fibrin glue.MethodsThis was a retrospective cohort study conducted in the cardiovascular surgery department of our Hospital in Rabat between June 2012 and June 2015. Fibrin glue (Tissucol® of BAXTER) was used in one group with an haemostatic aim. The pre and post-operative clinical data of the patients were analyzed and compared with data from patients who were operated without the use of fibrin glue because it was not yet available in the hospital. The clinical parameters were collected analyzed using the SPSS 13.0 software.ResultsOne hundred ten patients were included in this study. The fibrin glue was used intraoperatively in 55 patients and not used in 55 patients. 43 (39.1%) had cyanogenic diseases and 67 (60.9%) had non-cyanogenic pathologies. The volume of transfused red blood cells was lower in patients in whom we used biological glue (p = 0.005), as well as the number of days spent in intensive care (p = 0.02). However, the difference was not significant between the two groups for other parameters such as bleeding volume per kg, the number of units of fresh frozen plasma and the platelet units count transfused.ConclusionsThe results we found show that fibrin glue reduces the duration of hospitalization in resuscitation and reduces the number of units of transfused red blood cells to patients after surgery. However, it does not reduce significantly the total postoperative bleeding volume per weight, the number of fresh frozen plasma units or platelets units transfused. The fibrin glue could therefore be of moderate benefit in pediatric cardiac surgery.

Botulinum toxin for the treatment of dystonia and pain in corticobasal syndrome

BackgroundDystonia is a key symptom in corticobasal syndrome (CBS), and upper limb dystonia is the most common phenotype. Dystonia‐associated pain is frequently reported and can be disabling, with poor benefit from oral treatments.Aims of the StudyTo investigate the role of botulinum toxin A (BoTNA) in the treatment of dystonia and associated pain in CBS.MethodsTen consecutive patients with a clinical diagnosis of probable CBS and dystonia with/without associated pain were treated with BoTNA every 3 months. Treatment efficacy was assessed during the first follow‐up visit, three months after the first injection, by means of caregiver impression (CI), evaluation of muscle tone with the Ashworth scale (AS), severity of pain measured with the visual analog scale (VAS).ResultsNine subjects underwent at least three treatments, four patients discontinued for progressive reduction in efficacy or disease progression, five patients are ongoing with good response, and one completed the 10th treatment. No local or systemic side effects were reported, and levodopa equivalent daily dose remained unchanged in most cases during the observational period. Significant improvement of AS was recorded (from 2.9 ± 0.7 to 2.0 ± 0.5, p = 0.003). CI ranged from mild to moderate benefit. All patients reported efficacy on pain, with a significant reduction of VAS score (from 7.7 ± 1.7 to 1.7 ± 0.7 in the Pain group, p = 0.016).ConclusionsOur study confirms safety, efficacy, and tolerability of BoTNA in the treatment of dystonia associated with CBS. Local treatment should be considered as a valid alternative to oral treatment modulation mainly in the presence of associated pain.

Benefits and limitations of TKIs in patients with medullary thyroid cancer: a systematic review and meta-analysis

Introduction Tyrosine kinase inhibitors (TKIs) have been used in patients with advanced medullary thyroid carcinoma (MTC); however, data on their effectiveness and safety are limited. The aim of this systematic review and meta-analysis was to document clinical response and toxicities of TKIs in advanced MTC. Methods We systematically searched major databases for articles or abstracts on TKI use in MTC patients until May 2018. Objective response (OR), defined as the sum of complete + partial response, expressed as percentage, was our primary endpoint, while disease stability, disease progression (DP), median progression-free survival (PFS), and drug discontinuation rate due to adverse events (AEs) were secondary endpoints. Pooled percentages, PFS time, and 95% CIs were reported. Results Thirty-three publications were finally included in the analysis: 1 phase IV, 2 phase III trials evaluating vandetanib and cabozantinib, respectively, 20 phase I or II studies, and the remaining 10 studies of retrospective-observational nature. OR was documented in 28.6% (95% CI 25.9-31.9) of patients. Stable disease was recorded in 46.2% (95% CI 43.3-49.1). Overall, DP was observed in 22.9% (95% CI 20.4-27.6). Grade 3 or more AEs occurred in 48.5% (95% CI 45.5-51.5) of patients, and drug discontinuation was reported in 44.7% (95% CI 41.7-47.6). In general, use of TKIs conferred a PFS of 23.3 months (95% CI 21.07-25.5). In particular, vandetanib induced an OR in 33.8% (95% CI 29.6-38.0) of patients and cabozantinib in 27.7% (95% CI 22.05-33.4). DP occurred in 23.7% (95% CI 19.9-27.6) with vandetanib use and in 22.6% (95% CI 17.4-27.9) in cabozantinib-treated patients. Sorafenib, the third most frequently studied drug, showed intermediate efficacy, but higher discontinuation rates. Conclusion Treatment with TKIs in MTC patients with progressive disease is associated with a moderate therapeutic benefit, with achievement of either disease stability or partial response in 73%. The toxicity of these drugs is not negligible, but it is, nonetheless, manageable.

Determinants of regret in elderly dialysis patients.

In Singapore, most elderly end-stage renal disease (ESRD) patients choose dialysis over palliative management. However, dialysis may not be the optimal treatment option given only moderate survival benefits and high costs and treatment burden compared to non-dialysis management. Elderly patients may therefore come to regret this decision. This study investigated: (i) extent of patients' decision regret after starting dialysis, and (ii) potentially modifiable predictors of regret: satisfaction with chronic kidney disease education, decisional conflict, and decision-making involvement. The present study was a cross-sectional study of 103 dialysis patients above 70 years of age, surveyed at Singapore General Hospital's renal medicine clinics between March and June 2017. Participants reported their levels of decision regret on the Decision Regret Scale (DRS), retrospective decisional conflict on the Decisional Conflict Scale, information satisfaction, and decision-making involvement. In total, 81% of participants reported no decision regret (DRS score < 50), 11% ambivalence (DRS = 50), and 8% regret (DRS >50). In individual DRS items, 19% felt dialysis had done them harm and 16% would not make the same decision again. In multivariable analyses, lower information satisfaction [b = -0.07 (95% CI: -0.13, -0.01)] and decisional conflict [b = 0.004 (95% CI: 0.002, 0.006)] were significantly associated with decision regret. Although the majority of elderly dialysis patients were comfortable with their decision to start dialysis, a proportion was ambivalent or regretted this choice. Regret was more likely among those who experienced decisional conflict and/or expressed poorer information satisfaction. Healthcare professionals should recognize these risk factors and take steps to minimize chances of regret among this population subset.

Effect of biodiversity conservation on livelihood of rural dwellers in Onaara Local Government Area of Oyo state

Biodiversity has proven to be an important source of traditional medicines for people in developing countries, particularly those in remote and normally more poverty-stricken areas of the developing world where access to formal health care is limited. Therefore, Effect of biodiversity conservation on livelihood of rural dwellers in OnaAra Local Government Area of Oyo state was investigated. A multi-stage sampling procedure was used through well structure questionnaire and interviews to gather collect information from 150 rural dweller. Data were analyzed using frequency counts, percentage and means and Chi-square at 0.05% level of significance. The result of analysis revealed that most (54.1%) of the respondents are males and they are in their active age, married with majority (51.4%) had secondary education, with about 1-10years of experience of biodiversity conservation was recorded as the highest percentage. Furthermore, the result revealed on the statement of livelihoods that 56.8%of physical assets is the income generated from the use of hire labor on the farm, 86.5% natural assets on biodiversity conservation and also in human assets, mostly 75.7% of biodiversity conservation assist the dwellers to take care of their families. Chi-square analysis revealed that, among socio-economic characteristics of the respondents, Conclusively, the result reveals that respondents had high benefits from biodiversity conservation with increase income of 62.2%, and 60% of the respondents have moderate benefits that are derive from biodiversity conservation which has led to employment opportunities for most people. It is therefore recommended that Government should put in place policies and laws that will govern farmers, residents that will promote preservation of biodiversity, also Government should construct good roads that will enhance recreational benefit rendered by conservation this will lead to employment opportunities and other benefit.

Addition of transcutaneous electrical nerve stimulation to therapeutic exercise and activities of daily living does not enhance the development of quadriceps strength and voluntary activation: a randomized controlled trial

Purpose: Therapeutic exercise (TE) is recommended for improving lower extremity muscle function in individuals with knee osteoarthritis (KOA). Specific rehabilitative efforts are made to enhance quadriceps strength, as quadriceps weakness is a risk factor of KOA onset and is associated with worse physical performance and increased disability in those with KOA. Unfortunately, improving quadriceps strength remains a common clinical problem in those with KOA, as many individuals with KOA are unable to voluntarily activate motor neurons innervating the quadriceps. Transcutaneous electrical stimulation (TENS), applied to the knee, has been found to increase motor neuron pool excitability of the quadriceps in experimental knee joint effusion models. Preliminary evidence from a small laboratory-based study suggests using TENS in combination with TE may improve quadriceps strength and voluntary activation in individuals with KOA compared to TE alone. It remains unknown if TENS applied during supervised TE and activities of daily living will enhance the development of quadriceps strength and voluntary activation in individuals with KOA and voluntary activation deficits. The purpose of our study was to determine if maximal voluntarily isometric contraction (MVIC) strength and voluntarily quadriceps activation could be improved by the addition of TENS to activities of daily living and a progressive supervised TE regimen (TENS+TE). Methods: Ninety individuals with radiographic (Kellgren-Lawrence grading 2-4) and symptomatic KOA (Western Ontario and McMaster University Osteoarthritis Index function subscale score >31%), as well as voluntary quadriceps activation deficits (< 92% on the involved limb, which was determined as the limb causing the most disability in those with bilateral KOA) were included in a phase II, double-blinded randomized controlled trial. Individuals were stratified based on level of voluntarily quadriceps activation and radiographic KOA severity prior to being randomized into 1 of 3 groups including: 1) TENS+TE (n=32, 18 females, 61±7 years old, 30.0±5.7body mass index [BMI]); 2) Sham TENS+TE (n=29, 19 females, 63±7 years old, 29.2±3.3 BMI); or 3) TE Only (n=29, 14 females, 63±8 years old, 27.8±4.5BMI). Quadriceps MVIC was assessed using a HUMAC Norm dynamometer with the knee in 60° of flexion and peak torque values were normalized to body mass (Nm/kg). Voluntary activation was assessed during the MVIC, as described above, using a burst superimposition technique and voluntary activation was expressed as a percent of full activation using the central activation ratio (CAR). Measurements were collected at baseline, following completion of the 4-week intervention (Post 1), as well as 4-weeks following completion of the intervention (Post 2). All individuals received standardized, progressive TE directed by a licensed physical therapist to specifically increase quadriceps strength. The TE intervention consisted of 10 visits scheduled over a 28-day period. Individuals in the TENS+TE group received an active TENS unit used to apply a strong, sensory stimulus to the knee joint and were instructed to use the TENS during all TE sessions, as well as 8 hours per day when they were the most physically active. Individuals in the Sham TENS+TE group were provided the same stimulator designed to emit no current after 20 seconds of initial stimulation. Separate, mixed effects models were used to determine differences between groups over time for MVIC and CAR between baseline and Post 1, as well as baseline and Post 2. We controlled for baseline values, age, sex, BMI at baseline, and number of TE sessions attended for each analysis. Results: Of the 90 total individuals enrolled, 91% and 86% of the sample was retained at the Post 1 and Post 2 follow-up testing time points, respectively. There were no differences in MVIC between groups at Post 1 (P=0.32) or Post 2 (P=0.45), while all groups significantly improved from baseline at Post 1 (P<0.001) and Post 2 (P<0.001; Table 1). Similarly, There were no differences for CAR between groups at Post 1 (P=0.47) or Post 2 (P=0.83), while all groups significantly improved from baseline at Post 1 (P<0.001) and Post 2 (P<0.001). Conclusions: All groups improved MVIC and CAR over the 4-week intervention, which were sustained at 8-weeks; yet TENS did not provide any added benefit for enhancing the effects of TE on MVIC or CAR. Our data suggest standardized, progressive TE was a catalyst for improvement in MVIC and CAR. Previous research has demonstrated only moderate sustainable benefits for physical function and strength following TE. Future work should determine if our inclusion criteria, which specifically selected individuals with low voluntary activation and disability, played a role in identifying individuals who would respond to TE.Tabled 1Mean±Standard Deviation of Quadriceps MVIC and CARQuadriceps Maximal Voluntary Isometric Contraction Normalized to Body Mass (Nm/Kg)BaselinePost 1Post 2TENS + TE1.31±0.521.52±0.58*1.50±0.58*Sham TENS + TE1.28±0.461.51±0.49*1.53±0.48*TE Only1.27±0.521.54±0.59*1.54±0.57*Quadriceps Central Activation Ratio (Percent of full activation)TENS + TE80.54±11.7790.50±10.95*87.47±9.89*Sham TENS + TE78.17±12.1985.92±12.54*85.81±12.45*TE Only77.52±13.8487.47±10.35*86.67±11.76** = Greater than Baseline Open table in a new tab

Sequential Bone-Marrow Cell Delivery of VEGFA/S1P Improves Vascularization and Limits Adverse Cardiac Remodeling After Myocardial Infarction in Mice.

Microvascular dysfunction and resulting tissue hypoxia is a major contributor to the pathogenesis and evolution of cardiovascular diseases (CVD). Diverse gene and cell therapies have been proposed to preserve the microvasculature or boost angiogenesis in CVD, with moderate benefit. This study tested in vivo the impact of sequential delivery by bone-marrow (BM) cells of the pro-angiogenic factors vascular endothelial growth factor (VEGFA) and sphingosine-1-phosphate (S1P) in a myocardial infarction model. For that, mouse BM cells were transduced with lentiviral vectors coding for VEGFA or sphingosine kinase (SPHK1), which catalyzes S1P production, and injected them intravenously 4 and 7 days after cardiac ischemia-reperfusion in mice. Sequential delivery by transduced BM cells of VEGFA and S1P led to increased endothelial cell numbers and shorter extravascular distances in the infarct zone, which support better oxygen diffusion 28 days post myocardial infarction, as shown by automated 3D image analysis of the microvasculature. Milder effects were observed in the remote zone, together with increased proportion of capillaries. BM cells delivering VEGFA and S1P also decreased myofibroblast abundance and restricted adverse cardiac remodeling without major impact on cardiac contractility. The results indicate that BM cells engineered to deliver VEGFA/S1P angiogenic factors sequentially may constitute a promising strategy to improve micro-vascularization and oxygen diffusion, thus limiting the adverse consequences of cardiac ischemia.

Efficacy of Chondroitin Sulfate in Patients with Knee Osteoarthritis: A Comprehensive Meta-Analysis Exploring Inconsistencies in Randomized, Placebo-Controlled Trials.

IntroductionThere are some controversies about treatment modalities in osteoarthritis (OA), including chondroitin sulfate (CS). The objective of this study was to determine whether CS is effective at alleviating pain and improving function in patients with knee OA and to identify the factors that explain inconsistencies in clinical trial results.MethodsWe conducted a systematic review of randomized, placebo-controlled trials, searching the databases Medline, Cochrane central register for controlled trials and Scopus. Random effects meta-analysis was then performed, using tau2 and I2 statistics to assess heterogeneity. The pain and Lequesne index (LI) scores were expressed as standardized mean differences (SMDs), with a 95% confidence interval (CI). Heterogeneity was explored by stratifying the analyses according to pre-specified study-level characteristics and assessing the sources of funnel plot asymmetry.ResultsThe inclusion criteria yielded 18 trials. Overall, CS significantly but inconsistently reduced pain (SMD: − 0.63; 95% CI: − 0.91, − 0.35; I2 = 94%) and improved function (SMD: − 0.82; 95% CI: − 1.31, − 0.33; I2 = 95%). When limiting the analysis to studies with a low risk of bias, the pharmaceutical grade CS of IBSA origin showed a greater reduction in pain (SMD: − 0.25; 95% CI: − 0.34, − 0.16; I2 = 75%) and function (SMD: − 0.33; 95% CI: − 0.47, − 0.20; I2 = 53%, p = 0.07) compared with the other preparations (SMDPain: − 0.08; 95% CI: − 0.19, + 0.02; I2 = 20%; SMDFunction: − 0.18; 95% CI: − 0.36, +0.01; I2 = 0%). Assessing funnel plot asymmetry in the studies with a low risk of bias, we found strong correlations between the treatment effects and study size (pain: rS = 0.93; LI: rS = 0.86; p < 0.05). Ultimately, there was no residual heterogeneity in the CS effects when the smallest studies were removed from the analyses.ConclusionThis new meta-analysis suggests that CS provides a moderate benefit for pain and has a large effect on function in knee OA, however with large inconsistency. The risks of bias, brand and study size were the factors explaining heterogeneity among the clinical trial results.Electronic supplementary materialThe online version of this article (10.1007/s12325-019-00921-w) contains supplementary material, which is available to authorized users.

Efficacy and safety of duloxetine in osteoarthritis: a systematic review and meta-analysis.

About 21% of adults with osteoarthritis (OA) are diagnosed with concomitant depression in addition to chronic pain. Duloxetine, an anti-depressant medication, has been recently approved for managing Knee OA. We performed a systematic review to ascertain the efficacy and safety of duloxetine for OA. We searched MEDLINE, EMBASE, Web of Science, Google Scholar, and the Cochrane Database from inception to December 2018. Randomized clinical trials (RCTs) assessing the efficacy and/or safety of duloxetine versus placebo in OA patients were included. Data extraction and quality assessment were undertaken by two independent reviewers. Seven RCTs (n = 2,102 participants) met our inclusion criteria, and five RCTs (n = 1,713) were eligible for meta-analysis. The results of our analyses indicate that duloxetine has statistically significant, moderate benefits on pain, function, and quality of life in knee OA patients for up to 13 weeks. Reported incidences of gastrointestinal adverse events were three to four times higher in participants who received duloxetine versus placebo. Duloxetine may be an effective treatment option for individuals with knee OA, but use of the drug is associated with a significantly higher risk of adverse events. Patient preferences and clinicians’ judgment must be considered before the initiation of duloxetine.

Smartphone colorimetric detection of calcium and magnesium in water samples using a flow injection system

Water hardness has implications for both human health and industry. The main components that make water hard are calcium and magnesium. The magnesium in hard water may provide a moderate health benefit, but calcium can cause serious problems in industrial processes. This paper presents a rapid-response, reliable and convenient device developed to measure calcium and magnesium ion concentrations continuously in water samples by using a smartphone analysis of colorness change. The ion detection is based on phase extraction equilibria in a specific ion-exchange substance membrane that contains an ionophore (selectively binding to specific ions), a chromoionophore (a lipophilic pH indicator), an ionic salt (a cation exchanger), a polymer (PVC) and a plasticizer. The device is built on a PDMS fluidic layer with six parallel detection chambers that allows the water samples to flow through at a specific rate to these chambers. An Android smartphone App was developed to acquire the color images after the ions exchange across the membrane, and the analysis of target ion concentration can be realized by the pre-loaded calibration curves. The results show that the colorimetric sensor is capable of determining Ca2+ concentration in an acetate buffer solution (pH = 5.3) and total hardness in a Tris-HCl buffer solution (pH = 7.2), covering the range of normal water hardness (from soft to very hard). The measurements on real samples were analyzed by both Image J and the App and were compared with results from a commercial hardness kit and inductively coupled plasma mass spectrometry (ICP-MS), demonstrating the accuracy and precision of our colorimetric sensor compared to a commercial sensor. This cost-effective device and automatic analytical smartphone app can be combined easily as a ready-to-go sensor for monitoring Ca2+ and Mg2+ continuously and simultaneously, which is convenient for use in resource-limited areas.

The effects of collagen peptides on muscle damage, inflammation and bone turnover following exercise: a randomized, controlled trial

This study examined whether consuming collagen peptides (CP) before and after strenuous exercise alters markers of muscle damage, inflammation and bone turnover. Using a double-blind, independent group’s design, 24 recreationally active males consumed either 20 g day−1 of CP or a placebo control (CON) for 7 days before and 2 days after performing 150 drop jumps. Maximal isometric voluntary contractions, countermovement jumps (CMJ), muscle soreness (200 mm visual analogue scale), pressure pain threshold, Brief Assessment of Mood Adapted (BAM +) and a range of blood markers associated with muscle damage, inflammation and bone turnover C-terminal telopeptide of type 1 collagen (β-CTX) and N-terminal propeptides of type 1 pro-collagen (P1NP) were measured before supplementation (baseline; BL), pre, post, 1.5, 24 and 48 h post-exercise. Muscle soreness was not significantly different in CP and CON (P = 0.071) but a large effect size was evident at 48 h post-exercise, indicative of lower soreness in the CP group (90.42 ± 45.33 mm vs. CON 125.67 ± 36.50 mm; ES = 2.64). CMJ height recovered quicker with CP than CON at 48 h (P = 0.050; CP 89.96 ± 12.85 vs. CON 78.67 ± 14.41% of baseline values; ES = 0.55). There were no statistically significant effects for the other dependent variables (P > 0.05). β-CTX and P1NP were unaffected by CP supplementation (P > 0.05). In conclusion, CP had moderate benefits for the recovery of CMJ and muscle soreness but had no influence on inflammation and bone collagen synthesis.

Party survival in parliament: Explaining party durability in lower‐house parliaments

AbstractApproximately 70 per cent of the parties emerging in the post‐Second World War era failed to keep their seats in parliament. Party survival is an important issue, especially in parliamentary democracies, where parties are the means through which voters’ preferences are linked to government policy outputs. Using an event history modeling framework, and data from 37 democracies, covering 830 parties, this article analyses two questions regarding party durability. First, when do parties fail? Second, which parties survive longer? The article shows that most parties fail at the beginning of their lifespan, and disappear before the end of their fourth term in parliament. Moreover, it is found that moderate policy position, distinct ideology and participation in governing coalitions increase the duration of party survival, even when controlling for party size. This article contributes to the extensive literature about the electoral benefits of ideological moderation and distinct policy positions by showing the long‐term benefits of these factors. Moreover, the long‐term benefit of party participation in government in terms of survival overcomes the short‐term cost of ruling.

Treatments of Posttraumatic Stress Disorder in Civilian Populations

Posttraumatic stress disorder is a chronic, heterogeneous disorder for which a multitude of psychotherapies, pharmaceuticals, and immerging treatment programs are available. Majority of efficacy studies focus on Caucasian male military populations, which may be a reason why not all patients respond to treatment with long-term positive outcomes. Additionally, effects of treatment on symptom clusters have been neglected. This work reviews treatment of PTSD and its symptom clusters exclusively in civilian populations, which have been historically under-examined in the literature. Exposure therapy stands at the forefront of successful PTSD treatment and offers a more cost-effective solution to pharmacotherapy; however, refugees and patients with comorbid depression may not experience such strong benefits. For exposure therapy and other forms of psychotherapy, non-inferiority studies point to promise of internet-delivered and telemedicine-based methods for reaching populations that may not have access to in-person care. SSRIs are the most widely used pharmaceutical treatment for PTSD; moderate initial benefits are observed yet long-term retention and outcomes may be enhanced by adjunct treatment. Again, refugees are a group that experiences lesser benefit. Research has begun to explore efficacy of treatments for individual symptom clusters, with hyperarousal benefiting most from currently available modalities. Avoidance, intrusion, negative thoughts and beliefs, and dissociation are symptoms requiring more research for focused interventions. Treatment of PTSD has evolved to (1) include equivalent proportions of men and women, along with focused female-exclusive cohorts; (2) explore novel methods of treatment online and in various cultural contexts; and (3) less focus on medication as evidenced by current clinical trials. In addition to further efficacy and safety studies in more diverse ethnic populations, work is needed to examine what therapies are best for targeting specific symptom clusters of PTSD. This research will drive precision treatment, and such research is beginning to point towards underlying mechanisms of pathology and change.

Prophylactic efficacy of a human monoclonal antibody against MERS-CoV in the common marmoset

Effective antiviral treatments for MERS-CoV are urgently needed. LCA60 is a MERS-CoV-neutralizing monoclonal antibody isolated from a convalescent MERS patient. Previously, it was shown that treatment with LCA60 resulted in reduced disease and virus titers in mouse models of MERS-CoV infection. Here, we tested the prophylactic efficacy of LCA60 in the common marmoset model of MERS-CoV infection. Intravenous administration of LCA60 one day before virus challenge resulted in high levels of MERS-CoV-neutralizing activity in circulating blood. Clinically, there was a moderate benefit of treatment with LCA60 including reduced respiratory involvement. Although viral lung loads were not reduced in LCA60-treated animals as compared to controls, there were fewer pathological changes in the lungs. Thus, prophylactic LCA60 treatment could be implemented to reduce disease burden in contacts of confirmed MERS-CoV patients.

Pregabalin for neuropathic pain in adults.

Pregabalin for neuropathic pain in adults.

Pertinence clinique en population dépressive d’un médiateur thérapeutique axé sur les ressources personnelles : évaluation par protocole individuel de type arrêt—reprise sur une patiente hospitalisée pour dépression

IntroductionThe low to moderate benefit of current care on optimal functioning in depressed patient encourages the development and evaluation of new interventions in this area. ObjectiveThis study aims at the clinical evaluation by single case of a serious game focused on personal resources in depressed population. MethodThe recommendations of the Single-Case Reporting Guideline In BEhavioural Interventions (SCRIBE) Statement were respected to design and report the results of this single-case research (Tate et al., 2016). A Withdrawal/Reversal ABA design has been applied to a young patient hospitalized for depression. Each phase contained 3 measurement opportunities spaced 7 to 10 days apart. In intervention phase B, a serious game was introduced in positive psychotherapy workshops without replacing the patient's usual care. ResultsIn the patient, serious game had a clinically significant benefit on depression, psychological well-being and affects. On the other hand, an increase in stress and anxiety levels, as well as a progressive decrease in the feeling of autonomy were also observed. ConclusionSerious game as a therapeutic mediator seems to have demonstrated its effectiveness for the patient. The reduction in depression coupled with the increase in stress and anxiety points out a favourable progression of the patient's problem. Elements specific to the patient's intra-individual problem were highlighted and could shed light on her clinical management.

A Randomized Clinical Trial of Immediate versus Delayed Glasses for Moderate Hyperopia in 1- and 2-Year-Olds

Two strategies were compared for managing moderate hyperopia without manifest strabismus among 1- and 2-year-old children: (1) immediate prescription of glasses versus (2) observation without glasses unless reduced distance visual acuity (VA), reduced stereoacuity, or manifest strabismus. Prospective randomized clinical trial. A total of 130 children aged 1 to 2 years with hyperopia between+3.00 diopters (D) and+6.00 D spherical equivalent (SE) in at least 1 eye, anisometropia ≤1.50 D SE, and astigmatism ≤1.50 D based on cycloplegic refraction and no manifest strabismus. Participants were randomly assigned to glasses (1.00 D less than full cycloplegic hyperopia) versus observation and followed every 6 months for 3 years. Glasses were prescribed to those assigned to observation if they met prespecified deterioration criteria of distance VA or near stereoacuity below age norms, or development of manifest strabismus. At the 3-year primary outcome examination, participants were classified as failing the randomized management regimen if distance VA or stereoacuity was below age norms or manifest strabismus was observed (each with and without correction in trial frames, confirmed by masked retest, irrespective of whether deterioration had occurred previously), or if strabismus surgery had been performed. Of the 106 participants (82%) completing the 3-year primary outcome examination, failure occurred in 11 (21%) of 53 in the glasses group and 18 (34%) of 53 in the observation group (difference=-13%; 95% confidence interval [CI],-31 to 4; P= 0.14). Sixty-two percent (95% CI, 49-74) in the observation group and 34% (95% CI, 23-48) in the glasses group met deterioration criteria (requiring glasses if not wearing). For 1- and 2-year-olds with uncorrected moderate hyperopia (+3.00 D to+6.00 D SE), our estimates of failure, after 3 years of 6-month follow-ups, are inconclusive and consistent with a small to moderate benefit or no benefit of immediate prescription of glasses compared with careful observation (with glasses only if deteriorated).