Moderate Benefit Research Articles

Occupational Therapy Interventions to Improve Activities of Daily Living for Community-Dwelling Older Adults: A Systematic Review.

This systematic review aimed to synthesize the effects of interventions within the scope of occupational therapy to improve performance of activities of daily living (ADLs) in community-dwelling older adults. Searches were conducted in CINAHL, the Cochrane Database of Systematic Reviews, MEDLINE, PsycINFO, and OTseeker. Empirical studies published between 1995 and 2015 were individually screened and appraised by two reviewers. Forty-three studies met the review inclusion and exclusion criteria. Physical exercise was the most common intervention approach. Physical exercise interventions for frail older adults showed a moderate benefit, but no benefits were found for older adults without noticeable difficulty in ADLs. For older adults with difficulty in ADLs, there was a high benefit of using home-based intervention. The findings of this systematic review highlight the importance of addressing older adults' living environment in intervention to promote independence in ADLs.

Acupuncture for hip osteoarthritis.

Hip osteoarthritis (OA) is a major cause of pain and functional limitation. Few hip OA treatments have been evaluated for safety and effectiveness. Acupuncture is a traditional Chinese medical therapy which aims to treat disease by inserting very thin needles at specific points on the body. To assess the benefits and harms of acupuncture in patients with hip OA. We searched Cochrane CENTRAL, MEDLINE, and Embase all through March 2018. We included randomized controlled trials (RCTs) that compared acupuncture with sham acupuncture, another active treatment, or no specific treatment; and RCTs that evaluated acupuncture as an addition to another treatment. Major outcomes were pain and function at the short term (i.e. < 3 months after randomization) and adverse events. We used standard methodological procedures expected by Cochrane. Six RCTs with 413 participants were included. Four RCTs included only people with OA of the hip, and two included a mix of people with OA of the hip and knee. All RCTs included primarily older participants, with a mean age range from 61 to 67 years, and a mean duration of hip OA pain from two to eight years. Approximately two-thirds of participants were women. Two RCTs compared acupuncture versus sham acupuncture; the other four RCTs were not blinded. All results were evaluated at short term (i.e. four to nine weeks after randomization).In the two RCTs that compared acupuncture to sham acupuncture, the sham acupuncture control interventions were judged believable, but each sham acupuncture intervention was also judged to have a risk of weak acupuncture-specific effects, due to placement of non-penetrating needles at the correct acupuncture points in one RCT, and the use of penetrating needles not inserted at the correct points in the other RCT. For these two sham-controlled RCTs, the risk of bias was low for all outcomes.The combined analysis of two sham-controlled RCTs gave moderate quality evidence of little or no effect in reduction in pain for acupuncture relative to sham acupuncture. Due to the small sample sizes in the studies, the confidence interval includes both the possibility of moderate benefit and the possibility of no effect of acupuncture (120 participants; Standardized Mean Difference (SMD) -0.13, (95% Confidence Interval (CI) -0.49 to 0.22); 2.1 points greater improvement with acupuncture compared to sham acupuncture on 100 point scale (i.e., absolute percent change -2.1% (95% CI -7.9% to 3.6%)); relative percent change -4.1% (95% CI -15.6% to 7.0%)). Estimates of effect were similar for function (120 participants; SMD -0.15, (95% CI -0.51 to 0.21)). No pooled estimate, representative of the two sham-controlled RCTs, could be calculated or reported for the quality of life outcome.The four other RCTs were unblinded comparative effectiveness RCTs, which compared (additional) acupuncture to four different active control treatments.There was low quality evidence that addition of acupuncture to the routine primary care that RCT participants were receiving from their physicians was associated with statistically significant and clinically relevant benefits, compared to the routine primary physician care alone, in pain (1 RCT; 137 participants; mean percent difference -22.9% (95% CI -29.2% to -16.6%); relative percent difference -46.5% (95% CI -59.3% to -33.7%)) and function (mean percent difference -19.0% (95% CI -24.41 to -13.59); relative percent difference -38.6% (95% CI -49.6% to -27.6%)). There was no statistically significant difference for mental quality of life and acupuncture showed a small, significant benefit for physical quality of life.The effects of acupuncture compared with either advice plus exercise or NSAIDs are uncertain.We are also uncertain whether acupuncture plus patient education improves pain, function, and quality of life, when compared to patient education alone.In general, the overall quality of the evidence for the four comparative effectiveness RCTs was low to very low, mainly due to the potential for biased reporting of patient-assessed outcomes due to lack of blinding and sparse data.Information on safety was reported in four RCTs. Two RCTs reported minor side effects of acupuncture, which were primarily minor bruising, bleeding, or pain at needle insertion sites. Four RCTs reported on adverse events, and none reported any serious adverse events attributed to acupuncture. Acupuncture probably has little or no effect in reducing pain or improving function relative to sham acupuncture in people with hip osteoarthritis. Due to the small sample size in the studies, the confidence intervals include both the possibility of moderate benefits and the possibility of no effect of acupuncture. One unblinded trial found that acupuncture as an addition to routine primary physician care was associated with benefits on pain and function. However, these reported benefits are likely due at least partially to RCT participants' greater expectations of benefit from acupuncture. Possible side effects associated with acupuncture treatment were minor.

DOAC use in patients with chronic kidney disease

SummaryDirect oral anticoagulants (DOACs) are increasingly prescribed substances in patients with indication for effective anticoagulation. Patients with chronic kidney disease (CKD) have a high burden of cardiovascular risk and are more likely to develop atrial fibrillation (AF) than patients without CKD. Patients with mild to moderate CKD benefit from DOACs, especially when having intolerance to vitamin K-antagonists (VKA). DOACs may in some cases be considered in patients with rare renal disease and hypercoagulabilic state. DOACs are to a large extent eliminated by renal excretion. Since prospective randomised data in CKD patients are sparse, the decision for anticoagulative therapy is challenging especially in patients with severe renal impairment. The direct factor Xa-inhibitors are approved for use even in patients with an estimated glomerular filtration rate (eGFR) between 15 and 30 ml/min. Careful monitoring of renal function on a regular basis is essential before initiation and after start of DOAC, especially for patients at risk for acute renal failure (elderly, diabetics, patients with preexisting kidney disease). None of the DOACs is approved in CKD patients with end-stage-renal-disease (ESRD) with or without dialysis. DOACs are not recommended for kidney transplant patients under immunosuppression with calcineurin inhibitors. In these patients conventional therapy with VKA is the only option, which has to be monitored closely since it has potential adverse effects.Nachdruck aus und zu zitieren als: Hämostaseologie 2017; 37: 286–294 https://doi.org/10.5482/HAMO-17-01-1657857

End of moderation: the radicalization of AKP in Turkey

ABSTRACTTurkey’s Justice and Development Party, AKP, was for many years believed to be paramount in ushering in a new era of moderate Islamism. However, in recent years, AKP has troublingly reversed course. From violent repression of the Gezi protests of 2013 to the 2016 abortive coup and subsequent crackdown on opposition, the party has lost all semblance of moderate Islamism and radicalized. If AKP had truly moderated, how could the party have changed in such a short period of time? What explains the radicalization of AKP? First, we argue that the strategic benefits of moderation far outweighed its costs, rendering it analytically improbable to determine whether AKP’s actions were genuine or merely strategic. Second, we show that AKP has been in a process of radicalization characterized by the adoption of anti-system, anti-democratic, and violent tactics and rhetoric since 2011. The disappearance of domestic and international structural constraints created the requisite background conditions for the party’s radicalization. Radicalization was facilitated by what we call ‘Erdoganization’, an ongoing de-institutionalization process within which Tayyip Erdogan gained complete control over the party. Additionally, a series of four “external shocks” threatened the party’s primary goal of gaining hegemony and caused the party to radicalize.

Optimal design of intersecting bimodal transit networks in a grid city

The urban transit system in a real city usually has two major components: a sparse express (e.g. rail) network and a dense local (e.g. bus) network. The two networks intersect and interweave with each other throughout the city to furnish various route options for serving transit patrons with distinct ODs. The optimal design problem of this bimodal transit system, however, has not been well explored in the literature, partly due to the difficulty of modeling the patrons’ complex route choice behavior in the bimodal networks. In light of this, we formulate parsimonious continuum models for minimizing the total cost of the patrons and the transit agency for an intersecting bimodal transit network in a grid city, where the perpendicular local and express lines intersect at transfer stops. Seven distinct route types are identified in this network, which represent realistic intra- and inter-modal route options. A lower-level assignment problem between these routes is embedded in the upper-level network design optimization problem. We develop an efficient method to find near-optimal designs of the intersecting network. Numerical results unveil a number of insightful findings, e.g., that sizable cost savings are observed for the intersecting bimodal design as compared to the single-mode designs for moderate to high demand levels, and that only moderate benefits are observed as compared to the trunk-feeder designs under certain operating conditions. We also show that the conventional practice of designing the local and express networks separately would greatly undermine the benefit of the bimodal system.

Effects of Non-Driving Related Task Modalities on Takeover Performance in Highly Automated Driving

Aim of the study was to evaluate the impact of different non-driving related tasks (NDR tasks) on takeover performance in highly automated driving. During highly automated driving, it is allowed to engage in NDR tasks temporarily. However, drivers must be able to take over control when reaching a system limit. There is evidence that the type of NDR task has an impact on takeover performance, but little is known about the specific task characteristics that account for performance decrements. Thirty participants drove in a simulator using a highly automated driving system. Each participant faced five critical takeover situations. Based on assumptions of Wickens's multiple resource theory, stimulus and response modalities of a prototypical NDR task were systematically manipulated. Additionally, in one experimental group, the task was locked out simultaneously with the takeover request. Task modalities had significant effects on several measures of takeover performance. A visual-manual texting task degraded performance the most, particularly when performed handheld. In contrast, takeover performance with an auditory-vocal task was comparable to a baseline without any task. Task lockout was associated with faster hands-on-wheel times but not altered brake response times. Results showed that NDR task modalities are relevant factors for takeover performance. An NDR task lockout was highly accepted by the drivers and showed moderate benefits for the first takeover reaction. Knowledge about the impact of NDR task characteristics is an enabler for adaptive takeover concepts. In addition, it might help regulators to make decisions on allowed NDR tasks during automated driving.

Moderate UV-A supplementation benefits tomato seed and seedling invigoration: a contribution to the use of UV in seed technology

Abstract The production, processing and consumption of Solanum lycopersicum L. fruits are increasing worldwide, demanding technologies to improve tomato growth efficiency. Germination is a critical step for intensification of crop production and conditions plants’ vigor, a crucial benchmark in plant market. Ultraviolet radiation supplementation is emerging in seed technology as it increases plant growth with no impact on the environment, although its use in crops’ nurseries still remains an open field. In the present work, seeds/seedlings of three commercial cultivars (‘Oxheart’, ‘Cherry’ and ‘Roma’) were grown for 15 days under three different ultraviolet (UV)-conditions. The results demonstrated the benefits of supplementing seeds/seedlings with moderate UV-A dose, being evident an acceleration/synchronization of germination rates, higher biomass and cotyledon area, and a stimulation of photosynthetic pigments and anthocyanins in all cultivars analysed. UV-B showed a cultivar dependence effect: ‘Cherry’ cultivar was in general not affected by the moderate UV-B dose used, but ‘Roma’ and ‘Oxheart’ showed a delay in germination and a seedling biomass decrease, in parallel with a decrease in chlorophylls and carotenoids. Both UV-A/B supplements reduced the H2O2 and MDA seedling levels, but the antioxidant battery was stimulated (e.g., peroxidases that use guaiacol as a substrate (GPX)) as well as the phenol level and the antiradical activity. The Principal Component Analysis (PCA) validates the clear distinction between cultivars and UV-condition effects. These data demonstrate the benefits of UV-A supplementation of tomato seeds pointing out to an “eustress” beneficial of UV-A in seedlings growth and vigor. A possible application of UV-A supplementation to other crops is discussed.

Telephone psychotherapy in multiple sclerosis: A systematic review and meta-analysis.

The objective of the study was to review the evidence for the effectiveness of telephone psychotherapy on psychological outcomes in people with multiple sclerosis (MS). We conducted a systematic search of EMBASE, PsycINFO, PsycARTICLES, MEDLINE, CINAHL, Web of Science, and hand-searched relevant journals to identify randomized controlled trials (RCTs) that evaluated the effectiveness of telephone psychotherapy on psychological outcomes in people with MS (last search completed on October 1, 2015). The methodological quality of each included trial was assessed, based on a standardized list of methodological criteria. Where available, data were extracted and combined in a meta-analysis to compute effect size estimates. Eleven RCTs and 1,104 participants were identified. The meta-analysis found a moderate effect of the intervention on depression (SMD 0.47 [95% confidence interval 0.21-0.73]). The meta-analysis also found small to moderate short-term effects of the intervention on fatigue, quality of life, MS symptoms, physical activity, and medication adherence, compared with controls and other interventions. RCT designs were heterogeneous. All studies had at least 1 high or unclear risk of bias. Telephone psychotherapy provides small and moderate benefits in depression, fatigue, quality of life, MS symptoms, physical activity, and medication adherence in the short term. Few gains were sustained in the long term. Studies of better quality are needed. (PsycINFO Database Record

Towards an optimal treatment algorithm for metastatic pancreatic ductal adenocarcinoma (PDA).

Chemotherapy remains the mainstay of treatment for advanced pancreatic ductal adenocarcinoma (pda). Two randomized trials have demonstrated superiority of the combination regimens folfirinox (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) and gemcitabine plus nab-paclitaxel over gemcitabine monotherapy as a first-line treatment in adequately fit subjects. Selected pda patients progressing to first-line therapy can receive secondline treatment with moderate clinical benefit. Nevertheless, the optimal algorithm and the role of combination therapy in second-line are still unclear. Published second-line pda clinical trials enrolled patients progressing to gemcitabine-based therapies in use before the approval of nab-paclitaxel and folfirinox. The evolving scenario in second-line may affect the choice of the first-line treatment. For example, nanoliposomal irinotecan plus 5-fluouracil and leucovorin is a novel second-line option which will be suitable only for patients progressing to gemcitabine-based therapy. Therefore, clinical judgement and appropriate patient selection remain key elements in treatment decision. In this review, we aim to illustrate currently available options and define a possible algorithm to guide treatment choice. Future clinical trials taking into account sequential treatment as a new paradigm in pda will help define a standard algorithm.

Adjuvant therapy for resected stage III melanoma patients: high-dose interferon-alpha versus ipilimumab combined with kinases inhibitors.

High-dose interferon-alpha remains the first-line treatment in the adjuvant therapy of metastatic melanoma. More recently, high-dose pegylated interferon-alpha-2b has been approved by the US Food and Drug Administration. Actually, an adjuvant therapy alternative to high-dose interferon-alpha is represented by ipilimumab. Moreover, combination therapy of IFN-alpha or ipilimumab with tyrosine kinase inhibitors has been proved in patients with specific mutations. It is mandatory to understand what the best adjuvant treatment is for resected metastatic melanoma patients, particularly at stage III-N1, in terms of overall survival rather than recurrence-free survival. The ECOG 1609 clinical trial compared high-dose interferon-alpha and ipilimumab alone or combined with tyrosine kinase inhibitors for the treatment of early metastatic melanoma. In the past, ECOG 1684, 1690 and 1694 trials showed improvement in recurrence-free survival more than overall survival for high-risk melanoma patients (stage IIB-III) treated with high-dose interferon-alpha, whereas more recently the EORTC 18991 trial reported successful therapeutic results in terms of recurrence-free survival rather than overall survival for stage III-N1 melanoma patients treated with high-dose pegylated interferon-alpha-2b. Toxicity was more acceptable within one year of treatment. Randomized trials have demonstrated that ipilimumab as second-line therapy is able to increase dose-dependent overall survival rates in advanced melanoma patients despite severe but reversible immune-related adverse events. Old tyrosine kinase inhibitors have been used in combination with interferon for the treatment of advanced melanoma patients with moderate benefits and increased toxicity, but new selective drugs seem to be more efficacious. Early metastatic melanoma patients (stage III-N1) should be the principal subset to be treated with the most suitable adjuvant therapy to achieve the best overall survival. New schedules have to be tested with high-dose interferon-alpha and ipilimumab alone or combined with tyrosine kinase inhibitors while waiting for results from ECOG 1609.

Modeling Poliovirus Transmission in Pakistan and Afghanistan to Inform Vaccination Strategies in Undervaccinated Subpopulations.

Due to security, access, and programmatic challenges in areas of Pakistan and Afghanistan, both countries continue to sustain indigenous wild poliovirus (WPV) transmission and threaten the success of global polio eradication and oral poliovirus vaccine (OPV) cessation. We fitted an existing differential-equation-based poliovirus transmission and OPV evolution model to Pakistan and Afghanistan using four subpopulations to characterize the well-vaccinated and undervaccinated subpopulations in each country. We explored retrospective and prospective scenarios for using inactivated poliovirus vaccine (IPV) in routine immunization or supplemental immunization activities (SIAs). The undervaccinated subpopulations sustain the circulation of serotype 1 WPV and serotype 2 circulating vaccine-derived poliovirus. We find a moderate impact of past IPV use on polio incidence and population immunity to transmission mainly due to (1) the boosting effect of IPV for individuals with preexisting immunity from a live poliovirus infection and (2) the effect of IPV-only on oropharyngeal transmission for individuals without preexisting immunity from a live poliovirus infection. Future IPV use may similarly yield moderate benefits, particularly if access to undervaccinated subpopulations dramatically improves. However, OPV provides a much greater impact on transmission and the incremental benefit of IPV in addition to OPV remains limited. This study suggests that despite the moderate effect of using IPV in SIAs, using OPV in SIAs remains the most effective means to stop transmission, while limited IPV resources should prioritize IPV use in routine immunization.

Flexible Electricity Use for Heating in Markets with Renewable Energy

Using electricity for heating can contribute to decarbonization and provide flexibility to integrate variable renewable energy. We analyze the case of electric storage heaters in German 2030 scenarios with an open-source electricity sector model. Making customary night-time storage heaters temporally more flexible offers only moderate benefits because renewable availability during daytime is limited in the heating season. As storage heaters feature only short-term heat storage, they also cannot reconcile the seasonal mismatch of heat demand in winter and high renewable availability in summer. Generally, flexible electric heaters increase the use of generation technologies with low variable costs, which are not necessarily renewables.

Mode of tele-communication and software used by children with hearing impairment

Objective: The study is being conducted to find out mode of tele-communication and software used by children with hearing impairment. Methodology: This cross-sectional study was done at special education centers and schools in Lahore and Sheikhupura. Data was collected from children with hearing impairment by using a questionnaire of 11 items about the modes of tele-communication and software used by children with hearing impairment. Sample size was 362 which was calculated by using online sample size calculator. The population includes male and female children with mild, moderate, severe and profound hearing impairment studying in special education schools of Lahore and Sheikhupura. All these children use hearing aid and have congenital bilateral hearing loss. Results: This study shows that almost 80% population of children with hearing impairment know about computer and mobile. They also have awareness about the use of computer, Facebook, e-mail etc. In addition, 40 to 50% children with hearing impairment use Skype, Facebook and e-mail as a communication tool. Conclusion: The conclusion from this study is that most of the children use computer and mobile on daily basis in schools and homes for communication. Mild to moderate hearing loss children benefit from these devices between the ages of 10 to 20 y.

Which patients with moderate hypoxemia benefit from long-term oxygen therapy? Ways forward.

Long-term oxygen therapy (LTOT) improves prognosis in patients with COPD and chronic severe hypoxemia. The efficacy in moderate hypoxemia (tension of arterial oxygen; on air, 7.4−8.0 kPa) was questioned by a recent large trial. We reviewed the evidence to date (five randomized trials; 1,191 participants, all with COPD). Based on the current evidence, the survival time may be improved in patients with moderate hypoxemia with secondary polycythemia or right-sided heart failure, but not in the absence of these signs. Clinically, LTOT is not indicated in moderate hypoxemia except in the few patients with polycythemia or signs of right-sided heart failure, which may reflect more chronic and severe hypoxemia.

Acupuncture for the relief of hot flashes in breast cancer patients: A systematic review and meta-analysis of randomized controlled trials and observational studies.

To critically assess the effectiveness and safety of acupuncture for treating hot flashes (HFs) among breast cancer (BC) patients, and to get much more highly compelling evidence then to guide clinical practice. Comprehensive systematic literature searches were carried out for identifying randomized controlled trials and observational studies (OSs) published before January 2015. The meta-analysis (MA) was performed by Review Manager 5 software if data could be merged routinely, if not descriptions would be given. A total of 18 studies were eligible ultimately. With respect to HFs frequency, the MA during treatment showed a significant difference (MD = -1.78, 95% confidence intervals [95% CIs]: -3.42--0.14), but no statistical differences were observed when posttreatment or follow-up period. While electroacupuncture versus applied relaxation, they both helped to promote HFs markedly but did not reveal statistically significance between them. Referring to Kupperman's index, all the treatment brought out great assistance when compared with baseline conditions, and there was significant difference between real acupuncture sham acupuncture (posttreatment: MD = -4.40, 95% CI: -6.77--2.03; follow-up: MD = -4.30, 95% CI: -6.52--2.08). In terms of OS, 7 prospective single arm studies focused on exploring the efficacy of traditional acupuncture, and all revealed moderate or great benefit for BC patients suffering from HFs. Acupuncture still appeared to be an efficacious therapeutic strategy, especially for the less/no side effects. Because of its widespread acceptance and encouraging effectiveness for improving HFs, much more high-quality studies are in need urgently.

Three paths to more encompassing supplementary pensions

AbstractIn pension systems characterized by low or moderate state benefits, reliance on voluntary private pensions creates a dualism of access to adequate retirement income. This dualism is expected to persist over time. Yet while some private-heavy pension systems continue to rely on dualising voluntarism, since the 1980s most have introduced regulatory reforms to make private pensions more encompassing. This paper uses fuzzy-set Qualitative Comparative Analysis to identify three paths to the regulatory extension of private pension coverage – collective self-regulation, top-down regulation in Continental Europe, and top-down regulation in Anglophone countries. A case study of the UK then shows how it is that unions have been able to bring about more encompassing private pensions in Anglophone countries, despite strong employer opposition, weak formal influence in policymaking, and a weak institutional capacity for collective self-regulation.

Effects of telephone call intervention on cardiovascular risk factors in T2DM: A meta-analysis

Background Mobile health interventions utilising telephone calls are promising tools for diabetes management. However, there is still a lack of convincing evidence demonstrating their beneficial effects on cardiovascular risk factors. The aim of this meta-analysis of randomised controlled trials was to assess the effect of telephone calls on glycaemic control and other cardiovascular risk factors in type 2 diabetes mellitus patients. Methods Two independent reviewers searched three online databases (PubMed, the Cochrane Library and EMBASE) to identify relevant English-language randomised controlled trials up to September 2017. Randomised controlled trials that assessed the effects of telephone calls on glycaemic control and other cardiovascular risk factors in type 2 diabetes mellitus patients were included. Effect size was calculated for changes in glycosylated haemoglobin A1c, weight, blood pressure and lipid levels using fixed- or random-effects models. Results Eighteen studies involving 3954 patients were included in the meta-analysis. Compared with usual care, telephone calls significantly decreased glycosylated haemoglobin A1c, by 0.12% (95% confidence interval: −0.22% to −0.02%). Univariate regression analysis showed that none of the covariates (number of participants, baseline age, baseline glycosylated haemoglobin A1c, duration of diabetes, call maker, number of calls and duration of study) had an impact on glycosylated haemoglobin A1c. For other cardiovascular risk factors, telephone calls significantly reduced systolic blood pressure by 0.19 mm Hg (95% confidence interval: −0.34% to −0.03%) but non-significantly changed diastolic blood pressure, body mass index, low-density lipoprotein cholesterol, total cholesterol, triglyceride or high-density cholesterol levels. Conclusions This meta-analysis supports the hypothesis that telephone calls offer moderate benefits for glycosylated haemoglobin A1c and systolic blood pressure reduction among type 2 diabetes mellitus patients. However, the data remain insufficient regarding the association of telephone calls with lowered diastolic blood pressure, body mass index or improved lipoprotein profiles.

An economic evaluation of Alexander Technique lessons or acupuncture sessions for patients with chronic neck pain: A randomized trial (ATLAS).

ObjectivesTo assess the cost-effectiveness of acupuncture and usual care, and Alexander Technique lessons and usual care, compared with usual GP care alone for chronic neck pain patients.MethodsAn economic evaluation was undertaken alongside the ATLAS trial, taking both NHS and wider societal viewpoints. Participants were offered up to twelve acupuncture sessions or twenty Alexander lessons (equivalent overall contact time). Costs were in pounds sterling. Effectiveness was measured using the generic EQ-5D to calculate quality adjusted life years (QALYs), as well as using a specific neck pain measure–the Northwick Park Neck Pain Questionnaire (NPQ).ResultsIn the base case analysis, incremental QALY gains were 0.032 and 0.025 in the acupuncture and Alexander groups, respectively, in comparison to usual GP care, indicating moderate health benefits for both interventions. Incremental costs were £451 for acupuncture and £667 for Alexander, mainly driven by intervention costs. Acupuncture was likely to be cost-effective (ICER = £18,767/QALY bootstrapped 95% CI £4,426 to £74,562) and was robust to most sensitivity analyses. Alexander lessons were not cost-effective at the lower NICE threshold of £20,000/QALY (£25,101/QALY bootstrapped 95% CI -£150,208 to £248,697) but may be at £30,000/QALY, however, there was considerable statistical uncertainty in all tested scenarios.ConclusionsIn comparison with usual care, acupuncture is likely to be cost-effective for chronic neck pain, whereas, largely due to higher intervention costs, Alexander lessons are unlikely to be cost-effective. However, there were high levels of missing data and further research is needed to assess the long-term cost-effectiveness of these interventions.

The use of methylphenidate to relieve fatigue.

To review recent evidence on the efficacy and safety of methylphenidate as a symptomatic treatment of patients with cancer-related fatigue (CRF). Five clinical trials published since 2011 were identified. Two of these concluded that methylphenidate is more efficacious than placebo in providing relief from CRF, but the remaining three showed no difference in favour of methylphenidate. The studies were heterogeneous as per the dosage, scales used for evaluating fatigue and the target group studied. None of the studies detected serious reactions, and only mild and infrequent side-effects of methylphenidate were reported. Three new metanalyses show the slightly superior effect of methylphenidate compared to placebo in CRF. Overall, literature supports the existence of moderate benefit of methylphenidate in CRF, backed up by weak evidence. Future studies should aim at better identifying the profile of patients who would benefit most from this pharmacological intervention.

Therapeutic Benefit and Gene Network Regulation by Combined Gene Transfer of Apelin, FGF2, and SERCA2a into Ischemic Heart.

Despite considerable advances in cardiovascular disease treatment, heart failure remains a public health challenge. In this context, gene therapy appears as an attractive approach, but clinical trials using single therapeutic molecules result in moderate benefit. With the objective of improving ischemic heart failure therapy, we designed a combined treatment, aimed to simultaneously stimulate angiogenesis, prevent cardiac remodeling, and restore contractile function. We have previously validated IRES-based vectors as powerful tools to co-express genes of interest. Mono- and multicistronic lentivectors expressing fibroblast growth factor 2 (angiogenesis), apelin (cardioprotection), and/or SERCA2a (contractile function) were produced and administrated by intramyocardial injection into a mouse model of myocardial infarction. Data reveal that combined treatment simultaneously improves vessel number, heart function parameters, and fibrosis prevention, due to FGF2, SERCA2a, and apelin, respectively. Furthermore, addition of SERCA2a in the combination decreases cardiomyocyte hypertrophy. Large-scale transcriptome analysis reveals that the triple treatment is the most efficient in restoring angiogenic balance as well as expression of genes involved in cardiac function and remodeling. Our study validates the concept of combined treatment of ischemic heart disease with apelin, FGF2, and SERCA2a and shows that such therapeutic benefit is mediated by a more effective recovery of gene network regulation.