Aims
To estimate the relative treatment effect between the fixed‐ratio combinations iGlarLixi and IDegLira (glucagon‐like peptide 1 receptor agonist with basal insulin) in people with type 2 diabetes ...inadequately controlled on a glucagon‐like peptide 1 receptor agonist.
Materials and Methods
A systematic literature review of randomized controlled trials followed by an indirect treatment comparison was performed to compare the efficacy and safety of the available fixed‐ratio combinations. Main outcomes were glycated haemoglobin (HbA1c) change and target achievement <6.5% and <7.0% (<48 and <53 mmol/mol), fasting plasma glucose, self‐monitored plasma glucose, body weight, and incidence and rate of hypoglycaemia.
Results
From 4850 s screened, 78 qualified for full‐text article review and two randomized controlled trials were included. Baseline characteristics were similar in the two studies. The mean difference at 26 weeks between IDegLira and iGlarLixi was −0.36 (95% credible intervals −0.58, −0.14) % −3.9 (−6.3, −1.5) mmol/mol for HbA1c and −1.0 (−1.6, −0.4) mmol/L for fasting plasma glucose. No significant differences were found in HbA1c target attainment, preprandial or postprandial self‐monitored plasma glucose, or body weight change. Formal comparisons of hypoglycaemia were limited by differences in definitions between the studies: in non‐sulphonylurea users, incidence was 28% for IDegLira (‘confirmed’ at ≤3.1 mmol/L); for iGlarLixi, incidence was 9% (‘documented symptomatic’ at <3.0 mmol/L).
Conclusions
Results of this indirect treatment comparison using two studies suggest iGlarLixi and IDegLira appear to offer similar benefits for HbA1c target achievement. However, the findings suggest differences in other glycaemia results and hypoglycaemia, which may reflect differences in study design and titration approaches.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
•This is the first meta-analysis of risk factors for IMD across all age groups.•HIV+ status, passive smoke exposure, and crowded living spaces increase risk of IMD.•Increased risk for IMD-related ...mortality was related to age and serogroup.•There is a lack of research reporting on interactions between risk factors.
To describe risk factors (RFs) and quantify their effects in invasive meningococcal disease (IMD) and associated mortality across all age groups based on the available published literature.
A systematic literature review (SLR) was conducted via MEDLINE® and Embase. Study selection, data extraction, and quality assessment were performed by two independent reviewers. Associations between RFs and outcomes were quantified via a meta-analysis (MA).
Seventy-four studies (date range 1950 – 2018) were included in the SLR. Statistically significant RFs for contracting IMD identified from the SLR (within-study) included previous IMD infection and young age (0 – 4 years). MA indicated that significant RFs for contracting IMD (11 studies) were: HIV-positive status, passive smoke exposure, and crowded living space. In the MA for IMD-related mortality risk (11 studies), age 25 – 45 years (vs. 0 – 5 years) and serogroup C (vs. serogroup B) were significantly associated with increased risk.
Previous findings of higher risk for IMD contraction with smoke exposure and crowded living conditions in children/adolescents have been extended by this SLR/MA to all age groups. We provide strong evidence for higher risk of IMD in HIV-positive individuals, and confirm previous findings of higher IMD-related mortality risk in adults aged 25 – 45.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Knee osteoarthritis (KOA) is a debilitating disease characterized by chronic pain, stiffness, and decreased mobility. Intra-articular injectable therapies show good clinical efficacy in improving ...symptoms; however, these therapies and their comparators (intra-articular saline) have been associated with a large underlying placebo effect. We aimed to describe the existing evidence on the challenges, hypotheses, and potential solutions to mitigate the intra-articular placebo effect in clinical trials in KOA. A targeted literature review was conducted by searching Embase, MEDLINE®, and CENTRAL using predefined study selection criteria. All eligible studies identified were extracted for relevant data, and results were narratively summarized. Forty-three studies were included following screening. Challenges associated with the intra-articular placebo effect included its ability to mask the comparative efficacy of active treatments in trials (n = 7 studies), long-lasting effects (up to 6 months; n = 3), and substantial variation of placebo effect sizes across populations (n = 3). Hypotheses for the mechanism of the placebo effect included aspiration of synovial fluid during administration (n = 6) and dilution of inflammatory mediators (n = 2). Factors affecting the placebo effect size were more invasive routes of administration (e.g., injection versus oral; n = 4) and patient expectations (n = 2). Proposed solutions included the suggestion for readers to weigh the relevance of clinical trial evidence against the presence of large underlying placebo effects (n = 9), discontinuation of intra-articular saline as an appropriate placebo (n = 5), and inclusion of ‘no treatment’ or sham injection as a control (n = 4). The intra-articular placebo effect is a well-documented occurrence in KOA clinical trials, and it is suggested that it be accounted for when designing randomized controlled trials. Awareness and understanding of the intra-articular placebo effect in KOA are required for fair interpretation of clinical trial evidence.
Objectives
Cancer diagnoses at later stages are associated with a decrease in health-related quality of life (HRQOL). Health state utility values (HSUVs) reflect preference-based HRQOL and can vary ...based on cancer type, stage, treatment, and disease progression. Detecting and treating cancer at earlier stages may lead to improved HRQOL, which is important for value assessments. We describe published HSUVs by cancer type and stage.
Methods
A systematic review was conducted using Embase, MEDLINE
®
, EconLit, and gray literature to identify studies published from January 1999 to September 2019 that reported HSUVs by cancer type and stage. Disutility values were calculated from differences in reported HSUVs across cancer stages.
Results
From 13,872 publications, 27 were eligible for evidence synthesis. The most frequent cancer types were breast (
n
= 9), lung (
n
= 5), colorectal (
n
= 4), and cervical cancer (
n
= 3). Mean HSUVs decreased with increased cancer stage, with consistently lower values seen in stage IV or later-stage cancer across studies (e.g., − 0.74, − 0.44, and − 0.51 for breast, colorectal, and cervical cancer, respectively). Disutility values were highest between later-stage (metastatic or stage IV) cancers compared to earlier-stage (localized or stage I–III) cancers.
Conclusions
This study provides a summary of HSUVs across different cancer types and stages that can inform economic evaluations. Despite the large variation in HSUVs overall, a consistent decline in HSUVs can be seen in the later stages, including stage IV. These findings indicate substantial impairment on individuals’ quality of life and suggest value in early detection and intervention.
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CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Clopidogrel monotherapy is guideline-recommended in symptomatic peripheral artery disease (PAD). The advent of new antithrombotic strategies prompts an updated analysis of available evidence on ...antiplatelet therapy for PAD.
We searched MEDLINE, Embase and CENTRAL through January 2019 for randomised controlled trials and observational studies comparing antiplatelet therapies as monotherapy, dual therapy, or combination with anticoagulants. Efficacy (major adverse cardiovascular events, acute or chronic limb ischaemia, vascular amputation, peripheral revascularisation) and safety (all-cause mortality and overall bleeding) outcomes were evaluated via Bayesian network meta-analyses.
We analysed 26 randomised controlled trials. Clopidogrel (hazard ratio, HR, 0.78; 95% credible interval CrI 0.65-0.93) and ticagrelor (HR 0.80; 95% CrI 0.65-0.98) significantly reduced major adverse cardiovascular events risk compared with aspirin. No significant difference was observed for dual antiplatelet therapy with clopidogrel and aspirin. Vorapaxar significantly reduced limb ischaemia and revascularisation compared with placebo, while dual antiplatelet therapy with clopidogrel and aspirin showed a trend for reduced risk of amputation compared with aspirin (risk ratio 0.68; 95% CrI 0.43-1.04). For all-cause mortality, picotamide, vorapaxar, dipyridamole with aspirin, and ticlopidine showed a significantly lower risk of all-cause mortality vs aspirin. Clopidogrel and ticagrelor showed similar overall bleeding risk vs aspirin, while dual antiplatelet therapy with clopidogrel and aspirin significantly increased bleeding risk.
This updated network meta-analysis confirms that clopidogrel significantly decreases the risk of major adverse cardiovascular events compared with aspirin, without increasing bleeding risk. Clopidogrel should remain a mainstay of PAD treatment, at least in patients at higher bleeding risk.
With the advent of smart sensing technology, mobile and wearable devices can provide continuous and objective monitoring and assessment of motor function outcomes. We aimed to describe the existing ...scientific literature on wearable and mobile technologies that are being used or tested for assessing motor functions in mobility-impaired and healthy adults and to evaluate the degree to which these devices provide clinically valid measures of motor function in these populations. A systematic literature review was conducted by searching Embase, MEDLINE, CENTRAL (January 1, 2015, to June 24, 2020), the United States and European Union clinical trial registries, and the United States Food and Drug Administration website using predefined study selection criteria. Study selection, data extraction, and quality assessment were performed by 2 independent reviewers. A total of 91 publications representing 87 unique studies were included. The most represented clinical conditions were Parkinson disease (n=51 studies), followed by stroke (n=5), Huntington disease (n=5), and multiple sclerosis (n=2). A total of 42 motion-detecting devices were identified, and the majority (n=27, 64%) were created for the purpose of health care–related data collection, although approximately 25% were personal electronic devices (eg, smartphones and watches) and 11% were entertainment consoles (eg, Microsoft Kinect or Xbox and Nintendo Wii). The primary motion outcomes were related to gait (n=30), gross motor movements (n=25), and fine motor movements (n=23). As a group, sensor-derived motion data showed a mean sensitivity of 0.83 (SD 7.27), a mean specificity of 0.84 (SD 15.40), a mean accuracy of 0.90 (SD 5.87) in discriminating between diseased individuals and healthy controls, and a mean Pearson r validity coefficient of 0.52 (SD 0.22) relative to clinical measures. We did not find significant differences in the degree of validity between in-laboratory and at-home sensor-based assessments nor between device class (ie, health care–related device, personal electronic devices, and entertainment consoles). Sensor-derived motion data can be leveraged to classify and quantify disease status for a variety of neurological conditions. However, most of the recent research on digital clinical measures is derived from proof-of-concept studies with considerable variation in methodological approaches, and much of the reviewed literature has focused on clinical validation, with less than one-quarter of the studies performing analytical validation. Overall, future research is crucially needed to further consolidate that sensor-derived motion data may lead to the development of robust and transformative digital measurements intended to predict, diagnose, and quantify neurological disease state and its longitudinal change.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Up to half of the population have introverted personalities. Workplace diversity can lead to increased productivity, creativity and problem-solving. Understanding introversion in relation to ...workplace performance and creativity and how to encourage inclusion of introverts would benefit employers and employees. We describe the evidence defining and evaluating introversion, prevalence of introversion across groups, and strategies for promoting workplace inclusion of introverts. We searched MEDLINE
®
, Embase, and PsycINFO up to February 11, 2021. Of 2,724 records, 21 studies were included. Introversion definitions were generally negative and dated. Robust prevalence data were unavailable, and no studies aimed to test strategies for promoting workplace inclusion of introversion. Nevertheless, literature suggests that employees who identify with modern definitions of introversion may benefit from individualized workplace strategies such as flexible working environments, work/home-life boundaries, varied team composition, provision of social support, and relaxation training. Further empirical studies in the industrial setting with robust designs using modernized personality definitions are warranted to support the development of effective strategies to increase inclusion of different personalities in the workplace.
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BFBNIB, NUK, PILJ, SAZU, UL, UM, UPUK
Background
There are limited comparative data on safety and efficacy within commonly used Vaughan‐Williams (VW) class III antiarrhythmic drugs (AADs) for maintenance of sinus rhythm in adults with ...atrial fibrillation (AF).
Hypothesis
We hypothesized that dronedarone and sotalol, two commonly prescribed VW class III AADs with class II properties, have different safety and efficacy effects in patients with nonpermanent AF.
Methods
A systematic literature review was conducted searching MEDLINE®, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) up to June 15, 2021 (NCT05279833). Clinical trials and observational studies that evaluated safety and efficacy of dronedarone or sotalol in adults with AF were included. Bayesian random‐effects network meta‐analysis (NMA) was used to quantify comparative safety and efficacy. Where feasible, we performed sensitivity analyses by including only randomized controlled trials (RCTs).
Results
Of 3581 records identified through database searches, 37 unique studies (23 RCTs, 13 observational studies, and 1 nonrandomized trial) were included in the NMA. Dronedarone was associated with a statistically significantly lower risk of all‐cause death versus sotalol (hazard ratio HR = 0.38 95% credible interval, CrI: 0.19, 0.74). The association was numerically similar in the sensitivity analysis (HR = 0.46 95% CrI: 0.21, 1.02). AF recurrence and cardiovascular death results were not significantly different between dronedarone and sotalol in all‐studies and sensitivity analyses.
Conclusion
The NMA findings indicate that, across all clinical trials and observational studies included, dronedarone compared with sotalol was associated with a lower risk of all‐cause death, but with no difference in AF recurrence.
A systematic literature review and network meta‐analysis was conducted to assess the comparative safety and efficacy of dronedarone versus sotalol, two commonly used Vaughan‐Williams class III antiarrhythmic drugs, for maintenance of sinus rhythm in adults with atrial fibrillation (AF). Across all clinical trials and observational studies analyzed, dronedarone was associated with a lower risk of all‐cause death versus sotalol. Cardiovascular death and recurrence of AF were not significantly different between dronedarone and sotalol.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Shift work is a necessary part of many industries; however, it can have detrimental effects on health over time.
This study investigated the effect of a massage intervention on the cardiac autonomic ...activity and blood inflammatory markers of healthy medical residents working night shifts.
This trial was conducted at British Columbia Children's and Women's Hospital between February 2014 and June 2016.
Included participants were generally healthy medical residents and were working rotating night shifts on a regular basis.
This was a randomized, controlled, crossover, open-label trial (NCT02247089).
Participants received either a 30-min massage intervention or reading control after consecutive periods of night shift.
The primary outcome was high frequency, a proxy for the cardiac parasympathetic activity, measured via heart rate variability. Secondary outcomes included other heart rate variability measures, blood markers of inflammation, and blood pressure.
Twelve participants were recruited (nine female) with median age of 28 years. There was no significant difference between the massage intervention and the reading control for the primary outcome, (median relative change between pre- and postmassage interquartile range: 62% -1 to 150, pre- and postreading: 14% -10 to 51,
= .16). Similarly, there was no difference with respect to blood inflammatory markers and blood pressure. Median high frequency significantly increased between pre- and postmassage (185 vs. 358 ms
,
= .04).
This pilot study found no statistically significant difference between the massage intervention and the reading control; however, we did observe a significant increase in median high frequency from before massage to after massage, indicative of increased parasympathetic activity. This study may help inform planning of larger trials evaluating massage interventions on the activity of the autonomic nervous system and managing shift work stress.
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