Literature provides a moderate level of evidence for the beneficial effects of incisional negative pressure wound therapy (iNPWT) on scar quality. The purpose of this study was to establish if iNPWT ...results in improved scar outcomes in comparison to the standard of care. Therefore, a within‐patient randomised controlled, open‐label trial was conducted in transgender men undergoing gender‐affirming mastectomies. A unilateral side was randomised to receive iNPWT (PICO™, Smith&Nephew) without suction drains and contrastingly the standard dressing (Steri‐Strips™) with suction drain. Scar quality and questionnaires were bilaterally measured by means of objective assessments and patient‐reported outcome measures (PROM) at 1, 3 and 12 months. Objective scar outcomes were scar pliability (Cutometer®), colouration (DSM‐II) and scar width (3‐D imaging). PROM outcomes were related to scars (POSAS and SCAR‐Q) and body satisfaction (BODY‐Q). From 85 included patients, 80 were included for analyses. No significant difference between treatments was seen in the quantitative outcomes of scar pliability, colour, and width. For qualitative scar outcomes, several significant findings for iNPWT were found for several subscales of the POSAS, SCAR‐Q, and BODY‐Q. These effects could not be substantiated with linear mixed‐model regression, signifying no statically more favourable outcome for either treatment option. In conclusion, this study demonstrated that some PROM outcomes were more favourable for the iNPWT compared to standard treatment. In contrast, the quantitative outcomes showed no beneficial effects of iNPWT on scar outcomes. This suggests that iNPWT is of little benefit as a scar‐improving therapy.
Blood pressure (BP) response to renal denervation (RDN) is highly variable and its effectiveness debated. A procedural end point for RDN may improve consistency of response. The objective of the ...current analysis was to look for the association between renal nerve stimulation (RNS)-induced BP increase before and after RDN and changes in ambulatory BP monitoring (ABPM) after RDN. Fourteen patients with drug-resistant hypertension referred for RDN were included. RNS was performed under general anesthesia at 4 sites in the right and left renal arteries, both before and immediately after RDN. RNS-induced BP changes were monitored and correlated to changes in ambulatory BP at a follow-up of 3 to 6 months after RDN. RNS resulted in a systolic BP increase of 50±27 mm Hg before RDN and systolic BP increase of 13±16 mm Hg after RDN (P<0.001). Average systolic ABPM was 153±11 mm Hg before RDN and decreased to 137±10 mm Hg at 3- to 6-month follow-up (P=0.003). Changes in RNS-induced BP increase before versus immediately after RDN and changes in ABPM before versus 3 to 6 months after RDN were correlated, both for systolic BP (R=0.77, P=0.001) and diastolic BP (R=0.79, P=0.001). RNS-induced maximum BP increase before RDN had a correlation of R=0.61 (P=0.020) for systolic and R=0.71 (P=0.004) for diastolic ABPM changes. RNS-induced BP changes before versus after RDN were correlated with changes in 24-hour ABPM 3 to 6 months after RDN. RNS should be tested as an acute end point to assess the efficacy of RDN and predict BP response to RDN.
Tourette syndrome (TS) is a model neuropsychiatric disorder thought to arise from abnormal development and/or maintenance of cortico-striato-thalamo-cortical circuits. TS is highly heritable, but its ...underlying genetic causes are still elusive, and no genome-wide significant loci have been discovered to date. We analyzed a European ancestry sample of 2,434 TS cases and 4,093 ancestry-matched controls for rare (< 1% frequency) copy-number variants (CNVs) using SNP microarray data. We observed an enrichment of global CNV burden that was prominent for large (> 1 Mb), singleton events (OR = 2.28, 95% CI 1.39–3.79, p = 1.2 × 10−3) and known, pathogenic CNVs (OR = 3.03 1.85–5.07, p = 1.5 × 10−5). We also identified two individual, genome-wide significant loci, each conferring a substantial increase in TS risk (NRXN1 deletions, OR = 20.3, 95% CI 2.6–156.2; CNTN6 duplications, OR = 10.1, 95% CI 2.3–45.4). Approximately 1% of TS cases carry one of these CNVs, indicating that rare structural variation contributes significantly to the genetic architecture of TS.
•Rare structural variants contribute significantly to the genetic architecture of TS.•Increased global CNV burden is driven by large, rare, clinically relevant events.•NRXN1 deletions and CNTN6 duplications confer a substantial increase in TS risk.
Tourette syndrome is highly genetic, but identifying definitive disease susceptibility genes has been challenging. Huang et al. report two genome-wide, significant, recurrent, rare copy-number variants (NRXN1 deletions and CNTN6 duplications), each conferring a substantial increase in TS risk.
Context: In animal experiments, high plasma concentrations of free fatty acids (FFAs) are associated with increased triglyceride (TG) stores in liver and heart, and impaired cardiac function. In ...humans caloric restriction increases plasma FFA levels.
Objective: Our objective was to assess the effects of progressive caloric restriction on myocardial and hepatic TG content and myocardial function.
Design: This was a prospective intervention study.
Participants: This study included 10 lean healthy men.
Interventions: Three-day partial (471 kcal/d) and complete starvation was performed.
Outcome Measures: Plasma levels of FFA, myocardial and hepatic TG content, and myocardial function were calculated.
Results: Plasma FFA increased from 0.6 ± 0.4 mmol/liter to 1.2 ± 0.4 and to 1.9 ± 0.7 mmol/liter, after partial and complete starvation, respectively (P < 0.001). Myocardial TG content increased from 0.35 ± 0.14% to 0.59 ± 0.27%, and 1.26 ± 0.49%, respectively (P < 0.01). The ratio between the early diastole and atrial contraction decreased from 2.2 ± 0.4 to 2.1 ± 0.4 (P = 0.7) and 1.8 ± 0.4, respectively (P < 0.01), and diastolic early deceleration from 3.4 ± 0.7 ml/sec2 × 10−3 to 2.9 ± 0.5 and 2.8 ± 0.9 ml/sec2 × 10−3, respectively (P < 0.05). Hepatic TG content decreased after partial starvation (from 2.23 ± 2.24% to 1.43 ± 1.33%; P < 0.05) but did not change upon complete starvation.
Conclusions: Progressive caloric restriction induces a dose-dependent increase in myocardial TG content and a dose-dependent decrease in diastolic function in lean healthy men. Hepatic TG content showed a differential response to progressive caloric restriction, indicating that redistribution of endogenous TG stores is tissue specific.
The molecular mechanisms causing smoking‐induced health decline are largely unknown. To elucidate the molecular pathways involved in cause and consequences of smoking behavior, we conducted a ...genome‐wide gene expression study in peripheral blood samples targeting 18 238 genes. Data of 743 smokers, 1686 never smokers and 890 ex‐smokers were available from two population‐based cohorts from the Netherlands. In addition, data of 56 monozygotic twin pairs discordant for ever smoking were used. One hundred thirty‐two genes were differentially expressed between current smokers and never smokers (P < 1.2 × 10−6, Bonferroni correction). The most significant genes were G protein‐coupled receptor 15 (P < 1 × 10−150) and leucine‐rich repeat neuronal 3 (P < 1 × 10−44). The smoking‐related genes were enriched for immune system, blood coagulation, natural killer cell and cancer pathways. By taking the data of ex‐smokers into account, expression of these 132 genes was classified into reversible (94 genes), slowly reversible (31 genes), irreversible (6 genes) or inconclusive (1 gene). Expression of 6 of the 132 genes (three reversible and three slowly reversible) was confirmed to be reactive to smoking as they were differentially expressed in monozygotic pairs discordant for smoking. Cis‐expression quantitative trait loci for GPR56 and RARRES3 (downregulated in smokers) were associated with increased number of cigarettes smoked per day in a large genome‐wide association meta‐analysis, suggesting a causative effect of GPR56 and RARRES3 expression on smoking behavior. In conclusion, differential gene expression patterns in smokers are extensive and cluster in several underlying disease pathways. Gene expression differences seem mainly direct consequences of smoking, and largely reversible after smoking cessation. However, we also identified DNA variants that may influence smoking behavior via the mediating gene expression.
A genome‐wide gene expression study for smoking was conducted. To explore the causes or consequences of smoking behavior, data of 743 smokers, 1686 never‐smokers and 890 ex‐smokers were used, as well as a sample of monozygotic twins discordant for smoking. Gene expression patterns of smokers significantly differed from non‐smokers. Differences were mainly direct consequences of smoking, and largely reversible after smoking cessation. In addition, some DNA variants were identified that may influence smoking behavior via the mediating gene expression.
The components of thyrotropic feedback control are well established in mainstream physiology and endocrinology, but their relation to the whole system’s integrated behavior remains only partly ...understood. Most modeling research seeks to derive a generalized model for universal application across all individuals. We show how parameterizable models, based on the principles of control theory, tailored to the individual, can fill these gaps. We develop a system network describing the closed-loop behavior of the hypothalamus–pituitary (HP)–thyroid interaction and the set point targeted by the control system at equilibrium. The stability of this system is defined by using loop gain conditions. Defined points of homeostasis of the hypothalamus–pituitary–thyroid (HPT) feedback loop found at the intersections of the HP and thyroid transfer functions at the boundaries of normal reference ranges were evaluated by loop gain calculations. At equilibrium, the feedback control approaches a point defined in both dimensions by a TSH–FT4 coordinate for which the loop gain is greater than unity. This model describes the emergence of homeostasis of the HPT axis from characteristic curves of HP and thyroid, thus supporting the validity of the translation between physiological knowledge and clinical reference ranges.
To assess the efficacy of bright light therapy (BLT) in reducing depressive symptoms in patients with Parkinson disease (PD) and major depressive disorder (MDD) compared to a control light.
In this ...double-blind controlled trial, we randomized patients with PD and MDD to treatment with BLT (±10,000 lux) or a control light (±200 lux). Participants were treated for 3 months, followed by a 6-month naturalistic follow-up. The primary outcome of the study was the Hamilton Depression Rating Scale (HDRS) score. Secondary outcomes were objective and subjective sleep measures and salivary melatonin and cortisol concentrations. Assessments were repeated halfway, at the end of treatment, and 1, 3, and 6 months after treatment. Data were analyzed with a linear mixed-model analysis.
We enrolled 83 participants. HDRS scores decreased in both groups without a significant between-group difference at the end of treatment. Subjective sleep quality improved in both groups, with a larger improvement in the BLT group (B SE = 0.32 0.16,
= 0.04). Total salivary cortisol secretion decreased in the BLT group, while it increased in the control group (B SE = -8.11 3.93,
= 0.04).
BLT was not more effective in reducing depressive symptoms than a control light. Mood and subjective sleep improved in both groups. BLT was more effective in improving subjective sleep quality than control light, possibly through a BLT-induced decrease in cortisol levels.
NCT01604876.
This study provides Class I evidence that BLT is not superior to a control light device in reducing depressive symptoms in patients with PD with MDD.
Internet-based cognitive behavioral therapy (iCBT) services for common mental health disorders have been found to be effective. There is a need for strategies that improve implementation in routine ...practice. One-size-fits-all strategies are likely to be ineffective. Tailored implementation is considered as a promising approach. The self-guided integrated theory-based Framework for intervention tailoring strategies toolkit (ItFits-toolkit) supports local implementers in developing tailored implementation strategies. Tailoring involves identifying local barriers; matching selected barriers to implementation strategies; developing an actionable work plan; and applying, monitoring, and adapting where necessary.
This study aimed to compare the effectiveness of the ItFits-toolkit with implementation-as-usual (IAU) in implementing iCBT services in 12 routine mental health care organizations in 9 countries in Europe and Australia.
A stepped-wedge cluster randomized trial design with repeated measures was applied. The trial period lasted 30 months. The primary outcome was the normalization of iCBT delivery by service providers (therapists, referrers, IT developers, and administrators), which was measured with the Normalization Measure Development as a proxy for implementation success. A 3-level linear mixed-effects modeling was applied to estimate the effects. iCBT service uptake (referral and treatment completion rates) and implementation effort (hours) were used as secondary outcomes. The perceived satisfaction (Client Satisfaction Questionnaire), usability (System Usability Scale), and impact of the ItFits-toolkit by implementers were used to assess the acceptability of the ItFits-toolkit.
In total, 456 mental health service providers were included in this study. Compared with IAU, the ItFits-toolkit had a small positive statistically significant effect on normalization levels in service providers (mean 0.09, SD 0.04; P=.02; Cohen d=0.12). The uptake of iCBT by patients was similar to that of IAU. Implementers did not spend more time on implementation work when using the ItFits-toolkit and generally regarded the ItFits-toolkit as usable and were satisfied with it.
The ItFits-toolkit performed better than the usual implementation activities in implementing iCBT services in routine practice. There is practical utility in the ItFits-toolkit for supporting implementers in developing and applying effective tailored implementation strategies. However, the effect on normalization levels among mental health service providers was small. These findings warrant modesty regarding the effectiveness of self-guided tailored implementation of iCBT services in routine practice.
ClinicalTrials.gov NCT03652883; https://clinicaltrials.gov/ct2/show/NCT03652883.
RR2-10.1186/s13063-020-04686-4.
Longitudinal observational cohort studies in cancer patients are important to move research and clinical practice forward. Continued study participation (study retention) is of importance to maintain ...the statistical power of research and facilitate representativeness of study findings. This study aimed to investigate study retention and attrition (drop-out) and its associated sociodemographic and clinical factors among head and neck cancer (HNC) patients and informal caregivers included in the Netherlands Quality of Life and Biomedical Cohort Study (NET-QUBIC).
NET-QUBIC is a longitudinal cohort study among 739 HNC patients and 262 informal caregivers with collection of patient-reported outcome measures (PROMs), fieldwork data (interview, objective tests and medical examination) and biobank materials. Study retention and attrition was described from baseline (before treatment) up to 2-years follow-up (after treatment). Sociodemographic and clinical characteristics associated with retention in NET-QUBIC components at baseline (PROMs, fieldwork and biobank samples) and retention in general (participation in at least one component) were investigated using Chi-square, Fisher exact or independent t-tests (p< 0.05).
Study retention at 2-years follow-up was 80% among patients alive (66% among all patients) and 70% among caregivers of patients who were alive and participating (52% among all caregivers). Attrition was most often caused by mortality, and logistic, physical, or psychological-related reasons. Tumor stage I/II, better physical performance and better (lower) comorbidity score were associated with participation in the PROMs component among patients. No factors associated with participation in the fieldwork component (patients), overall sample collection (patients and caregivers) or PROMs component (caregivers) were identified. A better performance and comorbidity score (among patients) and higher age (among caregivers) were associated with study retention at 2-years follow-up.
Retention rates were high at two years follow-up (i.e. 80% among HNC patients alive and 70% among informal caregivers with an active patient). Nevertheless, some selection was shown in terms of tumor stage, physical performance, comorbidity and age, which might limit representativeness of NET-QUBIC data and samples. To facilitate representativeness of study findings future cohort studies might benefit from oversampling specific subgroups, such as patients with poor clinical outcomes or higher comorbidity and younger caregivers.
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