Prevalence of obstructive sleep apnea after treatment for advanced T-stage head and neck cancer.

PURPOSE: Treatment of head and neck cancer (HNC) may lead to obstructive sleep apnea (OSA), but conclusive results on the prevalence of OSA are lacking. The objective of this study is to investigate the prevalence of OSA in a cohort of patients treated for advanced T-stage HNC. METHODS: A cross-sectional study was conducted in two tertiary cancer care centers including patients at least 1 year after treatment with curative intent with surgery and/or (chemo)radiotherapy ((C)RT) for advanced T-staged (T3-4) cancer of the oral cavity, oropharynx, hypopharynx, or larynx. A polysomnography (PSG) was performed in all participants. OSA was defined as an apnea-hypopnea index (AHI) of 15 events/h or higher or an AHI of 5 events/h and higher with OSA related symptoms, such as sleeping problems, daytime dysfunction and/or cardiac/metabolic comorbidities collected through file review and questionnaires. RESULTS: Of the 67 participants, 48 (72%, 95% CI 59-82%) were diagnosed with OSA. Possible risk factors are male gender, higher BMI, greater neck circumference, more nicotine pack years, cardiometabolic comorbidities, use of medication with sleepiness as side effect, present tonsils, lower T-stage (T3 vs. T4 stage), higher AJCC stage and a HPV-negative tumor. CONCLUSION: In this population of advanced T-stage HNC patients, the prevalence of OSA was 72%, which is considerably higher than in the general population (2-50%). Given the high prevalence, screening of this entire subgroup for OSA may be indicated. Future studies to identify high risk factors and develop an OSA screening protocol are needed.

Intention to leave, depersonalisation and job satisfaction in physicians and nurses: a cross-sectional study in Europe.

The European healthcare sector faces a significant shortage of healthcare workers. Assessing the prevalence of this issue and understanding its direct and indirect determinants are essential for formulating effective recruitment programs and enhancing job retention strategies for physicians and nurses. A multicentric cross-sectional study was conducted, involving 381 physicians and 1351 nurses recruited from eight European hospitals in Belgium, the Netherlands, Italy, and Poland. The study focused on assessing turnover intentions among healthcare workers based on the Job Demands-Resources model, using an online questionnaire. Structural equation models were employed to test the data collection questionnaires' construct validity and internal consistency. The turnover intention was assessed by agreement with the intention to leave either the hospital or the profession. Among physicians, 17% expressed an intention to leave the hospital, while 9% intended to leave the profession. For nurses, the figures were 8.9% and 13.6%, respectively. The internal consistency of the questionnaires exceeded 0.90 for both categories of health workers. Depersonalization and job dissatisfaction were identified as direct determinants of turnover intention, with work engagement being particularly relevant for nurses. We found a higher intention to leave the hospital among physicians, while nurses were more prone to leave their profession. To mitigate turnover intentions, it is recommended to focus on improving job satisfaction, work engagement and fostering a positive working climate, thereby addressing depersonalisation and promoting job retention.

Differential expression pattern of Bcl-2 family members in B and T cells in systemic lupus erythematosus and rheumatoid arthritis.

OBJECTIVE: This study aimed to evaluate the expression level of anti-apoptotic Bcl-2 family proteins in B and T cells in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in relation to disease activity and the effect of various Bcl-2 family inhibitors (BH3 mimetics) as potential treatment. METHODS: We included 14 SLE patients, 12 RA patients, and 13 healthy controls to study anti-apoptotic Bcl-2, Bcl-XL, and Mcl-1 expression and cell survival in different B and T cell subsets using stimulation assays and intracellular flow cytometry. Effect of various BH3 mimetics was assessed by cell viability analyses. RESULTS: In SLE, significant differences in Bcl-2 family members were confined to the B cell compartment with decreased induction of Bcl-XL (p ≤ 0.05) and Mcl-1 (p ≤ 0.001) upon CpG stimulation. In RA, we did not observe any differences in expression levels of Bcl-2 family proteins. Expression patterns did not correlate with disease activity apart from decreased induction of Mcl-1 in B cells in active SLE. After in vitro stimulation with CpG, plasmablasts were more viable after treatment with three different BH3 mimetics compared to naïve or memory B cells in control and patient cells. After activation, Mcl-1 inhibition was most effective in reducing plasmablast and T cell viability, however, less in patients than controls. CONCLUSION: Our study provides evidence for the increased differential expression pattern of Bcl-2 family members in B and T cell subsets of patients with SLE compared to controls. Tested BH3 mimetics showed higher efficacy in controls compared to both autoimmune diseases, though nonsignificant due to low patient numbers.

Patterns in bottlenecks for implementation of health promotion interventions: a cross-sectional observational study on intervention-context interactions in the Netherlands.

BACKGROUND: From a complex systems perspective, implementation should be understood as the introduction of an intervention in a context with which it needs to interact in order to achieve its function in terms of improved health. The presence of intervention-context interactions could mean that during implementation particular patterns of crucial interaction points might arise. We examined the presence of - and regularities in - such 'bottlenecks for implementation', as this could create opportunities to predict and intervene in potential implementation problems. METHODS: We conducted a cross-sectional observational study against the background of municipal intersectoral policymaking in the Netherlands. We asked implementers of health promotion interventions to identify bottlenecks by rating the presence and importance of conditions for implementation in a range of intervention systems. We used descriptive statistics to characterize these systems (by their behaviour change method, health theme and implementation setting) and the conditions that acted as bottlenecks. After stratifying bottlenecks by intervention system and the system's characteristics, we tested our hypotheses by comparing the number and nature of the bottlenecks that emerged. RESULTS: More than half of the possible conditions were identified as a bottleneck for implementation. Bottlenecks occurred in all categories of conditions, e.g., relating to the implementer, the intervention, and political and administrative support, and often connected with intersectoral policymaking, e.g., relating to the co-implementer and the co-implementer's organization. Both our hypotheses were supported: (1) Each intervention system came across a unique set of - a limited number of - conditions hampering implementation; (2) Most bottlenecks were associated with the characteristics of the system in which they occurred, but bottlenecks also appeared in the absence of such an association, or remained absent in the presence thereof. CONCLUSIONS: We conclude that intervention-context interactions in integrated health policymaking may lead to both regularities and variations in bottlenecks for implementation. Regularities may partly be predicted by the function of an intervention system, and may serve as the basis for building the capacity needed for the structural changes that can bring about long-lasting health improvements. Variations may point at the need for flexibility in further tailoring the implementation approach to the - mostly unpredictable - problems at individual sites.

Exercise knowledge, barriers and motivators among LRRK2 G2019S mutation carriers.

INTRODUCTION: People with a Gly2019Ser mutation in the leucine-rich repeat kinase 2 (LRRK2 G2019S) are at increased risk of developing Parkinson's disease (PD). Recent evidence suggests that exercise may delay or prevent the development of clinically overt symptoms of PD in people at risk of PD. We determined whether LRRK2 G2019S mutation carriers with and without manifest PD are aware of the relationship between exercise and PD and how they differ in awareness, barriers and motivators to exercise. METHODS: We deployed a survey among 4422 LRRK2 G2019S mutation carriers. In total, 505 (11.4%) of them completed the survey, of whom 105 had self-reported manifest PD. RESULTS: Ninety-two percent of the LRRK2 G2019S mutation carriers with manifest PD and 63% of those with non-manifest PD were aware of the relationship between exercise and PD. Lack of motivation was the top barrier for those without manifest PD, while having an injury/disability was the most common barrier for those with manifest PD. Improvement of body functioning was the top motivator for both. CONCLUSION: The fact that many at-risk individuals are not aware of the importance of exercise and would exercise more with fewer barriers creates opportunities for trials using exercise as a possible prevention strategy for PD.

Effects of major urban redesign on sedentary behavior, physical activity, active transport and health-related quality of life in adults.

BACKGROUND: The built environment is increasingly recognized as a determinant for health and health behaviors. Existing evidence regarding the relationship between environment and health (behaviors) is varying in significance and magnitude, and more high-quality longitudinal studies are needed. The aim of this study was to evaluate the effects of a major urban redesign project on physical activity (PA), sedentary behavior (SB), active transport (AT), health-related quality of life (HRQOL), social activities (SA) and meaningfulness, at 29-39 months after opening of the reconstructed area. METHODS: PA and AT were measured using accelerometers and GPS loggers. HRQOL and sociodemographic characteristics were assessed using questionnaires. In total, 241 participants provided valid data at baseline and follow-up. We distinguished three groups, based on proximity to the intervention area: maximal exposure group, minimal exposure group and no exposure group. RESULTS: Both the maximal and minimal exposure groups showed significantly different trends regarding transport-based PA levels compared to the no exposure group. In the exposure groups SB decreased, while it increased in the no exposure group. Also, transport-based light intensity PA remained stable in the exposure groups, while it significantly decreased in the no exposure group. No intervention effects were found for total daily PA levels. Scores on SA and meaningfulness increased in the maximal exposure group and decreased in the minimal and no exposure group, but changes were not statistically significant. CONCLUSION: The results of this study emphasize the potential of the built environment in changing SB and highlights the relevance of longer-term follow-up measurements to explore the full potential of urban redesign projects. TRIAL REGISTRATION: This research was retrospectively registered at the Netherlands Trial Register (NL8108).

Exposure-response analyses of BRAF- and MEK-inhibitors dabrafenib plus trametinib in melanoma patients.

INTRODUCTION: Dabrafenib and trametinib are currently administered at fixed doses, at which interpatient variability in exposure is high. The aim of this study was to investigate whether drug exposure is related to efficacy and toxicity in a real-life cohort of melanoma patients treated with dabrafenib plus trametinib. PATIENTS AND METHODS: An observational study was performed in which pharmacokinetic samples were collected as routine care. Using estimated dabrafenib Area Under the concentration-time Curve and trametinib trough concentrations (Cmin), univariable and multivariable exposure-response analyses were performed. RESULTS: In total, 140 patients were included. Dabrafenib exposure was not related to either progression-free survival (PFS) or overall survival (OS). Trametinib exposure was related to survival, with Cmin ≥ 15.6 ng/mL being identified as the optimal threshold. Median OS was significantly longer in patients with trametinib Cmin ≥ 15.6 ng/mL (22.8 vs. 12.6 months, P = 0.003), with a multivariable hazard ratio of 0.55 (95% CI 0.36-0.85, P = 0.007). Median PFS in patients with trametinib Cmin levels ≥ 15.6 ng/mL (37%) was 10.9 months, compared with 6.0 months for those with Cmin below this threshold (P = 0.06). Multivariable analysis resulted in a hazard ratio of 0.70 (95% CI 0.47-1.05, P = 0.082). Exposure to dabrafenib and trametinib was not related to clinically relevant toxicities. CONCLUSIONS: Overall survival of metastasized melanoma patients with trametinib Cmin levels ≥ 15.6 ng/mL is ten months longer compared to patients with Cmin below this threshold. This would theoretically provide a rationale for therapeutic drug monitoring of trametinib. Although a high proportion of patients are underexposed, there is very little scope for dose increments due to the risk of serious toxicity.

B-cell and T-cell receptor repertoire in chronic inflammatory demyelinating polyneuropathy, a prospective cohort study.

The immunopathophysiological mechanisms underlying chronic inflammatory demyelinating polyneuropathy (CIDP) in an individual patient are largely unknown. Better understanding of these mechanisms may aid development of biomarkers and targeted therapies. Both B- and T-cell dominant mechanisms have been implicated. We therefore investigated whether B-cell and T-cell receptor (BCR/TCR) repertoires might function as immunological biomarkers in CIDP. In this prospective cohort study, we longitudinally sampled peripheral blood of CIDP patients in three different phases of CIDP: starting induction treatment (IT), starting withdrawal from IVIg maintenance treatment (MT), and patients in remission (R). BCR and TCR repertoires were analyzed using RNA based high throughput sequencing. In baseline samples, the number of total clones, the number of dominant BCR and TCR clones and their impact on the repertoire was similar for patients in the IT, MT, and remission groups compared with healthy controls. Baseline samples in the IT or MT did not predict treatment response or potential relapse at follow-up. Treatment responders in the IT group showed a potential IVIg-induced increase in the number of dominant BCR clones and their impact at follow-up (baseline1.0 [IQR 1.0-2.8] vs. 6 m 3.5 [0.3-6.8]; P < .05, Wilcoxon test). Although the BCR repertoire changed over time, the TCR repertoire remained robustly stable. We conclude that TCR and BCR repertoire distributions do not predict disease activity, treatment response or response to treatment withdrawal.

Optimizing Moxifloxacin Dose in MDR-TB Participants with or without Efavirenz Coadministration Using Population Pharmacokinetic Modeling.

Moxifloxacin is included in some treatment regimens for drug-sensitive tuberculosis (TB) and multidrug-resistant TB (MDR-TB). Aiming to optimize dosing, we described moxifloxacin pharmacokinetic and MIC distribution in participants with MDR-TB. Participants enrolled at two TB hospitals in South Africa underwent intensive pharmacokinetic sampling approximately 1 to 6 weeks after treatment initiation. Plasma drug concentrations and clinical data were analyzed using nonlinear mixed-effects modeling with simulations to evaluate doses for different scenarios. We enrolled 131 participants (54 females), with median age of 35.7 (interquartile range, 28.5 to 43.5) years, median weight of 47 (42.0 to 54.0) kg, and median fat-free mass of 40.1 (32.3 to 44.7) kg; 79 were HIV positive, 29 of whom were on efavirenz-based antiretroviral therapy. Moxifloxacin pharmacokinetics were described with a 2-compartment model, transit absorption, and elimination via a liver compartment. We included allometry based on fat-free mass to estimate disposition parameters. We estimated an oral clearance for a typical patient to be 17.6 L/h. Participants treated with efavirenz had increased clearance, resulting in a 44% reduction in moxifloxacin exposure. Simulations predicted that, even at a median MIC of 0.25 (0.06 to 16) mg/L, the standard daily dose of 400 mg has a low probability of attaining the ratio of the area under the unbound concentration-time curve from 0 to 24 h to the MIC (fAUC0-24)/MIC target of >53, particularly in heavier participants. The high-dose WHO regimen (600 to 800 mg) yielded higher, more balanced exposures across the weight ranges, with better target attainment. When coadministered with efavirenz, moxifloxacin doses of up to 1,000 mg are needed to match these exposures. The safety of higher moxifloxacin doses in clinical settings should be confirmed.

The association between biomarker angiopoietin-like protein five and obstructive sleep apnea in patients undergoing bariatric surgery.

PURPOSE: Obstructive sleep apnea (OSA) is prevalent in the bariatric population. OSA should be recognized in patients undergoing bariatric surgery preoperatively to prevent peri- and post-operative complications. Lipid metabolism-related biomarkers are associated with OSA. Triglyceride metabolism is, among others, regulated by angiopoietin-like protein five (ANGPTL5). We aimed to evaluate the level of ANGPTL5 in patients with OSA of different severity levels before and after bariatric surgery. METHODS: We performed a single-center prospective cohort study including a consecutive series of patients who underwent bariatric surgery. We collected the clinical data, polysomnography (PSG) or polygraphy (PG) parameters, and plasma derived via venipuncture before and 6 to 12 months after surgery. Lipid profile, glucose levels, and ANGPTL5 levels were assessed. ANGPTL5 levels were measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS: The study included 88 patients for analysis. The patients were divided into two subgroups: no or mild OSA (apnea-hypopnea index (AHI) < 15 events/hour, n = 57) and moderate-to-severe OSA (AHI ≥ 15 events/hour, n = 31). The ANGPTL5 level was higher in the moderate-to-severe OSA group (20.5 [15.6, 26.5] ng/mL) compared to the no or mild OSA group (16.3 [12.5, 19.4] ng/mL) (p = 0.008). A significant positive correlation was observed between ANGPTL5 and AHI (ρ = 0.256, p = 0.017), apnea index (AI) (ρ = 0.318, p = 0.003), and triglyceride levels (ρ = 0.240, p = 0.025). ANGPTL5 levels were reduced significantly after bariatric surgery in both moderate-to-severe OSA (15.6 [10.3, 18.7] ng/mL) and no or mild OSA (13.4 [9.2, 15.8] ng/mL) groups, though to a lower level in the group without or mild OSA. Post-surgery, the significant positive correlation between ANGPTL5 and AHI (ρ = 0.210, p = 0.047), AI (ρ = 0.230, p = 0.034), and triglyceride (ρ = 0.397, p < 0.001) remained. CONCLUSION: The data showed increased levels of ANGPTL5 in patients with moderate-to-severe OSA. Both AHI and ANGPTL5 levels decreased significantly after bariatric surgery. We also report an association between ANGPTL5 levels and OSA severity.

Effects of maxillomandibular advancement on respiratory function and facial aesthetics in obstructive sleep apnoea patients with versus without maxillomandibular deficiency.

The aim of this study was to compare the effects of maxillomandibular advancement (MMA) on respiratory function between obstructive sleep apnoea (OSA) patients with and without maxillomandibular deficiency, and to compare the changes in facial aesthetics after MMA between the two groups. MMA-treated patients who had both baseline and follow-up polysomnography (PSG) data and lateral cephalograms were enrolled in this retrospective study. In addition to PSG and cephalometric data, patient satisfaction with postoperative breathing and facial aesthetics, and overall satisfaction with the treatment were assessed. Twenty-one patients were classified as not having maxillomandibular deficiency (without-deficiency group) and 40 patients as having maxillomandibular deficiency (with-deficiency group). The improvements in respiratory parameters (e.g., apnoea-hypopnoea index) and patient satisfaction with postoperative breathing were comparable in the two groups (P = 0.094-0.713). The changes in facial profile measurements (e.g., nasal prominence, nasolabial angel, and lip positions relative to the true vertical line) and patient satisfaction with postoperative facial aesthetics were also comparable in the two groups (P = 0.148-0.983). In conclusion, no significant difference in the effects of MMA on respiratory function and facial aesthetics between OSA patients with and without maxillomandibular deficiency was observed.

Increased plasma ANGPTL7 levels with increased obstructive sleep apnea severity.

Background: Weight-loss surgery is one of the recommended methods for treating obstructive sleep apnea (OSA) in obese patients. While weight reduction is critical to relieve symptoms of OSA, the biochemical factors involved in post-surgery improvement are still unknown. We aimed to explore the link between ANGPTL7 and OSA in patients with different OSA severity. Furthermore, we examined the effect of treating OSA with bariatric surgery on ANGPTL7 level. Methods: We quantified levels of circulating ANGPTL7 in fasting plasma and adipose tissue samples of 88 participants before and after bariatric surgery. Confocal microscopy analyses were also performed to assess the ANGPTL7 expression in subcutaneous white adipose tissue biopsies obtained from people with moderate-to-severe OSA compared to those with none or mild OSA. The study involved 57 individuals with none or mild OSA and 31 patients with moderate-to-severe OSA. Results: Levels of circulating ANGPTL7 were significantly higher in people with moderate-to-severe OSA (1440 ± 1310 pg/ml) compared to the none or mild OSA group (734 ± 904 pg/ml, p = 0.01). The increase in ANGPTL7 correlated significantly and positively with the apnea-hypopnea index (AHI, r = .226, p = .037), and AHI-supine (r = .266, p = .019) in participants with moderate-to-severe OSA. Multivariate logistic regression analysis demonstrated an association between ANGPTL7 and OSA severity (log2 ANGPTL7; OR =1.24, p = 0.024). ANGPTL7 levels exhibited significant positive correlations with the levels of TG and oxLDL (p-value = 0.002 and 0.01 respectively). Bariatric surgery reduced the levels of both ANGPTL7 and AHI significantly. Conclusion: Here we report significantly increased levels of ANGPTL7 both in the circulation and in adipose tissue of patients with OSA, which concurred with increased inflammation and OSA severity. Levels of ANGPTL7 decreased significantly as OSA showed a significant improvement post-surgery supporting a potential role for ANGPTL7 in either OSA progression or a role in an OSA-related mechanism.

Therapeutic drug monitoring-based precision dosing of oral targeted therapies in oncology: a prospective multicenter study.

BACKGROUND: Oral targeted therapies show a high pharmacokinetic (PK) interpatient variability. Even though exposure has been positively correlated with efficacy for many of these drugs, these are still dosed using a one-size-fits-all approach. Consequently, individuals have a high probability to be either underexposed or overexposed, potentially leading to suboptimal outcomes. Therapeutic drug monitoring, which is personalized dosing based on measured systemic drug concentrations, could address these problems. PATIENTS AND METHODS: Patients were enrolled in this prospective multicenter study (www.trialregister.nl; NL6695) if they started treatment with one of the 24 participating oral targeted therapies. Primary outcome was to halve the proportion of underexposed patients, compared with historical data. PK sampling was carried out after 4, 8 and 12 weeks, and every 12 weeks thereafter. In case of Cmin below the predefined target and manageable toxicity, a pharmacokinetically guided intervention was proposed (i.e. checking compliance and drug-drug interactions, concomitant intake with food, splitting intake moments or dose increments). RESULTS: In total, 600 patients were included of whom 426 patients are assessable for the primary outcome and 552 patients had ≥1 PK sample(s) available and were therefore assessable for the overall analyses. Pharmacokinetically guided dosing reduced the proportion of underexposed patients at the third PK measurement by 39.0% (95% confidence interval 28.0% to 49.0%) compared with historical data. At the third PK measurement, 110 out of 426 patients (25.8%) had a low exposure. In total, 294 patients (53.3%) had ≥1 PK sample(s) below the preset target at a certain time point during treatment. In 166 of these patients (56.5%), pharmacokinetically guided interventions were carried out, which were successful in 113 out of 152 assessable patients (74.3%). CONCLUSIONS: Pharmacokinetically guided dose optimization of oral targeted therapies was feasible in clinical practice and reduced the proportion of underexposed patients considerably.

Visualizing changes in physical activity behavioral patterns after redesigning urban infrastructure.

The aim of this study was to explore effects of a major urban reconstruction on physical activity (PA) behavior by comparing PA intensity hotspots before and after the tunneling of a highway with a new infrastructure prioritized for walking and cycling. In total, 126 individuals participated before and after the tunneling. GPS loggers and accelerometers were used to assess location and PA levels. A geographic information system (GIS) was used to perform optimized hotspot analyses on PA data, both on transport and stationary data points. The results showed several changes in PA hotspots on trip data, even if total PA levels did not change. At follow-up, PA intensity hotspots were more connected, with the new infrastructure as a central connection. This was true for higher and lower educated individuals. Therefore, if changes in the built environment do not result in changes on population-level outcomes, this does not imply that they have no impact on behavior.

Effectiveness and implementation of a multidisciplinary lifestyle focused approach in the treatment of inpatients with mental illness (MULTI +): a stepped wedge study protocol.

BACKGROUND: People with mental illness have a reduced life expectancy compared to the general population. Despite the increasing evidence for the efficacy of lifestyle interventions there is little change in routine clinical care. This discrepancy is often referred to as the implementation gap and has caused a need for effectiveness and implementation research in real-world settings. Our study assesses the effectiveness and implementation of a multidisciplinary lifestyle focused approach in the treatment of inpatients with mental illness (MULTI +). METHODS: An open cohort stepped wedge cluster randomized trial in inpatients psychiatric wards of GGz Centraal, the Netherlands. The wards are divided into three clusters based on geographical region. These clusters are randomly allocated to one of the three pre-defined steps to integrate MULTI + . MULTI + can be tailored to fit individual psychiatric wards and includes 10 core components aimed at improving lifestyle factors. The primary outcome is to investigate the difference in the mean QRISK3 score of patients receiving MULTI + compared to patients receiving TAU. Secondary outcomes include somatic and mental health outcomes, lifestyle factors, and implementation factors. Findings will be analysed using mixed model analyses. DISCUSSION: The MULTI + study is the first large-scale study evaluating the long-term effects of a multidisciplinary, multicomponent approach aimed at improving lifestyle factors in routine inpatient mental health care. A limitation of this study is the risk of missing data due to the large-scale, real-world setting of this study. Furthermore, implementation monitoring and external events that may influence outcomes could be difficult to account for. Strengths of this study are the focus on effectiveness as well as implementation and the inclusion of both patient and health care professionals' perspectives. Effectiveness studies in routine clinical care can advance our knowledge on lifestyle interventions in real-world settings. TRIAL REGISTRATION: ClinicalTrials.gov registration. Identifier: NCT04922749 . Retrospectively registered 3th of June 2021.

Design of the PERSPECTIVE study: PERsonalized SPEeCh Therapy for actIVE conversation in Parkinson's disease (randomized controlled trial).

OBJECTIVE: To evaluate the effectiveness of personalized and home-based speech therapy on quality of life, intelligibility, and social participation for people with Parkinson's disease (PD) who have a reduced intelligibility of speech. BACKGROUND: Speech problems in PD have a profound negative impact on social interaction and quality of life. Evidence for speech therapy in PD is growing, but more work remains needed to explore its full potential. Efficacy exists for highly intensive standardized speech treatment programs, but not all patients can comply with this rather intense intervention, especially the more severely affected ones. Here, we aim to study the effectiveness of personalized and home-based (remote) speech therapy in PD on quality of life and speech. The intervention will be supported by a dedicated speech training app. We expect that this approach will improve speech intelligibility and quality of life in patients irrespective of disease stage. METHODS: We will perform a single blind, randomized controlled trial, comparing 8 weeks of speech therapy to no intervention using a waiting list design. A total of 215 PD patients with problems in intelligibility will be recruited by 12 highly experienced speech therapists. All patients will be measured at baseline and after 8 weeks (primary endpoint). Additionally, the experimental group will be re-assessed one more time, after a wash-out period of 24 weeks. The control group will receive deferred treatment after 8 weeks, but without additional follow-up assessments. Our primary outcome is quality of life (as measured with PDQ-39). Secondary outcomes include speech and voice quality, intelligibility, severity of voice and speech complaints, and caregiver burden. RESULTS: The inclusion of participants has started on March 1, 2019, and is expected to be finalized on April 1, 2021. We expect to have the first results in January 2022. CONCLUSIONS: We will investigate the effectiveness of speech therapy in PD. Particular strengths of our study include a randomized and single-blinded design, the personalized treatment approach, the inclusion of PD patients irrespective of disease stage or severity of the speech complaint, the long-term follow-up, the adequate power, and the use of a patient-relevant primary endpoint. This will allow us to draw firm conclusions about the effectiveness of personalized and remote speech therapy for PD patients in all disease stages. TRIAL REGISTRATION: ClinicalTrials.gov NCT03963388 . Registered on May 24, 2019.

The predictive value of drug-induced sleep endoscopy for treatment success with a mandibular advancement device or positional therapy for patients with obstructive sleep apnea.

PURPOSE: As drug-induced sleep endoscopy (DISE) can provide additional diagnostic information on collapse patterns of the upper-airway, it is widely used in patients with obstructive sleep apnea (OSA). Although more controversial, DISE may also predict the success of treatment with a mandibular advancement device (MAD) and/or positional therapy (PT). In 2018, we proposed a prediction model to investigate the predictive value of passive maneuvers during DISE - such as jaw thrust and changes in body position - on upper-airway patency. Based on the outcomes of various studies, we then adjusted our DISE protocol to better mimic the effect of a MAD, PT, or a combination of both. The aim of this study was to verify whether or not our adjustments would increase the value of DISE as a selection tool. METHODS: This single-center retrospective cohort study involved a consecutive series of patients with OSA. Patients were included if a DISE had been performed in supine and non-supine sleeping position and with and without a boil-and-bite MAD in situ between December 2018 and February 2020. The VOTE scoring system was used to evaluate the obstruction at four levels of the upper-airway. RESULTS: Among 94 patients included. the median apnea-hypopnea index (AHI) was 16.2 (events/h). As a temporary MAD during DISE reduced obstruction by 54% and jaw thrust by 57%, both mimicked the effect of the custom-made MADs referred to in the literature, which reduces the AHI by 60%. Head-and-trunk rotation reduced obstruction by 55% and thus mimicked the effect of PT, which is known to reduce the AHI by 50%. CONCLUSION: A jaw thrust, a temporary MAD, and head-and-trunk rotation during DISE all seem to mimic the treatment effects of MAD and PT. These findings may be of added value when choosing OSA treatment. To prove the predictive value of these maneuvers during DISE, a prospective study should be performed.

Standardized framework to report on the role of sleeping position in sleep apnea patients.

PURPOSE: Sleep apnea is a multifactorial illness which can be differentiated in various physiological phenotypes as a result of both anatomical and non-anatomical contributors (e.g., low respiratory arousal threshold, high loop gain). In addition, the frequency and duration of apneas, in the majority of patients with OSA, are influenced by sleeping position. Differences in characteristics between non-positional patients (NPP) and positional patients (PP) suggest another crucial phenotype distinction, a clinical phenotype focusing on the role of sleeping position on sleep apnea. Since this clinical phenotype distinction has therapeutic implications, further research is necessary to better understand the pathophysiology behind this phenotypic trait and to improve management of PP. Therefore, we suggest a standardized framework that emphasizes the role of sleeping position when reporting clinical and research data on sleep apnea. METHODS: We identified 5 key topics whereby a standardized framework to report on the role of sleeping position would be of added value: (1) sleep study data, (2) anatomical, morphological and physiological factors, (3) drug-induced sleep endoscopy (DISE) findings, (4) sleep apnea management, and (5) effectiveness versus efficacy of positional therapy in sleep apnea management. We performed a literature search to identify evidence to describe and support the rationale behind these 5 main recommendations. RESULTS: In this paper, we present the rationale behind this construct and present specific recommendations such as reporting sleep study indices (disease severity) and sleep time spent in various sleeping positions. The same is suggested for DISE findings and effect of treatment. Sleep study indices (disease severity), anatomical, morphological, and physiological factors in sleep apnea patients should be reported separately for PP and NPP. CONCLUSION: Applying these suggestions in future research will improve patient care, assist in better understanding of this dominant phenotype, and will enhance accurate comparisons across studies and future investigations.

Does partnership diversity in intersectoral policymaking matter for health promoting intervention packages' composition? A multiple-case study in the Netherlands.

Intersectoral policymaking to improve public health includes integrated health promotion (HP) intervention packages that address a variety of health behavior determinants. The involvement of different partners is assumed to be necessary to implement such integrated packages. We examined how partnership diversity was associated with the composition of intervention packages implemented in Dutch municipalities. In a longitudinal multiple-case study (2012-14), we collected questionnaire data among 31 project leaders and 152 intervention implementers in 31 (alliances of) municipalities. Package composition was assessed in terms of intervention strategies, implementation settings and targeted behavioral determinants. Partnership diversity during the adoption and implementation phases was assessed in terms of the actors and sectors, as well as private partners and citizens involved. The association between partnership diversity and package composition was examined using crosstabs. Almost all packages integrated multiple strategies, but mostly education, facilitation and case finding, in multiple, but mostly health and public settings, such as schools. The packages targeted diverse behavioral determinants, although mainly personal and social environmental factors. A variety of partners from multiple sectors was involved, during both adoption and implementation of the packages. However, partners from the health, welfare and education sectors were mostly involved. More partnership diversity, especially during implementation, was associated with more integrated intervention packages. In intersectoral policymaking, investment in diversely composed partnerships seems worthwhile for implementing integrated intervention packages. However, investments in other conditions, like framing health issues and network management, are also needed to make environmental determinants of health behavior the object of HP.