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Objectives: Influenza is responsible for considerable health and economic burden every year. Especially older adults are vulnerable for influenza infection and its complications due to immunosenescence and often-underlying medical conditions. Recently, the innovative quadrivalent high-dose influenza vaccine (QIV-HD) has become available in Europe. Through its enhanced immunogenicity, QIV-HD offers improved protection for older adults against respiratory as well as cardiovascular complications. We estimated the potential impact—specifically in terms of hospital admissions and related costs—of a hypothetical past switch from QIV-Standard dose (SD) to QIV-HD in The Netherlands. Methods: Estimates of hospitalizations for the older adults vaccinated with QIV-SD were derived from the seasons 2010/2011-2017/2018. Subsequently, the number of respiratory infections and cardiovascular complications of influenza were estimated for the year 2019/2020 for both QIV-SD and QIV-HD. To calculate the overall corresponding savings, costs for hospital complications, derived from literature, were used. Results: When QIV-HD would have been used instead of QIV-SD during the season 2019/2020, an additional 220 hospitalizations would have been averted among older adults of 60 years and older in the Netherlands. This corresponds to savings of €1 219 779 (uncertainty interval: 1 089 813-1 348 549), of which 69% is attributable to cardiovascular-related hospitalizations. Conclusions: We demonstrate that a relevant improvement in influenza vaccination among older adults in The Netherlands can be achieved by switching from the current QIV-SD to QIV-HD. Not only comes a switch from QIV-SD to QIV-HD with a significant reduction in pressure on hospital capacity but also with notable cost savings.

Vitamin K deficiency is common among kidney transplant recipients (KTRs) and likely contributes to progressive vascular calcification and stiffness. In this single-center, randomized, double-blind, placebo-controlled trial, we aimed to investigate the effects of vitamin K supplementation on the primary end point, serum calcification propensity (calciprotein particle maturation time, T50), and secondary end points arterial stiffness (pulse wave velocity [PWV]) and vitamin K status in 40 vitamin K-deficient KTRs (plasma dephosphorylated uncarboxylated matrix Gla protein [dp-ucMGP] ≥500 pmol/L). Participants (35% female; age, 57 ± 13 years) were randomized 1:1 to vitamin K2 (menaquinone-7, 360 μg/day) or placebo for 12 weeks. Vitamin K supplementation had no effect on calcification propensity (change in T50 vs baseline +2.3 ± 27.4 minutes) compared with placebo (+0.8 ± 34.4 minutes; Pbetween group = .88) but prevented progression of PWV (change vs baseline -0.06 ± 0.26 m/s) compared with placebo (+0.27 ± 0.43 m/s; Pbetween group = .010). Vitamin K supplementation strongly improved vitamin K status (change in dp-ucMGP vs baseline -385 [-631 to -269] pmol/L) compared with placebo (+39 [-188 to +183] pmol/L; Pbetween group < .001), although most patients remained vitamin K-deficient. In conclusion, vitamin K supplementation did not alter serum calcification propensity but prevented progression of arterial stiffness, suggesting that vitamin K has vascular effects independent of calciprotein particles. These results set the stage for longer-term intervention studies with vitamin K supplementation in KTRs.TRIAL REGISTRY: EU Clinical Trials Register (EudraCT Number: 2019-004906-88) and the Dutch Trial Register (NTR number: NL7687).

Patients with multimorbidity increasingly impact healthcare systems, both in primary care and in hospitals. This is particularly true in Internal Medicine. This population associates with higher mortality rates, polypharmacy, hospital readmissions, post-discharge syndrome, anxiety, depression, accelerated age-related functional decline, and development of geriatric syndromes, amongst others. Internists and Hospitalists, in one of their roles as Generalists, are increasingly asked to attend to these patients, both in their own Departments as well as in surgical areas. The management of polypathology and multimorbidity, however, is often complex, and requires specific clinical skills and corresponding experience. In addition, patients' needs, health-care environment, and routines have changed, so emerging and re-emerging specific competences and approaches are required to offer the best coordinated, continuous, and comprehensive integrated care to these populations, to achieve optimal health outcomes and satisfaction of patients, their relatives, and staff. This position paper proposes a set of emerging and re-emerging competences for internal medicine specialists, which are needed to optimally address multimorbidity now and in the future.

This paper estimates the effect of in utero exposure to adverse events on late life diabetes, cardiovascular disease risks and cognition deficiency. We merge data on the regional violence during the Cultural Revolution and the excessive death rates during the Chinese Great Famine with data from the China Health and Retirement Longitudinal Study survey. Results show that female babies who were exposed in utero to the famine have higher diabetes risks, while male babies who were exposed to the Cultural Revolution are shown to have lower cognitive abilities.

The disaggregation and geographic dispersion of global value chains (GVCs) have expanded the responsibility of international buyers from firm-level corporate social responsibility (CSR) towards social sustainability of their emerging country suppliers. We theorize, in this paper, that the effectiveness of lead firms’ GVC governance strategies for social sustainability—which can be audit-based or cooperation-based—depends on the local institutional context of the supplier. Supplier country institutions exert legal and civil society pressures for social sustainability, which shape suppliers’ attitude and receptiveness towards lead firm requests. Using unique primary data from 356 garment and footwear suppliers in 11 emerging countries, which supply to Western European or North American buyers, we show that GVC governance strategies are particularly effective for suppliers’ social sustainability implementation when there is ‘contextual fit’ with local institutional pressures for social sustainability in the supplier country. Our study identifies the boundary conditions of GVC governance modes, and demonstrates a complementary relationship between organizational arrangements and their institutional-level counterparts in the context of social sustainability.

Background and aimsDiagnosed and undiagnosed Type 2 Diabetes (T2D) remains a challenge in high-income countries. In addition, the presence of T2D can cause further disease burden because of its high susceptibility to complications. Nevertheless, there is limited evidence of socio-economic gradients in undiagnosed T2D and its complications in a large population cohort. We investigated this using the Dutch Lifelines Cohort Study (Lifelines).Methods and resultsWithin Lifelines, baseline data of 102 163 adults aged 30 and above were collected from 2007 to 2013. The associations of Socio-Economic Status (SES), indicated by monthly household income, with the prevalence of T2D status and the number of T2D complications were assessed using multinomial Poisson and linear regressions with adjustments for age and sex. The prevalence of diagnosed and undiagnosed T2D was, respectively, 3.0% and 3.0% in the low SES group compared to 1.1% and 1.8% in the high SES group. Individuals with lower SES were at higher risk of having undiagnosed T2D (relative risk ratio (rrr) [95% CI]: 1.63 [1.47–1.81] for low SES and 1.16 [1.05–1.29] for middle SES) and diagnosed T2D, compared with those with high SES. Lower SES was positively associated with the number of T2D complications (low SES vs. high SES (ref); B [95% CI]: 0.15 [0.13–0.16]).ConclusionComplementing the known socio-economic gradients in diagnosed T2D, we document socio-economic gradients in undiagnosed T2D and T2D complications in a single, large general representative population. Furthermore, individuals with low SES with diagnosed or undiagnosed T2D were more susceptible to T2D complications.

Objective The study aimed to evaluate the psychometric properties of KDQOL-36 Bahasa Indonesia in hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) patients in Indonesia. Methods The psychometric analysis was conducted in three hospitals offering both HD and CAPD. The validity was assessed through structural, convergent, and known-group validity, while reliability was evaluated using internal consistency and test–retest reliability. Results The study involved 370 participants of which 71% received HD treatment. No floor and ceiling effects ( Conclusion The study supports the validity and reliability of both generic and kidney-specific domains of KDQOL-36 Bahasa Indonesia to evaluate quality of life in patients with HD and CAPD in Indonesia. As health-related quality of life is a crucial predictor of patient outcomes, this report contributes new evidence about validity and reliability to recommend the use of KDQOL-36 Bahasa Indonesia in dialysis centers.

Objectives: Cost-effectiveness analyses (CEAs) generally assume constant drug prices throughout the model time horizon, yet it is known that prices are not constant, often with price decreases near loss of exclusivity (LOE). This study explores the impact of using dynamic drug-specific prices on the incremental cost-effectiveness ratio (ICER) using selected reproduced case studies.Methods: Case studies were selected following explicit criteria to reflect a variety of drug characteristics. For each drug, a published CEA model was identified, replicated, and modified with dynamic real-world pricing data, to compare ICERs based on constant drug prices with estimates obtained when including drug life cycle pricing. The impact of dynamic real-world pricing—inclusive LOE—was analyzed using a single patient cohort and multiple cohorts over time.Results: Fluvastatin, alendronic acid + colecalciferol combination therapy, letrozole and clopidogrel were selected as case studies. Inclusion of real-world pricing data compared with applying constant prices reduced the ICER in a single-cohort setting up to 43%. In the multicohort analyses, further reductions of the ICERs were observed of up to 113%. The ICERs were sensitive to the period of drug usage relative to the models’ time horizons, the relative proportions of drug costs in the overall treatment costs, and timing of LOE compared with the cost year of the original analysis.Conclusions: Assuming dynamic drug prices may lead to more representative ICER estimates. Future CEAs for drugs could account for predicted and disaggregated life cycle price developments based on retrospective data.

Background Chronic obstructive pulmonary disease (COPD) is a prevalent lung disease. It is assumed that severe patients will receive better treatment in specialised care centres but the prevalence of severe COPD in primary care is high. Integrated primary care services combine input from several sources and advice from pulmonologists to provide general practitioners with support needed to improve diagnosis and treatment of patients with COPD. Objectives To evaluate patient-reported outcomes and costs of managing patients classified as GOLD D in an integrated primary care service over 12 months. Methods Patients were included in this 1-year prospective cohort study if they met the 2014 GOLD D criteria, were aged >= 40 years and gave written informed consent for this study. Recruitment took place through the patients' general practitioners. The primary outcome was health status, assessed with the Clinical COPD Questionnaire (CCQ) and COPD Assessment Test (CAT). Secondary outcomes included self-reported exacerbations, quality-adjusted life years and health(care)-related costs. Results Forty-nine patients were included. At baseline, the mean CAT score was 15.9 and the median CCQ score was 1.7. After 12 months, scores had improved by 2.3 (95% confidence interval, 0.8-3.7) and 0.4 (95% confidence interval, 0.2-0.7), respectively. Percentage of patients with >= 2 exacerbations in the past 12 months also decreased from baseline (77.6%) to 12 months (16.7%). Changes in mean quarterly costs were small. Conclusion An integrated service for COPD based in primary care may improve the health status of patients with a large burden of disease while not increasing health care costs.

Stated preference studies in which information on the willingness to trade-off between the benefits and harms of medicines is elicited from patients or other stakeholders are becoming increasingly mainstream. Such trade-offs can mathematically be represented by a weighted additive function, with the weights, whose ratios determine how much an individual is willing to trade-off between the treatment attributes, being the response vector for the statistical analysis. One way of eliciting trade-off information is through multi-dimensional thresholding (MDT), which is a bisection-based approach that results in increasingly tight bounds on the values of the weights ratios. While MDT is cognitively less demanding than other, more direct elicitation methods, its use complicates the statistical analysis as it results in weights data that are region censored. In this article, we present a simulated maximum likelihood (SML) procedure for fitting a Dirichlet population model directly to the region-censored weights data and perform a series of computational experiments to compare the proposed SML procedure to a naive approach in which a Dirichlet distribution is fitted to the centroids of the weights boundaries obtained with MDT. The results indicate that the SML procedure consistently outperformed the centroid-based approach, with the centroid-based approach requiring three bisection steps per trade-off to achieve a similar precision as the SML procedure with one bisection step per trade-off. Using the newly proposed SML procedure, MDT can be applied with smaller sample sizes or with fewer questions compared to the more naive centroid-based approach that was applied in previous applications of MDT.

STUDY QUESTION Is a thin endometrial lining before ovulation triggering more prevalent in patients utilizing preimplantation genetic testing for monogenic disease (PGT-M) compared to the regular IVF/ICSI population and is this associated with prior hormonal contraceptive use? SUMMARY ANSWER Thin ( WHAT IS KNOWN ALREADY Thin endometrial lining has been associated with lower pregnancy rates in IVF/ICSI cycles and increased chances of miscarriage and low birth weight. Endometrial thinning and atrophy occur during hormonal contraceptive use. Patients utilizing PGT-M typically use hormonal contraceptives up until treatment to avoid the risk of conception of a genetically affected child. Whether this could negatively affect endometrial thickness achieved during subsequent IVF/ICSI cycles is not known. STUDY DESIGN, SIZE, DURATION A retrospective case control study was performed, including all PGT-M patients attending the University Medical Centre Groningen (cases), between 2009 and 2018. The control group consisted of two non-PGT IVF/ICSI patients for each PGT-M patient, matched for age and treatment period. PARTICIPANTS/MATERIALS, SETTING, METHODS First cycles of 122 PGT-M patients and 240 controls were included. Cessation interval of hormonal contraceptives was categorized as late cessation (cessation 1 year prior to treatment). Endometrial thickness was routinely measured on the day of hCG triggering or 1 day prior. The prevalence of an endometrial lining or MAIN RESULTS AND THE ROLE OF CHANCE Thin endometrial lining on the day of hCG triggering was found significantly more often in the PGT-M group, compared to controls: 32% vs 11% (mean difference 21.0%, 95% CI: 11.7, 30.3%). As expected, more patients in the PGT-M group ceased their hormonal contraception late (8 mm (20.0% vs 1.7%, mean difference 18.3%, 95% CI: 2.3, 34.3%). A trend towards lower birth weight and gestation- and gender-adjusted birth weight (z-score) was also found in this group. No statistically significant differences were detected in pregnancy rate, live birth rate, or incidence of preterm delivery or SGA. Within the control group, no statistically significant differences were found in outcomes between patients with an endometrial lining 8 mm. LIMITATIONS, REASONS FOR CAUTION The study is retrospective. Various types of hormonal contraceptives were reported which possibly exert different effects on the endometrial lining. In relation to pregnancy outcome measures, numbers were very limited; therefore, no firm conclusions should be drawn. WIDER IMPLICATIONS OF THE FINDINGS This study provides further insight into the role of prior hormonal contraceptive use as a possible contributor to the occurrence of thin endometrial lining during ART treatment. Future studies should provide more information on its clinical relevance, to determine whether PGT-M patients can be reassured, or should be counselled to stop hormonal contraceptive use and change to an alternative contraceptive method prior to PGT treatment. STUDY FUNDING/COMPETING INTERESTS No specific funding was used and no conflicts of interests are declared. TRIAL REGISTRATION NUMBER N/A.

During the COVID-19 pandemic, a 13.6 per cent reduction in the number of surgical procedures performed was observed in 2020. Despite great pressure on healthcare, the COVID-19 pandemic did not cause an increase in adverse surgical outcomes, and oncological surgery-related duration of hospital and ICU stay were significantly shorter.Background The COVID-19 pandemic caused disruption of regular healthcare leading to reduced hospital attendances, repurposing of surgical facilities, and cancellation of cancer screening programmes. This study aimed to determine the impact of COVID-19 on surgical care in the Netherlands. Methods A nationwide study was conducted in collaboration with the Dutch Institute for Clinical Auditing. Eight surgical audits were expanded with items regarding alterations in scheduling and treatment plans. Data on procedures performed in 2020 were compared with those from a historical cohort (2018-2019). Endpoints included total numbers of procedures performed and altered treatment plans. Secondary endpoints included complication, readmission, and mortality rates. Results Some 12 154 procedures were performed in participating hospitals in 2020, representing a decrease of 13.6 per cent compared with 2018-2019. The largest reduction (29.2 per cent) was for non-cancer procedures during the first COVID-19 wave. Surgical treatment was postponed for 9.6 per cent of patients. Alterations in surgical treatment plans were observed in 1.7 per cent. Time from diagnosis to surgery decreased (to 28 days in 2020, from 34 days in 2019 and 36 days in 2018; P < 0.001). For cancer-related procedures, duration of hospital stay decreased (5 versus 6 days; P < 0.001). Audit-specific complications, readmission, and mortality rates were unchanged, but ICU admissions decreased (16.5 versus 16.8 per cent; P < 0.001). Conclusion The reduction in the number of surgical operations was greatest for those without cancer. Where surgery was undertaken, it appeared to be delivered safely, with similar complication and mortality rates, fewer admissions to ICU, and a shorter hospital stay.Lay Summary COVID-19 has had a significant impact on healthcare worldwide. Hospital visits were reduced, operating facilities were used for COVID-19 care, and cancer screening programmes were cancelled. This study describes the impact of the COVID-19 pandemic on Dutch surgical healthcare in 2020. Patterns of care in terms of changed or delayed treatment are described for patients who had surgery in 2020, compared with those who had surgery in 2018-2019. The study found that mainly non-cancer surgical treatments were cancelled during months with high COVID-19 rates. Outcomes for patients undergoing surgery were similar but with fewer ICU admissions and shorter hospital stay. These data provide no insight into the burden endured by patients who had postponed or cancelled operations.

Background: Low health literacy (HL) can lead to worse health outcomes for patients with chronic diseases and could also lead to worse postoperative outcomes. This retrospective cohort study investigates the association between HL and postoperative textbook outcome (TO) after hepato-pancreato-biliary (HPB) cancer surgery. Methods: Patients that consented and underwent surgery for a premalignant andmalignant HPB tumor were included. Preoperatively, HL was measured by the brief health literacy screen (BHLS). Patients were categorized as having low or adequate HL. Primary outcome was TO (length of hospital stay (LOS) ≤ 75th percentile; and no severe complication; and no readmission and mortality within 30 days after discharge). Secondary outcomes were LOS and emergency department (ED) visits within 30 days after discharge. Results: In total, 137 patients were included, of whom thirty-six patients had low HL. In patients with low HL (vs. adequate HL), rate of TO was lower (55.6% vs. 72.3%; p = 0.095), LOS was significantly longer (13.5 vs. 9 days; p = 0.007) and there was only a slight difference in ED visits (14.3% vs. 11.0%; p = 0.560). Patients with low HL had a significant lower chance of achieving TO (OR 0.400, 95%-CI 0.169–0.948; p = 0.037). Conclusion: Low HL leads to worse postoperative outcome after HPB cancer surgery. Better preoperative education and guidance of patients with low HL could lead to better postoperative outcomes. Therefore, HL could be the next modifiable risk factor before major surgery.

OBJECTIVE: To describe treatment patterns, low-density lipoprotein cholesterol (LDL-C) levels and healthcare resource utilization (HCRU) in the Netherlands in 2018 of patients with hypercholesterolaemia or mixed dyslipidaemia at high or very high cardiovascular (CV) risk. METHODS: From the PHARMO Database Network adult patients with a diagnosis or receiving lipid lowering therapy (LLT) between 2009 and 2018 were selected. Patients at high or very high CV risk according to 2016 ESC/EAS guidelines with recorded LDL-C levels who were treated with LLT or were characterized as statin intolerant in 2018 were included. LLT treatment patterns, LDL-C levels and HCRU (General Practitioner [GP] consultations and hospitalizations) were assessed. RESULTS: The study population included 54,346 patients, of which 70% were at very high CV risk and 30% at high CV risk. The majority (93%) received statin monotherapy, mostly of moderate (73%) or high (15%) intensity. Only 3% received a combination of statin and ezetimibe. Statin intolerance, based on a treatment algorithm, was estimated at 3%. Average LDL-C decreased with LLT intensity. Overall, 74% reached LDL-C

BACKGROUND: Survival of kidney transplant recipients (KTR) is low compared with the general population. Low muscle mass and muscle strength may contribute to lower survival, but practical measures of muscle status suitable for routine care have not been evaluated for their association with long-term survival and their relation with each other in a large cohort of KTR.METHODS: Data of outpatient KTR ≥ 1 year post-transplantation, included in the TransplantLines Biobank and Cohort Study (ClinicalTrials.gov Identifier: NCT03272841), were used. Muscle mass was determined as appendicular skeletal muscle mass indexed for height 2 (ASMI) through bio-electrical impedance analysis (BIA), and by 24-h urinary creatinine excretion rate indexed for height 2 (CERI). Muscle strength was determined by hand grip strength indexed for height 2 (HGSI). Secondary analyses were performed using parameters not indexed for height 2. Cox proportional hazards models were used to investigate the associations between muscle mass and muscle strength and all-cause mortality, both in univariable and multivariable models with adjustment for potential confounders, including age, sex, body mass index (BMI), estimated glomerular filtration rate (eGFR) and proteinuria. RESULTS: We included 741 KTR (62% male, age 55 ± 13 years, BMI 27.3 ± 4.6 kg/m 2), of which 62 (8%) died during a median [interquartile range] follow-up of 3.0 [2.3-5.7] years. Compared with patients who survived, patients who died had similar ASMI (7.0 ± 1.0 vs. 7.0 ± 1.0 kg/m 2; P = 0.57), lower CERI (4.2 ± 1.1 vs. 3.5 ± 0.9 mmol/24 h/m 2; P < 0.001) and lower HGSI (12.6 ± 3.3 vs. 10.4 ± 2.8 kg/m 2; P < 0.001). We observed no association between ASMI and all-cause mortality (HR 0.93 per SD increase; 95% confidence interval [CI] [0.72, 1.19]; P = 0.54), whereas CERI and HGSI were significantly associated with mortality, independent of potential confounders (HR 0.57 per SD increase; 95% CI [0.44, 0.81]; P = 0.002 and HR 0.47 per SD increase; 95% CI [0.33, 0.68]; P < 0.001, respectively), and associations of CERI and HGSI with mortality remained independent of each other (HR 0.68 per SD increase; 95% CI [0.47, 0.98]; P = 0.04 and HR 0.53 per SD increase; 95% CI [0.36, 0.76]; P = 0.001, respectively). Similar associations were found for unindexed parameters. CONCLUSIONS: Higher muscle mass assessed by creatinine excretion rate and higher muscle strength assessed by hand grip strength are complementary in their association with lower risk of all-cause mortality in KTR. Muscle mass assessed by BIA is not associated with mortality. Routine assessment using both 24-h urine samples and hand grip strength is recommended, to potentially target interdisciplinary interventions for KTR at risk for poor survival to improve muscle status.

Background and objectives: To date, employment figures of kidney transplant recipients in Europe are inconsistent. Additionally, little is known about work functioning of employed kidney transplant recipients and work functioning trajectories before and after transplantation.Design, setting, participants, & measurements: Data from the ongoing TransplantLines Biobank and Cohort study and from community-dwelling employed adults were used. Health-related work functioning of kidney transplant recipients was assessed with the Work Role Functioning Questionnaire 2.0 and compared with potential kidney donors and community-dwelling employed adults.Results: We included 668 kidney transplant recipients of working age (59% men, age 51±11 years) at median 3 (interquartile range, 2–10) years after transplantation, 246 potential kidney donors of working age (43% men, age 53±9 years), and 553 community-dwelling employed adults (70% men, age 45±11 years). The proportion of employed kidney transplant recipients was lower compared with potential kidney donors (56% versus 79%). If employed, the work functioning score of kidney transplant recipients was slightly lower compared with employed potential kidney donors yet higher compared with community-dwelling employed adults (medians 91 [interquartile range, 76–98], 94 [interquartile range, 85–99], and 88 [interquartile range, 79–95], respectively). Backward linear regression analyses revealed that lower educational level, having a kidney from a deceased donor, presence of tingling or numbness of hands or feet, presence of concentration/memory problems, presence of anxiety, and presence of severe fatigue were independently associated with lower work functioning among kidney transplant recipients. Additional subgroup analyses showed that work functioning scores were lower before transplantation than at 12 months after transplantation (83 [interquartile range, 66–93] versus 92 [interquartile range, 88–98], respectively; P=0.002).Conclusions: Stable employed kidney transplant recipients report to function well at work. In addition, this study shows that self-reported work functioning is higher after successful kidney transplantation compared with before transplantation.Clinical Trial registry name and registration number: TransplantLines Biobank and Cohort study, NCT03272841

Objectives: Spinal muscular atrophy (SMA) is a rare genetic disorder that causes progressive muscle weakness and paralysis. In its most common and severe form, the majority of untreated infants die before 2 years of age. Early detection and treatment, ideally before symptom onset, maximize survival and achievement of age-appropriate motor milestones, with potentially substantial impact on health-related quality of life. Therefore, SMA is an ideal candidate for inclusion in newborn screening (NBS) programs. We evaluated the cost-effectiveness of including SMA in the NBS program in The Netherlands.Methods: We developed a cost-utility model to estimate lifetime health effects and costs of NBS for SMA and subsequent treatment versus a treatment pathway without NBS (ie, diagnosis and treatment after presentation with overt symptoms). Model inputs were based on literature, local data, and expert opinion. Sensitivity and scenario analyses were conducted to assess model robustness and validity of results.Results: After detection of SMA by NBS in 17 patients, the number of quality-adjusted life-years gained per annual birth cohort was estimated at 320 with NBS followed by treatment compared with treatment after clinical SMA diagnosis. Total healthcare costs, including screening, diagnostics, treatment, and other healthcare resource use, were estimated to be €12 014 949 lower for patients identified by NBS.Conclusions: NBS for early identification and treatment of SMA versus later symptomatic treatment after clinical diagnosis improves health outcomes and is less costly and, therefore, is a cost-effective use of resources. Results were robust in sensitivity and scenario analyses.

It is well documented that obesity decreases natural fertility among men and women as well as pregnancy chances after conventional infertility and assisted reproductive technology (ART)-based treatments. Moreover, pregnancy complications are increased in women with overweight and obesity. General guidelines on the treatment of obesity recommend lifestyle intervention, including diet and exercise as the first-line treatment, coupled with or without medical treatments, such as weight loss medication or bariatric surgery, to reduce complications of obesity in adults. In the context of infertility in various countries and infertility clinics, there is a body mass index limit for public refund of infertility treatment of women with obesity. In this respect, it is important to investigate the evidence of effects of lifestyle intervention preceding infertility treatment on reproductive outcomes. The combined results of 15 randomized controlled trials (RCTs) of the effectiveness of preconception lifestyle intervention on reproductive outcomes documented in the latest systemic review and meta-analysis, together with the most recent RCT performed in 2022 are discussed. The current evidence suggests that greater weight loss and increase in clinical pregnancy, live birth, and natural conception rates after lifestyle intervention compared with no intervention were observed, but it seems no beneficial effect of lifestyle intervention preceding ART was observed on these parameters. With respect to potential harm of lifestyle intervention, there is no significant increased risk of early pregnancy loss, although the most recent RCT (not included in the systematic review and meta-analysis) showed a trend toward an increased risk. Complications during pregnancy, such as early pregnancy loss and maternal as well as fetal and neonatal complications, are underreported in most studies and need further analysis in an individual participant data meta-analysis. Limitations of the studies as well as future perspectives and challenges in this field of research will be highlighted.

Objective We aimed to assess the cost-effectiveness of screening smokers and ex-smokers for lung cancer in the Netherlands. Methods A Markov model was used to evaluate the health effects and costs of lung cancer screening from the healthcare perspective. The effects and costs of ten screening scenarios with different start and stop ages of screening were examined across a lifetime horizon in a cohort of 100,000 smokers and ex- smokers 50 years and older. Results The incremental cost-effectiveness ratios (ICERs) of screening smokers and ex-smokers aged 50–60 years, 50–70 years, and 50 years and older are below the cost-effectiveness threshold of € 20,000 per quality adjusted life year (QALY) gained. Screening 50–60-year-old smokers and ex-smokers was the most cost-effective scenario with an ICER of € 14,094 per QALY gained. However, screening smokers and ex-smokers 50 years and older yielded the highest QALYs and resulted in an ICER of € 16,594 per QALY, which is below the threshold of € 20,000 per QALY. All screening scenarios compared to no screening resulted in CERs between the € 14,000 and € 16,000 per QALY gained. The efficiency frontier showed that screening smokers and ex-smokers in the age groups 70 years and older, 60–70 years, 60 years and older are excluded by extended dominance by no screening, screening smokers and ex-smokers aged 50–60 years and 50–70 years. Conclusion This study showed that lung cancer screening is cost-effective in the Netherlands.

Background In older adults, the burden of respiratory syncytial virus (RSV) resembles that of influenza and may even be considered worse due to the lack of preventive interventions. This study was performed to identify the available literature on RSV infection in older adults, and to provide updated exploratory results of the cost-effectiveness of a hypothetical RSV vaccine in the Netherlands and the United Kingdom. Methods A literature search was performed in Medline and EMBASE on 11 November 2019, which served as input for a static decision-tree model that was used to estimate the EJP, for an RSV vaccine applying different willingness-to-pay (WTP) thresholds. WTP thresholds applied were €20 000 and €50 000 per quality-adjusted life-year for the Netherlands, and £20 000 and £30 000 per quality-adjusted life-year for the United Kingdom. Analyses were—in line with country-specific guidelines—conducted from a societal perspective for the Netherlands and a third-party payer perspective for the United Kingdom. The robustness of the cost-effectiveness results was tested in sensitivity analysis. Results After screening the literature, 3 studies for the Netherlands and 6 for the United Kingdom remained to populate the country-specific models. In the base case analysis for the Netherlands (mean RSV incidence, 3.32%), justifiable vaccine prices of €16.38 and €50.03 were found, based on applying the lower and higher WTP thresholds, respectively. Similarly, for the United Kingdom (mean incidence, 7.13%), vaccine prices of £72.29 and £109.74 were found, respectively. Conclusion RSV vaccination may well be cost-effective in both the Netherlands and the United Kingdom, depending on the exact RSV incidence, vaccine effectiveness and price. However, sensitivity analysis showed that the results were robust based on varying the different parameter estimates and assumptions. With RSV vaccines reaching the final stages of development, a strong need exists for cost-effectiveness studies to understand economically justifiable pricing of the vaccine.

To assess the cost-effectiveness of app-based treatment for female stress, urgency or mixed urinary incontinence (UI) compared with care-as-usual in Dutch primary care.A pragmatic, randomised controlled, superiority trial.Primary care in the Netherlands from 2015 to 2018, follow-up at 12 months.Women with ≥2 UI-episodes per week, access to mobile apps, wanting treatment.The standalone app included conservative management for UI with motivation aids (e.g. reminders). Care-as-usual delivered according to the Dutch GP guideline for UI.Costs and cost-effectiveness and -utility were assessed from a societal perspective, based on incontinence impact adjusted life years (IIALYs), quality adjusted life years (QALYs) and medical, non-medical and productivity costs. Information on costs was obtained with the iMCQ and iPCQ questionnaires (medical consumption and productivity cost questionnaires).In all, 262 women were andomised equally to app or care-as-usual; 89 (68%) and 83 (63%) attended follow-up, respectively. Costs were lower for app-based treatment with € -161 (95% confidence interval [CI -180 to -151) per year. Cost-effectiveness showed small mean differences in effect for IIALY (0.04) and QALY (-0.03) and thus larger incremental cost-effectiveness ratios (ICER: -€3696) and incremental cost-utility ratios (ICUR: €6379).App-based treatment is a cost-effective alternative to care-as-usual for women with UI in Dutch primary care.App-treatment for female urinary incontinence cost-effective compared to care-as-usual in general practice after 12 months.

Contains fulltext : 287584.pdf (Publisher’s version ) (Closed access) WHAT IS KNOWN AND OBJECTIVE: Alpha-blockers have been associated with orthostatic hypotension (OH). We aimed to assess the prevalence of OH measured with beat-to-beat blood pressure monitoring in older male outpatients who used alpha-blockers for lower urinary tract symptoms (LUTS). In addition, we investigated associations of OH with duration of alpha-blocker use, concomitant medication use and comorbidity. METHODS: Cross-sectional explorative study in a urology outpatient clinic. Older white males ≥65 years using alpha-blockers for LUTS were included. Blood pressure responses to standing up from supine were recorded using a validated beat-to-beat blood pressure device (Finapres). Prevalence rates were derived from the beat-to-beat data to include OH measured between 60-110 s (OH), impaired recovery OH at 40 s (OH[40]), initial OH (IOH) and normal orthostatic response. Subgroups were defined based on duration of alpha-blocker use, polypharmacy, and Charlson comorbidity index (CCI), to obtain relative risks. RESULTS AND DISCUSSION: Sixty-five patients were included. Median age was 75 years (range 65-92). The prevalence of OH was 7.7% (n = 5). The prevalence of OH(40) was 16.9% (n = 11) and of IOH 38.5% (n = 25). Thirty-six patients (55.4%) had a normal orthostatic response. The relative risk of OH for the subgroup using ≥ 10 medications (n = 13) was 6.0 (95%CI 1.1-32.3). For the subgroup with multimorbidity (CCI ≥3, n = 11) this was 7.4 (95%CI 1.4-39.0). Recent initiation of alpha-blocker use (

Objective Health care expenditures for children with functional constipation (FC) are high, while conservative management is successful in only 50% of the children. The aim is to evaluate whether adding physiotherapy to conventional treatment (CT) is a cost-effective strategy in the management of children with FC aged 4–18 years in primary care. Methods A cost-effectiveness analysis was performed alongside a randomized controlled trial (RCT) with 8-month follow-up. Costs were assessed from a societal perspective, effectiveness included both the primary outcome (treatment success defined as the absence of FC and no laxative use) and the secondary outcome (absence of FC irrespective of laxative use). Uncertainty was assessed by bootstrapping and cost-effectiveness acceptability curves (CEACs) were displayed. Results One hundred and thirty-four children were randomized. The incremental cost-effectiveness ratio (ICER) for one additional successfully treated child in the physiotherapy group compared with the CT group was €24,060 (95% confidence interval [CI] €−16,275 to €31,390) and for the secondary outcome €1,221 (95% CI €−12,905 to €10,956). Subgroup analyses showed that for children with chronic laxative use the ICER was €2,134 (95% CI −24,975 to 17,192) and €571 (95% CI 11 to 3,566), respectively. At a value of €1,000, the CEAC showed a probability of 0.53 of cost-effectiveness for the primary outcome, and 0.90 for the secondary outcome. Conclusions Physiotherapy added to CT as first-line treatment for all children with FC is not cost-effective compared with CT alone. Future studies should consider the cost-effectiveness of physiotherapy added to CT in children with chronic laxative use. Trial registration The RCT is registered in the Netherlands Trial Register (NTR4797), on the 8th of September 2014. The first child was enrolled on the 2nd of December 2014. https://www.trialregister.nl/trial/4654.

Immune modulation is a key therapeutic approach for allergic diseases, asthma and autoimmunity. It can be achieved in an antigen-specific manner via allergen immunotherapy (AIT) or in an endotype-driven approach using biologicals that target the major pathways of the type 2 (T2) immune response: immunoglobulin (Ig)E, interleukin (IL)-5 and IL-4/IL-13 or non-type 2 response: anti-cytokine antibodies and B-cell depletion via anti-CD20. Coronavirus disease 2019 (COVID-19) vaccination provides an excellent opportunity to tackle the global pandemics and is currently being applied in an accelerated rhythm worldwide. The vaccine exerts its effects through immune modulation, induces and amplifies the response against the severe acute respiratory syndrome coronavirus (SARS-CoV-2). Thus, as there may be a discernible interference between these treatment modalities, recommendations on how they should be applied in sequence are expected. The European Academy of Allergy and Clinical Immunology (EAACI) assembled an expert panel under its Research and Outreach Committee (ROC). This expert panel evaluated the evidence and have formulated recommendations on the administration of COVID-19 vaccine in patients with allergic diseases and asthma receiving AIT or biologicals. The panel also formulated recommendations for COVID-19 vaccine in association with biologicals targeting the type 1 or type 3 immune response. In formulating recommendations, the panel evaluated the mechanisms of COVID-19 infection, of COVID-19 vaccine, of AIT and of biologicals and considered the data published for other anti-infectious vaccines administered concurrently with AIT or biologicals.

Objectives There are several instruments to assess health-related quality of life (HRQoL) in chronic rhinosinusitis (CRS). Unfortunately, none of them evaluates all three health domains (physical, social and psychological) important to assess the overall well-being of the patient. The Endoscopic Endonasal Sinus and Skull Base Surgery Questionnaire (EES-Q) does assess all these elements. Initially, the EES-Q is validated to evaluate the impact of endoscopic endonasal surgery (EES) on HRQoL. The aim of this study is to assess whether EES-Q outcomes differ in patients with CRS compared with healthy individuals. Therefore, extending the use of the EES-Q for all CRS patients. Design Cross-sectional study. Setting Tertiary referral hospital. Participants One hundred patients with uncontrolled CRS (50% with nasal polyps) scheduled to receive EES. The questionnaire was completed preoperatively. Healthy control subjects (n = 100) without any history of sinusitis or a known current medical treatment at a hospital were included. Main outcome measures Mann-Whitney U test was performed to identify differences in EES-Q scores (domain scores and EES-Q score). Results The median EES-Q score in CRS patients (33.8) was significantly higher (p < 0.001) than in the control group (10.4). As well as the physical (52.5 vs. 16.4, p < 0.001), psychological (13.8 vs. 5.0, p < 0.001) and social (37.5 vs. 2.5, p < 0.001) domain scores. Conclusions With this study, we are extending the use of the EES-Q. It indicates that the EES-Q can be a valuable clinical tool to assess multidimensional HRQoL in all patients with CRS.

Romy Deviandri,1– 3 Hugo C van der Veen,1 Andri MT Lubis,4 Ghuna A Utoyo,5 Inge van den Akker-Scheek,1 Maarten J Postma6– 9 1Department of Orthopedic Surgery, University of Groningen/ University Medical Center Groningen, Groningen, the Netherlands; 2Department of Physiology-Faculty of Medicine, Universitas Riau, Pekanbaru, Indonesia; 3Department of Orthopedics-Sports Injury, Arifin Achmad Hospital, Pekanbaru, Indonesia; 4Department of Orthopedics-Faculty of Medicine, Universitas Indonesia/Cipto Mangunkusumo Hospital, Jakarta, Indonesia; 5Department of Orthopedics-Faculty of Medicine, Universitas Padjadjaran/ Hasan Sadikin Hospital, Bandung, Indonesia; 6Department of Health Sciences, University of Groningen/ University Medical Center Groningen, Groningen, the Netherlands; 7Department of Economics-Faculty of Economics & Business, University of Groningen, Groningen, the Netherlands; 8Department of Pharmacology & Therapy, Universitas Airlangga, Surabaya, Indonesia; 9Department Center of Excellence in Higher Education for Pharmaceutical Care Innovation, Universitas Padjadjaran, Bandung, IndonesiaCorrespondence: Romy Deviandri, Department of Orthopedic Surgery, University of Groningen/ University Medical Center Groningen, Hanzeplein 1, Groningen, 9713 GZ, the Netherlands, Email r.deviandri@rug.nl; romydeviandri@lecturer.unri.ac.idObjective: The number of anterior cruciate ligament reconstruction (ACLR) procedures is increasing. However, ACLR procedures are likely to be underbudgeted in a developing country like Indonesia. This study aimed to analyze costs for ACLR procedures in Indonesia’s resource-limited context, determine the burden of ACLR, and suggest national prices for ACLR reimbursement.Methods: A retrospective observational study was conducted between 1 January and 31 December 2019 on the cost of ACLR from a payer perspective using inpatient billing records in four hospitals. The national burden of ACLR was calculated, and projected national prices for reimbursement were determined.Results: Of 80 ACLRs, 53 (66%) were isolated ACLRs and 27 (34%) ACLRs were combined with meniscus treatment. Mean hospital costs incurred per ACLR procedure were US$ 2853, with the dominant cost relating to orthopedic implant prices (US$ 1,387.80). The costs of ACLR with combined meniscus treatment were estimated as being 35% higher than isolated ACLR. The national burden of ACLR showed a total budget of US$ 367.4 million per 100,000 patients (0.03% of GDP) for ACLR with additional meniscus treatment and US$ 271.3 million per 100,000 patients (0.02% of GDP) for isolated ACLR.Conclusion: ACLR procedures in Indonesia are likely underbudgeted. Adjustments of reimbursement prices for ACLR are needed to facilitate adequate access of Indonesians to the procedures. This study demonstrated varying costs determined for ACLR in Indonesia, which entails that a new reimbursement system with improvement of national prices should become the core of transformation.Keywords: ACL tear, meniscus injury, cost, developing countries, BPJS

Background Wound healing and scar formation depends on a plethora of factors. Given the impact of abnormal scar formation, interventions aimed to improve scar formation would be most advantageous. The tissue stromal vascular fraction (tSVF) of adipose tissue is composed of a heterogenous mixture of cells embedded in extracellular matrix. It contains growth factors and cytokines involved in wound-healing processes, eg, parenchymal proliferation, inflammation, angiogenesis, and matrix remodeling. Objectives The aim of this study was to investigate the hypothesis that tSVF reduces postsurgical scar formation. Methods This prospective, double-blind, placebo-controlled, randomized trial was conducted between 2016 and 2020. Forty mammoplasty patients were enrolled and followed for 1 year. At the end of the mammoplasty procedure, all patients received tSVF in the lateral 5 cm of the horizontal scar of 1 breast and a placebo injection in the contralateral breast to serve as an intrapatient control. Primary outcome was scar quality measure by the Patient and Observer Scar Assessment Scale (POSAS). Secondary outcomes were obtained from photographic evaluation and histologic analysis of scar tissue samples. Results Thirty-four of 40 patients completed follow-up. At 6 months postoperation, injection of tSVF had significantly improved postoperative scar appearance as assessed by the POSAS questionnaire. No difference was observed at 12 months postoperation. No improvement was seen based on the evaluation of photographs and histologic analysis of postoperative scars between both groups. Conclusions Injection of tSVF resulted in improved wound healing and reduced scar formation at 6 months postoperation, without any noticeable advantageous effects seen at 12 months. Level of Evidence: 2

RATIONALE & OBJECTIVE: Heavy metals are known to induce kidney damage and recent studies have linked minor exposures to cadmium and arsenic with increased risk of kidney allograft failure, yet the potential association of lead (Pb) with late graft failure in kidney transplant recipients (KTR) remains unknown.STUDY DESIGN: Prospective cohort study in the Netherlands.SETTING & PARTICIPANTS: We studied outpatient KTR (n=670) with a functioning graft for ≥1 year recruited at a university setting (2008-2011, NCT02811835) and followed, on average, for 4.9 (IQR, 3.4‒5.5) years. Additionally, end-stage kidney disease patients (n=46) enrolled in the ongoing TransplantLines Cohort and Biobank Study (2016-2017, NCT03272841) were studied at admission for transplantation and at 3, 6, 12, and 24 months after transplantation.EXPOSURE: Plasma Pb was log2 transformed to estimate the association with outcomes per doubling of plasma Pb concentration and also considered categorically as tertiles of the Pb distribution.OUTCOME: Kidney graft failure (restart of dialysis or re-transplantation) with the competing event of death with a functioning graft.ANALYTICAL APPROACH: Multivariable-adjusted cause-specific hazards models where follow-up of KTR who died with a functioning graft was censored.RESULTS: Median baseline plasma Pb was 0.31 (IQR, 0.22─0.45) μg/L among all KTRs. During follow-up, 78 (12%) KTR developed graft failure. Higher plasma Pb was associated with increased risk of graft failure (HR 1.59, 95% CI 1.14‒2.21 per doubling; P=0.006) independent of age, sex, transplant characteristics, eGFR, proteinuria, smoking status, alcohol intake, and plasma concentrations of cadmium and arsenic. These findings remained materially unchanged after additional adjustment for dietary intake and were consistent with those of analyses examining Pb categorically. In serial measurements, plasma Pb was significantly higher at admission for transplantation than at 3-months post-transplant (P=0.001), after which it remained stable over 2 years of follow-up (P=0.2).LIMITATIONS: Observational study design.CONCLUSIONS: Pretransplant plasma Pb concentrations, which fall after transplantation, are associated with increased risk of late kidney allograft failure. These findings warrant further studies to evaluate whether preventive or therapeutic interventions to decrease plasma Pb may represent novel risk-management strategies to decrease the rate of kidney allograft failure.

Background Health literacy is the ability to deal with information related to one’s health. Patients with low health literacy have poor disease-management skills for chronic diseases, such as chronic kidney disease (CKD). This could influence the number and combination of their diseases. Methods We included adult patients with CKD stages 1–5 from the Lifelines Study (n = 2,742). We assessed the association between low health literacy and the number and patterns of comorbidities, considering them globally and stratified by age and sex, using multinomial logistic regression and latent class analysis, respectively. Results Low health literacy was associated with a higher number of comorbidities in the crude models, and after adjustment for age, sex, eGFR, smoking, and BMI. In the crude model, the OR for low health literacy increased from 1.71 (1.25–2.33) for two comorbidities to 2.71 (2.00–3.68) for four comorbidities. In the fully-adjusted model, the associations remained significant with a maximum OR of 1.70 (1.16–2.49) for four comorbidities. The patterns of multimorbidity were similar for low and adequate health literacy, overall and by sex, bur tended to be different for patients older than 65. Older patients with low health literacy had higher comorbidity prevalence and a relatively greater share of cardiovascular, psychiatric, and central nervous system diseases. Conclusions Among CKD patients, low health literacy is associated with more multimorbidity. Health literacy is not associated with patterns of multimorbidity in younger patients, but a difference was observed in older ones. Improving low health literacy could be an intervention efficient also in decreasing multimorbidity in CKD patients. Graphical abstract

Background: Improving maternal lifestyle before conception may prevent the adverse effects of maternal obesity on their children’s future cardiovascular disease (CVD) risk. In the current study, we examined whether a preconception lifestyle intervention in women with obesity could alter echocardiographic indices of cardiovascular health in their children. Methods: Six years after a randomized controlled trial comparing the effects of a 6-month preconception lifestyle intervention in women with obesity and infertility prior to fertility care to prompt fertility care, 315 of the 341 children conceived within 24 months after randomization were eligible for this study. The intervention was aimed at weight loss (≥5% or until BMI < 29 kg/m 2). Children underwent echocardiographic assessment of cardiac structure and function, conducted by a single pediatric cardiologist, blinded to group allocation. Results were adjusted for multiple variables including body surface area, age, and sex in linear regression analyses. Results: Sixty children (32 girls, 53%) were included, mean age 6.5 years (SD 1.09). Twenty-four children (40%) were born to mothers in the intervention group. Children of mothers from the intervention group had a lower end-diastolic interventricular septum thickness (−0.88 Z-score, 95%CI −1.18 to −0.58), a lower left ventricle mass index (−8.56 g/m 2, 95%CI −13.09 to −4.03), and higher peak systolic and early diastolic annular velocity of the left ventricle (1.43 cm/s 95%CI 0.65 to 2.20 and 2.39 cm/s 95%CI 0.68 to 4.11, respectively) compared to children of mothers from the control group. Conclusions: Children of women with obesity, who underwent a preconception lifestyle intervention, had improved cardiac structure and function; a thinner interventricular septum, lower left ventricle mass, and improved systolic and diastolic tissue Doppler velocities. Despite its high attrition rates, our study provides the first experimental human evidence suggesting that preconception lifestyle interventions may present a method of reducing CVD risk in the next generation. Clinical trial registration: LIFEstyle study: Netherlands Trial Register: NTR1530 (https://www.trialregister.nl/trial/1461). This follow-up study was approved by the medical ethics committee of the University Medical Centre Groningen (METC code: 2008/284).

Background: Experimental and epidemiological studies indicate an association between exposure to particulate matter (PM) air pollution and increased risk of type 2 diabetes. In view of the high and increasing prevalence of diabetes, we aimed to quantify the burden of type 2 diabetes attributable to PM2·5 originating from ambient and household air pollution.Methods: We systematically compiled all relevant cohort and case-control studies assessing the effect of exposure to household and ambient fine particulate matter (PM2·5) air pollution on type 2 diabetes incidence and mortality. We derived an exposure–response curve from the extracted relative risk estimates using the MR-BRT (meta-regression—Bayesian, regularised, trimmed) tool. The estimated curve was linked to ambient and household PM2·5 exposures from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019, and estimates of the attributable burden (population attributable fractions and rates per 100 000 population of deaths and disability-adjusted life-years) for 204 countries from 1990 to 2019 were calculated. We also assessed the role of changes in exposure, population size, age, and type 2 diabetes incidence in the observed trend in PM2·5-attributable type 2 diabetes burden. All estimates are presented with 95% uncertainty intervals.Findings: In 2019, approximately a fifth of the global burden of type 2 diabetes was attributable to PM2·5 exposure, with an estimated 3·78 (95% uncertainty interval 2·68–4·83) deaths per 100 000 population and 167 (117–223) disability-adjusted life-years (DALYs) per 100 000 population. Approximately 13·4% (9·49–17·5) of deaths and 13·6% (9·73–17·9) of DALYs due to type 2 diabetes were contributed by ambient PM2·5, and 6·50% (4·22–9·53) of deaths and 5·92% (3·81–8·64) of DALYs by household air pollution. High burdens, in terms of numbers as well as rates, were estimated in Asia, sub-Saharan Africa, and South America. Since 1990, the attributable burden has increased by 50%, driven largely by population growth and ageing. Globally, the impact of reductions in household air pollution was largely offset by increased ambient PM2·5.Interpretation: Air pollution is a major risk factor for diabetes. We estimated that about a fifth of the global burden of type 2 diabetes is attributable PM2·5 pollution. Air pollution mitigation therefore might have an essential role in reducing the global disease burden resulting from type 2 diabetes.Funding: Bill & Melinda Gates Foundation.

BACKGROUND: Postoperative pancreatic fistula is a frequent and potentially lethal complication after pancreatoduodenectomy. Several models have been developed to predict postoperative pancreatic fistula risk. This study was performed to evaluate the quality of reporting of postoperative pancreatic fistula prediction models after pancreatoduodenectomy using the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) checklist that provides guidelines on reporting prediction models to enhance transparency and to help in the decision-making regarding the implementation of the appropriate risk models into clinical practice. METHODS: Studies that described prediction models to predict postoperative pancreatic fistula after pancreatoduodenectomy were searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The TRIPOD checklist was used to evaluate the adherence rate. The area under the curve and other performance measures were extracted if reported. A quadrant matrix chart is created to plot the area under the curve against TRIPOD adherence rate to find models with a combination of above-average TRIPOD adherence and area under the curve. RESULTS: In total, 52 predictive models were included (23 development, 15 external validation, 4 incremental value, and 10 development and external validation). No risk model achieved 100% adherence to the TRIPOD. The mean adherence rate was 65%. Most authors failed to report on missing data and actions to blind assessment of predictors. Thirteen models had an above-average performance for TRIPOD checklist adherence and area under the curve. CONCLUSION: Although the average TRIPOD adherence rate for postoperative pancreatic fistula models after pancreatoduodenectomy was 65%, higher compared to other published models, it does not meet TRIPOD standards for transparency. This study identified 13 models that performed above average in TRIPOD adherence and area under the curve, which could be the appropriate models to be used in clinical practice.

We examine how project complexity influences the choice of a project management strategy and present a framework that facilitates managers in selecting a suitable project management strategy. We distinguish the complexity of project domains from two dimensions, the degree of structural complexity and the degree of dynamic complexity, resulting in four generic project types. Four generic project management strategies are identified that match these project types. This complexity framework for project management allows key players to determine a better project management strategy and related practices given its content, the internal context, and the external environment.

Background: Respiratory syncytial virus (RSV) causes a considerable disease burden in young children globally, but reliable estimates of RSV-related costs and health-related quality-of-life (HRQoL) are scarce. This study aimed to evaluate the RSV-associated costs and HRQoL effects in infants and their caregivers in four European countries. Methods: Healthy term-born infants were recruited at birth and actively followed up in four European countries. Symptomatic infants were systematically tested for RSV. Caregivers recorded the daily HRQoL of their child and themselves, measured by a modified EQ-5D with Visual Analogue Scale, for 14 consecutive days or until symptoms resolved. At the end of each RSV episode, caregivers reported healthcare resource use and work absenteeism. Direct medical costs per RSV episode were estimated from a healthcare payer’s perspective and indirect costs were estimated from a societal perspective. Means and 95% confidence intervals (CI) of direct medical costs, total costs (direct costs + productivity loss) and quality-adjusted life-day (QALD) loss per RSV episode were estimated per RSV episode, as well as per subgroup (medical attendance, country). Results: Our cohort of 1041 infants experienced 265 RSV episodes with a mean symptom duration of 12.5 days. The mean (95% CI) cost per RSV episode was €399.5 (242.3, 584.2) and €494.3 (317.7, 696.1) from the healthcare payer’s and societal perspective, respectively. The mean QALD loss per RSV episode of 1.9 (1.7, 2.1) was independent of medical attendance (in contrast to costs, which also differed by country). Caregiver and infant HRQoL evolved similarly. Conclusion: This study fills essential gaps for future economic evaluations by prospectively estimating direct and indirect costs and HRQoL effects on healthy term infants and caregivers separately, for both medically attended (MA) and non-MA laboratory-confirmed RSV episodes. We generally observed greater HRQoL losses than in previous studies which used non-community and/or non-prospective designs.

Consumer wearables health data may reflect the impact of pancreatic cancer and its treatment on cardiorespiratory fitness and the subsequent recovery after treatment. The patient is a 65-year-old male treated for borderline resectable pancreatic cancer. Treatment consisted of four courses of FOLFIRINOX neoadjuvant chemotherapy, a Whipple procedure with a right hemicolectomy and venous segment resection, and eight courses of adjuvant FOLFIRINOX chemotherapy. Physical activity and moderate to vigorous physical activity declined after the onset of symptoms, increased in the weeks before surgery, declined after surgery and then gradually recovered during and after adjuvant chemotherapy. Estimated VO2max remained stable during neoadjuvant chemotherapy, sharply decreased after surgery and then gradually recovered. Heart rate at rest increased and heart rate variability decreased after the onset of symptoms reaching their highest and lowest values after surgery. Both gradually returned to baseline seven months after the last course of chemotherapy. The physical impact of pancreatic cancer and its treatment and recovery was in this case reflected on consumer wearable health data. Seven months after the last chemotherapy recovery was close to baseline values.

Smart inhalers are electronic monitoring devices which are promising in increasing medication adherence and maintaining asthma control. A multi-stakeholder capacity and needs assessment is recommended prior to implementation in healthcare systems. This study aimed to explore perceptions of stakeholders and to identify anticipated facilitators and barriers associated with the implementation of smart digital inhalers in the Dutch healthcare system. Data were collected through focus group discussions with female patients with asthma (n = 9) and healthcare professionals (n = 7) and through individual semi-structured interviews with policy makers (n = 4) and smart inhaler developers (n = 4). Data were analysed using the Framework method. Five themes were identified: (i) perceived benefits, (ii) usability, (iii) feasibility, (iv) payment and reimbursement, and (v) data safety and ownership. In total, 14 barriers and 32 facilitators were found among all stakeholders. The results of this study could contribute to the design of a tailored implementation strategy for smart inhalers in daily practice.

PurposeThe Lifelines Reproductive Origins of Adult Health and Disease (Lifelines-ROAHD) cohort provides a uniquely detailed dataset allowing investigations of determinants of reproductive health as well as the influence of reproductive events on future health and disease of mother and child(ren). Lifelines-ROAHD cohort is embedded in the population-based Lifelines cohort study.ParticipantsIn total, 5412 women of reproductive age (20–45 years) were included in the Lifelines-ROAHD cohort, in the period 2017–2018.Findings to dateIn the population, 45.6% of the women indicated that they had a natural menstrual cycle. In total, 908 women (16.8%) consulted a healthcare provider for infertility; subsequently diagnosed fertility problems were anovulation (24.4%), male partner infertility problems (22.5%) or unexplained infertility (22.2%). Women underwent various consecutive assisted reproductive treatments, for example, ovulation induction (19.8%) or in vitro fertilisation (5.4%). In total, 2808 women experienced 6158 pregnancies and 5068 births. Adverse pregnancy outcomes were miscarriage (14.3%), ectopic pregnancy (0.9%) or termination of pregnancy or medical abortion (2.0 %). The modes of delivery were vaginal births (74.9%), instrumental vaginal births (11.9%), elective caesarean section (3.9%) and emergency caesarean section (9.3%). Birth outcomes were born alive at term (93.6%), born alive (very) pre-term (5.8%), stillbirth (0.316%) and neonatal death (0.197%). Additional data about 2660 most recent pregnancies showed that 19.9% of the women had irregular working hours. One year postpartum, women indicated adverse physical health issues in one or more domains, range 0.5%–12.5%. They also indicated adverse psychological health issues in one or more domains, range 0.7%–1.6%, and 1.6% experienced diminished sexual health.Future plansDue to the embedding of Lifelines-ROAHD cohort in the original Lifelines cohort, the women will be longitudinally followed. Additionally, we aim to collect data with a second online questionnaire aiming to complete women’s reproductive histories, by collecting data about potential first and subsequent pregnancies conceived after the date of completion of baseline Lifelines-ROAHD cohort.

In het Nederlandse zorgstelsel is het zorgaanbod niet langer groter dan de vraag. Concurrentie is verleden tijd en de zoektocht naar een nieuwe basis is begonnen. De balans tussen zorg en gezondheid moet worden hersteld. Regio’s krijgen een centralere rol en wettelijk verankerde gezondheidsdoelen staan op de agenda. Hoe komt dit nieuwe stelsel eruit te zien?

BACKGROUND: The aim of this study is to explore problems in radiotherapy for breast cancer patients in Yogyakarta, Indonesia, focusing on overall treatment time (OTT) and completion rate.METHODS: A retrospective cohort study was conducted based on data from the Insurance Unit at a tertiary hospital in Yogyakarta, Indonesia. The study included all female outpatients with breast cancer who were treated with radiotherapy from January to December 2017 and met the inclusion criteria. The primary outcomes were OTT and completion rate. The secondary outcomes included the number of radiotherapy fractions, radiotherapy doses, number of radiotherapy interruption days, and reasons for radiotherapy interruption. The chi-squared and Mann-Whitney U tests were used to assess the differences in outcomes between two insurance schemes (JKN-PBI (Beneficiaries of Health Insurance Contribution Assistance) and JKN-NON-PBI (Non-Beneficiaries of Health Insurance Contribution Assistance)).RESULTS: The sample included 285 breast cancer patients (mean age: 53 years). The median OTT was 38 days (IQR: 17-48 days), with 123 (43.2%) patients having prolonged OTT. The completion rate was 57.9%. No significant differences in OTT (44.4% vs. 35.7%, p = 0.445) and completion rate (57.2% vs. 61.9%, p = 0.569) were found between the JKN-NON-PBI and JKN-PBI groups, respectively. In all, the data reported 3,022 interrupted days of radiotherapy across a total of 227 patients. The most common reason for radiotherapy interruption was unknown.CONCLUSION: There are problems in timely delivery and low completion rate of radiotherapy among breast cancer patients in Indonesia. There are no significant differences in OTT and completion rate between the insurance schemes.

Background Diabetic retinopathy (DR) is a microvascular complication of diabetes highly associated to cardiovascular disease and diabetic kidney disease. However, these associations are not thoroughly investigated at an early type 2 diabetes disease stage. This study therefore evaluated the association between baseline DR status and development of cardiovascular events (CVEs), microalbuminuria, and kidney function decline and in persons with type 2 diabetes and normal urinary albumin excretion. Methods Post-hoc analysis of the PRIORITY study including 1758 persons with type 2 diabetes and normoalbuminuria followed for a median of 2.5 (IQR: 2.0–3.0) years. The study was originally designed to investigate a urinary proteomic risk classifier predictor of microalbuminuria development. DR at baseline was defined as non-proliferative and proliferative abnormalities, macular oedema, or history of laser treatment. Cox models were fitted to investigate the association of DR status with development of 1) a CVE composite defined as non-fatal myocardial infarction, stroke, coronary artery bypass graft, percutaneous coronary intervention, hospitalization for heart failure, or all-cause mortality; 2) persistent microalbuminuria (urinary albumin-creatinine ratio > 30mg/g); and 3) chronic kidney disease (CKD) G3 (eGFR 2). Models were adjusted for relevant risk factors. Results At baseline, 304 (17.3%) had DR. Compared to persons without DR, they were older (mean ± SD: 62.7 ± 7.7 vs 61.4 ± 8.3 years, p = 0.019), had longer diabetes duration (17.9 ± 8.4 vs. 10.6 ± 7.0 years, p 1c (62 ± 13 vs. 56 ± 12 mmol/mol, p

Contains fulltext : 291422.pdf (Publisher’s version ) (Open Access) BACKGROUND: Large inter-surgeon variability exists in technical anatomical resectability assessment of colorectal cancer liver-only metastases (CRLM) following induction systemic therapy. We evaluated the role of tumour biological factors in predicting resectability and (early) recurrence after surgery for initially unresectable CRLM. METHODS: 482 patients with initially unresectable CRLM from the phase 3 CAIRO5 trial were selected, with two-monthly resectability assessments by a liver expert panel. If no consensus existed among panel surgeons (i.e. same vote for (un)resectability of CRLM), conclusion was based on majority. The association of tumour biological (sidedness, synchronous CRLM, carcinoembryonic antigen and RAS/BRAF(V600E) mutation status) and technical anatomical factors with consensus among panel surgeons, secondary resectability and early recurrence (

Background One of the challenges in living kidney donor screening is to estimate remaining kidney function after donation. Here we developed a new model to predict post-donation measured glomerular filtration rate (mGFR) from pre-donation serum creatinine, age and sex. Methods In the prospective development cohort (TransplantLines, n = 511), several prediction models were constructed and tested for accuracy, precision and predictive capacity for short- and long-term post-donation 125I-iothalamate mGFR. The model with optimal performance was further tested in specific high-risk subgroups (pre-donation eGFR 65 years) and validated in internal (n = 509) and external (Mayo Clinic, n = 1087) cohorts. Results In the development cohort, pre-donation estimated GFR (eGFR) was 86 ± 14 mL/min/1.73 m2 and post-donation mGFR was 64 ± 11 mL/min/1.73 m2. Donors with a pre-donation eGFR ≥90 mL/min/1.73 m2 (present in 43%) had a mean post-donation mGFR of 69 ± 10 mL/min/1.73 m2 and 5% of these donors reached an mGFR 65 years of age [bias 0.003 mL/min/1.73 m2 (IQR 9)]. Conclusions We developed a novel post-donation mGFR prediction model based on pre-donation serum creatinine, age and sex.

Background Urinary metabolites of vitamin E, i.e., α- and γ-carboxyethyl hydroxychroman (α- and γ-CEHC), have gained increasing attention and have been proposed as novel biomarkers of vitamin E intake and status. However, there are insufficient data on the relationship of plasma α-tocopherol and γ-tocopherol and dietary vitamin E intake with 24 h urinary excretions of α- and γ-CEHC. Objectives We aimed to (1) investigate the associations of urinary α- and γ-CEHC/creatinine ratios and 24 h urinary excretions of α- and γ-CEHC with plasma α- and γ-tocopherol, respectively; (2) investigate the associations of urinary α- and γ-CEHC/creatinine ratios and 24 h urinary excretions of α- and γ-CEHC with dietary vitamin E intake, and we hypothesize that 24 h urinary excretions of α- and γ-CEHC will better correlate with vitamin E intake than urinary α- and γ-CEHC/creatinine ratios. Design 24 h Urine and plasma samples were collected from 1519 participants (60–75 years, male: 50%) included in the Lifelines-MINUTHE Study for the assessments of urinary α- and γ-CEHC/creatinine ratios and 24 h urinary excretions of α- and γ-CEHC, and plasma α- and γ-tocopherol. Among those participants, dietary vitamin E intake data from 387 participants were available from an externally validated Flower-Food Frequency Questionnaire (FFQ). The associations of plasma α- and γ-tocopherol, dietary vitamin E intake, with urinary α- and γ-CEHC were assessed using multivariate linear regressions. Results 24 h Urinary excretion of α-CEHC (median (IQR): 0.9 (0.3–2.4) µmol) was less than that of γ-CEHC (median (IQR): 1.5 (0.5–3.5) µmol). After adjustment for covariates, we found that 24 h urinary α-CEHC excretion and urinary α-CEHC/creatinine ratio were both positively associated with plasma α-tocopherol (std.beta: 0.06, p = 0.02; std.beta: 0.06, p = 0.01, respectively). Furthermore, the sum of 24 h urinary α- and γ-CEHC excretions was positively associated with dietary vitamin E intake (std.beta: 0.08; p = 0.03), whereas there was no relation between urinary α- and γ-CEHC/creatinine ratios and vitamin E intake. No association was observed neither between plasma α- and γ-tocopherol and dietary vitamin E intake, nor between urinary γ-CEHC and plasma γ-tocopherol. Conclusion Our study confirmed our hypothesis that 24 h urinary α- and γ-CEHC excretions would be a better marker for dietary vitamin E intake than urinary α- and γ-CEHC/creatinine ratios. Considering that both 24 h urinary α- and γ-CEHC excretions and α- and γ-CEHC/creatinine ratios were also associated with plasma α-tocopherol status, we suggest that 24 h urinary α- and γ-CEHC excretions could be used to assess overall vitamin E status.

Background. The effect of pregnancy on the course of estimated glomerular filtration rate (eGFR) is unknown in kidney transplant recipients (KTRs). Methods. We conducted a nationwide multicenter cohort study in KTRs with pregnancy (>20 wk) after kidney transplantation (KT). Annual eGFRs after KT until death or graft loss and additional eGFRs before each pregnancy were collected according to protocol. Changes in eGFR slope before and after each pregnancy were analyzed by generalized estimating equations multilevel analysis adjusted for transplant vintage. Results. We included 3194 eGFR measurements before and after pregnancy in 109 (55%) KTRs with 1, 78 (40%) with 2, and 10 (5%) with 3 pregnancies after KT. Median follow-up after first delivery post-KT was 14 y (interquartile range, 18 y). Adjusted mean eGFR prepregnancy was 59 mL/min/1.73 m2(SEM [standard error of the mean] 1.72; 95% confidence interval [CI], 56-63), after the first pregnancy 56 mL/min/1.73 m2(SEM 1.70; 95% CI, 53-60), after the second pregnancy 56 mL/min/1.73 m2(SEM 2.19; 95% CI, 51-60), and after the third pregnancy 55 mL/min/1.73 m2(SEM 8.63; 95% CI, 38-72). Overall eGFR slope after the first, second, and third pregnancies was not significantly worse than prepregnancy (P = 0.28). However, adjusted mean eGFR after the first pregnancy was 2.8 mL/min/1.73 m2(P = 0.08) lower than prepregnancy. Conclusions. The first pregnancy has a small, but insignificant, effect on eGFR slope in KTRs. Midterm hyperfiltration, a marker for renal reserve capacity, was associated with better eGFR and death-censored graft survival. In this KTR cohort with long-term follow-up, no significant effect of pregnancy on kidney function was detected.

We estimate the association between parental housing wealth and children’s marriage prospects in China by drawing data from the China Health and Retirement Longitudinal Survey (CHARLS). We focus on children aged 16–35 who were unmarried in 2011 and track their marriage outcomes in 2015. Our results show that parental housing wealth acts as a signal for males in the Chinese marriage market, which is characterized by a strongly unbalanced sex ratio. Males are more likely to get married if their parents own high-value houses, especially among rural households. The relationship is not significant for females.

Background Patients with potentially curable esophageal cancer can be treated with neo-adjuvant chemoradiotherapy followed by surgery or definitive chemoradiotherapy with curative intent. For frail older patients choosing the appropriate oncological treatment can be difficult, and data on geriatric deficits as determinants of treatment outcomes are not yet available. Objectives To describe the prevalence of geriatric deficits and to study their association with treatment discontinuation and mortality in older patients with potentially curable esophageal cancer. Material and Methods A cohort study was conducted in a Dutch tertiary care hospital including patients aged >= 70 years with primary stage I-IVA esophageal cancer. Geriatric screening and assessment data were collected. Outcomes were treatment discontinuation and one year all-cause mortality. Results In total, 138 patients with curable esophageal cancer were included. Mean age was 76.1 years (standard deviation 4.7), 54% had clinical stage III and 24% stage IVA disease. Most patients received neo-adjuvant chemoradiotherapy and surgery (41%), 32% definitive chemoradiotherapy and 22% palliative radiotherapy. Overall, one year all-cause mortality was 36%. Geriatric screening and assessment was performed in 94 out of 138 patients, of which 60% was malnourished, 20% dependent in Instrumental Activities of Daily Living (IADL) and 52% was frail. Malnutrition was associated with higher mortality risk (Hazard Ratio, 3.2; 95% Confidence Interval, 1.3-7.7)) independent of age, sex and tumor stage. Seventy-six out of 94 patients were treated with chemoradiotherapy, of which 23% discontinued treatment. Patients with IADL dependency and Charlson Comorbidity Index >= 1 discontinued treatment more often. Conclusion All-cause mortality within one year was high, irrespective of treatment modality. Treatment discontinuation rate was high, especially in patients treated with definitive chemoradiotherapy. Geriatric assessment associates with outcomes in older patients with esophageal cancer and may inform treatment decisions and optimization in future patients, but more research is needed to establish its predictive value.