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Background Little is known about the burden that overweight and obesity impose on Dutch society. The aim of this study is to examine this burden in terms of cost-of-illness and health-related quality of life. Method A bottom-up, prevalence-based burden of disease study from a societal perspective was performed. Cost-of-illness information including healthcare costs, patient and family costs, and other costs was obtained via the Treatment Inventory of Costs in Patients with psychiatric disorders (TiC-P) questionnaire. Health-related quality of life was assessed through the EuroQol (EQ-5D-5L) and the BODY-Q instruments. Non-parametric bootstrapping was applied to test for significant differences in costs. Subgroup analyses were performed on all outcomes. Results A total of 97 people with overweight and obesity completed the survey. Per respondent, mean healthcare costs were €2907, patient and family costs were €4037, and other costs were €4519, leading to a total societal cost of €11,463 per respondent per year. Total costs were significantly higher for respondents with obesity versus overweight and between low & intermediate versus highly educated respondents. The mean utility score of our population was 0.81. A significantly lower utility score was found for respondents with obesity in comparison with respondents with overweight. BODY-Q results show that respondents with obesity scored a significantly lower Rasch-score than did respondents with overweight in three scales. Respondents with a high education level and having paid work scored significantly higher Rasch-scores in two scales than did those with a low education level and without having paid work. The age group 19–29 have significantly higher Rasch-scores in three scales than respondents in the other two age categories. Conclusions Overweight and obesity have a considerable impact on the societal costs and on health-related quality of life. The results show that the impact of overweight and obesity go beyond the healthcare sector, as the other costs have the biggest share of the total costs. Another interesting finding of this study is that obesity leads to significant higher costs and lower health-related quality of life than overweight. These findings draw attention to policy making, as collective prevention and effective treatment are needed to reduce this burden.

Some anesthetics and sedatives have been shown to cause neurotoxic effects in laboratory animals. The FDA collaboration SmartTots recommends undertaking large-scale clinical studies and avoiding nonurgent surgical procedures requiring anesthesia in children younger than 3 years of age. General anesthetic and sedative drugs are administered to millions of infants, toddlers, and preschool children each year to facilitate life-saving surgery and other essential surgical or medical procedures. In the past two decades, mounting data from animal and observational human studies have raised concerns that general anesthetics may cause neurotoxic changes in the developing brain that lead to adverse neurodevelopmental outcomes later in life. To address the growing concern about the potential adverse consequences of general anesthesia in young patients, in 2009 the Food and Drug Administration (FDA) established a public–private partnership with the International Anesthesia Research Society (IARS) called . . .

To assess the association between muscle parameters (mass, strength, physical performance) and activities of daily living (ADL), quality of life (QoL), and health care costs. Cross-sectional Maastricht Sarcopenia Study (MaSS). Community-dwelling, assisted-living, residential living facility. 227 adults aged 65 and older. Muscle mass, hand grip strength and physical performance were assessed by bio-electrical impedance, JAMAR dynamometer and the Short Physical Performance Battery, respectively. Health outcomes were measured by the Groningen Activity Restriction Scale (disability in ADL) and the EQ-5D-5L (QoL). Health care costs were calculated based on health care use in the past three months. Muscle strength and physical performance showed a strong correlation with ADL, QoL, and health care costs (P<.01); for muscle mass no significant correlations were observed. Regression analyses showed that higher gait speed (OR 0.06, 95%CI 0.01-0.55) was associated with a lower probability of ADL disability. Furthermore, slower chair stand (OR 1.23, 95%CI 1.08-1.42), and more comorbidities (OR 1.58, 95%CI 1.23-2.02) were explanatory factors for higher ADL disability. Explanatory factors for QoL and costs were: more disability in ADL (OR 1.26, 95%CI 1.12-1.41 for QoL; B = 0.09, P<.01 for costs) and more comorbidities (OR 1.44, 95%CI 1.14-1.82 for QoL; B = 0.35, P<.01 for costs). Lower gait speed and chair stand were potential drivers of disability in ADL. Disability in ADL and comorbidities were associated with QoL and health care costs in community-dwelling older adults. Improving physical performance may be a valuable target for future intervention and research to impact health burden and costs.

SummaryAn earlier systematic review on interventions to improve adherence and persistence was updated. Fifteen studies investigating the effectiveness of patient education, drug regimen, monitoring and supervision, and interdisciplinary collaboration as a single or multi-component intervention were appraised. Multicomponent interventions with active patient involvement were more effective.IntroductionThis study was conducted to update a systematic literature review on interventions to improve adherence to anti-osteoporosis medications.MethodsA systematic literature review was carried out in Medline (using PubMed), Embase (using Ovid), Cochrane Library, Current Controlled Trials, ClinicalTrials.gov, NHS Centre for Review and Dissemination, CINHAL, and PsycINFO to search for original studies that assessed interventions to improve adherence (comprising initiation, implementation, and discontinuation) and persistence to anti-osteoporosis medications among patients with osteoporosis, published between July 2012 and December 2018. Quality of included studies was assessed.ResultsOf 585 studies initially identified, 15 studies fulfilled the inclusion criteria of which 12 were randomized controlled trials. Interventions were classified as (1) patient education (n = 9), (2) drug regimen (n = 3), (3) monitoring and supervision (n = 2), and (4) interdisciplinary collaboration (n = 1). In most subtypes of interventions, mixed results on adherence (and persistence) were found. Multicomponent interventions based on patient education and counseling were the most effective interventions when aiming to increase adherence and/or persistence to osteoporosis medications.ConclusionThis updated review suggests that patient education, monitoring and supervision, change in drug regimen, and interdisciplinary collaboration have mixed results on medication adherence and persistence, with more positive effects for multicomponent interventions with active patient involvement. Compared with the previous review, a shift towards more patient involvement, counseling and shared decision-making, was seen, suggesting that individualized solutions, based on collaboration between the patient and the healthcare provider, are needed to improve adherence and persistence to osteoporosis medications.

Neurosteroids are endogenous modulators of neuronal excitability and nervous system development and are being developed as anesthetic agents and treatments for psychiatric diseases. While gamma amino-butyric acid Type A (GABAA) receptors are the primary molecular targets of neurosteroid action, the structural details of neurosteroid binding to these proteins remain ill defined. We synthesized neurosteroid analogue photolabeling reagents in which the photolabeling groups were placed at three positions around the neurosteroid ring structure, enabling identification of binding sites and mapping of neurosteroid orientation within these sites. Using middle-down mass spectrometry (MS), we identified three clusters of photolabeled residues representing three distinct neurosteroid binding sites in the human α1β3 GABAA receptor. Novel intrasubunit binding sites were identified within the transmembrane helical bundles of both the α1 (labeled residues α1-N408, Y415) and β3 (labeled residue β3-Y442) subunits, adjacent to the extracellular domains (ECDs). An intersubunit site (labeled residues β3-L294 and G308) in the interface between the β3(+) and α1(-) subunits of the GABAA receptor pentamer was also identified. Computational docking studies of neurosteroid to the three sites predicted critical residues contributing to neurosteroid interaction with the GABAA receptors. Electrophysiological studies of receptors with mutations based on these predictions (α1-V227W, N408A/Y411F, and Q242L) indicate that both the α1 intrasubunit and β3-α1 intersubunit sites are critical for neurosteroid action.

In this trial comparing two protocols designed to reduce the risk of intraoperative awareness, a protocol that used the EEG-derived bispectral index was not superior to a protocol incorporating standard monitoring of end-tidal anesthetic-gas concentration. Unintended intraoperative awareness is defined as the experience and explicit recall of sensory perceptions during surgery, 1 which can lead to post-traumatic stress disorder in as many as 70% of those who experience it. 2 In patients at high risk for intraoperative awareness, the incidence of awareness may approach 1%. 3 – 5 An estimated 20,000 to 40,000 patients experience awareness yearly in the United States alone. 1 Some cases of awareness might occur as a result of inadequate anesthetic dosing 6 and therefore constitute potentially preventable medical errors. 7 A potent inhaled anesthetic agent is incorporated in the majority of general anesthetics, and concentrations of exhaled . . .

Neurosteroids (NS) are a class of steroids that are synthesized within the central nervous system (CNS). Various NS can either enhance or inhibit CNS excitability and they play important biological roles in brain development, brain function and as mediators of mood. One class of NS, 3α-hydroxy-pregnane steroids such as allopregnanolone (AlloP) or pregnanolone (Preg), inhibits neuronal excitability; these endogenous NS and their analogues have been therapeutically applied as anti-depressants, anti-epileptics and general anesthetics. While NS have many favorable properties as anesthetics (e.g. rapid onset, rapid recovery, minimal cardiorespiratory depression, neuroprotection), they are not currently in clinical use, largely due to problems with formulation. Recent advances in understanding NS mechanisms of action and improved formulations have rekindled interest in development of NS as sedatives and anesthetics. In this review, the synthesis of NS, and their mechanism of action will be reviewed with specific emphasis on their binding sites and actions on γ-aminobutyric acid type A (GABA A ) receptors. The potential advantages of NS analogues as sedative and anesthetic agents will be discussed.

PurposeNo clear consensus exists on which anterior surgical technique is most cost-effective for treating cervical degenerative disk disease (CDDD). One of the most common treatment options is anterior cervical discectomy with fusion (ACDF). Anterior cervical discectomy with arthroplasty (ACDA) was developed in an effort to reduce the incidence of clinical adjacent segment pathology and associated additional surgeries by preserving motion. This systematic review aims to evaluate the evidence regarding the cost-effectiveness of anterior surgical decompression techniques used to treat radiculopathy and/or myelopathy caused by CDDD.MethodsThe search was conducted in PubMed, EMBASE, Web of Science, CINAHL, EconLit, NHS-EED and the Cochrane Library. Studies were included if healthcare costs and utility or effectivity measurements were mentioned.ResultsA total of 23 studies were included out of the 1327 identified studies. In 9 of the 13 studies directly comparing ACDA and ACDF, ACDA was the most cost-effective technique, with an incremental cost effectiveness ratio ranging from $2.900/QALY to $98.475/QALY. There was great heterogeneity between the costs of due to different in- and exclusion criteria of costs and charges, cost perspective, baseline characteristics, and calculation methods. The methodological quality of the included studies was moderate.ConclusionThe majority of studies report ACDA to be a more cost-effective technique in comparison with ACDF. The lack of uniform literature impedes any solid conclusions to be drawn. There is a need for high-quality cost-effectiveness research and uniformity in the conduct, design and reporting of economic evaluations concerning the treatment of CDDD.Trial registrationPROSPERO Registration: CRD42020207553 (04.10.2020).

Computerised cognitive-behavioural therapy (CCBT) might offer a solution to the current undertreatment of depression. To determine the clinical effectiveness of online, unsupported CCBT for depression in primary care. Three hundred and three people with depression were randomly allocated to one of three groups: Colour Your Life; treatment as usual (TAU) by a general practitioner; or Colour Your Life and TAU combined. Colour Your Life is an online, multimedia, interactive CCBT programme. No assistance was offered. We had a 6-month follow-up period. No significant differences in outcome between the three interventions were found in the intention-to-treat and per protocol analyses. Online, unsupported CCBT did not outperform usual care, and the combination of both did not have additional effects. Decrease in depressive symptoms in people with moderate to severe depression was moderate in all three interventions. Online CCBT without support is not beneficial for all individuals with depression.

Perioperative organ injury contributes to morbidity and mortality of surgical patients. This cohort study included all elective and emergent surgeries in Germany over 4 years to address the impact of perioperative organ injuries on outcomes. We analyzed 28,350,953 cases. In-hospital mortality was 1.4% ( n  = 393,157), and 4.4% of cases ( n  = 1,245,898) experienced perioperative organ injury. Perioperative organ injury was associated with 9-fold higher odds of death and prolonged hospital stay by 11.2 days. Acute kidney injury had the highest incidence (2.0%) and was associated with 25.0% mortality. While delirium had the second highest incidence (1.5%), it was associated with the lowest mortality (10.8%). This was followed by acute myocardial infarction (incidence 0.6%, mortality 15.6%), stroke (incidence 0.6%, mortality 13.1%), pulmonary embolism (incidence 0.3%, mortality 20.0%), liver injury (incidence 0.1%, mortality 68.7%), and acute respiratory distress syndrome (incidence 0.1%, mortality 44.7%). These findings help prioritize interventions for preventing or treating individual types of perioperative organ injury. The impact of perioperative organ injury on surgical outcome is not well understood. Here the authors show the overall impact and the impact of individual perioperative organ injuries in 28 million surgical patients in Germany.