Assessing the excess costs of the in-hospital adverse events covered by the AHRQ's Patient Safety Indicators in Switzerland.

There currently exists no comprehensive and up-to date overview on the financial impact of the different adverse events covered by the Patient Safety Indicators (PSIs) from the Agency for Healthcare Research and Quality. We conducted a retrospective case-control study using propensity score matching on a national administrative data set of 1 million inpatients in Switzerland to compare excess costs associated with 16 different adverse events both individually and on a nationally aggregated level. After matching 8,986 cases with adverse events across the investigated PSIs to 26,931 controls, we used regression analyses to determine the excess costs associated with the adverse events and to control for other cost-related influences. The average excess costs associated with the PSI-related adverse events ranged from CHF 1,211 (PSI 18, obstetric trauma with instrument) to CHF 137,967 (PSI 10, postoperative acute kidney injuries) with an average of CHF 27,409 across all PSIs. In addition, adverse events were associated with 7.8-day longer stays, 2.5 times more early readmissions (within 18 days), and 4.1 times higher mortality rates on average. At a national level, the PSIs were associated with CHF 347 million higher inpatient costs in 2019, which corresponds to about 2.2% of the annual inpatient costs in Switzerland. By comparing the excess costs of different PSIs on a nationally aggregated level, we offer a financial perspective on the implications of in-hospital adverse events and provide recommendations for policymakers regarding specific investments in patient safety to reduce costs and suffering.

An overview of reviews and synthesis across 440 studies examines the importance of hospital readmission predictors across various patient populations.

OBJECTIVES: The scientific literature contains an abundance of prediction models for hospital readmissions. However, no review has yet synthesized their predictors across various patient populations. Therefore, our aim was to examine predictors of hospital readmissions across 13 patient populations. STUDY DESIGN AND SETTING: An overview of systematic reviews was combined with a meta-analytical approach. Two thousand five hundred four different predictors were categorized using common ontologies to pool and examine their odds ratios and frequencies of use in prediction models across and within different patient populations. RESULTS: Twenty-eight systematic reviews with 440 primary studies were included. Numerous predictors related to prior use of healthcare services (odds ratio; 95% confidence interval: 1.64; 1.42-1.89), diagnoses (1.41; 1.31-1.51), health status (1.35; 1.20-1.52), medications (1.28; 1.13-1.44), administrative information about the index hospitalization (1.23; 1.14-1.33), clinical procedures (1.20; 1.07-1.35), laboratory results (1.18; 1.11-1.25), demographic information (1.10; 1.06-1.14), and socioeconomic status (1.07; 1.02-1.11) were analyzed. Diagnoses were frequently used (in 37.38%) and displayed large effect sizes across all populations. Prior use of healthcare services showed the largest effect sizes but were seldomly used (in 2.57%), whereas demographic information (in 13.18%) was frequently used but displayed small effect sizes. CONCLUSION: Diagnoses and patients' prior use of healthcare services showed large effects both across and within different populations. These results can serve as a foundation for future prediction modeling.

Patient-reported experience is associated with higher future revenue and lower costs of hospitals.

BACKGROUND: Despite the established positive association between patient experience and patient volume, the relationship between patient experience and the financial performance of hospitals has not been studied thoroughly. METHODS: To investigate this relationship, we used longitudinal data from 132 Swiss acute-care hospitals from 2016 to 2019 to examine the associations between patient experience and the proportion of elective patients, revenue, costs, and profits of hospitals. To account for a potential time lag effect, we utilized annual patient experience data and employed multilevel mixed-effects regression modeling to investigate its association with the aforementioned financial performance indicators for the following year. RESULTS: Data for private and public hospitals were analyzed both separately and in combination, to account for the different proportions of elective patients in these types of hospitals. The resulting mixed models, revealed that for each year studied, the previous year's patient experience was positively associated with the current year's proportion of elective patients (ß = 0.09, p = 0.004, all hospitals) and revenue (ß = 1789.83, p = 0.037, private hospitals only), and negatively associated with costs (ß = - 1191.13, p = 0.017, all hospitals); but not significantly associated with future profits (ß = 629.12, p = 0.240, all hospitals). CONCLUSIONS: This analysis showed that better patient experience is associated with a higher proportion of elective patients, greater revenue, and lower costs. Our findings may assist hospital managers and regulators in identifying strategies to increase revenue and reduce costs.

Accounting for clustering in automated variable selection using hospital data: a comparison of different LASSO approaches.

BACKGROUND: Automated feature selection methods such as the Least Absolute Shrinkage and Selection Operator (LASSO) have recently gained importance in the prediction of quality-related outcomes as well as the risk-adjustment of quality indicators in healthcare. The methods that have been used so far, however, do not account for the fact that patient data are typically nested within hospitals. METHODS: Therefore, we aimed to demonstrate how to account for the multilevel structure of hospital data with LASSO and compare the results of this procedure with a LASSO variant that ignores the multilevel structure of the data. We used three different data sets (from acute myocardial infarcation, COPD, and stroke patients) with two dependent variables (one numeric and one binary), on which different LASSO variants with and without consideration of the nested data structure were applied. Using a 20-fold sub-sampling procedure, we tested the predictive performance of the different LASSO variants and examined differences in variable importance. RESULTS: For the metric dependent variable Duration Stay, we found that inserting hospitals led to better predictions, whereas for the binary variable Mortality, all methods performed equally well. However, in some instances, the variable importances differed greatly between the methods. CONCLUSION: We showed that it is possible to take the multilevel structure of data into account in automated predictor selection and that this leads, at least partly, to better predictive performance. From the perspective of variable importance, including the multilevel structure is crucial to select predictors in an unbiased way under consideration of the structural differences between hospitals.

Validity of 16 AHRQ Patient Safety Indicators to identify in-hospital complications: a medical record review across nine Swiss hospitals.

The validity of the Agency for Healthcare Research and Quality's Patient Safety Indicators (PSIs) has been established in the USA and Canada. However, these indicators are also used for hospital benchmarking and cross-country comparisons in other nations with different health-care settings and coding systems as well as missing present on admission (POA) flags in the administrative data. This study sought to comprehensively assess and compare the validity of 16 PSIs in Switzerland, where they have not been previously applied. We performed a medical record review using administrative and electronic medical record data from nine Swiss hospitals. Seven independent reviewers evaluated 1245 cases at various hospitals using retrospective data from the years 2014-18. True positives, false positives, positive predictive values (PPVs), and reasons for misclassification were compared across all investigated PSIs, and the documentation quality of the PSIs was examined. PSIs 6 (iatrogenic pneumothorax), 10 (postoperative acute kidney injury), 11 (postoperative respiratory failure), 13 (postoperative sepsis), 14 (wound dehiscence), 17 (birth trauma), and 18 and 19 (obstetric trauma with or without instrument) showed high PPVs (range: 90-99%) and were not strongly influenced by missing POA information. In contrast, PSIs 3 (pressure ulcer), 5 (retained surgical item), 7 (central venous catheter-related bloodstream infection), 8 (fall with hip fracture), and 15 (accidental puncture/laceration) showed low PPVs (range: 18-49%). In the case of PSIs 3, 8, and 12 (perioperative embolism/thrombosis), the low PPVs were largely due to the lack of POA information. Additionally, it was found that the documentation of PSI 3 in discharge letters could be improved. We found large differences in validity across the 16 PSIs in Switzerland. These results can guide policymakers in Switzerland and comparable health-care systems in selecting and prioritizing suitable PSIs for quality initiatives. Furthermore, the national introduction of a POA flag would allow for the inclusion of additional PSIs in quality monitoring.

Are temporal trends in retained foreign object rates after surgery in Switzerland impacted by increasing coding intensity? A retrospective analysis of hospital routine data from 2000 to 2019.

OBJECTIVES: Retained foreign objects (RFOs) after surgery can cause harm to patients and negatively impact clinician and hospital reputation. RFO incidence based on administrative data is used as a metric of patient safety. However, it is unknown how differences in coding intensity across hospitals and years impact the number of reported RFO cases. The objective of this study is to investigate the temporal trend of RFO incidence at a national level and the impact of changes in coding practices across hospitals and years. DESIGN: Retrospective study using administrative hospital data. SETTING AND PARTICIPANTS: 21 805 005 hospitalisations at 354 Swiss acute-care hospital sites PRIMARY AND SECONDARY OUTCOME MEASURES: RFO incidence over time, the distribution of RFOs across hospitals and the impact of differences in coding intensity across the hospitals and years. RESULTS: The annual RFO rate more than doubled between 2000 and 2019 (from 4.6 to 11.8 with a peak of 17.0 in 2014) and coincided with increasing coding intensity (mean number of diagnoses: 3.4, SD 2.0 in 2000; 7.40, SD 5.2 in 2019). After adjusting for patient characteristics, two regression models confirmed that coding intensity was a significant predictor of both whether RFO cases were reported at the hospital level (OR: 12.94; 95% CI: 7.38 to 22.68) and the number of reported cases throughout the period at the national level (Incidence Rate Ratio (IRR): 5.95; 95% CI: 1.11 to 31.82). CONCLUSIONS: Our results raise concerns about the use of RFO incidence for comparing hospitals, countries and years. Utilising coding indices could be employed to mitigate the effects of coding intensity on RFO rates.

Using exogenous organizational and regional hospital attributes to explain differences in case-mix adjusted hospital costs.

Diagnosis-related group (DRG) hospital reimbursement systems differentiate cases into cost-homogenous groups based on patient characteristics. However, exogenous organizational and regional factors can influence hospital costs beyond case-mix differences. Therefore, most countries using DRG systems incorporate adjustments for such factors into their reimbursement structure. This study investigates structural hospital attributes that explain differences in average case-mix adjusted hospital costs in Switzerland. Using rich patient and hospital-level data containing 4 million cases from 120 hospitals across 3 years, we show that a regression model using only five variables (number of discharges, ratio of emergency/ambulance admissions, rate of DRGs to patients, expected loss potential based on DRG mix, and location in large agglomeration) can explain more than half of the variance in average case-mix adjusted hospital costs, capture all cost variations across commonly differentiated hospital types (e.g., academic teaching hospitals, children's hospitals, birth centers, etc.), and is robust in cross-validations across several years (despite differing hospital samples). Based on our findings, we propose a simple practical approach to differentiate legitimate from inefficiency-related or unexplainable cost differences across hospitals and discuss the potential of such an approach as a transparent way to incorporate structural hospital differences into cost benchmarking and payment schemes.

Identification and assessment of a comprehensive set of structural factors associated with hospital costs in Switzerland.

Structural factors can influence hospital costs beyond case-mix differences. However, accepted measures on how to distinguish hospitals with regard to cost-related organizational and regional differences are lacking in Switzerland. Therefore, the objective of this study was to identify and assess a comprehensive set of hospital attributes in relation to average case-mix adjusted costs of hospitals. Using detailed hospital and patient-level data enriched with regional information, we derived a list of 23 cost predictors, examined how they are associated with costs, each other, and with different hospital types, and identified principal components within them. Our results showed that attributes describing size, complexity, and teaching-intensity of hospitals (number of beds, discharges, departments, and rate of residents) were positively related to costs and showed the largest values in university (i.e., academic teaching) and central general hospitals. Attributes related to rarity and financial risk of patient mix (ratio of rare DRGs, ratio of children, and expected loss potential based on DRG mix) were positively associated with costs and showed the largest values in children's and university hospitals. Attributes characterizing the provision of essential healthcare functions in the service area (ratio of emergency/ ambulance admissions, admissions during weekends/ nights, and admissions from nursing homes) were positively related to costs and showed the largest values in central and regional general hospitals. Regional attributes describing the location of hospitals in large agglomerations (in contrast to smaller agglomerations and rural areas) were positively associated with costs and showed the largest values in university hospitals. Furthermore, the four principal components identified within the hospital attributes fully explained the observed cost variations across different hospital types. These uncovered relationships may serve as a foundation for objectifying discussions about cost-related heterogeneity in Swiss hospitals and support policymakers to include structural characteristics into cost benchmarking and hospital reimbursement.

Gamma-hydroxybutyrate increases brain resting-state functional connectivity of the salience network and dorsal nexus in humans.

According to the triple network hypothesis the brain is equipped with three core neurocognitive networks: the default mode (DMN), the salience (SN), and the central executive (CEN) network. Moreover, the so called dorsal nexus, has met growing interest as it is a hub region connecting these three networks. Assessment of resting-state functional connectivity (rsFC) of these networks enables the elucidation of drug-induced brain alterations. Gamma-hydroxybutyrate (GHB) is a GHB/GABA-B receptor agonist that induces a paradoxical state of mixed stimulation and sedation at moderate doses, which makes it a valuable tool to investigate neural signatures of subjective drug effects. Employing a placebo-controlled, double-blind, randomized, cross-over design, we assessed the effects of GHB (35 mg/kg p. o.) in 19 healthy male subjects on DMN-, SN-, CEN-, and dorsal nexus-rsFC measured by functional magnet resonance imaging and applying independent component as well as seed-based analyses, while subjective drug effects were investigated using visual analog scales (VAS). Subjectively, GHB increased VAS ratings of a general drug effect, stimulation, and sedation. Intrinsic DMN-, and CEN-rsFC remained largely unchanged under GHB, but the drug increased SN-DMN-rsFC and SN-dorsal nexus-rsFC, while dorsal nexus-rsFC was reciprocally increased to both the SN (right anterior insula) and to the CEN (right middle frontal gyrus). Increased sedation significantly predicted the observed SN-dorsal nexus-rsFC. In conclusion, GHB generates a unique stimulant/sedative subjective state that is paralleled by a complex pattern of increased functional connectivity encompassing all three core neurocognitive networks of the brain, while increased SN-dorsal nexus-rsFC was demonstrated to be a potential signature of the sedative component of the drug effect.

The fear of being laughed at as additional diagnostic criterion in social anxiety disorder and avoidant personality disorder?

Social anxiety disorder (SAD) is the most common anxiety disorder and has considerable negative impact on social functioning, quality of life, and career progression of those affected. Gelotophobia (the fear of being laughed at) shares many similarities and has therefore been proposed as a subtype of SAD. This hypothesis has, however, never been tested in a clinical sample. Thus, the relationship between gelotophobia, SAD and avoidant personality disorder (APD) was investigated by examining a sample of 133 participants (64 psychiatric patients and 69 healthy controls matched for age and sex) using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (4th edition) and an established rating instrument for gelotophobia (GELOPH<15>). As expected, gelotophobia scores and the number of gelotophobic individuals were significantly higher among patients with SAD (n = 22) and APD (n = 12) compared to healthy controls and other psychiatric patients. Furthermore, gelotophobia scores were highest in patients suffering from both SAD and APD. In fact, all patients suffering from both disorders were also suffering from gelotophobia. As explained in the discussion, the observed data did not suggest that gelotophobia is a subtype of SAD. The findings rather imply that the fear of being laughed at is a symptom characteristic for both SAD and APD. Based on that, gelotophobia may prove to be a valuable additional diagnostic criterion for SAD and APD and the present results also contribute to the ongoing debate on the relationship between SAD and APD.

Gamma-Hydroxybutyrate Increases Resting-State Limbic Perfusion and Body and Emotion Awareness in Humans.

Gamma-hydroxybutyrate (GHB) is a GHB-/GABA-B receptor agonist inducing a broad spectrum of subjective effects including euphoria, disinhibition, and enhanced vitality. It is used as treatment for neuropsychiatric disorders including narcolepsy and alcohol withdrawal, but is also a drug of abuse. Non-medical users report enhancement of body and emotion awareness during intoxication. However, the neuronal underpinnings of such awareness alterations under GHB are unknown so far. The assessment of regional cerebral blood flow (rCBF) by pharmacological magnetic resonance imaging (phMRI) enables the elucidation of drug-induced functional brain alterations. Thus, we assessed the effects of GHB (35 mg/kg p.o.) in 17 healthy males on rCBF and subjective drug effects, using a placebo-controlled, double-blind, randomized, cross-over design employing arterial spin labeling phMRI. Compared to placebo, GHB increased subjective ratings for body and emotion awareness, and for dizziness (p<0.01-0.001, Bonferroni-corrected). A whole-brain analysis showed increased rCBF in the bilateral anterior cingulate cortex (ACC) and the right anterior insula under GHB (p<0.05, cluster-corrected). ACC and insula rCBF are correlated with relaxation, and body and emotion awareness (p<0.05-0.001, uncorrected). Interaction analyses revealed that GHB-induced increase of body awareness was accompanied by increased rCBF in ACC, whereas relaxation under GHB was accompanied by elevated rCBF in right anterior insula (p<0.05, uncorrected). In conclusion, enhancement of emotion and body awareness, and increased perfusion of insula and ACC bears implications both for the properties of GHB as a drug of abuse as well as for its putative personalized potential for specific therapeutic indications in affective disorders.

Neural underpinnings of prosexual effects induced by gamma-hydroxybutyrate in healthy male humans.

Gamma-hydroxybutyrate (GHB) is a GHB-/GABAB-receptor agonist currently used as treatment for narcolepsy but also as a drug of abuse. Non-medical GHB users have repeatedly reported prosexual effects including libido-enhancement and lowering of attractiveness standards for partner selection. Here, we examined the putative prosexual effects of oral GHB in healthy males in two experiments both employing randomized, placebo-controlled, double-blind, balanced, and cross-over study designs. In experiment I, subjective effects of 20 and 35mg/kg GHB vs. placebo were tested in 32 participants using the Sexual Arousal and Desire Inventory. In experiment II, brain reactivity towards erotic vs. neutral pictures was investigated in 15 participants using functional magnetic resonance imaging after 35mg/kg GHB vs. placebo. In experiment I, prosexual effects of GHB were shown by increased SADI ratings regarding physiological, evaluative, and motivational aspects of sexual arousal. In experiment II, erotic visual stimuli activated the bilateral insula, nucleus accumbens (NAcc), fusiform gyrus, thalamus, and left occipital pole under placebo. After GHB administration, even sexually neutral pictures of persons induced subjective sexual arousal and increased activation of the bilateral NAcc and right anterior cingulate cortex, which significantly correlated (left NAcc by trend). Moreover, a psychophysiological interaction analysis showed that GHB increased connectivity between NAcc and ventromedial prefrontal cortex during processing of visual erotic cues, i.e., in the condition in which subjective sexual arousal was highest. Our data show that GHB stimulates hedonic sexual functioning and lowers the threshold for erotic perception, which is related to increased susceptibility of mesolimbic reward pathways.

α2A -Adrenergic receptor polymorphisms and mRNA expression levels are associated with delay discounting in cocaine users.

Cocaine users characteristically display preferences for smaller immediate rewards over larger delayed rewards, and this delay discounting (DD) has been proposed as an endophenotype of cocaine addiction. Recent evidence suggests that the norepinephrine system and more specifically the α2A -adrenergic receptor (ADRA2A) are impacted by chronic cocaine use while also being potentially involved in the neural mechanisms underlying DD. Hence, we investigated the effects of ADRA2A polymorphisms and ADRA2A mRNA expression levels on DD of cocaine users and stimulant-naïve controls. Two hundred and twenty-three participants (129 cocaine users and 94 stimulant-naïve healthy controls) completed a computerized DD paradigm and were genotyped for three single nucleotide polymorphisms (SNPs; rs1800544, rs521674 and rs602618) in the ADRA2A gene, while their peripheral ADRA2A mRNA expression was quantified in whole blood samples. The three SNPs were in near-perfect linkage disequilibrium. Accordingly, significant group*genotype interactions were found for all three ADRA2A variants revealing steeper DD in cocaine users (but not in controls) carrying the G-allele of SNP rs1800544, the T-allele of rs521674 and the C-allele of rs602618. Similarly, high ADRA2A mRNA expression levels were significantly associated with a reduced tendency to choose smaller more immediate rewards (over larger delayed rewards) in cocaine users but not in controls. As the relationship between DD and cocaine use was moderated by ADRA2A SNPs and by peripheral ADRA2A gene expression, we propose that the norepinephrine system is involved in DD deficits observed in cocaine using individuals. Consequently, pharmacological compounds targeting ADRA2As might be considered for the symptom-specific treatment of delay aversion in stimulant addiction.

Uncontrollable and unpredictable stress interacts with subclinical depression and anxiety scores in determining anxiety response.

According to learned helplessness theory, uncontrollable stress is assumed to be a critical etiological factor in the pathogenesis of depression. In contrast, unpredictability of stressors is assumed to facilitate the development of sustained anxiety. Despite the frequent co-morbidity of depression and anxiety disorders, these two factors have rarely been studied simultaneously in humans. Therefore, we investigated whether there are interaction effects of uncontrollability and unpredictability on anxiety response in healthy participants. Seventy-nine healthy participants performed a visual dot probe task with emotional faces, while receiving mild electrical shocks in four different conditions (2 × 2 factorial design). In (un)controllable conditions, participants were (not) able to attenuate shock intensity. In (un)predictable conditions, participants were (not) able to anticipate shock occurrence. Before the experiment, participants' subclinical depression and anxiety scores were measured using the Beck Depression and Anxiety Inventories (BDI/BAI). During the experiment, continuous skin conductance and self-reported state anxiety were assessed and attentional biases towards angry faces were calculated. As expected, participants showed greater anxiety in uncontrollable compared to controllable and in unpredictable compared to predictable conditions. Additionally, anxiety decreased within the test sessions in participants with low BDI/BAI scores but not in participants with higher BDI/BAI scores. Most importantly, controllability and predictability interacted with each other and with BDI/BAI scores with regard to anxiety. Our results provide evidence that uncontrollability and unpredictability of stressors not only have separate but also interaction effects on several anxiety measures in susceptible individuals and may provide insights into the psychological mechanisms underlying a depressive/anxiety co-morbidity.

Serotonin Transporter and Tryptophan Hydroxylase Gene Variations Mediate Working Memory Deficits of Cocaine Users.

Cocaine users consistently develop working memory (WM) impairments but the mediating molecular mechanisms are unknown so far. Recent evidence suggests that the serotonin (5-HT) system is altered by chronic cocaine use, while also being involved in WM processing. Thus, we investigated the effects of genetic variations impacting 5-HT activity and of peripheral 5-HT transporter (5-HTT) mRNA expression on WM performance in cocaine users and stimulant naive controls. Two hundred twenty participants (126 cocaine users, 94 controls) were assessed with visuospatial, spatial, and verbal WM tasks, genotyped for the length polymorphism in the promoter region of the 5-HTT (5-HTTLPR), the variable number of tandem repeats in the second intron of the 5-HTT (VNTR In2), two single-nucleotide polymorphisms (rs4570625 and rs1386497) in the tryptophan hydroxylase-2 (TPH2) gene and quantified for peripheral 5-HTT mRNA expression in whole-blood samples. Several significant gene × environment interactions between 5-HT genotypes and cocaine use on WM emerged: in cocaine users, the long/long (5-HTTLPR), 9+10/9+10 (VNTR In2) and C/C (TPH2 rs1386497) genotypes were risk alleles for WM impairments, whereas in healthy controls these polymorphisms were associated with improved WM performance. Analogously, high 5-HTT mRNA levels were associated with worse executive WM performance in cocaine users but with increased performance in controls. These gene × environment interactions suggest that the 5-HT system has an important role in the development of cognitive deficits in chronic cocaine users. Hence, pharmacological compounds targeting 5-HT neurotransmission might be promising for the treatment of cognitive deficits in cocaine dependence.