Deficiency of the metabolic enzyme SCHAD in pancreatic β-cells promotes amino acid–sensitive hypoglycemia

Congenital hyperinsulinism of infancy (CHI) can be caused by a deficiency of the ubiquitously expressed enzyme short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD). To test the hypothesis that SCHAD-CHI arises from a specific defect in pancreatic β-cells, we created genetically engineered β-cell-specific (β-SKO) or hepatocyte-specific (L-SKO) SCHAD knockout mice. While L-SKO mice were normoglycemic, plasma glucose in β-SKO animals was significantly reduced in the random-fed state, after overnight fasting, and following refeeding. The hypoglycemic phenotype was exacerbated when the mice were fed a diet enriched in leucine, glutamine, and alanine. Intraperitoneal injection of these three amino acids led to a rapid elevation in insulin levels in β-SKO mice compared to controls. Consistently, treating isolated β-SKO islets with the amino acid mixture potently enhanced insulin secretion compared to controls in a low-glucose environment. RNA sequencing of β-SKO islets revealed reduced transcription of β-cell identity genes and upregulation of genes involved in oxidative phosphorylation, protein metabolism, and Ca2+ handling. The β-SKO mouse offers a useful model to interrogate the intra-islet heterogeneity of amino acid sensing given the very variable expression levels of SCHAD within different hormonal cells, with high levels in β- and δ-cells and virtually absent α-cell expression. We conclude that the lack of SCHAD protein in β-cells results in a hypoglycemic phenotype characterized by increased sensitivity to amino acid-stimulated insulin secretion and loss of β-cell identity.publishedVersio

An observational study: associations between nurse-reported hospital characteristics and estimated 30-day survival probabilities

Background There is a growing body of evidence for associations between the work environment and patient outcomes. A good work environment may maximise healthcare workers’ efforts to avoid failures and to facilitate quality care that is focused on patient safety. Several studies use nurse-reported quality measures, but it is uncertain whether these outcomes are correlated with clinical outcomes. The aim of this study was to determine the correlations between hospital-aggregated, nurse-assessed quality and safety, and estimated probabilities for 30-day survival in and out of hospital. Methods In a multicentre study involving almost all Norwegian hospitals with more than 85 beds (sample size=30, information about nurses’ perceptions of organisational characteristics were collected. Subscales from this survey were used to describe properties of the organisations: quality system, patient safety management, nurse–physician relationship, staffing adequacy, quality of nursing and patient safety. The average scores for these organisational characteristics were aggregated to hospital level, and merged with estimated probabilities for 30-day survival in and out of hospital (survival probabilities) from a national database. In this observational, ecological study, the relationships between the organisational characteristics (independent variables) and clinical outcomes (survival probabilities) were examined. Results Survival probabilities were correlated with nurse-assessed quality of nursing. Furthermore, the subjective perception of staffing adequacy was correlated with overall survival. Conclusions This study showed that perceived staffing adequacy and nurses’ assessments of quality of nursing were correlated with survival probabilities. It is suggested that the way nurses characterise the microsystems they belong to, also reflects the general performance of hospitals

Nurses’ reports of staffing adequacy and surgical site infections: a cross-sectional multi-centre study

Background: It is indicated that healthcare personnel’s perceptions of the work environment may reflect the clinical outcomes for the patients they care for. However, the body of evidence is inconsistent when it comes to the association between work environment and surgical site infection. Objectives: The aim of this study is to examine the associations between nurse-reported characteristics of the work environment and incidence of surgical site infections after total hip arthroplasty. Design and settings: This is a cross-sectional multicentre study conducted in 16 Norwegian hospitals. Participants: Clinical outcomes for 2885 patients >18 years that underwent total hip arthroplasty are combined with work environment descriptions from 320 nurses. Materials and methods: We combine data about surgical site infections from The Norwegian Surveillance System for Antibiotic Consumption and Healthcare-Associated Infections and hospital characteristics such as overall survival probability (from administrative patient data) and nurses’ reports of characteristics of the work environment (from a multicentre survey among nurses in Norwegian hospitals). Stepwise mixed-effects logistic regression model was performed to examine the associations between characteristics of the work environment and surgical site infections. Results: The incidence of surgical site infection among 2885 patients undergoing total hip arthroplasty in 16 Norwegian hospitals was 2.6%. Older age, elective procedures and high scores for staffing adequacy were associated with risk for surgical site infection. The association between high scores for adequate staffing and low risk for surgical site infections was present for patients that were admitted for an elective procedure, but not for patients admitted for a non-elective procedure. Conclusion: Our results show that the risk of surgical site infections after elective total hip arthroplasty was lower in hospitals where nurses assessed staffing as adequate. Our findings add to the existing literature that examines the linkage between work environment and clinical outcomes

Patient-reported outcome after treatment for definite Lyme neuroborreliosis

Objective To chart patient‐reported outcome measures (PROMs) in Norwegian patients treated for definite neuroborreliosis (NB). Material and Methods Adult patients treated for definite NB 1–10 years earlier supplied demographics, symptoms and treatment during NB, and answered validated questionnaires; Fatigue Severity Scale (FSS), Hospital Anxiety and Depression Scale (HADS), health‐related quality of life questionnaire (RAND‐36), and Patient Health Questionnaire (PHQ‐15). Results A higher proportion of NB‐treated persons reported severe fatigue, defined as FSS score ≥ 5, than in Norwegian normative data, but when removing persons with confounding fatigue associated comorbidities (n = 69) from the analyses, there was no difference between groups. Physical health‐related quality of life (RAND‐36 PCS), mean FSS score, proportions of persons reporting moderate or severe somatic symptom burden (PHQ‐15 score ≥ 10), anxiety (HADS‐A ≥ 8), or depression (HADS‐D ≥ 8) did not differ between NB‐treated persons and reference scores. Mental health‐related quality of life (RAND‐36 MCS) was poorer than in normative data (47.1 vs. 53.3), but associated with anxiety, depression and current moderate or severe somatic symptom burden, and not with NB characteristics. Conclusions Results on validated PROM questionnaires measuring fatigue, anxiety, depression, self‐reported somatic symptom burden, and physical health‐related quality did not differ between persons treated for definite NB 1–10 years earlier and reference scores. NB‐treated persons tended to report a slightly poorer mental health‐related quality of life than found in normative data, but when adjusting for confounders the causative connection is questionable. Overall, the long‐term prognosis of definite NB seems to be good

Effects of external inspection on sepsis detection and treatment: a study protocol for a quasiexperimental study with a stepped-wedge design

Introduction: Inspections are widely used in health care as a means to improve the health services delivered to patients. Despite their widespread use, there is little evidence of their effect. The mechanisms for how inspections can promote change are poorly understood. In this study, we use a national inspection campaign of sepsis detection and initial treatment in hospitals as case to: (1) Explore how inspections affect the involved organizations. (2) Evaluate what effect external inspections have on the process of delivering care to patients, measured by change in indicators reflecting how sepsis detection and treatment is carried out. (3) Evaluate whether external inspections affect patient outcomes, measured as change in the 30-day mortality rate and length of hospital stay. Methods and analysis: The intervention that we study is inspections of sepsis detection and treatment in hospitals. The intervention will be rolled out sequentially during 12 months to 24 hospitals. Our effect measures are change on indicators related to the detection and treatment of sepsis, the 30-day mortality rate and length of hospital stay. We collect data from patient records at baseline, before the inspections, and at 8 and 14 months after the inspections. We use logistic regression models and linear regression models to compare the various effect measurements between the intervention and control periods. All the models will include time as a covariate to adjust for potential secular changes in the effect measurements during the study period. We collect qualitative data before and after the inspections, and we will conduct a thematic content analysis to explore how inspections affect the involved organisations. Ethics and dissemination: The study has obtained ethical approval by the Regional Ethics Committee of Norway Nord and the Norwegian Data Protection Authority. It is registered at www.clinicaltrials.gov (Identifier: NCT02747121). Results will be reported in international peer-reviewed journals

Effects of external inspections on sepsis detection and treatment: a stepped-wedge study With cluster-level randomisation

Objective To evaluate the effects of external inspections on (1) hospital emergency departments’ clinical processes for detecting and treating sepsis and (2) length of hospital stay and 30-day mortality. Design Incomplete cluster-randomised stepped-wedge design using data from patient records and patient registries. We compared care processes and patient outcomes before and after the intervention using regression analysis. Setting Nationwide inspections of sepsis care in emergency departments in Norwegian hospitals. Participants 7407 patients presenting to hospital emergency departments with sepsis. Intervention External inspections of sepsis detection and treatment led by a public supervisory institution. Main outcome measures Process measures for sepsis diagnostics and treatment, length of hospital stay and 30-day all-cause mortality. Results After the inspections, there were significant improvements in the proportions of patients examined by a physician within the time frame set in triage (OR 1.28, 95% CI 1.07 to 1.53), undergoing a complete set of vital measurements within 1 hour (OR 1.78, 95% CI 1.10 to 2.87), having lactate measured within 1 hour (OR 2.75, 95% CI 1.83 to 4.15), having an adequate observation regimen (OR 2.20, 95% CI 1.51 to 3.20) and receiving antibiotics within 1 hour (OR 2.16, 95% CI 1.83 to 2.55). There was also significant reduction in mortality and length of stay, but these findings were no longer significant when controlling for time. Conclusions External inspections were associated with improvement of sepsis detection and treatment. These findings suggest that policy-makers and regulatory agencies should prioritise assessing the effects of their inspections and pay attention to the mechanisms by which the inspections might contribute to improve care for patients

Effects of external inspections on sepsis detection and treatment: a stepped-wedge study With cluster-level randomisation

Objective To evaluate the effects of external inspections on (1) hospital emergency departments’ clinical processes for detecting and treating sepsis and (2) length of hospital stay and 30-day mortality. Design Incomplete cluster-randomised stepped-wedge design using data from patient records and patient registries. We compared care processes and patient outcomes before and after the intervention using regression analysis. Setting Nationwide inspections of sepsis care in emergency departments in Norwegian hospitals. Participants 7407 patients presenting to hospital emergency departments with sepsis. Intervention External inspections of sepsis detection and treatment led by a public supervisory institution. Main outcome measures Process measures for sepsis diagnostics and treatment, length of hospital stay and 30-day all-cause mortality. Results After the inspections, there were significant improvements in the proportions of patients examined by a physician within the time frame set in triage (OR 1.28, 95% CI 1.07 to 1.53), undergoing a complete set of vital measurements within 1 hour (OR 1.78, 95% CI 1.10 to 2.87), having lactate measured within 1 hour (OR 2.75, 95% CI 1.83 to 4.15), having an adequate observation regimen (OR 2.20, 95% CI 1.51 to 3.20) and receiving antibiotics within 1 hour (OR 2.16, 95% CI 1.83 to 2.55). There was also significant reduction in mortality and length of stay, but these findings were no longer significant when controlling for time. Conclusions External inspections were associated with improvement of sepsis detection and treatment. These findings suggest that policy-makers and regulatory agencies should prioritise assessing the effects of their inspections and pay attention to the mechanisms by which the inspections might contribute to improve care for patients

Effects of external inspections on sepsis detection and treatment: a stepped-wedge study With cluster-level randomisation

Objective To evaluate the effects of external inspections on (1) hospital emergency departments’ clinical processes for detecting and treating sepsis and (2) length of hospital stay and 30-day mortality. Design Incomplete cluster-randomised stepped-wedge design using data from patient records and patient registries. We compared care processes and patient outcomes before and after the intervention using regression analysis. Setting Nationwide inspections of sepsis care in emergency departments in Norwegian hospitals. Participants 7407 patients presenting to hospital emergency departments with sepsis. Intervention External inspections of sepsis detection and treatment led by a public supervisory institution. Main outcome measures Process measures for sepsis diagnostics and treatment, length of hospital stay and 30-day all-cause mortality. Results After the inspections, there were significant improvements in the proportions of patients examined by a physician within the time frame set in triage (OR 1.28, 95% CI 1.07 to 1.53), undergoing a complete set of vital measurements within 1 hour (OR 1.78, 95% CI 1.10 to 2.87), having lactate measured within 1 hour (OR 2.75, 95% CI 1.83 to 4.15), having an adequate observation regimen (OR 2.20, 95% CI 1.51 to 3.20) and receiving antibiotics within 1 hour (OR 2.16, 95% CI 1.83 to 2.55). There was also significant reduction in mortality and length of stay, but these findings were no longer significant when controlling for time. Conclusions External inspections were associated with improvement of sepsis detection and treatment. These findings suggest that policy-makers and regulatory agencies should prioritise assessing the effects of their inspections and pay attention to the mechanisms by which the inspections might contribute to improve care for patients.publishedVersio