Evaluation of Complexity Measurement Tools for Correlations with Health-Related Outcomes, Health Care Costs and Impacts on Healthcare Providers: A Scoping Review.

Various tools to measure patient complexity have been developed. Primary care physicians often deal with patient complexity. However, their usefulness in primary care settings is unclear. This study explored complexity measurement tools in general adult and patient populations to investigate the correlations between patient complexity and outcomes, including health-related patient outcomes, healthcare costs, and impacts on healthcare providers. We used a five-stage scoping review framework, searching MEDLINE and CINAHL, including reference lists of identified studies. A total of 21 patient complexity management tools were found. Twenty-five studies examined the correlation between patient complexity and health-related patient outcomes, two examined healthcare costs, and one assessed impacts on healthcare providers. No studies have considered sharing information or action plans with multidisciplinary teams while measuring outcomes for complex patients. Of the tools, eleven used face-to-face interviews, seven extracted data from medical records, and three used self-assessments. The evidence of correlations between patient complexity and outcomes was insufficient for clinical implementation. Self-assessment tools might be convenient for conducting further studies. A multidisciplinary approach is essential to develop effective intervention protocols. Further research is required to determine these correlations in primary care settings.

Influence of anti-coronavirus disease 2019 policies on 10 pediatric infectious diseases.

BACKGROUND: To combat the coronavirus disease 2019 pandemic, many countries, including Japan, implemented policies limiting social activities and encouraging preventive behaviors. This study examines the influence of such policies on the trends of 10 infectious pediatric diseases: pharyngoconjunctival fever; group A streptococcal pharyngitis; infectious gastroenteritis; chickenpox; erythema infectiosum; hand, foot, and mouth disease; herpangina; respiratory syncytial virus; exanthem subitum; and mumps. METHODS: The research adopted a retrospective cohort study design. We collected data from Japan's National Epidemiological Surveillance Program detailing the incidences of the 10 diseases per pediatric sentinel site for a period beginning at 9 weeks before government-ordered school closures and ending at 9 weeks after the end of the state of emergency. We obtained corresponding data for the equivalent weeks in 2015-2019. We estimated the influence of the policies using a difference-in-differences regression model. RESULTS: For seven diseases (pharyngoconjunctival fever; group A streptococcal pharyngitis; infectious gastroenteritis; chickenpox; erythema infectiosum; hand, foot, and mouth disease; and herpangina), the incidence in 2020 decreased significantly during and after the school closures. Sensitivity analysis, in which the focus area was limited to the policy-implementation period or existing trend patterns, replicated these significant decreases for one of the above mentioned seven diseases - infectious gastroenteritis. CONCLUSIONS: Policies such as school closures and encouragement of preventive behaviors were associated with significant decreases in the incidences of most of the 10 diseases, which sensitivity analysis replicated in infectious gastroenteritis. To determine the long-term effects of these policies, prospective cohort studies are needed.

Development of a preoperative prediction model for new-onset diabetes mellitus after partial pancreatectomy: A retrospective cohort study.

ABSTRACT: Pancreatectomy is an invasive surgery that is sometimes associated with complications. New-onset diabetes mellitus sometimes develops after partial pancreatectomy and severely affects the patient's quality of life. This study aimed to develop a preoperative prediction model of new-onset diabetes mellitus after partial pancreatectomy, which will help patients and surgeons to achieve more easily better common decisions on regarding whether to perform partial pancreatectomy. This retrospective cohort study analyzed medical records of patients who underwent partial pancreatectomy (total pancreatectomy excluded) from April 1, 2008, to February 28, 2016, which were available in the database provided by Medical Data Vision Co., Ltd. (Tokyo, Japan). The predictors were preoperative age, body mass index, hemoglobin A1c level, blood glucose level, and indication for partial pancreatectomy. The outcome was the development of new-onset diabetes mellitus at 1 to 12 months after partial pancreatectomy. We used a logistic regression model and calculated the scores of each predictor. To determine test performance, we assessed discrimination ability using the receiver operating characteristic curve and calibration with a calibration plot and the Hosmer-Lemeshow test. We also performed internal validation using the bootstrap method. Of 681 patients, 125 (18.4%) had new-onset diabetes mellitus after partial pancreatectomy. The developed prediction model had a possible range of 0 to 46 points. The median score was 13, and the interquartile range was 9 to 22. The C-statistics of the receiver operating characteristic curve on the score to predict the outcome was .70 (95% confidence interval [CI], .65-.75). Regarding the test performance, the Hosmer-Lemeshow test was not significant (P = .17), and calibration was good. In the bootstrapped cohorts, the C-statistics was .69 (95% CI, .62-.76). We developed a preoperative prediction model for new-onset diabetes mellitus after partial pancreatectomy. This would provide important information for surgeons and patients when deciding whether to perform partial pancreatectomy.

Background styles in systematic review articles are not related to the publication in high-impact-factor journals: A meta-epidemiological study.

OBJECTIVES: To clarify the styles used in background sections of systematic reviews (SR) and to identify which styles if any were related to the publication in high-impact-factor (HIF) medical journals. METHOD: This was a cross-sectional study for original SR articles published in top 50 journals in MEDICINE, GENERAL & INTERNAL category in Journal Citation Reports 2018. We randomly included 90 articles from top 10 HIF journals and 90 from others, respectively. We conducted a content analysis to classify the background styles. We assessed the factors associated with the publication in HIF journals. RESULTS: We found 6 categories. We defined 6 categories as follows: Update of prior SR, New in scope than prior SR, Higher quality than prior SR, Completely new SR, Limitations of primary studies only, and Not presenting unknown in prior SR or primary studies. All 6 categories were not related to the publication in HIF journals. CONCLUSIONS: We found 6 categories of styles in background sections of SR, none of which however were related to publication in HIF journals. SR authors may wish to use any of these categories to communicate the importance of their research questions.

Seipin is necessary for normal brain development and spermatogenesis in addition to adipogenesis.

Seipin, encoded by BSCL2 gene, is a protein whose physiological functions remain unclear. Mutations of BSCL2 cause the most-severe form of congenital generalized lipodystrophy (CGL). BSCL2 mRNA is highly expressed in the brain and testis in addition to the adipose tissue in human, suggesting physiological roles of seipin in non-adipose tissues. Since we found BSCL2 mRNA expression pattern among organs in rat is similar to human while it is not highly expressed in mouse brain, we generated a Bscl2/seipin knockout (SKO) rat using the method with ENU (N-ethyl-N-nitrosourea) mutagenesis. SKO rats showed total lack of white adipose tissues including mechanical fat such as bone marrow and retro-orbital fats, while physiologically functional brown adipose tissue was preserved. Besides the lipodystrophic phenotypes, SKO rats showed impairment of spatial working memory with brain weight reduction and infertility with azoospermia. We confirmed reduction of brain volume and number of sperm in human patients with BSCL2 mutation. This is the first report demonstrating that seipin is necessary for normal brain development and spermatogenesis in addition to white adipose tissue development.

Leptin restores the insulinotropic effect of exenatide in a mouse model of type 2 diabetes with increased adiposity induced by streptozotocin and high-fat diet.

Leptin may reduce pancreatic lipid deposition, which increases with progression of obesity and can impair ß-cell function. The insulinotropic effect of glucagon-like peptide-1 (GLP-1) and the efficacy of GLP-1 receptor agonist are reduced associated with impaired ß-cell function. In this study, we examined whether leptin could restore the efficacy of exenatide, a GLP-1 receptor agonist, in type 2 diabetes with increased adiposity. We chronically administered leptin (500 µg·kg⁻¹·day⁻¹) and/or exenatide (20 µg·kg⁻¹·day⁻¹) for 2 wk in a mouse model of type 2 diabetes with increased adiposity induced by streptozotocin and high-fat diet (STZ/HFD mice). The STZ/HFD mice exhibited hyperglycemia, overweight, increased pancreatic triglyceride level, and reduced glucose-stimulated insulin secretion (GSIS); moreover, the insulinotropic effect of exenatide was reduced. However, leptin significantly reduced pancreatic triglyceride level, and adding leptin to exenatide (LEP/EX) remarkably enhanced GSIS. These results suggested that the leptin treatment restored the insulinotropic effect of exenatide in the mice. In addition, LEP/EX reduced food intake, body weight, and triglyceride levels in the skeletal muscle and liver, and corrected hyperglycemia to a greater extent than either monotherapy. The pair-feeding experiment indicated that the marked reduction of pancreatic triglyceride level and enhancement of GSIS by LEP/EX occurred via mechanisms other than calorie restriction. These results suggest that leptin treatment may restore the insulinotropic effect of exenatide associated with the reduction of pancreatic lipid deposition in type 2 diabetes with increased adiposity. Combination therapy with leptin and exenatide could be an effective treatment for patients with type 2 diabetes with increased adiposity.

Generation of leptin-deficient Lepmkyo/Lepmkyo rats and identification of leptin-responsive genes in the liver.

Leptin is one of the key molecules in maintaining energy homeostasis. Although genetically leptin-deficient Lep(ob)/Lep(ob) mice have greatly contributed to elucidating leptin physiology, the use of more than one species can improve the accuracy of analysis results. Using the N-ethyl-N-nitrosourea mutagenesis method, we generated a leptin-deficient Lep(mkyo)/Lep(mkyo) rat that had a nonsense mutation (Q92X) in leptin gene. Lep(mkyo)/Lep(mkyo) rats showed obese phenotypes including severe fatty liver, which were comparable to Lep(ob)/Lep(ob) mice. To identify genes that respond to leptin in the liver, we performed microarray analysis with Lep(mkyo)/Lep(mkyo) rats and Lep(ob)/Lep(ob) mice. We sorted out genes whose expression levels in the liver of Lep(mkyo)/Lep(mkyo) rats were changed from wild-type (WT) rats and were reversed toward WT rats by leptin administration. In this analysis, livers were sampled for 6 h, a relatively short time after leptin administration to avoid the secondary effect of metabolic changes such as improvement of fatty liver. We did the same procedure in Lep(ob)/Lep(ob) mice and selected genes whose expression patterns were common in rat and mouse. We verified their gene expressions by real-time quantitative PCR. Finally, we identified eight genes that primarily respond to leptin in the liver commonly in rat and mouse. These genes might be important for the effect of leptin in the liver.

Leptin activates hepatic 5'-AMP-activated protein kinase through sympathetic nervous system and α1-adrenergic receptor: a potential mechanism for improvement of fatty liver in lipodystrophy by leptin.

BACKGROUND: AMPK activation promotes glucose and lipid metabolism. RESULTS: Hepatic AMPK activities were decreased in fatty liver from lipodystrophic mice, and leptin activated the hepatic AMPK via the α-adrenergic effect. CONCLUSION: Leptin improved the fatty liver possibly by activating hepatic AMPK through the central and sympathetic nervous systems. SIGNIFICANCE: Hepatic AMPK plays significant roles in the pathophysiology of lipodystrophy and metabolic action of leptin. Leptin is an adipocyte-derived hormone that regulates energy homeostasis. Leptin treatment strikingly ameliorates metabolic disorders of lipodystrophy, which exhibits ectopic fat accumulation and severe insulin-resistant diabetes due to a paucity of adipose tissue. Although leptin is shown to activate 5'-AMP-activated protein kinase (AMPK) in the skeletal muscle, the effect of leptin in the liver is still unclear. We investigated the effect of leptin on hepatic AMPK and its pathophysiological relevance in A-ZIP/F-1 mice, a model of generalized lipodystrophy. Here, we demonstrated that leptin activates hepatic AMPK through the central nervous system and α-adrenergic sympathetic nerves. AMPK activities were decreased in the fatty liver of A-ZIP/F-1 mice, and leptin administration increased AMPK activities in the liver as well as in skeletal muscle with significant reduction in triglyceride content. Activation of hepatic AMPK with A769662 also led to a decrease in hepatic triglyceride content and blood glucose levels in A-ZIP/F-1 mice. These results indicate that the down-regulation of hepatic AMPK activities plays a pathophysiological role in the metabolic disturbances of lipodystrophy, and the hepatic AMPK activation is involved in the therapeutic effects of leptin.

Amylin improves the effect of leptin on insulin sensitivity in leptin-resistant diet-induced obese mice.

Leptin enhances insulin sensitivity in addition to reducing food intake and body weight. Recently, amylin, a pancreatic ß-cell-derived hormone, was shown to restore a weight-reducing effect of leptin in leptin-resistant diet-induced obesity. However, whether amylin improves the effect of leptin on insulin sensitivity in diet-induced obesity is unclear. Diet-induced obese (DIO) mice were infused with either saline (S), leptin (L; 500 µg·kg⁻¹·day⁻¹), amylin (A; 100 µg·kg⁻¹·day⁻¹), or leptin plus amylin (L/A) for 14 days using osmotic minipumps. Food intake, body weight, metabolic parameters, tissue triglyceride content, and AMP-activated protein kinase (AMPK) activity were examined. Pair-feeding and weight-matched calorie restriction experiments were performed to assess the influence of food intake and body weight reduction. Continuous L/A coadministration significantly reduced food intake, increased energy expenditure, and reduced body weight, whereas administration of L or A alone had no effects. L/A coadministration did not affect blood glucose levels during ad libitum feeding but decreased plasma insulin levels significantly (by 48%), suggesting the enhancement of insulin sensitivity. Insulin tolerance test actually showed the increased effect of insulin in L/A-treated mice. In addition, L/A coadministration significantly decreased tissue triglyceride content and increased AMPKα2 activity in skeletal muscle (by 67%). L/A coadministration enhanced insulin sensitivity more than pair-feeding and weight-matched calorie restriction. In conclusion, this study demonstrates the beneficial effect of L/A coadministration on glucose and lipid metabolism in DIO mice, indicating the possible clinical usefulness of L/A coadministration as a new antidiabetic treatment in obesity-associated diabetes.