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Insulin has complex effects on cell growth, metabolism and differentiation, and these effects are mediated by a cell-surface bound receptor and eventually a cascade of intracellular signaling events. Among the several metabolic and growth-promoting effects of insulin, insulin resistance is defined as an attenuated effect of insulin on glucose metabolism, primarily the limited export of blood glucose into skeletal muscle and adipose tissue. On the other hand, not all the signaling pathways and insulin-responsive tissues are equally affected, and some effects other than the metabolic actions of insulin are overexpressed. Ovaries and the adrenal glands are two examples of tissues remaining sensitive to insulin actions where insulin may contribute to increased androgen secretion. Polycystic ovary syndrome (PCOS) is the most common form of androgen excess disorder (AED), and its pathogenesis is closely associated with insulin resistance. Patients with idiopathic hirsutism also exhibit insulin resistance, albeit lower than patients with PCOS. Although it is not as evident as in PCOS, patients with congenital adrenal hyperplasia may have insulin resistance, which may be further exacerbated with glucocorticoid overtreatment and obesity. Among patients with severe insulin resistance syndromes, irrespective of the type of disease, hyperinsulinemia promotes ovarian androgen synthesis independently of gonadotropins. It is highly debated in whom and how insulin resistance should be diagnosed and treated among patients with AEDs, including PCOS. It is not suitable to administer an insulin sensitizer relying on only some mathematical models used for estimating insulin resistance. Instead, the treatment decision should be based on the constellation of the signs, symptoms and presence of obesity; acanthosis nigricans; and some laboratory abnormalities such as impaired glucose tolerance and impaired fasting glucose., Competing Interests: Conflict-of-interest statement: The authors declare that there are no conflicts of interest to disclose., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Some states have adopted Accountable Care Organization (ACO) models to transform their Medicaid programs, but little is known about their impact on health care outcomes and costs. Medicaid ACOs are uniquely positioned to improve childbirth outcomes because of the number of births covered by Medicaid. Using Healthcare Cost and Utilization Project hospital data, we examined the relationship between ACO adoption and (a) neonatal and maternal outcomes, and (b) cost per birth. We compared outcomes in states that have adopted ACO models in their Medicaid programs with adjacent states without ACO models. Implementation of Medicaid ACOs was associated with a moderate reduction in hospital costs per birth and decreased cesarean section rates. Results varied by state. We found no association between Medicaid ACOs and several birth outcomes, including infant inpatient mortality, low birthweight, neonatal intensive care unit utilization, and severe maternal morbidity. Improving these outcomes may require more time or targeted interventions.

Background: This case-control study was conducted to investigate the relationship between serum nesfatin-1 levels and nutritional status and blood parameters in patients diagnosed with metabolic syndrome., Methods: Thirty patients (case) diagnosed with metabolic syndrome according to National Cholesterol Education Program-Adult Treatment Panel III criteria were included. Thirty healthy subjects (control) matched with patients with metabolic syndrome in terms of age, gender and body mass index were included. Three-day food consumption records were obtained. Anthropometric indices were measured and body composition was determined by bioelectrical impedance method. Biochemical parameters and serum nesfatin-1 levels were measured after 8 hours of fasting., Results: Serum nesfatin-1 levels were 0.245±0.272 ng/mL in the case group and 0.528±0.987 ng/mL in the control group (p>0.05). There was a positive significant correlation between serum nesfatin-1 levels and body weight, waist and hip circumferences in the case group (p<0.05). Each unit increase in hip circumference measurement affects the levels of nesfatin by 0.014 times. In the control group, there was a positive significant correlation between body weight and serum nesfatin-1 levels (p<0.05). A significant correlation was detected between HbA1c and serum nesfatin-1 levels in the case group (p<0.05). A significant relationship was detected between dietary fibre intake and the serum nesfatin-1 levels in the case group (p<0.05)., Conclusions: Anthropometric indices and blood parameters were correlated with serum nesfatin-1 levels in patients with metabolic syndrome. More clinical trials may be performed to establish the relationship between serum nesfatin-1 levels and nutritional status., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

There are some studies regarding the presence/absence of oxidative stress in patients with hypogonadism with limited number of parameters. We aimed to investigate the effects of male hypogonadism and its treatment on oxidative stress parameters. Thirteen male patients with hypogonadotropic hypogonadism and 20 healthy subjects were involved in the study. Patients with hypogonadism were evaluated before and after six months of therapy. Markers indicating lipid and protein oxidation, total oxidant status (TOS) and total anti-oxidant capacity (TAC) were evaluated. Control subjects had significantly higher serum testosterone levels in comparison to hypogonadal patients before the treatment period. After the treatment of hypogonadism serum testosterone levels increased significantly. Myeloperoxidase (MPO) activity, levels of advanced oxidation protein products (AOPP), total lipid hydroperoxide and protein carbonyl compounds (PCC) were similar between the control subjects and the patient group before treatment. Pyrrolized protein and TOS were significantly lower and thiol levels and TAC were significantly higher in the control subjects than in patients with hypogonadism. Treatment of hypogonadism resulted in a significant decrease in AOPP levels while a significant increase was determined in TAC. No significant change was found in MPO activity. In conclusion, patients with hypogonadism have an increased status of oxidative stress which is at least partially improved after appropriate therapy.

Objective The insulin tolerance test (ITT) has been accepted as the gold standard test for assessing the integrity of the growth hormone (GH) - insulin-like growth factor (IGF-1) axis and the hypothalamic-pituitary-adrenal (HPA) axis. The goal of the test is to achieve clinical and biochemical hypoglycemia at a blood glucose level ≤ 40 mg/dL to effectively and correctly assess the HPA and GH-IGF-1 axes. In this study, the GH and cortisol responses of patients who achieved and failed to achieve biochemical hypoglycemia during an ITT were compared. Subjects and methods One hundred thirty-five patients with pituitary disorders were included in the study. Samples for blood glucose levels were obtained after clear symptoms of clinical hypoglycemia developed. The patients were enrolled in the hypoglycemic and nonhypoglycemic groups according to whether their plasma glucose level ≤ 40 mg/dL or > 40 mg/dL during an ITT, and the groups were compared in terms of their GH and cortisol responses. Results The mean age, body mass index and waist circumference of the two patient groups were found to be similar. The mean blood glucose level was significantly lower in the hypoglycemic group than in the nonhypoglycemic group (19.3 and 52.0 mg/dL, respectively). When the two groups were compared in terms of peak cortisol and GH responses, no statistically significant differences were found. Conclusion The data presented suggest that clinically symptomatic hypoglycemia is as effective as biochemically confirmed hypoglycemia during an ITT. Arch Endocrinol Metab. 2020;64(1):82-8.

Background: The Healthcare Cost and Utilization Project (HCUP), the nation's most complete source of all-payer hospital care data, supports analyses at the national, regional, state and community levels. However, national HCUP data are often used in inappropriate ways in studies of state-specific issues., Objective: To describe the opportunities and challenges of using HCUP data to conduct state health policy research and to provide empirical examples of what can go wrong when using the national HCUP data inappropriately., Research Design: Comparison of results from state-level analyses using national HCUP data and the state-specific HCUP data recommended by the Agency for Healthcare Research and Quality (AHRQ). Analyses included trends in state-specific rates of cesarean delivery and a difference-in-differences analysis of Connecticut's Medicaid expansion., Subjects: Hospital discharges from the 2004 to 2011 HCUP Nationwide Inpatient Samples (NIS) and State Inpatient Databases (SID)., Measures: Cesarean delivery rates, discharges per capita, and discharges by the payer., Results: State-level estimates derived from the NIS are volatile and often provide misleading policy conclusions relative to estimates from the SID., Conclusions: The NIS should not be used for state-level research. AHRQ provides resources to assist analysts with state-specific studies using SID files.

Background: There is uncertainty about the burden of hospitalization associated with respiratory syncytial virus (RSV) and influenza in children, including those with underlying medical conditions., Methods: We applied previously developed methodology to Health Care Cost and Utilization Project hospitalization data and additional data related to asthma diagnosis/previous history in hospitalized children to estimate RSV and influenza-associated hospitalization rates in different subpopulations of US children between 2003 and 2010., Results: The estimated average annual rates (per 100,000 children) of RSV-associated hospitalization with a respiratory cause (ICD-9 codes 460-519) present anywhere in the discharge diagnosis were 2,381 (95% CI(2252,2515)) in children <1 year of age; 710.6 (609.1, 809.2) (1 y old); 395 (327.7, 462.4) (2 y old); 211.3 (154.6, 266.8) (3 y old); 111.1 (62.4, 160.1) (4 y old); 72.3 (29.3, 116.4) (5-6 y of age); 35.6 (9.9,62.2) (7-11 y of age); and 39 (17.5, 60.6) (12-17 y of age). The corresponding rates of influenza-associated hospitalization were lower, ranging from 181 (142.5, 220.3) in <1 year old to 17.9 (11.7, 24.2) in 12-17 years of age. The relative risks for RSV-related hospitalization associated with a prior diagnosis of asthma in age groups <5 y ranged between 3.1 (2.1, 4.7) (<1 y old) and 6.7 (4.2, 11.8) (2 y old; the corresponding risks for influenza-related hospitalization ranged from 2.8 (2.1, 4) (<1y old) to 4.9 (3.8, 6.4) (3 y old)., Conclusion: RSV-associated hospitalization rates in young children are high and decline rapidly with age. There are additional risks for both RSV and influenza hospitalization associated with a prior diagnosis of asthma, with the rates of RSV-related hospitalization in the youngest children diagnosed with asthma being particularly high.

Background: Overweight and obesity were recently associated with a poor prognosis in patients with autosomal dominant polycystic kidney disease (ADPKD). Whether the metabolic consequences of obesity as defined by the metabolic syndrome (MS) are also linked with disease progression remains untested., Methods: Eligible ADPKD patients with different stages of CKD (n = 105) and 105 non-diabetic controls matched for CKD stage were enrolled in the study. Groups were evaluated at baseline for presence of MS, blood markers of metabolism, homeostasis model assessment of insulin resistance (HOMA-IR) score, and biochemical markers of inflammation (hs-CRP, IL-1β, IL-6, TNF-α and PON-1). MS was defined according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III). Patients were followed for 12 months and progression defined as a decrease in baseline eGFR > 10%., Results: MS and hypertension were more prevalent amongst ADPKD patients than in the control group. Meanwhile, markers of inflammation such as hs-CRP (3.63 [3.45-5.17] vs. 4.2 [3.45-8.99] mg/dL; p = 0.014), IL-6 (21.65 [14.1-27.49] vs. 24.9 [16.23-39.4] pg/mL; p = 0.004) and IL-1β (21.33 [15.8-26.4] vs. 26.78 [18.22-35] pg/mL; p < 0.001) levels were all more elevated in ADPKD patients than in non-diabetic CKD subjects. In multivariate analysis having a truncating PKD1 mutation predicted (OR 1.25 [1.09-1.43]; p = 0.002) fulfilling the MS criteria. Finally, ADPKD patients fulfilling MS criteria had a significantly more rapid progression during 12 months of follow-up than did those that did not (OR 3.28 [1.09-9.87]; p = 0.035)., Conclusions: Our data supports the notion that dysmetabolisms part of the ADPKD phenotype and associated with a poor outcome, especially in patients with a truncating PKD1 mutation.

Background: Rates of sepsis/septicemia hospitalization in the US have risen significantly during recent years. Antibiotic resistance and use may contribute to those rates through various mechanisms, including lack of clearance of resistant infections following antibiotic treatment, with some of those infections subsequently devolving into sepsis. At the same time, there is limited information on the effect of prescribing of certain antibiotics vs. others on the rates of septicemia and sepsis-related hospitalizations and mortality., Methods: We used multivariable linear regression to relate state-specific rates of outpatient prescribing overall for oral fluoroquinolones, penicillins, macrolides, and cephalosporins between 2011 and 2012 to state-specific rates of septicemia hospitalization (ICD-9 codes 038.xx present anywhere on a discharge diagnosis) in each of the following age groups of adults: (18-49y, 50-64y, 65-74y, 75-84y, 85 + y) reported to the Healthcare Cost and Utilization Project (HCUP) between 2011 and 2012, adjusting for additional covariates, and random effects associated with the ten US Health and Human Services (HHS) regions., Results: Increase in the rate of prescribing of oral penicillins by 1 annual dose per 1000 state residents was associated with increases in annual septicemia hospitalization rates of 0.19 (95% CI (0.02,0.37)) per 10,000 persons aged 50-64y, of 0.48(0.12,0.84) per 10,000 persons aged 65-74y, and of 0.81(0.17,1.40) per 10,000 persons aged 74-84y. Increase by 1 in the percent of African Americans among state residents in a given age group was associated with increases in annual septicemia hospitalization rates of 2.3(0.32,4.2) per 10,000 persons aged 75-84y, and of 5.3(1.1,9.5) per 10,000 persons aged over 85y. Average minimal daily temperature was positively associated with septicemia hospitalization rates in persons aged 18-49y, 50-64y, 75-84y and over 85y., Conclusions: Our results suggest positive associations between the rates of prescribing for penicillins and the rates of hospitalization with septicemia in US adults aged 50-84y. Further studies are needed to better understand the potential effect of antibiotic replacement in the treatment of various syndromes, including the potential impact of the recent US FDA guidelines on restriction of fluoroquinolone use, as well as the potential effect of changes in the practices for prescribing of penicillins on the rates of sepsis-related hospitalization and mortality.

Objective: To estimate the effects of the health insurance exchange and Medicaid coverage expansions on hospital inpatient and emergency department (ED) utilization rates, cost, and patient illness severity, and also to test the association between changes in outcomes and the size of the uninsured population eligible for coverage in states., Data Sources: Healthcare Cost and Utilization Project State Inpatient and Emergency Department Databases, 2011-2015, Nielsen Demographic Data, and the American Community Survey., Study Design: Retrospective study using fixed-effects regression to estimate the effects in expansion and nonexpansion states by age/sex demographic groups., Findings: In Medicaid expansion states, rates of uninsured inpatient discharges and ED visits fell sharply in many demographic groups. For example, uninsured inpatient discharge rates across groups, except young females, decreased by ≥39 percent per capita on average in expansion states. In nonexpansion states, uninsured utilization rates remained unchanged or increased slightly (0-9.2 percent). Changes in all-payer and private insurance rates were more muted. Changes in inpatient costs per discharge were negative, and all-payer inpatient costs per discharge declined <6 percent in most age/sex groups. The size of the uninsured population eligible for coverage was strongly associated with changes in outcomes. For example, among males aged 35-54 years in expansion states, there was a 0.793 percent decrease in the uninsured discharge rate per unit increase in the coverage expansion ratio (the ratio of the size of the population eligible for coverage to the size of the previously covered population within an age/sex/payer/geographic group)., Conclusions: Significant shifts in cost per discharge and patient severity were consistent with selective take-up of insurance. The "treatment intensity" of expansions may be useful for anticipating future effects., (© Health Research and Educational Trust.)

Objectives: Rates of hospitalization with sepsis/septicemia and associated mortality in the US have risen significantly during the last two decades. Antibiotic resistance may contribute to the rates of sepsis-related outcomes through lack of clearance of bacterial infections following antibiotic treatment during different stages of infection. However, there is limited information about the relationship between prevalence of resistance to various antibiotics in different bacteria and rates of sepsis-related outcomes., Methods: For different age groups of adults (18-49y, 50-64y, 65-74y, 75-84y, 85+y) and combinations of antibiotics/bacteria, we evaluated associations between state-specific prevalence (percentage) of resistant samples for a given combination of antibiotics/bacteria among catheter-associated urinary tract infections (CAUTIs) in the CDC Antibiotic Resistance Patient Safety Atlas data between 2011-2014, and rates of hospitalization with septicemia (ICD-9 codes 038.xx present on the discharge diagnosis) reported to the Healthcare Cost and Utilization Project (HCUP), as well as rates of mortality with sepsis (ICD-10 codes A40-41.xx present on death certificate)., Results: Among the different combinations of antibiotics/bacteria, prevalence of resistance to fluoroquinolones in Escherichia coli had the strongest association with septicemia hospitalization rates for individuals aged over 50y, and with sepsis mortality rates for individuals aged 18-84y. There were several positive correlations between prevalence of resistance for different combinations of antibiotics/bacteria and septicemia hospitalization/sepsis mortality rates in adults., Conclusions: These findings, and those from work on the relationship between antibiotic use and sepsis rates, support the association between use of/resistance to certain antibiotics and rates of sepsis-related outcomes, indicating the potential utility of antibiotic replacement., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: The prevalence of pituitary dysfunction is high following aneurysmal subarachnoid hemorrhage (aSAH) and when occurs it may contribute to residual symptoms of aSAH such as decreased cognition and quality of life. Hypopituitarism following aSAH may have non-specific, subtle symptoms and potentially serious consequences if remained undiagnosed., Methods: We reviewed the literature on epidemiology, pathophysiology, diagnostic methods and management of neuroendocrine changes after aSAH as well as on the impact of pituitary dysfunction on outcome of the patient., Results: The prevalence rates of pituitary dysfunction after aSAH varies greatly across studies due to different diagnostic methods, though growth hormone deficiency is generally the most frequently reported followed by adrenocorticotropic hormone, gonadotropin and thyroid stimulating hormone deficiencies. Pituitary deficiency tends to improve over time after aSAH but new onset deficiencies in chronic phase may also occur. There are no clinical parameters to predict the presence of hypopituitarism after aSAH. Age of the patient and surgical procedures are risk factors associated with development of hypopituitarism but the effect of pituitary dysfunction on outcome of the patient is not clear. Replacement of hypocortisolemia and hypothyroidism is essential but treatment of other hormonal insufficiencies should be individualized., Conclusions: Hypopituitarism following aSAH necessitates screening despite lack of gold standard evaluation tests and cut-off values in the follow up, because missed diagnosis may lead to untoward consequences.

Traumatic brain injury (TBI) is one of the major causes of disability and death, particularly in the young population. Recent clinical studies have demonstrated that TBI-induced pituitary dysfunction occurs more frequently than previously estimated, and this may contribute to delayed diagnosis and treatment of hormonal abnormalities. Today, the popularity of combative sports increases, and athletes who deal with these sports have risks of developing hypopituitarism attributed to repetitive TBIs. Pathogenesis and molecular mechanisms are not completely understood yet. Current studies suggest that athletes who had retired, especially from combative sports, should be screened for hypopituitarism. In this review, we aim to increase the awareness of medical communities, athletes, coaches, and athletic trainers about this issue by sharing the current studies regarding the pituitary dysfunction attributed to repetitive TBI associated with sports.

The past decade witnessed a dramatic increase in inpatient hospital payment rates for patients with private insurance relative to payment rates for those covered by Medicare. A natural question is whether the widening private-Medicare payment rate difference had implications for the hospital care received by patients just before and after turning 65-the age at which there is a substantial shift from private to Medicare coverage. Using a large discharge dataset covering the period 2001-2011, we tracked changes at age 65 in the following dimensions of hospital care: overall hospitalization rates, case mix, referral-sensitive surgeries, length of stay, full established charges, number of procedures, mortality, and composite measures of inpatient quality and patient safety. In all cases we found either no change or a change that was small and inconsistent with payment rate changes during the study period.

Objective: To estimate the effects of 2014 Medicaid expansions on inpatient outcomes., Data Sources: Health Care Cost and Utilization Project State Inpatient Databases, 2011-2014; population and unemployment estimates., Study Design: Retrospective study estimating effects of Medicaid expansions using difference-in-differences regression. Outcomes included total admissions, referral-sensitive surgical and preventable admissions, length of stay, cost, and patient illness severity., Findings: In 2014 quarter four, compared with nonexpansion states, Medicaid admissions increased (28.5 percent, p = .006), and uninsured and private admissions decreased (-55.1 percent, p = .001, and -6.6 percent, p = .052), whereas all-payer admissions showed little change. Uninsured expansion effects were negative for preventable admissions (-24.4 percent, p = .068), length of stay (-9.3 percent, p = .039), total cost (-9.2 percent, p = .128), and illness severity (-4.5 percent, p = .397). Significant positive expansion effects were found for Medicaid referral-sensitive surgeries (11.8 percent, p = .021) and patient illness severity (2.3 percent, p = .015). Private and all-payer expansion effects for outcomes other than admission volume were small and mainly nonsignificant (p > .05)., Conclusion: Medicaid expansions did not change all-payer admission volumes, but they were associated with increased Medicaid and decreased uninsured volumes. Results suggest those previously uninsured with greater needs for inpatient services were most likely to gain coverage. Compositional changes in uninsured and Medicaid admissions may be due to selection., (© Health Research and Educational Trust.)

Medicare Advantage plans have incentives and tools to optimize patient care. Therefore, Medicare Advantage hospitalizations may have lower cost and higher quality than similar traditional Medicare hospitalizations. We applied a coarsened matching approach to 2013 Healthcare Cost and Utilization Project hospital discharge data from 22 states to compare hospital cost, length of stay, and readmissions for Traditional Medicare and Medicare Advantage. We found that Medicare Advantage hospitalizations were substantially less expensive and shorter for mental health stays but costlier and longer for injury and surgical stays. We found little difference in the cost and length of medical stays and in readmission rates. One explanation is that Medicare Advantage plans use outpatient settings for many patients with behavioral health conditions and for injury and surgical patients with less complex health needs. Alternatively, the observed differences in behavioral health cost and length of stay may represent skimping on appropriate care.

Background: Research has suggested that growth in the Medicare Advantage (MA) program indirectly benefits the entire 65+-year-old population by reducing overall expenditures and creating spillover effects of patient care practices. Medicare programs and innovations initiated by the Affordable Care Act (ACA) have encouraged practices to adopt models applying to all patient populations, which may influence the continued benefits of MA program growth., Objective: This study investigated the relationship between MA program growth and inpatient hospital costs and utilization before and after the ACA., Methods: Primary data sources were 2005-2014 Health Care Cost and Utilization Project hospital data and 2004-2013 Centers for Medicare & Medicaid Services enrollment data. County-year-level regression analysis with fixed effects examined the relationship between Medicare managed care penetration and hospital cost per enrollee. We decomposed results into changes in utilization, severity, and severity-adjusted inpatient resource use. Analyses were stratified by whether the admission was urgent or nonurgent., Principal Findings: A 10% increase in MA penetration was associated with a 3-percentage point decrease in inpatient cost per Medicare enrollee before the ACA. This effect was more prominent in nonurgent admissions and diminished after the ACA., Conclusions: Results suggest that MA enrollment growth is associated with diminished spillover reductions in hospital admission costs after the ACA. We did not observe a strong relationship between MA enrollment and inpatient days per enrollee. Future research should examine whether spillover effects still are observed in outpatient settings.

Purpose: We evaluated the retinal effects of systemic metabolic changes clustered under the umbrella of metabolic syndrome (MetS) in comparison with age-matched healthy subjects., Methods: Spectral-domain optical coherence tomography (OCT) retinal segmentation analysis of 29 patients with MetS and 36 control subjects was performed. Patients with diabetes mellitus (DM), uncontrolled hypertension, retinopathy, high myopia or hyperopia, and posterior segment surgery, were excluded from analysis. The control group (CG) was selected from age- and sex-matched healthy lean subjects. Mean thickness values of individual retinal layers in nine macular early treatment of diabetic retinopathy study (ETDRS) subfields were determined., Results: The MetS group had a significantly thinner ganglion cell layer in two (MetS, 52.4 ± 5.1 μm; CG, 54.8 ± 3.8 μm; P = 0.030), thinner inner plexiform layer in three (MetS, 39.8 ± 4.4 μm; CG, 43.0 ± 3.5 μm; P = 0.003), thinner photoreceptor layer in seven (MetS, 79.4 ± 2.9 μm; CG, 81.1 ± 2.9 μm; P = 0.009) of nine ETDRS subfields. No difference was found in nerve fiber, inner nuclear, outer plexiform, and outer nuclear layers., Conclusions: The patients with MetS had thinner inner retinal layers and photoreceptor layer in OCT segmentation analysis, which suggests that inherent factors of MetS, such as insulin resistance and adipose tissue-derived inflammation, might have a neurodegenerative effect independent of the hyperglycemic levels associated with DM. Therefore, beyond glycemic control measures, weight reduction also might be advised to overweight patients with type 2 DM and MetS to prevent the occurrence of retinal neurodegeneration.

Objective: To assess the impact of hospital affiliation, centralization, and managed care plan ownership on inpatient cost and quality., Data Sources: Inpatient discharges from 3,957 community hospitals in 44 states and American Hospital Association Annual Survey data from 2010 to 2012., Study Design: We conducted a retrospective longitudinal regression analysis using hierarchical modeling of discharges clustered within hospitals., Data Collection: Detailed discharge data including costs, length of stay, and patient characteristics from the Healthcare Cost and Utilization Project State Inpatient Databases were merged with hospital survey data from the American Hospital Association., Principal Findings: Hospitals affiliated with health systems had a higher cost per discharge and better quality of care compared with independent hospitals. Centralized systems in particular had the highest cost per discharge and longest stays. Independent hospitals with managed care plans had a higher cost per discharge and better quality of care compared with other independent hospitals., Conclusions: Increasing prevalence of health systems and hospital managed care ownership may lead to higher quality but are unlikely to reduce hospital discharge costs. Encouraging participation in innovative payment and delivery reform models, such as accountable care organizations, may be more powerful options., (© Health Research and Educational Trust.)

Studies have linked Accountable Care Organizations (ACOs) to improved primary care, but there is little research on how ACOs affect care in other settings. We examined whether Medicare ACOs have improved hospital quality of care, specifically focusing on preventable inpatient mortality. We used 2008-2014 Healthcare Cost and Utilization Project hospital discharge data from 34 states' Medicare ACO and non-ACO hospitals in conjunction with data from the American Hospital Association Annual Survey and the Survey of Care Systems and Payment. We estimated discharge-level logistic regression models that measured the relationship between ACO affiliation and mortality following admissions for acute myocardial infarction, abdominal aortic aneurysm (AAA) repair, coronary artery bypass grafting, and pneumonia, controlling for patient demographic mix, hospital, and year. Our results suggest that, on average, Medicare ACO hospitals are not associated with improved mortality rates for the studied IQI conditions. Stakeholders may potentially consider providing ACOs with incentives or designing new programs for ACOs to target inpatient mortality reductions.

Physicians serve as the nexus of treatment decision-making in hospitalized patients; however, little empirical evidence describes the influence of individual physicians on hospital costs. In this study, we examine the extent to which hospital costs vary across physicians and physician characteristics. We used all-payer data from 2 states representing 15 237 physicians and 2.5 million hospital visits. Regression analysis and propensity score matching were used to understand the role of observable provider characteristics on hospital costs controlling for patient demographics, socioeconomic characteristics, clinical risk, and hospital characteristics. We used hierarchical models to estimate the amount of variation attributable to physicians. We found that the average cost of hospital inpatient stays registered to female physicians was consistently lower across all empirical specifications when compared with male physicians. We also found a negative association between physicians' years of experience and the average costs. The average cost of hospital inpatient stays registered to foreign-trained physicians was lower than US-trained physicians. We observed sizable variation in average costs of hospital inpatient stays across medical specialties. In addition, we used hierarchical methods and estimated the amount of remaining variation attributable to physicians and found that it was nonnegligible (intraclass correlation coefficient [ICC]: 0.33 in the full sample). Historically, most physicians have been reimbursed separately from hospitals, and our study shows that physicians play a role in influencing hospital costs. Future policies and practices should acknowledge these important dependencies. This study lends further support for alignment of physician and hospital incentives to control costs and improve outcomes.

Among various substances produced by C-cells, the most important one is calcitonin (CT) that is used for detection, post-operative follow-up and evaluation of individuals at risk of developing medullary thyroid carcinoma (MTC). However, the role of serum CT measurement in the evaluation of thyroid nodules has been widely discussed, and there is still no consensus about the role of CT in the initial evaluation of all thyroid nodules. Two patients with thyroid nodules whose fine-needle aspiration results were compatible with benign cytology besides having mildly elevated basal serum calcitonin levels were reported. Calcitonin responses (peak levels were 313 and 229 pg/mL, respectively) to calcium stimulation test were compatible with the possible diagnosis of MTC. However, the final diagnosis was papillary thyroid carcinoma of the thyroid gland. There are limited numbers of case reports showing such an increased serum calcitonin responses to calcium stimulation test associated with papillary or follicular thyroid carcinoma of the thyroid. We suggest to measure serum CT level once and in case of normal levels, no further CT measurement is necessary. Physicians should keep in mind that thyroid carcinomas other than MTCs may also be associated with high serum CT levels., Learning Points: Although serum calcitonin is a valuable tumor marker for MTC, it is well known that mild elevations may be seen in some other diseases such as Hashimoto thyroiditis, neuroendocrine tumors or due to medications such as proton pump inhibitors, calcium salts, beta blockers and glucocorticoids.Those two cases indicate that high calcitonin responses to calcium stimulation test, mimicking MTC, may also be seen in patients with papillary thyroid carcinoma although the mechanism is not clear.

Background: Trend analyses of opioid-related inpatient stays depend on the availability of comparable data over time. In October 2015, the US transitioned diagnosis coding from International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) to ICD-10-CM, increasing from ∼14,000 to 68,000 codes. This study examines how trend analyses of inpatient stays involving opioid diagnoses were affected by the transition to ICD-10-CM., Subjects: Data are from Healthcare Cost and Utilization Project State Inpatient Databases for 14 states in 2015-2016, representing 26% of acute care inpatient discharges in the US., Study Design: We examined changes in the number of opioid-related stays before, during, and after the transition to ICD-10-CM using quarterly ICD-9-CM data from 2015 and quarterly ICD-10-CM data from the fourth quarter of 2015 and the first 3 quarters of 2016., Results: Overall, stays involving any opioid-related diagnosis increased by 14.1% during the ICD transition-which was preceded by a much lower 5.0% average quarterly increase before the transition and followed by a 3.5% average increase after the transition. In stratified analysis, stays involving adverse effects of opioids in therapeutic use showed the largest increase (63.2%) during the transition, whereas stays involving abuse and poisoning diagnoses decreased by 21.1% and 12.4%, respectively., Conclusions: The sharp increase in opioid-related stays overall during the transition to ICD-10-CM may indicate that the new classification system is capturing stays that were missed by ICD-9-CM data. Estimates of stays involving other diagnoses may also be affected, and analysts should assess potential discontinuities in trends across the ICD transition.

This study examines the association between the quality of hospital discharge planning and all-cause 30-day readmissions and same-hospital readmissions. The sample included adults aged 18 years and older hospitalized in 16 states in 2010 or 2011 for acute myocardial infarction, heart failure, pneumonia, or total hip or joint arthroplasty. Data from the Hospital Consumer Assessment of Healthcare Providers and Systems measured discharge-planning quality at the hospital level. A generalized linear mixed model was used to estimate the contribution of patient and hospital characteristics to 30-day all-cause and same-hospital readmissions. Discharge-planning quality was associated with (a) lower rates of 30-day hospital readmissions and (b) higher rates of same-hospital readmissions for heart failure, pneumonia, and total hip or joint replacement. These results suggest that by improving inpatient discharge planning, hospitals may be able to influence their 30-day readmissions and increase the likelihood that readmissions will be to the same hospital.

Purpose: To evaluate choroidal thickness (CT) in patients with Cushing syndrome (CS) with enhanced depth imaging optical coherence tomography., Methods: Twenty-eight patients with CS and 38 healthy volunteers were enrolled in this observational cross-sectional study. Patients with newly diagnosed CS who have been admitted to Erciyes University Department of Endocrinology in 3 years time interval were compared with age- and sex-matched healthy volunteers. Choroidal thickness was measured at the fovea and 2 points nasal and 2 points temporal to the fovea with 500-μm intervals each., Results: Choroidal thickness measurements were higher in patients with CS than in the control group at all examination points; however, the difference was found to be significant at the center of the fovea (367.8 ± 94.4 μm vs. 329 ± 90.5 μm) and 1,000 μm temporal to the fovea. Choroidal thickness measurements were significantly higher in adrenocorticotrophic hormone (ACTH)-dependent CS group than in the control group at all measurement points (CT at fovea 388.2 ± 92.4 μm vs. 329.1 ± 90.5 μm). All CT measurements were found to be correlated with ACTH levels., Conclusion: Cushing syndrome is associated with increased CT. The ACTH-dependent CS may increase CT more than ACTH-independent CS. This effect may be directly related to ACTH itself or increased plasma cortisol levels or both.

Traumatic brain injury (TBI), a worldwide public health problem, has recently been recognized as a common cause of pituitary dysfunction. Circulating microRNAs (miRNAs) present in the sera are characteristically altered in many pathological conditions and have been used as diagnostic markers for specific diseases. It is with this goal that we planned to study miRNA expression in patients with TBI-induced hypopituitarism. Thirty-eight patients (27 male, 11 female; mean age, 43 ± 18 years) who had been admitted to the neurosurgery intensive care unit due to TBI were included in the acute phase of the study. In the chronic phase, miRNA expression profile blood samples were drawn from 25 patients who had suffered TBI 5 years ago. In the acute phase (on Days 1, 7, and 28), a substantial amount of patients (26%, 40%, and 53%; respectively) had hypopituitarism (acute adrenocorticotropic hormone deficiency). In the chronic phase eight of 25 patients (32%) had TBI-induced-hypopituitarism. Forty-seven age-gender-similar healthy controls (25 male, 22 female, mean age: 41 ± 14 years) were included in the study. In order to identify potential candidate miRNA/miRNAs whose levels had been altered in response to TBI-induced hypopituitarism, 740 miRNA expression analyses were performed in the sera of TBI patients by high throughput real-time polymerase chain reaction. Statistical analyses showed that miRNA-126-3p (miR-126-3p) and miRNA-3610 (miR-3610) were detected in the sera of patients who developed hypopituitarism on the 1st, 7th, and 28th days, and in the 5th year following TBI. In addition, miRNA-3907 showed statistically significant and constant dynamic changes on the 1st, 7th, and 28th days, and in the 5th year in the patients with TBI. Our results indicated that altered expression of miR-126-3p and miR-3610 may play an important role in the development of TBI-induced hypopituitarism.

Hypophysitis is generally accepted as an autoimmune disease which is characterized by inflammation and cellular infiltration of the pituitary gland. It can be either primary or secondary. In this review, treatment of primary hypophysitis of various histological subtypes are discussed. Management of primary hypophysitis is usually symptomatic aiming to reduce the size of the pituitary mass and/or replace deficient pituitary hormones. Observation with replacement for deficient pituitary hormones can be applied in some group of patients. Keeping the complications of surgery in mind, surgical intervention should be limited to cases with severe and/or deteriorating compressive signs or cases with inconclusive findings of hypophysitis in whom treatment would be based on histopathological examination. The most commonly used drugs in the treatment of hypophysitis are glucocorticoids. They are able to reduce the size of the mass lesion with their anti-inflammatory effects and sometimes pituitary functions may also recover. However, there is no consensus about the optimal duration and dose of glucocorticoid use. When glucocorticoids and/or surgery fail, azathioprine, methotrexate, cyclosporin A and novel immunotherapies can be tried as third or forth line treatment. Radiotherapy and radiosurgery have been seldom used for treatment of hypophysitis in order to reduce the mass effect.

Testicular torsion is a well-known medical emergency that can lead to pathological changes in the testicular tissues and male infertility. This investigation was undertaken to gain insight into the effects of an endothelin type A receptor antagonist (BQ123) on torsion-induced germ cell loss. Twenty-eight male Wistar albino rats were divided into four groups. In group I (control group), a sham operation to the left testis was performed. In group II (I/R injury), I/R injury was created by rotating the left testis 720° in a clockwise direction for 2 h and detorsing the testis after 2 h. In group III (I/R injury+BQ123), the rats were subjected to I/R injury and BQ123 injection (1 mg/kg, intravenous). In group IV (control+BQ123), the sham operated rats were subjected to BQ123. The testes of the rats were removed in all groups. Torsion-induced apoptosis and the effects of BQ123 were examined by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end labelling (TUNEL) technique, immunohistochemistry and western blotting. In group II, the number of TUNEL-positive cells increased after testicular torsion. Immunohistochemistry and western blotting showed that apoptotic proteins (active caspase 3 and Bax) were upregulated, and the anti-apoptotic protein Bcl2 was downregulated in I/R injury. The administration of BQ123 caused a significant decrease in the number of apoptotic cells and the expression of apoptotic proteins (p<0.05) when compared with the I/R injury group. No significant effect of BQ123 was observed in the testicular cells of group IV. This animal study provides evidence of the regulatory effects of BQ123 on torsion-induced testicular apoptosis.

Purpose: Hypothyroidism has profound effects on multiple organs and systems including cellular oxidative damage. Thus, we aimed to investigate the effects of acute hypothyroidism on oxidative stress in patients with differentiated thyroid carcinoma (DTC)., Patients: 33 patients with DTC were involved in the study. 23 healthy subjects matched for age and body mass index (BMI) served as control group. Fasting blood sample was obtained for the determination of blood chemistry, lipids, myeloperoxidase (MPO) activity, total lipid hydroperoxide (LHP), pyrrolized protein, protein carbonyl compounds (PCC), advanced oxidation protein products (AOPP) and thiol levels before and after thyroid hormone withdrawal (THW) in patients with DTC., Results: MPO activity, total LHP, pyrrolized protein, PCC and AOPP levels were significantly higher, but thiol levels were significantly lower in patients with DTC while on L-thyroxine treatment than those of healthy subjects. At acute hypothyroid status after THW, MPO activity, total LHP, pyrrolized protein, PCC and AOPP levels further increased, thiol levels further decreased in patients with DTC as compared to healthy subjects and to their on L-thyroxine treatment period., Conclusions: This study showed an increased oxidative stress in patients with DTC which is further exacerbated with acute hypothyroidism upon THW. This situation may have treatment implications such as antioxidant therapy, at least during THW., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: This retrospective multicenter study, centrally conducted and supported by the Society of Endocrinology and Metabolism of Turkey, aimed to evaluate the impact of free RET proto-oncogene testing in medullary thyroid carcinoma (MTC) patients. Surgical timing, adequacy of the treatment, and frequency of prophylactic thyroidectomy (PTx) in mutation carriers were also assessed., Methods: Genetic testing for MTC and pheochromocytoma was conducted between July 2008 and January 2012 in 512 patients. Application forms and RET mutation analyses of these patients whose blood samples were sent from various centers around Turkey were assessed retrospectively. An evaluation form was sent to the physicians of the eligible 319 patients who had confirmed sporadic MTC, familial MTC (FMTC), multiple endocrine neoplasia type 2 (MEN2), or who were mutation carriers. Physicians were asked to give information about the surgical history, latest calcitonin levels, morbidity, mortality, genetic screening, and PTx among family members. Twenty-five centers responded by filling in the forms of 192 patients., Results: Among the 319 patients, RET mutation was detected in 71 (22.3%). Cys634Arg mutation was the most prevalent mutation (43.7%), followed by Val804Met in 18 patients (25.4%), and Cys634Tyr in 6 patients (8.5%). Among 192 MTC patients, the diagnosis was sporadic MTC in 146 (76.4%), FMTC in 14 (7.3%), MEN2A in 15 patients (7.9%), and MEN2B in one patient. The number of mutation carriers among 154 apparently sporadic MTC patients was 8 (5.2%). Ten patients were submitted to PTx out of twenty-four mutation carriers at a mean age of 35±19 years., Conclusion: Turkish people have a similar RET proto-oncogene mutation distribution when compared to other Mediterranean countries. Despite free RET gene testing, the number of the PTx in Turkey is limited and relatively late in the life span of the carriers. This is mainly due to patient and family incompliance and incomplete family counselling.

Background: Pharmaceutical firms spend billions of dollars developing new therapies, which are often sold at a substantial premium over older therapies. The costs and benefits of these newer and more expensive drugs, however, are controversial. The empirical evidence on whether newer drugs can decrease overall healthcare expenditures may enable private and public health policymakers to develop new drug benefit structures. Objective: This paper investigates the impact of new drugs and drug classes on overall healthcare expenditures. The paper focuses on the level of reductions in total healthcare expenditures drawn from the replacement of other drugs with breakthrough drug classes. Methods: We used the Medical Expenditure Panel Survey (MEPS) data sets from 1996 to 2001. To measure the effect of important drugs prescribed for a given condition on the expenditures, we developed a model that captures the effect of important drugs on expenditures in a less restrictive way than the extant literature. Our analysis of these drug groupings offers several improvements over prior work. First, we treated all drugs with a similar pharmacology as the same, rather than assigning their therapeutic value based on year of introduction. Second, our approach recognizes that innovations emerge in waves and that drugs within a particular group are more similar therapeutically to each other than to other existing drugs, or other drugs introduced in the same or different years. Third, we separately estimated the effects of each of these groups of drugs on drug and non-drug expenditures. Finally, we measured the cost impact of drug use in a more general way than in the existing literature. We examined six different groups of breakthrough drugs, selective serotonin reuptake inhibitors, statins, angiotensin-converting-enzyme (ACE) inhibitors, histamine type 2 antagonists, proton pump inhibitors, calcium channel blockers and fluoroquinolones. Results: Our results demonstrate that drugs from breakthrough classes - except ACE inhibitors - are more expensive than other drugs. Next, we measured the impact of breakthrough drug classes and other drugs on total non-drug medical expenditures. The results indicate that important drugs significantly decrease total non-drug expenditures for all breakthrough classes, except fluoroquinolones. In general, the reduction in non-drug expenditures is many times larger than the increased drug expenditures. Conclusion: Breakthrough drug classes, with the exception of fluoroquinolones, substantially reduce overall healthcare expenditures.

Testosterone replacement therapy (TRT) in idiopathic hypogonadotrophic hypogonadism (IHH) slows the process of metabolic syndrome (MetS), diabetes mellitus, and cardiovascular diseases by its inversing effects on insulin resistance, dyslipidemia, and blood pressure. Since there are not enough data regarding the effects of gonadotropin replacement therapy (GRT), we aimed to investigate the impact of GRT on MetS parameters in IHH patients. Sixteen patients with IHH and 20 age and body mass index (BDI)-matched healthy controls were enrolled into the study. Patients were evaluated at baseline and 6 months after the GRT. Sex hormones, insulin like growth factor-1, prolactin, insulin, C-reactive protein (CRP), homocysteine, and lipid levels were measured at baseline and after the treatment. Anthropometric measurements, including BMI, body fat ratio (BFR), fat free mass (FFM), waist circumference, and waist-to-hip ratio (WHR), were also performed. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) index was calculated. Body fat ratio, triglyceride, HOMA-IR, and CRP levels were higher, whereas bone age, fat free mass, and creatinine levels were lower in the patients with hypogonadism. HOMA-IR indices and basal insulin levels decreased significantly after 6 months of GRT compared with baseline levels. Triglyceride levels, and BFRs diminished significantly by an accompanying decline in WHR. FFM of the patients increased following the GRT. No significant changes were detected in CRP, homocysteine, total and LDL-cholesterol levels. Similar to TRT, hCG treatment decreases HOMA-IR, triglyceride levels, BFR and WHRs, and increases FFM in patients with IHH., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: The purposes of the study were to compare serum total cortisol (STC), salivary cortisol (SaC) and calculated free cortisol (cFC) levels at baseline and after the adrenocorticotrophic hormone (ACTH) stimulation test in patients with severe sepsis (SS) and determine the suitability of use of SaC and cFC levels instead of STC for the diagnosis of adrenal insufficiency (AI) in patients with SS. And secondary aims of this study were to compare these parameters in patients with SS with healthy controls and check their effects on survival status of the patients., Methods: Thirty patients with SS (15 men and 15 women) were compared with 16 healthy controls. Low-dose (1 μg) ACTH stimulation test was performed to the patients on the first, seventh and 28th days of diagnosis of SS, but in control group, 1 μg ACTH stimulation test was performed only once. STC, SaC and cFC levels were measured during ACTH stimulation test., Results: Patients were categorized as having low or high baseline STC according to a cut-off level of 10 μg/dL. In high STC group, baseline and peak SaC levels were found to be 2.3 (0.2-9.0) and 3.4 (0.5-17.8) μg/dL on D1 and 1.1 (0.8-4.6) and 2.6 (1.3-2.9) μg/dL on D7, respectively. In the control group, baseline and peak SaC levels were 0.4 (0.1-1.4) and 1.1 (0.4-2.5) μg/dL, respectively. Baseline and peak SaC levels after ACTH stimulation were found to be higher in high STC group than in controls, but they were found to be similar in low STC and control groups. In high STC group, cFC levels were 0.3 (0.1-0.3) and 0.4 (0.3-0.7) μg/dL on D1 and 0.2 (0.1-0.3) and 0.4 (0.1-0.7) μg/dL on D7, respectively. In the control group, baseline and peak cFC levels were 1.7 (0.4-1.9) and 1.8 (1.0-6.6) μg/dL, respectively. cFC levels were found to be lower in patients with SS subgroups than in the control group. Baseline and stimulated STC, SaC and cFC levels did not differ according to the survival status. SaC, cFC and STC levels were found to be correlated with each other., Conclusions: SS is associated with increased SaC, but decreased cFC levels when baseline STC is assumed to be sufficient. When STC level is assumed to be insufficient, SaC levels remain unchanged, but cFC levels are decreased. Lower STC levels is not associated with increased mortality in patients with SS. More data are needed in order to suggest the use of SaC and cFC instead of STC., Trial Registration: ClinicalTrials.gov No: NCT02589431.

Sheehan's syndrome (SS) is a parturition-related pituitary disease resulting from severe postpartum hemorrhage and can present with varying degrees of pituitary insufficiency. Pathological and clinical findings of SS were first described by Harold L. Sheehan in the previous century. Although his definitions are still valid, various studies and reports including new data have subsequently been published. Additionally, the diagnosis of SS has often been overlooked and thus delayed for long years due to its nonspecific signs and symptoms. Therefore, a large number of patients may be remained undiagnosed and untreated. SS is not as rare as assumed in developed countries, probably due to migrant women and unawareness of physicians regarding the syndrome. In this review, we provide a detailed review of the epidemiology, etiopathogenesis, clinical, laboratory and radiological features, new diagnostic criteria, differential diagnosis, and treatment of SS.

Traumatic brain injury (TBI) is a crucially important public health problem around the world, which gives rise to increased mortality and is the leading cause of physical and psychological disability in young adults, in particular. Pituitary dysfunction due to TBI was first described 95 years ago. However, until recently, only a few papers have been published in the literature and for this reason, TBI-induced hypopituitarism has been neglected for a long time. Recent studies have revealed that TBI is one of the leading causes of hypopituitarism. TBI which causes hypopituitarism may be characterized by a single head injury such as from a traffic accident or by chronic repetitive head trauma as seen in combative sports including boxing, kickboxing, and football. Vascular damage, hypoxic insult, direct trauma, genetic predisposition, autoimmunity, and neuroinflammatory changes may have a role in the development of hypopituitarism after TBI. Because of the exceptional structure of the hypothalamo-pituitary vasculature and the special anatomic location of anterior pituitary cells, GH is the most commonly lost hormone after TBI, and the frequency of isolated GHD is considerably high. TBI-induced pituitary dysfunction remains undiagnosed and therefore untreated in most patients because of the nonspecific and subtle clinical manifestations of hypopituitarism. Treatment of TBI-induced hypopituitarism depends on the deficient anterior pituitary hormones. GH replacement therapy has some beneficial effects on metabolic parameters and neurocognitive dysfunction. Patients with TBI without neuroendocrine changes and those with TBI-induced hypopituitarism share the same clinical manifestations, such as attention deficits, impulsion impairment, depression, sleep abnormalities, and cognitive disorders. For this reason, TBI-induced hypopituitarism may be neglected in TBI victims and it would be expected that underlying hypopituitarism would aggravate the clinical picture of TBI itself. Therefore, the diagnosis and treatment of unrecognized hypopituitarism due to TBI are very important not only to decrease morbidity and mortality due to hypopituitarism but also to alleviate the chronic sequelae caused by TBI., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aim: To determine the impact of traumatic brain injury (TBI) and chest trauma (CT) on the number of peripheral blood (PB) stem cells in affected patients in comparison to normal controls. Additionally, the aim was to determine the relationship between CD34+ cell counts and TBI-induced hypothalamus-pituitary-adrenal axis dysfunction in the acute phase of trauma., Patients and Method: Thirty patients with TBI, 12 patients with CT and 53 healthy subjects were included in the study., Results: CD34+ cell counts within the first 24-48 hours of TBI were found to be lower than those obtained on the 7(th) day of TBI and those in the healthy controls. CD34+ cell counts obtained on the 2(nd) day of CT were lower than those in the healthy group, but did not differ from those measured on the 7(th) day of CT. There was no correlation between CD34+ cell counts and serum total cortisol (STC) levels on the 2(nd) and 7(th) days in the TBI or CT groups., Conclusion: An increase in CD34+ cell counts as observed on the 7(th) day in both TBI and CT groups suggested that CD34 changes were not specific to TBI. Moreover, this study showed for the first time that CD34 response was not affected by changes in cortisol levels induced by TBI and severity of TBI.

The aim of this study was to evaluate and compare the effects of spironolactone and spironolactone plus metformin treatments on body mass index (BMI), hirsutism score, hormone levels, and insulin resistance in women with polycystic ovary syndrome (PCOS). Thirty-seven patients with PCOS were randomly assigned to receive spironolactone 100 mg/d (spironolactone group, 18 patients) or spironolactone 100 mg/d plus metformin 2000 mg/d (combination group, 19 patients) for 12 months. BMI, modified Ferriman-Gallway score (FGS), serum levels of regarding hormones, and homeostasis model assessment of insulin resistance (HOMA-IR) index were assessed before and after the treatments. Six patients in the spironolactone group and four patients in the combination group reported inter-menstrual vaginal bleeding during treatments. In hirsutism scores, the spironolactone therapy resulted in 25.2% reduction, while combination therapy resulted in 28.3% reduction (p > 0.05, between groups). When the groups were compared in terms of percent changes in BMI, FGS, HOMA-IR, and hormone values other than free testosterone, no significant difference was noted. In the present study, FGSs were significantly decreased in both groups; however, combination therapy was not more effective than spironolactone alone in terms of BMI, FGS, hormone levels, or insulin resistance.

Objective: The aim of this study was to assess diagnostic values of insulin tolerance test (ITT), glucagon stimulation test (GST), and insulin like growth factor-I (IGF-I) level, to find optimal GH cut-off values for GST, and to evaluate efficiencies of patient age, gender, body-mass index (BMI), and additional pituitary hormone deficiencies (PHDs) in the diagnosis of growth hormone deficiency (GHD)., Study Design: This retrospective study involved 216 patients with a pituitary disease and 26 healthy controls. Age, gender, BMI, medical histories, and hormonal data including baseline and stimulated hormone values were evaluated. Three cut-off values for peak GH responses to stimulation tests were evaluated: (a) 3.00 µg/L on ITT, (b) 3.00 µg/L on GST, and (c) 1.07 µg/L on GST., Results: According to the ITT, GST with 3.00 µg/L cut-off, and GST with 1.07 µg/L cut-off, GHD was present in 86.1, 74.5, and 54.2 % patients, respectively. Patient age, BMI, and number of PHDs, but not gender, were found to be correlated with IGF-I and peak GH concentrations. All patients with an IGF-I concentration ≤95 ng/ml or ≥3 PHD had GHD. None of the patients with adequate GH response to the GST with 1.07 µg/L cut-off, but blunted responses to ITT and GST with 3.00 µg/L cut-off, had ≥3 PHDs. 12 out of 26 (46.2 %) healthy subjects failed the GST with 3.00 µg/L cut-off, but not with 1.07 µg/L cut-off., Conclusions: Patient age, IGF-I, BMI, and number of PHDs are efficient factors associated with the diagnosis of GHD. A 4 h GST with a diagnostic GH threshold of 1.07 µg/L seems to be a good diagnostic method for GHD.

Context: In sporadic acromegaly, overall AIP(mut) prevalence is reported as 3, 4.1 and 16 % in studies carried out across Europe. However, it is not known whether the prevalence shows any changes across different ethnicities. The aim of the study was to identify prevalence of AIP(mut) in a series of Turkish acromegalic patients., Patients and Methods: Direct sequencing of AIP gene was performed in 92 sporadic acromegalic patients., Results: One patient was found to have a new mutation in exon 6: g67.258,286 (G/A) heterozygote; (GGC/GAC; gly/asp). Apart from this new mutation, previously defined synonymous mutations in AIP gene were detected in seven patients (Exon 4; rs2276020; (GAC/GAT; asp/asp) and six patients were found to have five different intronic mutations in AIP gene which were not previously defined. The patient with pathogenic AIP(mut) presented at a young age and had an aggressive and treatment resistant tumour. The prevalence of AIP(mut) in Turkish patients was found to be 1 % in sporadic acromegaly in the present study. In addition, one synonymous mutation which was previously defined and six new intronic mutations have been described in Turkish acromegalic patients. All acromegalic patients with synonymous AIP(mut) presented with macroadenoma and majority of them had invasive tumour., Conclusion: The prevalence of AIP(mut) in Turkish patients was found to be 1 % in sporadic acromegaly in the present study. This ratio increases when younger age groups are taken into account 6 % among patients <30 years of age at the time of diagnosis of acromegaly. The clinical features of acromegaly, such as having large and invasive tumours, may be affected by the presence of synonymous AIP(mut).

Objective: Hirsutism results from hyperandrogenemia and/or exaggerated androgen responsiveness. Among various causes of hirsutism, some patients do not exhibit androgen excess which is called idiopathic hirsutism (IH). The pathogenesis of IH could not so far be clearly established., Design: To investigate the mRNA expression of aromatase enzyme and the other enzymes having functional roles in the steroidogenic pathway, in freshly obtained skin tissue from subumbilical skin and the arm of the patients with IH and healthy women., Methods: Twenty-one women with IH and 15 healthy women were included in the study. We aimed to determine mRNA expressions of genes associated with local androgen synthesis and metabolism (CYP11A1, STS, CYP19A1, SRD5A1, SRD5A2, HSD3B1, AR, COMT, ESR1, ESR2, HSD3B2, CYP17A1, SULT2A1, SULT1E1, HSD17B2, IL6, TGFB1, TNFA) from skin biopsy and blood samples of patients with IH and the data compared with healthy subjects., Results: Patients with IH exhibit significantly lower interleukin 6 (IL6) mRNA expression and higher steroid sulphatase (STS) and hydroxysteroid (17beta) dehydrogenase 2 (HSD17B2), gene mRNA expression, respectively, in the subumbilical region skin biopsies. Similarly, patients with IH exhibit significantly lower IL6 mRNA expression and higher STS and HSD17B2 gene mRNA expression, respectively, in the arm skin compared to healthy women's subumbilical region., Conclusions: In both arm and subumbilical skin biopsy of patients with IH, we observed an up-regulation of HSD17B2 and STS, decreased IL6 mRNA expression, probably determining an increase in the local amount of active androgens, which could then be used as substrate for other androgen metabolic routes., (© 2015 European Society of Endocrinology.)

Objective: To assess the association between aggregate unemployment and hospital discharges for acute myocardial infarction (AMI) among adults and seniors, 1995-2011., Data Sources/study Setting: Community hospital discharge data from states collected for the Healthcare Cost and Utilization Project (HCUP) State Inpatient Databases (SID) and economic data from the Bureau of Labor Statistics, 1995-2011., Study Design: Quarterly time series study of unemployment and aggregate hospital discharges in local areas using fixed effects to control for differences between local areas., Data Collection/extraction Methods: Secondary data on inpatient stays and unemployment rates aggregated to micropolitan and metropolitan areas., Principal Findings: For both adults and seniors, a 1 percentage point increase in the contemporaneous unemployment rate was associated with a statistically significant 0.80 percent (adults) to 0.96 percent (seniors) decline in AMI hospitalization during the first half of the study but was unrelated to the economic cycle in the second half of the study period., Conclusions: The study found evidence that the aggregate relationship between health and the economy may be shifting for cardiovascular events, paralleling recent research that has shown a similar shift for some types of mortality (Ruhm 2013), self-reported health, and inpatient use among seniors (McInerney and Mellor 2012)., (© Health Research and Educational Trust.)

Background: The Affordable Care Act (ACA) has increased rates of public and private health insurance in the United States. Increasing coverage could raise hospital revenue and reduce the need to shift costs to insured patients. The consequences of ACA on hospital revenues could be examined if payments were known for most hospitals in the United States. Actual payment data are considered confidential, however, and only charges are widely available. Payment-to-charge ratios (PCRs), which convert hospital charges to an estimated payment, have been estimated for hospitals in 10 states. Here we evaluated whether PCRs can be predicted for hospitals in states that do not provide detailed financial data., Methods: We predicted PCRs for 5 payer categories for over 1,000 community hospitals in 10 states as a function of state, market, hospital, and patient characteristics. Data sources included the Healthcare Cost and Utilization Project (HCUP) State Inpatient Databases, HCUP Hospital Market Structure file, Medicare Provider of Service file, and state information from several sources. We performed out-of-sample prediction to determine the magnitude of prediction errors by payer category., Results: Many individual, hospital, and state factors were significant predictors of PCRs. Root mean squared error of prediction ranged from 32 to over 100 % of the mean and varied considerably by which states were included or predicted. The cost-to-charge ratio (CCR) was highly correlated with PCRs for Medicare, Medicaid, and private insurance but not for self-pay or other insurance categories., Conclusions: Inpatient payments can be estimated with modest accuracy for community hospital stays funded by Medicare, Medicaid, and private insurance. They improve upon CCRs by allowing separate estimation by payer type. PCRs are currently the only approach to estimating fee-for-service payments for privately insured stays, which represent a sizable proportion of stays for individuals under age 65. Additional research is needed to improve the predictive accuracy of the models for all payers.

Phototrophic microorganisms disfigure the surfaces of different types of stone. Stone structure is damaged by the activity of photoautotrophic and other microorganisms. However, to date few, investigations have been undertaken into the relationship between microorganisms and the properties of different types of marble. In this study, biological activity of photoautotrophic microorganisms on three types of marble (Yatagan White, Giallo Anticato and Afyon White) was investigated under laboratory conditions over a short period of time. The three types of marble supported the growth of phototrophic microbial communities on their outer and inner layers, turning their original colour from white to a yellowish green colour. The porosity of the marble types facilitated filamentous microbial growth in the presence of water. Scanning electron microscope analysis revealed the accumulation of aggregates such as small spherical, fibrillar, calcified globular bodies on the inner surfaces of the marbles. This suggests that the microscopic characteristics of particular marble types may stimulate the growth of certain types of microorganisms.

The Centers for Medicare & Medicaid Services Hospital Readmission Reduction Program and the Centers for Medicare & Medicaid Innovations Bundled Payments for Care Improvement Initiative hold hospitals accountable for readmissions that occur at other hospitals. A few studies have described the extent to which hospital readmissions occur at the original place of treatment (i.e., same-hospital readmissions). This study uses data from 16 states to describe variation in same-hospital readmissions by patient characteristics across multiple conditions. We found that the majority of 30-day readmissions occur at the same hospital, although rates varied considerably by condition. A significant number of hospitals had very low rates of same-hospital readmissions, meaning that the majority of their readmissions went to other hospitals. Future research should examine why some hospitals are able to retain patients for a same-hospital readmission and others are not., (© The Author(s) 2015.)

Salivary cortisol (SC) has been increasingly used as a surrogate biomarker of free cortisol (FC) for the assessment of hypothalamo-pituitary-adrenal (HPA) axis, but there are not enough data regarding its use during ACTH stimulation tests. Therefore, we aimed to determine the responses of SC, calculated free cortisol (cFC) and free cortisol index (FCI) to ACTH stimulation tests in healthy adults. Forty-four healthy volunteers (24 men and 20 women) were included in the study. Low-dose (1 µg) and standard-dose (250 µg) ACTH stimulation tests were performed on two consecutive days. Basal and stimulated total cortisol (TC) and cortisol-binding globulin (CBG) levels and SC levels were measured during both doses of ACTH stimulation tests. cFC (by Coolens' equation) and FCI levels were calculated from simultaneously measured TC and CBG levels. The minimum SC, cFC, FCI levels after low-dose ACTH stimulation test were 0.21, 0.33, 16.06 µg/dL, and after standard-dose ACTH were 0.85, 0.46, 26.11 µg/dL, respectively, in healthy individuals who all had TC responses higher than 20 µg/dL. Peak CBG levels after both doses of ACTH stimulation tests were found to be higher in women than in men. So, by its effect, peak cFC and FCI levels were found to be lower in female than in male group. Neither TC nor SC levels were affected by gender. cFC and FCI levels depend on CBG levels and they are affected by gender. Cut-off levels for SC, cFC, FCI levels after both low- and standard-dose ACTH stimulation are presented. Studies including patients with adrenal insufficiency would be helpful to see the diagnostic value of these suggested cut-off levels.

Context: Diagnosis of secondary adrenal insufficiency and GH deficiency requires evaluation by dynamic stimulation tests in most cases. Although insulin tolerance test (ITT) is accepted as the gold-standard test for the evaluation of both hypothalamo-pituitary-adrenal (HPA) and (GH)-IGF-1 axes, the test is cumbersome. In clinical practice, low-dose adrenocorticotrophic hormone (ACTH) stimulation test is a sensitive, safe and easily applicable alternative to ITT. Although it takes more time, glucagon stimulation test (GST) is also a good alternative to ITT and can evaluate both axes., Objective: The primary aim of this study was to compare the ITT, low-dose ACTH and GSTs in the evaluation of HPA and GH-IGF-1 axes in patients with pituitary disorders and to evaluate the repeatability of all three tests., Design: ITT, low-dose ACTH and GSTs were performed in all 129 patients, and the tests were repeated in 66 of these patients., Setting: Erciyes University Medical School, Department of Endocrinology., Patients or Other Participants: One hundred and twenty-nine adult patients (76 women, 53 men) with pituitary disorder were included in the study., Main Outcome Measure(s): The cortisol and GH responses of patients to dynamic tests., Results: Peak cortisol levels obtained during ITT were significantly lower than the values obtained during both low-dose ACTH and GSTs. Peak cortisol levels obtained during the GST were lower than those found during the low dose ACTH stimulation test. Peak GH responses were found to be higher in GST than in ITT. All three tests had good reproducibility., Conclusions: Any of 3 tests can be used in the evaluation of the HPA axis and either GST or the ITT can be used in the evaluation of the GH-IGF-1 axis but cut-off levels for the insufficiency of HPA or GH-IGF-1 axis should be individualized for each test., (© 2014 John Wiley & Sons Ltd.)