Increased short- and long-term mortality following infections in dementia: a nationwide registry-based cohort study.

BACKGROUND AND PURPOSE: Mortality following infections in dementia has not yet been comprehensively explored. The aim of this cohort study was to investigate the short- and long-term mortality following infections in dementia. METHODS: Follow-up was from 1 January 2000 or the 65-year birthday until death, immigration, or 31 December 2015. Exposure was incident dementia and a first infection. The outcome was all-cause mortality. Mortality rate ratios (MRRs) were calculated using Poisson regression in 4 exposure groups (dementia yes/no, infection yes/no) by sex, infection site, and time since infection. RESULTS: 1,496,436 people were followed with 12,739,135 person-years. MRR in dementia/infection was 6.52 (95% confidence interval: 6.43-6.60) and was increased for infections of all sites. Increased mortality was short term (30 days) and long term (10 years). CONCLUSIONS: Increased mortality in people with dementia identifies them as a particularly vulnerable group that needs clinical attention.

General medical conditions and mortality in women with postpartum psychiatric disorders.

BACKGROUND: Psychiatric patients have an increased risk of general medical conditions and mortality, but no study has systematically explored these outcomes among women with mental disorders following childbirth (postpartum psychiatric disorders: PPD). Therefore, we aimed to investigate the risk of subsequent general medical conditions and mortality in women with a broad spectrum of PPD. METHODS: This register-based cohort study followed all Danish women born after January 1, 1960, until January 1, 2016. The exposure of interest was (i) mild-moderate PPD: first-ever prescription of psychotropic medication (ATC codes: N03-N07) and (ii) severe PPD: first-ever in- or out-patient contact to a psychiatric facility, both within six months postpartum. Outcomes of interest were (i) hospital-registered chronic medical conditions and (ii) mortality from natural and unnatural causes. We included 1 841 949 women representing 22 615 310 person-years at risk. RESULTS: Among 15 852 women with mild-moderate PPD and 4266 women with severe PPD, we found a higher risk of any subsequent general medical condition (mild-moderate PPD: IRR 1.25; 95% CI 1.20-1.31 and severe PPD: IRR 1.35; 95% CI: 1.24-1.48) when compared to the female background population. Mortality from both natural and unnatural causes was higher in both groups: Mild-moderate PPD: natural causes MRR 1.37; 95% CI: 1.17-1.61; unnatural causes MRR 1.52; 95% CI: 1.10-2.11, and severe PPD: natural causes MRR 1.42; 95% CI 1.02-2.00, and unnatural causes MRR 5.05; 95% CI: 3.40-7.51. CONCLUSIONS: This first overview of general medical prognosis in PPD shows that women at either end of the spectrum are at increased risk of subsequent chronic medical conditions and overall mortality.

Risk of homelessness after discharge from psychiatric wards in Denmark: a nationwide register-based cohort study.

OBJECTIVE: To examine the absolute and relative risk of homelessness following discharge from psychiatric wards in Denmark. METHODS: A nationwide, register-based, cohort study including people aged 18+ years discharged from psychiatric wards in Denmark between 1 January 2001 and 31 December 2015. We analysed associations between psychiatric diagnoses and risk of homelessness using survival analysis. RESULTS: A total of 126 848 psychiatric in-patients were included accounting for 94 835 person-years. The incidence of homelessness one year following discharge was 28.18 (95% CI 26.69-29.75) and 9.27 (95% CI 8.45-10.16) per 1000 person-years at risk in men and women respectively. The one-year cumulative probability of first homelessness after discharge from psychiatric wards was 1.58% (95% CI 1.48-1.68) in males and 0.55% (95% CI 0.50-0.61) in females. Substance use disorders increased the risk of homelessness after discharge with adjusted incidence rate ratios of 6.60 (95% CI 5.19-8.40) (men) and 13.06 (95% CI 9.31-18.33) (women), compared with depressive disorders. Prior history of homelessness was an important predictor for homelessness following discharge. CONCLUSIONS: The first year following discharge from psychiatric wards is a high-risk period of homelessness, especially when having a substance use disorder or a prior history of homeless shelter contact. Improved efforts to prevent homelessness are needed.

Schizophrenia and attendance in primary healthcare: a population-based matched cohort study.

Objective: Schizophrenia is associated with high mortality, somatic comorbidity and reduced life expectancy. The general practitioner (GP) plays a key role in the treatment of mental and physical multimorbidity. Nevertheless, it is unclear how much individuals with schizophrenia use primary healthcare. This study aims to investigate the yearly numbers of consultations in general practice for individuals with schizophrenia. Design and Setting: We performed a population-based matched cohort study of 21,757 individuals with schizophrenia and 435,140 age- and gender-matched references from Danish National Registers. Monthly general practice consultations were analysed using a generalized linear model with log link and assuming negative binomial distribution. Main outcome measures: Consultation rates in general practice up to17 years after index diagnosis. Results: Individuals with schizophrenia attended their GP more than references throughout the study period. The cases had 82% (95% CI: 78-87) and 76% (95% CI: 71-80) more consultations in primary care after 1 year and 5 years, respectively. Individuals with both schizophrenia and comorbid somatic illness attended even more. Conclusion: Individuals with schizophrenia are in regular contact with their GP, especially if they have comorbid illnesses. Whether an average of six consultations per year for individuals with schizophrenia is sufficient is up for debate. The study demonstrates a potential for an increased prevention and treatment of individuals with schizophrenia in general practice. KEY POINTS Schizophrenia is associated with high mortality, somatic comorbidity and reduced life expectancy. Little is known about the attendance pattern in primary care for individuals with schizophrenia. •We found high attendance rates in primary care for individuals diagnosed with schizophrenia from index diagnosis and at least 17 years after diagnosis, which suggests opportunities for earlier intervention to improve their somatic health. •We found an association between high illness comorbidity and increased risk of not attending the general practitioner. The most severely somatically and mentally ill individuals may thus be difficult to reach and support in the current healthcare system.

Increased mortality from somatic multimorbidity in patients with schizophrenia: a Danish nationwide cohort study.

OBJECTIVE: To investigate the association of single- and multimorbidity with mortality rates in patients with schizophrenia compared to the general population. METHOD: A nationwide cohort study including residents in Denmark between 1995 and 2015. The cohort was dichotomously divided by a diagnosis of schizophrenia. Somatic diseases included infections, cancer, endocrine, neurologic, cardiovascular, respiratory, digestive, skin, musculoskeletal, and urogenital diseases. Hazard ratios (HRs) and population attributable fractions (PAFs) were calculated. RESULTS: The cohort included 30 210 patients with schizophrenia [mean age (SD) = 32.6 (11.4), males = 57.2%], and 5 402 611 from the general population [mean age (SD) = 33.0 (14.5), males = 50.4%]. All number of somatic diseases were associated with an increased mortality in schizophrenia [HR = 16.3 (95% CI = 15.4-17.3) for 1 disease to 21.0 (95% CI = 19.1-23.0) for ≥5 diseases], using the general population with no somatic disease as reference. Across all somatic diseases, patients with schizophrenia showed a HR > 2, compared to the general population, and respiratory (PAF = 9.3%), digestive (PAF = 8.2%), and cardiovascular (PAF = 7.9%) diseases showed largest contributions to death. CONCLUSIONS: Patients with schizophrenia showed higher mortality on all levels of multimorbidity, and a doubled mortality rate across all somatic diseases, compared to the general population. The findings suggest that the clusters and trajectories of symptoms associated with schizophrenia is the main driver of the excess mortality.

Impact of severe mental illness on cancer stage at diagnosis and subsequent mortality: A population-based register study.

BACKGROUND: Excess mortality in individuals with severe mental illness (SMI) is often explained by physical comorbidity and suboptimal healthcare. Cancer is a prevalent cause of death, and tumour stage at diagnosis is a strong predictor of mortality. We aimed to study cancer incidence, disease stage at diagnosis and subsequent mortality in individuals with SMI compared to individuals without SMI. METHODS: The entire Danish population was followed in 1978-2013 using nationwide registries. Cancer incidence and subsequent mortality stratified by disease stage were compared in individuals with and without SMI. Cox regression was used to estimate incidence rate ratios (IRR) and mortality rate ratios (MRR). Cancer was examined overall and grouped by major aetiological factors. RESULTS: The overall cancer incidence rate was lower in males with SMI than in males without SMI; IRR = 0.89 (95% CI: 0.85-0.94), but rates were similar in females with SMI and without SMI; IRR = 1.03 (95% CI: 0.99-1.07). The overall mortality rate was higher in individuals with SMI than those without; MRR = 1.56 (95% CI: 1.48-1.64) for males and MRR = 1.49 (95% CI: 1.43-1.56) for females. Incidence rates and mortality rates showed similar estimates when stratified by tumour stage and aetiology. CONCLUSIONS: We found lower cancer incidence in males with SMI compared to males without SMI and similar incidence in the two groups of women. Higher subsequent mortality was found in both sexes with SMI. The excess mortality was not explained by more advanced stages of cancer; future studies should evaluate the effect of cancer treatment and rehabilitation.

Mortality in unipolar depression preceding and following chronic somatic diseases.

OBJECTIVE: It is largely unknown how depression prior to and following somatic diseases affects mortality. Thus, we examined how the temporal order of depression and somatic diseases affects mortality risk. METHOD: Data were from a Danish population-based cohort from 1995 to 2013, which included all residents in Denmark during the study period (N = 4 984 912). Nineteen severe chronic somatic disorders from the Charlson Comorbidity Index were assessed. The date of first diagnosis of depression and somatic diseases was identified. Multivariable Cox proportional Hazard models with time-varying covariates were constructed to assess the risk for all-cause and non-suicide deaths for individual somatic diseases. RESULTS: For all somatic diseases, prior and/or subsequent depression conferred a significantly higher mortality risk. Prior depression was significantly associated with a higher mortality risk when compared to subsequent depression for 13 of the 19 somatic diseases assessed, with the largest difference observed for moderate/severe liver disease (HR = 2.08; 95% CI = 1.79-2.44), followed by metastatic solid tumor (HR = 1.48; 95% CI = 1.39-1.58), and myocardial infarction (HR = 1.40; 95% CI = 1.34-1.49). CONCLUSION: A particularly high mortality risk was observed in the presence of prior depression for most somatic diseases. Future studies that assess the underlying mechanisms are necessary to adequately address the excessive mortality associated with comorbid depression.

Impact of local heating and cooling on skeletal muscle transcriptional response related to myogenesis and proteolysis.

PURPOSE: To determine the impact of local muscle heating and cooling on myogenic and proteolytic gene responses following resistance exercise. METHODS: Recreationally trained males (n = 12), age 25.3 ± 1.5, % body fat 13.6 ± 1.92, completed four sets of 8-12 repetitions of unilateral leg press and leg extension while heating one leg, and cooling the other. Muscle biopsies were taken from the vastus lateralis of each leg pre and 4 h post exercise. RESULTS: MyoD, FOXO1, and MuRF1 mRNA increased with exercise regardless of temperature (p < 0.05). Myostatin, MYF5, and atrogin-1 mRNA decreased with exercise regardless of temperature (p < 0.05). Myogenin, MRF4, and CASP3 mRNA were higher in the hot condition, compared to the cold (p < 0.05). PAX7 mRNA was lower in the hot compared to cold condition (p = 0.041). FOXO3 mRNA was higher in the cold compared to hot condition (p = 0.037). AKT1 and AKT2 were unaffected by either exercise or temperature. Femoral artery blood flow volume was higher in the hot (375.2 ± 41.2 ml min- 1), compared to the cold condition (263.5 ± 23.9 ml min- 1), p = 0.01. Tissue oxygen saturation was higher in the hot (71.7 ± 4.8%) than cold condition (55.3 ± 5.0%). CONCLUSION: These results suggest an impaired muscle growth response with local cold application compared to local heat application.

Increased use of primary care during 6 years of prodromal schizophrenia.

BACKGROUND: Early diagnosis is important for the course of schizophrenia. AIM: To investigate whether prodromal symptoms of schizophrenia lead to increased use of primary care. METHOD: A register-based cohort study of 21 894 cases with incident schizophrenia and 437 880 matched controls. RESULTS: Cases used daytime primary care 43% more than controls during the 6 years before diagnosis (IRR = 1.43; 95% CI: 1.39; 1.48) and 132% more during the last 2 months (IRR = 2.32; 95% CI: 2.27; 2.37), and 34% (IRR = 1.34; 95% CI: 1.23; 1.48) vs. 374% more for out-of-hours services (IRR = 3.74; 95% CI: 3.52; 3.98). Six years before index diagnosis, 30% of cases had at least one psychiatric contact without being diagnosed with schizophrenia, increasing to 75% 1 month before diagnosis. CONCLUSION: Increased help-seeking behaviour was seen at least 6 years before index diagnosis, suggesting a 'window' for earlier diagnosis of prodromal schizophrenia.

Simple and practical screening approach to identify HIV-infected individuals with depression or at risk of developing depression.

OBJECTIVES: Studies have shown that depression and other mental illnesses are under-diagnosed among HIV-infected individuals. The aim of this study was to evaluate the use of mental health history and questionnaire-based screening instruments to identify HIV-infected individuals at risk of depression. METHODS: The Beck Depression Inventory II (BDI-II) was used to assess the prevalence and severity of depressive symptoms among HIV-infected individuals attending two out-patient clinics in Denmark. HIV-infected individuals with a BDI-II score ≥ 20 were offered a clinical evaluation by a consultant psychiatrist. The BDI-II score was compared to the outcome of mental health history review, and to results obtained using the European AIDS Clinical Society (EACS) two-item depression screening tool. RESULTS: A total of 501 HIV-infected individuals were included in the study. Symptoms of moderate/major depression (BDI-II score ≥ 20) were observed in 111 patients (22%); 65 of these patients consulted a psychiatrist, of whom 71% were diagnosed with a co-existing disorder. The BDI-II score was compared to the outcome of a mental health history review, and to results obtained using the European AIDS Clinical Society (EACS) two-item depression screening tool. The two questions showed a sensitivity and specificity of 95% and 68%, respectively, for diagnosis of current depression or risk of depression. A previous psychiatric history and substance abuse were independently associated with an increased risk of depression. CONCLUSIONS: We suggest that the mental health of HIV-infected individuals should be reviewed and a "risk-flag" three-step approach should be used (1) to screen routinely with the two verbal questions suggested by the EACS, (2) to identify whether there is a risk of depression and then screen with the BDI-II, and (3) to identify whether there is still a risk and then perform a full evaluation and obtain an accurate psychiatric diagnosis by a psychiatrist.

Translational mixed-effects PKPD modelling of recombinant human growth hormone - from hypophysectomized rat to patients.

BACKGROUND AND PURPOSE: We aimed to develop a mechanistic mixed-effects pharmacokinetic (PK)-pharmacodynamic (PD) (PKPD) model for recombinant human growth hormone (rhGH) in hypophysectomized rats and to predict the human PKPD relationship. EXPERIMENTAL APPROACH: A non-linear mixed-effects model was developed from experimental PKPD studies of rhGH and effects of long-term treatment as measured by insulin-like growth factor 1 (IGF-1) and bodyweight gain in rats. Modelled parameter values were scaled to human values using the allometric approach with fixed exponents for PKs and unscaled for PDs and validated through simulations relative to patient data. KEY RESULTS: The final model described rhGH PK as a two compartmental model with parallel linear and non-linear elimination terms, parallel first-order absorption with a total s.c. bioavailability of 87% in rats. Induction of IGF-1 was described by an indirect response model with stimulation of kin and related to rhGH exposure through an Emax relationship. Increase in bodyweight was directly linked to individual concentrations of IGF-1 by a linear relation. The scaled model provided robust predictions of human systemic PK of rhGH, but exposure following s.c. administration was over predicted. After correction of the human s.c. absorption model, the induction model for IGF-1 well described the human PKPD data. CONCLUSIONS: A translational mechanistic PKPD model for rhGH was successfully developed from experimental rat data. The model links a clinically relevant biomarker, IGF-1, to a primary clinical end-point, growth/bodyweight gain. Scaling of the model parameters provided robust predictions of the human PKPD in growth hormone-deficient patients including variability.

Pre-eclampsia and first-onset postpartum psychiatric episodes: a Danish population-based cohort study.

BACKGROUND: Recent evidence suggests that postpartum psychiatric episodes may share similar etiological mechanisms with immune-related disorders. Pre-eclampsia is one of the most prevalent immune-related disorders of pregnancy. Multiple clinical features are shared between pre-eclampsia and postpartum psychiatric disorders, most prominently a strong link to first pregnancies. Therefore, we aimed to study if pre-eclampsia is a risk factor for first-onset postpartum psychiatric episodes. METHOD: We conducted a cohort study using the Danish population registry, with a total of 400 717 primiparous women with a singleton delivery between 1995 and 2011. First-lifetime childbirth was the main exposure variable and the outcome of interest was first-onset postpartum psychiatric episodes. The main outcome measures were monthly incidence rate ratios (IRRs), with the period 11-12 months after birth as the reference category. Adjustments were made for age, calendar period, reproductive history, and perinatal maternal health including somatic and obstetric co-morbidity. RESULTS: Primiparous women were at particularly high risk of first-onset psychiatric episodes during the first month postpartum [IRR 2.93, 95% confidence interval (CI) 2.53-3.40] and pre-eclampsia added to that risk (IRR 4.21, 95% CI 2.89-6.13). Having both pre-eclampsia and a somatic co-morbidity resulted in the highest risk of psychiatric episodes during the 3-month period after childbirth (IRR 4.81, 95% CI 2.72-8.50). CONCLUSIONS: We confirmed an association between pre-eclampsia and postpartum psychiatric episodes. The possible explanations for this association, which are not mutually exclusive, include the psychological impact of a serious medical condition such as pre-eclampsia and the neurobiological impact of pre-eclampsia-related vascular pathology and inflammation.

Parental history of psychiatric diagnoses and unipolar depression: a Danish National Register-based cohort study.

BACKGROUND: Depression is known to run in families, but the effects of parental history of other psychiatric diagnoses on depression rates are less well studied. Few studies have examined the impact of parental psychopathology on depression rates in older age groups. METHOD: We established a population-based cohort including all individuals born in Denmark after 1954 and alive on their 10th birthday (N = 29 76 264). Exposure variables were maternal and paternal history of schizophrenia, bipolar disorder, depression, anxiety or 'other' psychiatric diagnoses. Incidence rate ratios (IRRs) were estimated using Poisson regressions. RESULTS: Parental history of any psychiatric diagnosis increased incidence rates of outpatient (maternal: IRR 1.88, p < 0.0001; paternal: IRR 1.68, p < 0.0001) and inpatient (maternal: IRR 1.99, p < 0.0001; paternal: IRR 1.83, p < 0.0001) depression relative to no parental history. IRRs for parental history of non-affective disorders remained relatively stable across age groups, while IRRs for parental affective disorders (unipolar or bipolar) decreased with age from 2.29-3.96 in the youngest age group to 1.53-1.90 in the oldest group. IRR estimates for all parental diagnoses were similar among individuals aged ⩾41 years (IRR range 1.51-1.90). CONCLUSIONS: Parental history of any psychiatric diagnosis is associated with increased incidence rates of unipolar depression. In younger age groups, parental history of affective diagnoses is more strongly associated with rates of unipolar depression than non-affective diagnoses; however, this distinction disappears after age 40, suggesting that parental psychopathology in general, rather than any one disorder, confers risk for depression in middle life.

Post-illness-onset risk of offending across the full spectrum of psychiatric disorders.

BACKGROUND: The link between psychotic disorders and violent offending is well established; knowledge about risk of post-illness-onset offending across the full spectrum of psychiatric disorders is lacking. We aimed to compare rates of any offending and violent offending committed after the onset of illness, according to diagnostic group, with population controls. METHOD: A 25% random sample of the Danish population (n = 521 340) was followed from their 15th birthday until offending occurred. Mental health status was considered as a time-varying exposure in a Poisson regression model used to examine the duration from service contact to the offence. RESULTS: Males with any psychiatric contact had an incidence rate ratio (IRR) of 2.91 [95% confidence interval (CI) 2.80-3.02] for any offending; 4.18 (95% CI 3.99-4.38) for violent offending. Associations were stronger for women (IRR 4.17, 95% CI 3.95-4.40 for any offending; 8.02, 95% CI 7.20-8.94 for violent offending). Risk was similar across diagnostic groups for any offending in males, while variation between diagnostic groups was seen for male violent and female offending, both any and violent. CONCLUSIONS: Risk of offending, particularly violent offending, was elevated across a range of mental disorders following first contact with mental health services. The extent of variation in strength of effect across diagnoses differed by gender.

Factors associated with risk of depression and relevant predictors of screening for depression in clinical practice: a cross-sectional study among HIV-infected individuals in Denmark.

OBJECTIVES: Depression and psychiatric disorders are frequent among HIV-infected individuals. The aim of this study was to determine the prevalence of depression and describe the psychiatric history of HIV-infected individuals in an out-patient clinic in Denmark and to identify factors of clinical importance that may be used to identify patients at risk of depression. METHODS: In 2013, 212 HIV-infected patients were included in a questionnaire study. We used the Beck Depression Inventory II (BDI-II) to assess the prevalence and severity of depressive symptoms. Patients with a BDI-II score ≥ 20 were offered a clinical evaluation by a consultant psychiatrist. Logistic regression was used to determine predictors associated with risk of depression. RESULTS: Symptoms of depression (BDI-II score ≥ 14) were observed in 75 patients (35%), and symptoms of moderate to major depression (BDI-II score ≥ 20) in 55 patients (26%). There was also a high prevalence of co-occurring mental illness. In a multivariate model, self-reported stress, self-reported perception that HIV infection affects all aspects of life, self-reported poor health, not being satisfied with one's current life situation, previous alcohol abuse, nonadherence to antiretroviral therapy and previously having sought help because of psychological problems were independently associated with risk of depression. CONCLUSIONS: Symptoms of depression and co-occurring mental illness are under-diagnosed and under-treated among HIV-infected individuals. We recommend that screening of depression should be conducted regularly to provide a full psychiatric profile to decrease the risk of depression and improve adherence and quality of life in this population.

Mortality and life expectancy of people with alcohol use disorder in Denmark, Finland and Sweden.

OBJECTIVE: To analyse mortality and life expectancy in people with alcohol use disorder in Denmark, Finland and Sweden. METHOD: A population-based register study including all patients admitted to hospital diagnosed with alcohol use disorder (1,158,486 person-years) from 1987 to 2006 in Denmark, Finland and Sweden. RESULTS: Life expectancy was 24-28 years shorter in people with alcohol use disorder than in the general population. From 1987 to 2006, the difference in life expectancy between patients with alcohol use disorder and the general population increased in men (Denmark, 1.8 years; Finland, 2.6 years; Sweden, 1.0 years); in women, the difference in life expectancy increased in Denmark (0.3 years) but decreased in Finland (-0.8 years) and Sweden (-1.8 years). People with alcohol use disorder had higher mortality from all causes of death (mortality rate ratio, 3.0-5.2), all diseases and medical conditions (2.3-4.8), and suicide (9.3-35.9). CONCLUSION: People hospitalized with alcohol use disorder have an average life expectancy of 47-53 years (men) and 50-58 years (women) and die 24-28 years earlier than people in the general population.

Long-term mortality of persons with severe mental illness and diabetes: a population-based cohort study in Denmark.

BACKGROUND: Persons with severe mental illness (SMI) have excess mortality, which may partly be explained by their high prevalence of diabetes. METHOD: We compared the overall and cause-specific mortality in persons with SMI and diabetes with that of the general Danish population between 1997 and 2009 by linking data from Danish national registries. RESULTS: The cohort counted 4 734 703 persons, and during follow-up 651 080 persons died of whom 1083 persons had SMI and diabetes. Compared with the background population, the overall mortality rate ratios (MRRs) for persons with SMI and diabetes were 4.14 [95% confidence interval (CI) 3.81-4.51] for men and 3.13 (95% CI 2.88-3.40) for women. The cause-specific MRRs for persons with SMI and diabetes were lowest for malignant neoplasms (women: MRR = 1.98, 95% CI 1.64-2.39; men: MRR = 2.08, 95% CI 1.69-2.56) and highest for unnatural causes of death (women: MRR = 12.31, 95% CI 6.80-22.28; men: MRR = 7.89, 95% CI 5.51-11.29). The cumulative risks of death within 7 years of diabetes diagnosis for persons with SMI and diabetes were 15.0% (95% CI 12.4-17.6%) for those younger than 50 years, 30.7% (95% CI 27.8-33.4%) for those aged 50-69 years, and 63.8% (95% CI 58.9-68.2%) for those aged 70 years or older. Among persons suffering from both diseases, 33.4% of natural deaths were attributed to diabetes and 14% of natural deaths were attributed to the interaction between diabetes and SMI. CONCLUSIONS: Long-term mortality is high for persons with SMI and diabetes. This calls for effective intervention from a coordinated and collaborating healthcare system.

Impact of moderate interval exercise versus supine rest on the pharmacokinetics and pharmacodynamic profiles of subcutaneously administered growth hormone in adult growth hormone deficient patients.

BACKGROUND: Diurnal variation in serum growth hormone (s-GH) levels after exogenous GH delivery has previously been reported in patients with no endogenous GH secretion. Changes in postural position or physical activity, leading to changes in blood flow and/or lymphatic drainage may be underlying explanations. PRIMARY OBJECTIVES: The primary aim of this study is to study a possible impact of exercise and supine rest on pharmacokinetics (PK) and day-to-day variation of subcutaneously (s.c.) administered GH in adult GH deficient (AGHD) patients. SECONDARY OBJECTIVE: The secondary aim of this study is to compare s-IGF-I, s-insulin, and plasma (p)-glucose profiles after a carbohydrate rich breakfast following s.c. GH injection vs. continuous infusion. DESIGN AND METHODS: During supine rest eight AGHD males (59.8±8 years, BMI 29.7±4.9 kg/m(2)) were treated with one daily s.c. GH injections of 3 mg/24 h for 48 h (treatment sessions A, B) or a continuous s.c. GH infusion of 3 mg/24 h for 60 h (treatment sessions C, D). Exercise comprised 1 h bicycling with 50 W load on two consecutive days during treatment sessions B and D. RESULTS: Administration of GH as a bolus injection, but not as a continuous GH infusion, resulted in about 32% higher s-GH levels during exercise (60 min) as well as 30 min after (s-GH logAUC(B-A) difference was 0.28; 95% CI: 0.14-0.4; p<0.001). However, the total s-GH(AUC 0-24 h) (p=0.75) and s-IGF-I(AUC0-48 h) levels (p=0.51) remained unchanged between the two occasions. P-glucose and insulin profiles were significantly higher after carbohydrate rich breakfast before first and second dosing both following s.c. GH injection and continuous infusion (p<0.05). CONCLUSIONS: Moderate exercise intermittently increased s-GH levels. These changes seem to have no clinical short-term relevance, since total s-GH(24 h) and s-IGF-I(48 h) levels were unaffected.

HIV-infected individuals with high coping self-efficacy are less likely to report depressive symptoms: a cross-sectional study from Denmark.

OBJECTIVES: Having effective ways to cope helps HIV-infected individuals maintain good psychological and physical well-being. This study investigated the relationship between coping self-efficacy levels, as determined by the Coping Self-Efficacy Scale (CSE), HIV status disclosure, and depression in a Danish cohort. METHODS: In 2008, the CSE was administered to 304 HIV-infected individuals to measure their confidence in their ability to cope with HIV infection. HIV status disclosure was assessed on a three-point scale: living openly with the disease, partly openly, or secretly. The Beck Depression Inventory (BDI) was used to assess depression prevalence and severity. RESULTS: The CSE score was significantly related to depression (Spearman's rho = -0.71; the test of H0: BDI and coping, probability >t=0.0001). There was a significant relationship between higher CSE scores and living openly with HIV. The risk of depression was four times higher in HIV-infected individuals who did not disclose their HIV status (i.e. who lived 'secretly'; odds ratio = 4.1) than in individuals who lived openly. CONCLUSION: Those with low CSE scores were more likely to report living secretly with HIV and to be depressed. Disclosing HIV may constitute a social stressor, and a lack of coping self-efficacy may increase the likelihood of non-disclosure and depression. Interventions that enhance self-efficacy may help in managing the demands of daily life with HIV, increase disclosure, and reduce depression.