Increased risk of hospitalization, intensive care and death due to COVID-19 in patients with adrenal insufficiency: A Swedish nationwide study.

BACKGROUND: Patients with adrenal insufficiency (AI) have excess morbidity and mortality related to infectious disorders. Whether patients with AI have increased morbidity and mortality from COVID-19 is unknown. METHODS: In this linked Swedish national register-based cohort study, patients with primary and secondary AI diagnosis were identified and followed from 1 January 2020 to 28 February 2021. They were compared with a control cohort from the general population matched 10:1 for age and sex. The following COVID-19 outcomes were studied: incidence of COVID-19 infection, rates of hospitalization, intensive care admission and death. Hazard ratios (HR) with 95% confidence intervals (95% CI) adjusted for socioeconomic factors and comorbidities were estimated using Cox regression analysis. RESULTS: We identified 5430 patients with AI and 54,300 matched controls: There were 47.6% women, mean age was 57.1 (standard deviation 18.1) years, and the frequency of COVID-19 infection was similar, but the frequency of hospitalization (2.1% vs. 0.8%), intensive care (0.3% vs. 0.1%) and death (0.8% vs. 0.2%) for COVID-19 was higher in AI patients than matched controls. After adjustment for socioeconomic factors and comorbidities, the HR (95% CI) was increased for hospitalization (1.96, 1.59-2.43), intensive care admission (2.76, 1.49-5.09) and death (2.29, 1.60-3.28). CONCLUSION: Patients with AI have a similar incidence of COVID-19 infection to a matched control population, but a more than twofold increased risk of developing a severe infection or a fatal outcome. They should therefore be prioritized for vaccination, antiviral therapy and other appropriate treatment to mitigate hospitalization and death.

Acromegaly management in the Nordic countries: A Delphi consensus survey.

OBJECTIVE: Acromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries. METHODS: A Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1-7). Consensus was defined as ≥80% of panelists rating their agreement as ≥5 or ≤3 on the Likert-type scale. RESULTS: Consensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists. CONCLUSION: This consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.

Headache in patients with non-functioning pituitary adenoma before and after transsphenoidal surgery - a prospective study.

PURPOSE: To study the long-term effect of transsphenoidal surgery (TSS) on headache in patients with non-functioning pituitary adenoma (NFPA) and identify factors predicting headache relief following TSS. METHODS: We evaluated headache in 101 consecutive patients with NFPA who underwent TSS from September 2015 to December 2021, preoperatively and 12-months post-surgery, by using the Migraine Disability Assessment (MIDAS) questionnaire. Health-related quality of life (QoL) was assessed using the EQ-5D visual analogue scale (EQ-VAS). RESULTS: Of 101 patients, 27 (27%) experienced disabling preoperative headache. Among these, the median total MIDAS score improved from 60 (interquartile range (IQR): 19-140) to 10 (IQR: 0-49) (P = 0.004). Additionally, headache frequency over a 90-day period decreased from 45 (IQR: 25-83) to 6 (IQR: 3-36) days (P = 0.002), and headache intensity decreased from 5 (IQR: 4-7) to 4 (IQR: 2-7) (P = 0.016) at 12-months post-surgery. At 12 months post-surgery, 18 (67%) of 27 patients with preoperatively disabling headache showed clinically relevant improvement of their headache, 4 (15%) showed deterioration, and 5 (19%) remained unchanged. In patients with clinically relevant improvement of their headache, the EQ-VAS score improved from 50 (IQR: 30 - 7) to 80 (IQR: 65-86) (P < 0.001). Of the 74 patients with no preoperative headache, 11 (15%) developed postoperative headache. We identified no clinical factors predicting postoperative headache relief. CONCLUSION: The study supports that clinically significant and long-lasting improvements of disabling headache and QoL can be achieved with TSS in a substantial number of patients with NFPA.

Hypotension during transsphenoidal pituitary surgery associated with increase in plasma levels of brain injury markers.

BACKGROUND: Patients undergoing pituitary surgery may experience short- and long-term postoperative morbidity. Intraoperative factors such as hypotension might be a contributing factor. Our aim was to investigate the association between intraoperative hypotension and postoperative plasma levels of tau, neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) as markers of perioperative brain injury. METHODS: Between June 2016 and October 2017, 35 patients from the Gothenburg Pituitary Tumor Study were included. For tau, NfL, and GFAP, concentrations were measured in plasma samples collected before and immediately following surgery, and on postoperative days 1 and 5. The difference between the highest postoperative value and the value before surgery was used for analysis (∆taupeak , ∆NfLpeak , ∆GFAPpeak ). Intraoperative hypotension was defined as the area under the curve of an absolute threshold below 70 mmHg (AUC70) and a relative threshold below 20% (AUC20%) of the baseline mean arterial blood pressure. RESULTS: Plasma tau and GFAP were highest immediately following surgery and on day 1, while NfL was highest on day 5. There was a positive correlation between AUC20% and both ∆taupeak (r2 = .20, p < .001) and ∆NfLpeak (r2 = .26, p < .001). No association was found between AUC20% and GFAP or between AUC70 and ∆taupeak , ∆NfLpeak or ∆GFAPpeak . CONCLUSION: Intraoperative relative, but not absolute, hypotension was associated with increased postoperative plasma tau and NfL concentrations. Patients undergoing pituitary surgery may be vulnerable to relative hypotension, but this needs to be validated in future prospective studies.

The importance of personal documentation for patients living with long-term illness symptoms after pituitary surgery: A Constructivist Grounded Theory study.

INTRODUCTION: Despite surgical treatment, pituitary adenomas often cause long-term illness symptoms, that profoundly impact patients' quality of life physically, psychologically and socially. Healthcare professionals often fail to recognize and discuss the ensuing problems. Personal documentation, such as symptom monitoring, reflective writing or even posts on social media, may help this patient group to manage their daily life and support communication of their care needs. Documentation strategies and the role of documentation for people with long-term symptoms after pituitary adenoma surgery are currently unknown. AIM: To examine the effects and strategies of documenting symptoms, activities and physical and emotional well-being among people living with long-term pituitary adenoma. METHODS: In this Constructivist Grounded Theory study, 12 individuals living with long-term illness symptoms after pituitary adenoma surgery described their documentation strategies in in-depth interviews using teleconferencing and photo-elicitation between August and October 2020. RESULTS: Strategies for documentation included analogue and digital media. One core category (Exercising autonomy) and three categories describing processes (Gaining insight, Striving for control and Sharing) emerged from the analysis. These three interrelated processes become an expression of autonomy to manage life and make sense of chronic illness. Personal documentation is a flexible tool that is used more extensively in times of ill health and less in times of relative well-being. Sharing documentation with healthcare professionals facilitated care planning and sharing with friends and family fostered emotional well-being. CONCLUSION: Personal documentation is a valuable resource for managing life after pituitary adenoma surgery. The current findings may be relevant to other chronic illnesses. Further research exploring potential tools for personal documentation is needed. PATIENT OR PUBLIC CONTRIBUTION: We deliberately chose a Constructivist Grounded Theory approach for this interview study. Using Constructivist Grounded Theory, we gave people living with long-term symptoms a voice, allowing them to freely speak about managing their illness in connection with personal documentation. The theoretical sampling approach enabled us to invite participants that could provide a broad overview of the landscape of personal documentation.

Cancer incidence in a Swedish cohort with high exposure to perfluoroalkyl substances in drinking water.

BACKGROUND: The use of firefighting foams at a military airport resulted in high levels of perfluorinated substances (PFAS) in the drinking water distributed to one-third of households in the Swedish municipality of Ronneby between the mid-1980s and the end of 2013. METHOD: The Ronneby Register Cohort, a large cohort comprising all individuals (N = 60,507) who ever lived in the Ronneby municipality during the period of drinking water contamination, was linked to the Swedish Cancer Register 1985-2016. Individual exposure was classified based on comprehensive data on yearly residential address and water distribution. External analysis explored standardized cancer incidence ratios (SIR) for residents never, or ever, residing in the contaminated water district, compared with those residing in other towns in the same county as reference population. Cox models provided hazard ratios (HR) for different exposure groups within the cohort. RESULTS: 5,702 individuals with cancer were identified. SIR for overall cancer was 1.04 for men (95%CI 0.96-1.12) and 0.89 for women (95%CI 0.82-0.96) who ever lived in the contaminated drinking water area. Kidney cancer, which was reported with increased risk in C8 study, showed somewhat elevated HR in this study (HR 1.27; 95%CI 0.85-1.89). The HR was modestly elevated for bladder cancer (HR 1.32; 95%CI 1.01-1.72), and reduced for prostate cancer (HR 0.83; 95%CI 0.71-0.98). In subjects who ever lived in the contaminated water area during 2005-2013, when exposure was estimated to be highest, higher risks for kidney cancer (HR 1.84; 95%CI 1.00-3.37) but lower for prostate cancer (HR 0.76; 95%CI 0.59-0.98) were observed. CONCLUSION: Analysis of this large cohort exposed to high levels of PFAS, dominated by PFHxS and PFOS, revealed no evidence for an overall increased risk of cancer. A moderately increased risk of kidney cancer was observed, in accordance with previous findings after PFAS exposure dominated by PFOA.

Finding the Person in Electronic Health Records. A Mixed-Methods Analysis of Person-Centered Content and Language.

The co-creation and sharing of documentation of person-centered care is important, but challenging in clinical practice. Online access to health records is considered essential to increase patient participation and empowerment in person-centered care provision. The aims of this study were (1) to identify the extent of person-centered content in medical inpatient records and discharge letters; (2) to describe the characteristics of the language and rhetoric used in discharge letters. This was a concurrent, mixed-methods study involving a deductive, quantitative analysis of person-centered content in 69 Patient Accessible Electronic Health Records from patients with pituitary tumors, and an iterative, qualitative language analysis of a nested sample of 57 discharge letters. Both the content and language of inpatient records were mostly patient-centered. Records were concerned with the documentation of symptoms and medical and care interventions. There was little person-centered documentation of patients' preferences, wishes and needs, and shared decision-making. In the discharge letters, written for the patients, some physicians had attempted to write in a person-centered way, using plain language and a narrative. However, most wrote in a style that was reflective of their discourse community, using abbreviations and medical terms. Established norms for documentation in healthcare are a barrier to person-centered documentation. Patients' needs and preferences about documentation should be explored to increase understanding of how person-centered documentation can be achieved in clinical practice.

Growth hormone deficiency and replacement therapy in adults: Impact on survival.

In a seminal paper from 1990, Rosen and Bengtsson suggested that hypopituitary patients with a presumed growth hormone (GH) deficiency (GHD) have an excess mortality. Later studies have confirmed this finding but have also shown that the cause of the increased risk of death in these patients is multifactorial, including unreplaced GHD as well as non-physiological replacement therapy of other deficiencies, the etiology of hypopituitarism, and the side effects of tumor treatment. Only a few studies have investigated mortality in hypopituitary patients with GHD receiving GH replacement therapy (GHRT): these studies are retrospective observational studies with a wide range of underlying diseases but most of them show a mortality that is not different from the general population. Even though the research field of survival in GHD patients with and without GHRT is lacking prospective randomized trials, the evidence suggests that GHD in hypopituitary patients contributes to an excess mortality and modern replacement therapy including GHRT will result in a mortality that is approaching normal. Herein, we review the literature in the field of survival in GHD patients with and without GHRT. In addition, we outline the most important issues when evaluating studies in this area.

Associations between perfluoroalkyl substances and thyroid hormones after high exposure through drinking water.

BACKGROUND: The reported associations for several per- and polyfluoroalkyl substance (PFAS) with thyroid hormones are inconsistent in epidemiological studies. The purpose of the current study was to investigate the possible association of thyroid hormones in relation to serum levels of perfluorohexane sulfonate, perfluorooctane sulfonate and perfluorooctanoic acid, in a Swedish general population, highly exposed through contaminated drinking water, and if the associations with PFAS remained in a comparison to a reference group based only on residency in areas with contrasting PFAS levels. METHOD: 3297 participants from Ronneby, a municipality with drinking water highly contaminated by PFAS (exposed group), and a reference group (N = 226) from a nearby municipality with non-contaminated drinking water supply were included. Regression analysis was used to investigate the associations between PFAS exposure, assessed as exposure groups (Ronneby and reference groups) and measured serum PFAS levels, and thyroid hormone levels, with adjustments for age, sex and BMI. RESULT: No cross-sectional associations were found between PFAS and thyroid hormones in adults and seniors except for a positive association between PFAS and fT4 in males over 50. Higher thyroid hormone levels were found in the preteen children from Ronneby compared to the reference group. In contrast, within Ronneby, there was weak evidence of associations between increased PFAS levels and decreased fT3 in preteen boys, and decreased TSH in teenage males. No such pattern was found in preteen and teenage girls. CONCLUSION: The present study found no consistent evidence to support association of PFAS with thyroid hormones.

Prevalence of Nelson's syndrome after bilateral adrenalectomy in patients with cushing's disease: a systematic review and meta-analysis.

PURPOSE: Bilateral adrenalectomy (BA) still plays an important role in the management of Cushing's disease (CD). Nelson's syndrome (NS) is a severe complication of BA, but conflicting data on its prevalence and predicting factors have been reported. The aim of this study was to determine the prevalence of NS, and identify factors associated with its development. DATA SOURCES: Systematic literature search in four databases. STUDY SELECTION: Observational studies reporting the prevalence of NS after BA in adult patients with CD. DATA EXTRACTION: Data extraction and risk of bias assessment were performed by three independent investigators. DATA SYNTHESIS: Thirty-six studies, with a total of 1316 CD patients treated with BA, were included for the primary outcome. Pooled prevalence of NS was 26% (95% CI 22-31%), with moderate to high heterogeneity (I2 67%, P < 0.01). The time from BA to NS varied from 2 months to 39 years. The prevalence of NS in the most recently published studies, where magnet resonance imaging was used, was 38% (95% CI 27-50%). The prevalence of treatment for NS was 21% (95% CI 18-26%). Relative risk for NS was not significantly affected by prior pituitary radiotherapy [0.9 (95% CI 0.5-1.6)] or pituitary surgery [0.6 (95% CI 0.4-1.0)]. CONCLUSIONS: Every fourth patient with CD treated with BA develops NS, and every fifth patient requires pituitary-specific treatment. The risk of NS may persist for up to four decades after BA. Life-long follow-up is essential for early detection and adequate treatment of NS.

Autograft type affects muscle strength and hop performance after ACL reconstruction. A randomised controlled trial comparing patellar tendon and hamstring tendon autografts with standard or accelerated rehabilitation.

PURPOSE: To evaluate and compare changes in quadriceps and hamstring strength and single-leg-hop (SLH) test performance over the first 24 postoperative months in patients who underwent anterior cruciate ligament reconstruction (ACLR) with bone-patellar tendon-bone (BPTB) or hamstring tendon (HT) autografts and followed either a standard or an accelerated rehabilitation protocol. METHODS: A total of 160 patients undergoing ACLR were randomised in four groups depending on the graft that was used and the rehabilitation protocol (40 BPTB/standard rehab, 40 BPTB/accelerated rehab, 40 HT/standard rehab, 40 HT/accelerated rehab). Isokinetic concentric quadriceps and hamstring strength at 90°/s and the SLH test performance were assessed preoperatively and 4,6,8,12 and 24 months postoperatively. The results were reported as the limb symmetry index (LSI) at the same time point. Linear mixed models were used to compare the groups at the different time points. RESULTS: An average quadriceps strength LSI of 78.4% was found preoperatively. After ACLR, the LSI first decreased at 4 months and then increased from 6 to 24 months, reaching an overall value of 92.7% at the latest follow-up. The BPTB group showed a significantly decreased LSI at 4, 6, 8 and 12 months compared with the HT group. No significant differences between the graft groups were found at 24 months. An average hamstring strength LSI of 84.6% was found preoperatively. After ACLR, the LSI increased from 4 to 24 months in the BTPB group. In the HT group, the LSI first decreased at 4 months and then increased from 6 to 24 months. An LSI of 97.1% and 89.1% was found at the latest follow-up for the BPTB and the HT group, respectively. The HT group showed a significantly decreased LSI at all follow-ups compared with the BPTB group. An average SLH test LSI of 81% was found preoperatively. After ACLR, the LSI increased from 4 to 24 months, reaching 97.6% overall at the latest follow-up. The BPTB group showed a significantly decreased LSI only at 4 months postoperatively compared with the HT group. No significant differences in any of the three tests were found between the standard and accelerated rehabilitation groups for either of the graft groups at any time point. CONCLUSION: Muscle strength and SLH test performance recovered progressively after ACLR overall, but they did not all fully recover, as the injured leg performed on average less than 100% compared with the uninjured leg even 24 months postoperatively. After ACLR, inferior quadriceps strength and a poorer SLH test performance were found at 4, 6, 8 and 12 months and at 4 months, respectively, for the BTPB group compared with the HT group. Persistent, inferior hamstring strength was found at all postoperative follow-ups in the HT group. Rehabilitation, standard or accelerated, had no significant impact on the recovery of muscle strength and SLH test performance after ACLR in any of the graft groups. LEVEL OF EVIDENCE: Level I.

High prescription rate of oral glucocorticoids in children and adults: A retrospective cohort study from Western Sweden.

OBJECTIVE: Glucocorticoids (GCs) are a cornerstone in treating various common and uncommon diseases. The aim of this study was to estimate the prevalence of GC use in terms of doses associated with risk of tertiary adrenal insufficiency in adults and children, and treatment indications. METHODS: This was a retrospective cohort study. Information on dispensed prescriptions was obtained from the Swedish Prescribed Drug Register. Patients with prescriptions of prednisolone (or equivalent dose of other GCs) ≥5 mg daily for ≥21 days between 2007 and 2014 were included. Information on concurrent diseases was obtained from the Swedish National Patient Register and the Västra Götaland Regional Healthcare Database. RESULTS: Of 1 585 335 inhabitants in Västra Götaland County, 223 211 were included in the study (women 55.6%). Mean age was 48 ± 24 years. Period prevalence of oral GC use during the 8-year study period was 14.1%. The highest prevalence (27.4%) was in men aged 80-89 years and lowest (7.5%) in men 10-19 years of age. The period prevalence in children 0-9 years of age was 10.6%. COPD and asthma were the most common indications for treatment (17.2%) followed by allergy (12.5%) and malignant neoplasms (11.5%). Allergy was the most frequent indication (20.5%) in children and adolescents. CONCLUSION: Between 2007 and 2014, every seventh inhabitant in western Sweden received a GC prescription at doses associated with risk of developing tertiary adrenal insufficiency. These findings illustrate the importance of awareness of the potential development of tertiary adrenal insufficiency in both paediatric and adult patients.

High exposure to perfluorinated compounds in drinking water and thyroid disease. A cohort study from Ronneby, Sweden.

Per- and polyfluoroalkyl substances (PFAS) are extremely persistent manmade substances. Apart from exposure through food and indoor air and dust, humans can be exposed through drinking water if the surface or groundwater is contaminated. In 2013 very high levels of PFOS and PFHxS were found in the drinking water from one of the two waterworks supplying the municipality of Ronneby, Sweden. A cohort was formed, including all individuals who had lived at least one year in Ronneby during the period 1980-2013 (ñ63,000). Each year, addresses that got their drinking water from the contaminated water works were identified. Through the Swedish personal identity number, each individual was linked to registers providing diagnoses and prescriptions for hyper- and hypothyroidism. In total, 16,150 individuals had ever been exposed. The hazard ratios did not indicate any excess risk of hyperthyroidism among those with contaminated water. For hypothyroidism, the risk of being prescribed medication was significantly increased among women with exposure during the mid part of the study period (but not men). However, the association with period of exposure was non-monotonic, so the significance is considered to be a chance finding. Our research was limited by the relatively simple exposure assessment.

Non-functioning pituitary adenomas: indications for pituitary surgery and post-surgical management.

PURPOSE: Non-functioning pituitary adenomas (NFPAs) are associated with impaired well-being, increased comorbidities, and reduced long-term survival. Data on optimal management of NFPAs around surgical treatment are scarce, and postoperative treatment and follow-up strategies have not been evaluated in prospective trials. Here, we review the preoperative, perioperative, and early postoperative management of patients with NFPAs. METHODS: We searched Medline and the Cochrane Library for articles published in English with the following items "Pituitary neoplasms AND Surgery" and "Surgery AND Hypopituitarism". Studies containing detailed analyses of the management of NFPAs in adult patients, including pituitary surgery, endocrine care, imaging, ophthalmologic assessment and long-term outcome were reviewed. RESULTS: Treatment options for NFPAs include active surveillance, surgical resection, and radiotherapy. Pituitary surgery is currently recommended as first-line treatment in patients with visual impairment due to adenomas compressing the optic nerves or chiasma. Radiotherapy is reserved for large tumor remnants or tumor recurrence following one or more surgical attempts. There is no consensus of optimal pre-, peri-, and postoperative management such as timing, frequency, and duration of endocrine, radiologic, and ophthalmologic assessments as well as management of smaller tumor remnants or tumor recurrence. CONCLUSIONS: In clinical practice, there is a great variation in the treatment and follow-up of patients with NFPAs. We have, based on available data, suggested an optimal management strategy for patients with NFPAs in relation to pituitary surgery. Prospective trials oriented at drawing up strategies for the management of NFPAs are needed.

The incidence of Cushing's disease: a nationwide Swedish study.

BACKGROUND: Studies on the incidence of Cushing's disease (CD) are few and usually limited by a small number of patients. The aim of this study was to assess the annual incidence in a nationwide cohort of patients with presumed CD in Sweden. METHODS: Patients registered with a diagnostic code for Cushing's syndrome (CS) or CD, between 1987 and 2013 were identified in the Swedish National Patient Registry. The CD diagnosis was validated by reviewing clinical, biochemical, imaging, and histopathological data. RESULTS: Of 1317 patients identified, 534 (41%) had confirmed CD. One-hundred-and-fifty-six (12%) patients had other forms of CS, 41 (3%) had probable but unconfirmed CD, and 334 (25%) had diagnoses unrelated to CS. The mean (95% confidence interval) annual incidence between 1987 and 2013 of confirmed CD was 1.6 (1.4-1.8) cases per million. 1987-1995, 1996-2004, and 2005-2013, the mean annual incidence was 1.5 (1.1-1.8), 1.4 (1.0-1.7) and 2.0 (1.7-2.3) cases per million, respectively. During the last time period the incidence was higher than during the first and second time periods (P < 0.05). CONCLUSION: The incidence of CD in Sweden (1.6 cases per million) is in agreement with most previous reports. A higher incidence between 2005 and 2013 compared to 1987-2004 was noticed. Whether this reflects a truly increased incidence of the disease, or simply an increased awareness, earlier recognition, and earlier diagnosis can, however, not be answered. This study also illustrates the importance of validation of the diagnosis of CD in epidemiological research.

Challenges to patient centredness - a comparison of patient and doctor experiences from primary care.

BACKGROUND: We designed this observational study to investigate the level of patients' and doctors' ratings of patient-centred aspects of the primary care consultation. METHODS: Questionnaire study with patients and doctors. Consecutive patients in a primary care setting and 16 doctors responding post visit. Results are presented as proportions with 95% confidence intervals. RESULTS: 411 questionnaires, 223 from patients and 188 from doctors, covered 251 consultations. Both patients and doctors gave the highest possible estimations on the aspects of patient-centred communication and satisfaction less frequently when the patient had other reasons for visit than purely somatic. Unlike the doctors' estimations, the frequency of highest possible estimations in patient responses dropped if the patients had two to six reasons for visit rather than one. Among the six patient-centred aspects, both patients and doctors gave the highest possible estimation least frequently on the aspect of shared decision-making. CONCLUSION: The results suggest that the nature of the reason, as well as the number of reasons for visit, interferes with the doctors' level of patient-centred communication. Our results furthermore confirm the findings of previous studies that doctors insufficiently involve patients in their care.

An attenuated rate of leg muscle protein depletion and leg free amino acid efflux over time is seen in ICU long-stayers.

BACKGROUND: There is extensive documentation on skeletal muscle protein depletion during the initial phase of critical illness. However, for intensive care unit (ICU) long-stayers, objective data are very limited. In this study, we examined skeletal muscle protein and amino acid turnover in patients with a prolonged ICU stay. METHODS: Patients (n = 20) were studied serially every 8-12 days between days 10 and 40 of their ICU stay as long as patients stayed in the ICU. Leg muscle protein turnover was assessed by measurements of phenylalanine kinetics, for which we employed a stable isotope-labeled phenylalanine together with two-pool and three-pool models for calculations, and results were expressed per 100 ml of leg volume. In addition, leg muscle amino acid flux was studied. RESULTS: The negative leg muscle protein net balance seen on days 10-20 of the ICU stay disappeared by days 30-40 (p = 0.012). This was attributable mainly to an increase in the de novo protein synthesis rate (p = 0.007). It was accompanied by an attenuated efflux of free amino acids from the leg. Leg muscle protein breakdown rates stayed unaltered (p = 0.48), as did the efflux of 3-methylhistidine. The arterial plasma concentrations of free amino acids did not change over the course of the study. CONCLUSIONS: In critically ill patients with sustained organ failure and in need of a prolonged ICU stay, the initial high rate of skeletal muscle protein depletion was attenuated over time. The distinction between the acute phase and a more prolonged and more stable phase concerning skeletal muscle protein turnover must be considered in study protocols as well as in clinical practice. TRIAL REGISTRATION: Australian New Zealand Trial Registry, ACTRN12616001012460 . Retrospectively registered on 1 August 2016.

Prevalence and treatment of central hypogonadism and hypoandrogenism in women with hypopituitarism.

PURPOSE: Women with hypopituitarism have increased morbidity and mortality, and hypogonadism has been suggested to be a contributing mechanism. The purpose of this study was to investigate the prevalence of central hypogonadism and hypoandrogenism in women with hypopituitarism at a single Swedish center. METHODS: All consecutive women (n = 184) who commenced growth hormone (GH) replacement therapy at Sahlgrenska University Hospital in Gothenburg between 1995 and 2015 were included. In accordance with the Endocrine Society Clinical Practice Guidelines, strict criteria, based on menstrual history combined with laboratory measurements, were used to define central hypogonadism. Hypoandrogenism was defined as subnormal levels of dehydroepiandrosterone sulfate and/or androstenedione. RESULTS: Central hypogonadism was present in 78% of the women, in 75% of those ≤ 52 years and in 82% of those > 52 years of age. Hypoandrogenism was found in 61% of all the women and in 92% of those with adrenocorticotropic hormone (ACTH) deficiency. The estrogen substitution rate in hypogonadal women ≤ 52 years was lower than the hormonal substitution rate in the other pituitary hormone axes (74% versus 100%, P < 0.001). The use of estrogen substitution tended to decrease between 2000 and 2016. Few women received androgen treatment. CONCLUSIONS: In this first study of hypogonadism in women with hypopituitarism, using stringent diagnostic criteria for hypogonadism, the prevalence of central hypogonadism and low androgen levels was high and estrogen substitution was insufficient. Further studies are needed to elucidate the importance of hypogonadism and insufficient sex steroid replacement for the increased morbidity in hypopituitary women.

Assessing the degree of residual confounding: a cohort study on the association between disability pension and mortality.

Background: Previous studies showed that disability pensioners have a higher risk of premature death than others, but residual confounding has been suggested. The aim was to assess the degree of residual confounding of the association between disability pension (DP) and risk of premature death. Methods: Prospective cohort study of everyone aged 19-64 years, living in Sweden 31 December 2004 (n = 5 406 469), followed up through 2010. Mortality hazard rates over time were estimated for three groups; incident disability pensioners during 2005 from start of DP (February-December 2005), prevalent disability pensioners (January 2005 or since before), and individuals not on DP in January 2005, after standardizing populations to characteristics of the incident disability pensioners, stratified by previous hospitalization or not. If DP has no immediate effect on mortality, incident disability pensioners and those not on DP should initially have similar hazard rates, thereby, allowing assessment of the degree of residual confounding. Results: For those not previously hospitalized, the mortality hazard rate on the first DP day was: 3.07 (95% CI 2.21, 4.36), 2.09 (1.78, 2.48) and 0.78 (0.73, 0.84) per thousand person-years for incident, prevalent, and non DP, respectively. Among previously hospitalized these figures were: 21.67 (17.73, 26.24), 17.00 (15.76, 18.51) and 18.88 (18.14, 19.64) respectively. Hazard ratios were 1.15 (0.94, 1.40) in the strata with and 3.94 (2.78, 5.57) in the strata without, previous hospitalization comparing incident DP with non-DP. Conclusions: Substantial residual confounding was found in the association between DP and premature death among those not previously hospitalized.

Time trends of mortality in patients with non-functioning pituitary adenoma: a Swedish nationwide study.

PURPOSE: Patients with non-functioning pituitary adenomas (NFPA), especially women, have increased mortality. The aim of this study was to investigate whether mortality in NFPA patients has changed during the last two decades. METHODS: This was a nationwide population-based study including 2795 patients (1502 men, 1293 women) diagnosed with NFPA between 1997 and 2011. Patients were identified and followed in Swedish National Health Registries. Standardized mortality ratios (SMRs) with 95 % confidence intervals were calculated for three time periods at first NFPA diagnosis using the general population as reference. RESULTS: Mean (±SD) age at NFPA diagnosis was 58.9 ± 16.8 years. Mean (range) follow-up time was 8.3 (0-18) years, resulting in 20,517 patient-years at risk. Surgical treatment and radiotherapy were used in 53 and 5 %, respectively. The prevalence of hypopituitarism was 64 % during the first time period of diagnosis and then declined gradually during the study period (P value for trend <0.0001). The use of pituitary surgery and radiotherapy remained stable. In women, mortality was increased for patients diagnosed between 1997 and 2006 but not for those diagnosed between 2007 and 2011. The SMR in men remained stable throughout the study and did not differ from the general population. During the last time period, 2007-2011, the SMR between men and women did not differ. CONCLUSIONS: While mortality in men with NFPA remains normal and stable during the last two decades, mortality in women has declined. Decreasing prevalence of pituitary insufficiency may be a plausible explanation for this positive development.