Return to work after COVID-19 infection - A Danish nationwide registry study.

OBJECTIVES: This study aimed to explore return to work after COVID-19 and how disease severity affects this. STUDY DESIGN: This is a Nationwide Danish registry-based cohort study using a retrospective follow-up design. METHODS: Patients with a first-time positive SARS-CoV-2 polymerase chain reaction test between 1 January 2020 and 30 May 2020, including 18-64 years old, 30-day survivors, and available to the workforce at the time of the first positive test were included. Admission types (i.e. no admission, admission to non-intensive care unit [ICU] department and admission to ICU) and return to work was investigated using Cox regression standardised to the age, sex, comorbidity and education-level distribution of all included subjects with estimates at 3 months from positive test displayed. RESULTS: Among the 7466 patients included in the study, 81.9% (6119/7466) and 98.4% (7344/7466) returned to work within 4 weeks and 6 months, respectively, with 1.5% (109/7466) not returning. Of the patients admitted, 72.1% (627/870) and 92.6% (805/870) returned 1 month and 6 months after admission to the hospital, with 6.6% (58/870) not returning within 6 months. Of patients admitted to the ICU, 36% (9/25) did not return within 6 months. Patients with an admission had a lower chance of return to work 3 months from positive test (relative risk [RR] 0.95, 95% confidence interval [CI] 0.94-0.96), with the lowest chance in patients admitted to an ICU department (RR 0.54, 95% CI 0.35-0.72). Female sex, older age, and comorbidity were associated with a lower chance of returning to work. CONCLUSION: Hospitalised patients with COVID-19 infection have a lower chance of returning to work with potential implications for postinfection follow-up and rehabilitation.

Increased long-term risk of heart failure and other adverse cardiac outcomes in dermatomyositis and polymyositis: Insights from a nationwide cohort.

BACKGROUND: Mounting evidence suggests that dermatomyositis/polymyositis (DM/PM) are associated with increased risk of atherosclerotic events and venous thromboembolism. However, data on the association between DM/PM and other cardiac outcomes, especially heart failure (HF), are scarce. OBJECTIVES: To examine the long-term risk and prognosis associated with adverse cardiac outcomes in patients with DM/PM. METHODS: Using Danish administrative registries, we included all patients ≥18 years with newly diagnosed DM/PM (1996-2018). Risks of incident outcomes were compared with non-DM/PM controls from the background population (matched 1:4 by age, sex, and comorbidity). In a secondary analysis, we compared mortality following HF diagnosis between DM/PM patients with HF and non-DM/PM patients with HF (matched 1:4 by age and sex). RESULTS: The study population included 936 DM/PM patients (median age 58.5 years, 59.0% women) and 3744 matched non-DM/PM controls. The median follow-up was 6.9 years. Absolute 10-year risks of incident outcomes for DM/PM patients vs matched controls were as follows: HF, 6.98% (CI, 5.16-9.16%) vs 4.58% (3.79-5.47%) (P = 0.002); atrial fibrillation, 10.17% (7.94-12.71%) vs 7.07% (6.09-8.15%) (P = 0.005); the composite of ICD implantation/ventricular arrhythmias/cardiac arrest, 1.99% (1.12-3.27%) vs 0.64% (0.40-0.98%) (P = 0.02); and all-cause mortality, 35.42% (31.64-39.21%) vs 16.57% (15.10-18.10%) (P < 0.0001). DM/PM with subsequent HF was associated with higher mortality compared with HF without DM/PM (adjusted hazard ratio 1.58 [CI, 1.01-2.47]). CONCLUSION: Patients with DM/PM had a higher associated risk of HF and other adverse cardiac outcomes compared with matched controls. Among patients developing HF, a history of DM/PM was associated with higher mortality.

Incidence of acute myocardial infarction-related cardiogenic shock during corona virus disease 19 (COVID-19) pandemic.

AIMS: The hospitalization of patients with MI has decreased during global lockdown due to the COVID-19 pandemic. Whether this decrease is associated with more severe MI, e.g. MI-CS, is unknown. We aimed to examine the association of Corona virus disease (COVID-19) pandemic and incidence of acute myocardial infarction with cardiogenic shock (MI-CS). METHODS: On March 11, 2020, the Danish government announced national lock-down. Using Danish nationwide registries, we identified patients hospitalized with MI-CS. Incidence rates (IR) and incidence rate ratios (IRR) were used to compare MI-CS before and after March 11 in 2015-2019 and in 2020. RESULTS: We identified 11,769 patients with MI of whom 696 (5.9%) had cardiogenic shock in 2015-2019. In 2020, 2132 MI patients were identified of whom 119 had cardiogenic shock (5.6%). The IR per 100,000 person years before March 11 in 2015-2019 was 9.2 (95% CI: 8.3-10.2) and after 8.9 (95% CI: 8.0-9.9). In 2020, the IR was 7.5 (95% CI: 5.8-9.7) before March 11 and 7.7 (95% CI: 6.0-9.9) after. The IRRs comparing the 2020-period with the 2015-2019 period before and after March 11 (lockdown) were 0.81 (95% CI: 0.59-1.12) and 0.87 (95% CI: 0.57-1.32), respectively. The IRR comparing the 2020-period during and before lockdown was 1.02 (95% CI: 0.74-1.41). No difference in 7-day mortality or in-hospital management was observed between study periods. CONCLUSION: We could not identify a significant association of the national lockdown on the incidence of MI-CS, along with similar in-hospital management and mortality in patients with MI-CS.

Preheart failure comorbidities and impact on prognosis in heart failure patients: a nationwide study.

BACKGROUND: Data regarding the impact of preheart failure (HF) comorbidities on the prognosis of HF are scarce, especially in the younger HF patients. OBJECTIVES: To investigate pre-existing comorbidities in HF patients versus matched controls and to assess their impact on mortality. METHODS: We included all first-time in-hospital and outpatient diagnoses of HF from 1995 to 2017, and comorbidities antedating the HF-diagnosis in the Danish nationwide registries. HF patients were matched with up to five controls. One-year all-cause mortality rates and population attributable risk (PAR) were estimated for three separate age groups (≤50, 51-74 and >74 years). RESULTS: Totally 280 002 patients with HF and 1 166 773 controls were included. Cardiovascular comorbidities, for example, cerebrovascular disease and ischaemic heart disease were more frequent in the oldest (17.9% and 29.7% in HF vs. 9.8% and 10.7% in controls) compared to the youngest age group (3.9% and 15.2% in HF vs. 0.7% and 0.9% in controls). Amongst patients with HF, 1-year mortality rates (per 100 person-years) were highest amongst those with >1 noncardiovascular comorbidity: ≤50 years (10.4; 9.64-11.3), 51-74 years (23.3; 22.9-23.7), >74 years (58.5; 57.9-59.0); hazard ratios 245.18 (141.45-424.76), 45.85 (42.77-49.15) and 24.5 (23.64-25.68) for those ≤50, 51-74 and >74 years, respectively. For HF patients ≤50 years, PAR was greatest for hypertension (17.8%), cancer (14.1%) and alcohol abuse (8.5%). For those aged >74 years, PAR was greatest for hypertension (23.6%), cerebrovascular disease (6.2%) and cancer (7.2%). CONCLUSIONS: Heart failure patients had a higher burden of pre-existing comorbidities, compared to controls, which adversely impacted prognosis, especially in the young.

Low N-terminal pro-brain natriuretic peptide levels are associated with non-alcoholic fatty liver disease in patients with type 2 diabetes.

AIM: Natriuretic peptides (NPs) have emerged as important regulators of lipid metabolism. Reduced levels of NPs are reported in obesity and in patients with type 2 diabetes (T2D). This NP deficiency may affect their ectopic fat distribution and lead to high risk of non-alcoholic fatty liver disease (NAFLD). METHODS: In this cross-sectional study, the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and liver fat content was quantified using 1H-magnetic resonance spectroscopy in 120 patients with T2D. RESULTS: NAFLD (defined as liver fat content ≥ 5.6%) was found in 57 (48%) of the T2D patients, who also had significantly lower NT-proBNP (P = 0.002) levels compared with patients without NAFLD, but did not differ as regards the presence of cardiovascular disease (CVD) or in kidney function. After adjusting for potential confounders (age, gender, HbA1c, BMI, HOMA2-IR, CVD, eGFR), the odds ratio for the presence of NAFLD was increased by 2.9 (P = 0.048) for NT-proBNP levels < 45 ng/L. In a multivariable linear regression model, the relationship with NT-proBNP was further analyzed as a continuous variable, and was independently and inversely associated with increasing liver fat content after full adjustment (P = 0.031). CONCLUSION: Reduced plasma NT-proBNP levels are independently associated with high liver fat content in patients with T2D. The present study suggests that NP deficiency may play a role in the development of NAFLD in T2D.

A prospective three-year follow-up study on the clinical significance of anti-neuronal antibodies in acute psychiatric disorders.

The clinical significance of anti-neuronal antibodies for psychiatric disorders is controversial. We investigated if a positive anti-neuronal antibody status at admission to acute psychiatric inpatient care was associated with a more severe neuropsychiatric phenotype and more frequent abnormalities during clinical work-up three years later. Patients admitted to acute psychiatric inpatient care who tested positive for N-methyl-D-aspartate receptor (NMDAR), contactin-associated protein 2 (CASPR2) and/or glutamic acid decarboxylase 65 (GAD65) antibodies (n = 24) were age - and sex matched with antibody-negative patients (1:2) from the same cohort (n = 48). All patients were invited to follow-up including psychometric testing (e.g. Symptom Checklist-90-Revised), serum and cerebrospinal fluid (CSF) sampling, EEG and 3 T brain MRI. Twelve antibody-positive (ab+) and 26 antibody-negative (ab-) patients consented to follow-up. Ab+ patients had more severe symptoms of depression (p = 0.03), psychoticism (p = 0.04) and agitation (p = 0.001) compared to ab- patients. There were no differences in CSF analysis (n = 6 ab+/12 ab-), EEG (n = 7 ab+/19 ab-) or brain MRI (n = 7 ab+/17 ab-) between the groups. In conclusion, anti-neuronal ab+ status during index admission was associated with more severe symptoms of depression, psychoticism and agitation at three-year follow-up. This supports the hypothesis that anti-neuronal antibodies may be of clinical significance in a subgroup of psychiatric patients.

Evolution of sociality in spiders leads to depleted genomic diversity at both population and species levels.

Across several animal taxa, the evolution of sociality involves a suite of characteristics, a "social syndrome," that includes cooperative breeding, reproductive skew, primary female-biased sex ratio, and the transition from outcrossing to inbreeding mating system, factors that are expected to reduce effective population size (Ne). This social syndrome may be favoured by short-term benefits but come with long-term costs, because the reduction in Ne amplifies loss of genetic diversity by genetic drift, ultimately restricting the potential of populations to respond to environmental change. To investigate the consequences of this social life form on genetic diversity, we used a comparative RAD-sequencing approach to estimate genomewide diversity in spider species that differ in level of sociality, reproductive skew and mating system. We analysed multiple populations of three independent sister-species pairs of social inbreeding and subsocial outcrossing Stegodyphus spiders, and a subsocial outgroup. Heterozygosity and within-population diversity were sixfold to 10-fold lower in social compared to subsocial species, and demographic modelling revealed a tenfold reduction in Ne of social populations. Species-wide genetic diversity depends on population divergence and the viability of genetic lineages. Population genomic patterns were consistent with high lineage turnover, which homogenizes the genetic structure that builds up between inbreeding populations, ultimately depleting genetic diversity at the species level. Indeed, species-wide genetic diversity of social species was 5-8 times lower than that of subsocial species. The repeated evolution of species with this social syndrome is associated with severe loss of genomewide diversity, likely to limit their evolutionary potential.

Prevalence of serum anti-neuronal autoantibodies in patients admitted to acute psychiatric care.

BACKGROUND: Autoimmune encephalitis associated with anti-neuronal antibodies may be challenging to distinguish from primary psychiatric disorders. The significance of anti-neuronal antibodies in psychiatric patients without clear evidence of autoimmune encephalitis is unknown. We investigated the serum prevalence of six anti-neuronal autoantibodies in a cohort of unselected patients admitted to acute psychiatric care. METHOD: Serum was drawn from 925 patients admitted to acute psychiatric in-patient care. Psychiatric diagnoses were set according to International Classification of Diseases (ICD)-10 criteria. Antibody analysis was performed with an indirect immunofluorescence test for N-methyl d-aspartate receptor (NMDAR) antibodies and five other anti-neuronal autoantibodies of the immunoglobulin (Ig) classes IgA, IgG and IgM isotype. RESULTS: Anti-neuronal autoantibodies were found in 11.6% of patients: NMDAR antibodies in 7.6%, contactin-associated protein-like 2 (CASPR2) antibodies in 2.5%, glutamic acid decarboxylase-65 (GAD65) antibodies in 1.9%, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antibodies in 0.1%. Leucine-rich glioma-inactivated protein-1 (LGI1) and γ-aminobutyric acid B (GABAB) receptor antibodies were not detected. NMDAR antibodies of class IgG were present in five patients only (0.5%). NMDAR antibodies of all Ig classes were equally prevalent in patients with and without psychosis. There were no significant differences in antibody prevalence in the different diagnostic categories, except for a higher odds ratio of being NMDAR antibody positive for patients without a specific psychiatric diagnosis. CONCLUSIONS: NMDAR IgG autoantibodies, which are known to be strongly associated with anti-NMDAR encephalitis, were rarely found. CASPR2 and GAD65 antibodies were more frequently encountered in the present study than previously reported. Further research on the clinical significance of anti-neuronal autoantibodies in patients with acute psychiatric symptoms is needed.

Association between left ventricular global longitudinal strain and natriuretic peptides in outpatients with chronic systolic heart failure.

BACKGROUND: Both impaired left ventricular (LV) global longitudinal strain (GLS) and increased plasma concentrations of natriuretic peptides(NP) are associated with a poor outcome in heart failure (HF). Increased levels of NP reflect increased wall stress of the LV. However, little is known about the relationship between LV GLS and NP. This aim of this study was to evaluate the relationship between the echocardiographic measure LV GLS and plasma levels of NP. METHODS: We prospectively included 149 patients with verified systolic HF at the baseline visit in an outpatient HF clinic. LV GLS was assessed by two dimension speckle tracking and plasma concentrations of N-terminal-pro-brain-natriuretic-peptide (NT-proBNP) and pro-atrial-natriuretic-peptide (proANP) were analysed. RESULTS: The patients had a median age of 70 years, 28.2 % were females, 26.5 % were in functional class III-IV, median left ventricular ejection fraction (LVEF) was 33 % and median LV GLS was -11 %. LV GLS was associated with increased plasma concentrations of NT-proBNP and proANP in multivariate logistic regression (NT-proBNP: Odds RatioGLS: 7.25, 95 %-CI: 2.48-21.1, P < 0.001 and proANP: Odds RatioGLS: 3.26, 95-%-CI: 1.28-8.30, P = 0.013) and linear regression (NT-proBNP: ßGLS: 1.19, 95 %-CI: 0.62-1.76, P < 0.001 and proANP: ßGLS: 0.42, 95-%-CI: 0.11-0.72, P = 0.007) models after adjustment for traditional confounders (age, gender, body-mass-index, atrial fibrillation, renal function) and left atrial volume index. CONCLUSION: Impaired LV GLS is associated with increased plasma concentrations of NP and our data suggest that left ventricular myocardial mechanics estimated by LV GLS reflects myocardial wall stress in chronic systolic HF.

Inbreeding depression across a nutritional stress continuum.

Many natural populations experience inbreeding and genetic drift as a consequence of nonrandom mating or low population size. Furthermore, they face environmental challenges that may interact synergistically with deleterious consequences of increased homozygosity and further decrease fitness. Most studies on inbreeding-environment (I-E) interactions use one or two stress levels, whereby the resolution of the possible stress and inbreeding depression interaction is low. Here we produced Drosophila melanogaster replicate populations, maintained at three different population sizes (10, 50 and a control size of 500) for 25 generations. A nutritional stress gradient was imposed on the replicate populations by exposing them to 11 different concentrations of yeast in the developmental medium. We assessed the consequences of nutritional stress by scoring egg-to-adult viability and body mass of emerged flies. We found: (1) unequivocal evidence for I-E interactions in egg-to-adult viability and to a lesser extent in dry body mass, with inbreeding depression being more severe under higher levels of nutritional stress; (2) a steeper increase in inbreeding depression for replicate populations of size 10 with increasing nutritional stress than for replicate populations of size 50; (3) a nonlinear norm of reaction between inbreeding depression and nutritional stress; and (4) a faster increase in number of lethal equivalents in replicate populations of size 10 compared with replicate populations of size 50 with increasing nutritional stress levels. Our data provide novel and strong evidence that deleterious fitness consequences of I-E interactions are more pronounced at higher nutritional stress and at higher inbreeding levels.

A Drosophila laboratory evolution experiment points to low evolutionary potential under increased temperatures likely to be experienced in the future.

The ability to respond evolutionarily to increasing temperatures is important for survival of ectotherms in a changing climate. Recent studies suggest that upper thermal limits may be evolutionary constrained. We address this hypothesis in a laboratory evolution experiment, encompassing ecologically relevant thermal regimes. To examine the potential for species to respond to climate change, we exposed replicate populations of Drosophila melanogaster to increasing temperatures (0.3 °C every generation) for 20 generations, whereas corresponding replicate control populations were held at benign thermal conditions throughout the experiment. We hypothesized that replicate populations exposed to increasing temperatures would show increased resistance to warm and dry environments compared with replicate control populations. Contrasting replicate populations held at the two thermal regimes showed (i) an increase in desiccation resistance and a decline in heat knock-down resistance in replicate populations exposed to increasing temperatures, (ii) similar egg-to-adult viability and fecundity in replicate populations from the two thermal regimes, when assessed at high stressful temperatures and (iii) no difference in nucleotide diversity between thermal regimes. The limited scope for adaptive evolutionary responses shown in this study highlights the challenges faced by ectotherms under climate change.

Abnormal glucose metabolism is associated with reduced left ventricular contractile reserve and exercise intolerance in patients with chronic heart failure.

AIMS: To investigate the associations between glucose metabolism, left ventricular (LV) contractile reserve, and exercise capacity in patients with chronic systolic heart failure (HF). METHODS AND RESULTS: From an outpatient HF clinic, 161 patients with systolic HF were included (mean age 70 ± 10 years, 69% male, 59% had ischaemic heart disease, mean LV ejection fraction (LVEF) 37 ± 9%). Thirty-four (21%) patients had known diabetes mellitus (DM). Oral glucose tolerance testing (OGTT) classified patients without a prior DM diagnosis as normal glucose tolerance (NGT), impaired glucose tolerance or new DM. All patients completed low-dose dobutamine echocardiography (LDDE) and 154 patients a 6-min walking distance test (6MWD). Compared with patients with NGT, patients with known DM had lower resting LVEF (33.4 vs. 39.1%, P < 0.05) and higher E/e' (13.9 vs. 11.4, P < 0.05). During LDDE, an increase in LVEF could be observed in all glycemic groups (mean 8.2% absolute increase), but the contractile reserve was lower in patients with known DM (-5.4%, P = 0.001) and new DM (-3.5%, P = 0.035) compared to patients with NGT. 6MWD was lower in known DM (349 m) and new DM (379 m) compared with NGT (467 m) (P < 0.001). Differences in clinical variables, resting echocardiographic parameters or contractile reserve, did not explain the exercise intolerance related to diabetes. CONCLUSION: Diabetes, known or newly detected by OGTT, is independently associated with reduced LV contractile reserve and exercise intolerance in outpatients with systolic HF. These findings may offer one explanation for the excess mortality related to diabetes in HF.

Effect of estimated glomerular filtration rate on plasma concentrations of B-type natriuretic peptides measured with multiple immunoassays in elderly individuals.

OBJECTIVE: This study was designed to quantify the crude and adjusted effects of estimated glomerular filtration rate (eGFR) on N-terminal-pro-brain-natriuretic peptide (proBNP) measured with three immunoassays and brain natriuretic peptide (BNP) in elderly individuals. DESIGN: Cross-sectional study. SETTING: 474 elderly outpatients with suspected heart failure (prevalence 13%) from the primary care. MAIN OUTCOME MEASURES: The effects of eGFR on proBNP, measured with three different immunoassays (Roche Diagnostics, Oslo and Copenhagen), and BNP (Shionogi) concentrations were evaluated by multiple linear regression models. RESULTS: In univariate analyses the effect of a 10% decrease in eGFR on proBNP concentrations was a 15% (95% confidence interval 11% to 18%), 9% (5% to 13%) and 21% (14% to 28%) increase. In multivariate models the effect was a 7% (3% to 11%), 4% (2% to 6%) and 13% (4% to 20%) increase. The effect of a 10% decrease in eGFR on BNP concentrations (Shionogi) was a 10% (5% to 15%) (univariate) and a 4% (1% to 9%) (multivariate) increase. CONCLUSIONS: The effect of eGFR on proBNP measured with three different immunoassays and BNP is modest and within the same range. The effect of eGFR on proBNP and BNP concentrations is reduced substantially after adjustment for important clinical and echocardiographic confounders. These findings should be considered before renal function is offered as an explanation for increased proBNP or BNP levels.

N-terminal pro brain natriuretic peptide predicts mortality in patients with end-stage renal disease in hemodialysis.

Concentrations of N-terminal pro brain natriuretic peptide (NT-proBNP) increase in patients with heart failure and other cardiovascular (CV) diseases and are strong prognostic markers. In patients with end-stage renal disease (ESRD) in hemodialysis (HD), levels of NT-proBNP are almost always raised. In ESRD patients undergoing HD, we aimed at (i) identifying the factors that affect levels of NT-proBNP, (ii) determining the effect of HD on NT-proBNP, and (iii) determining the prognostic impact of NT-proBNP. A total of 109 patients underwent physical examination, electrocardiogram, and echocardiography. Serum NT-proBNP was measured before and after HD (Elecsys 2010). NT-proBNP levels were markedly elevated (pre-HD 4079 pg/ml, post-HD 2759 pg/ml, P<0.001). There was a strong inverse correlation between NT-proBNP and left ventricular ejection fraction (LVEF) (P=0.043), 24-h urine production (P=0.006), and K(t)/V (efficacy of dialysis) (P=0.016) and a positive correlation with left ventricular hypertrophy (LVH) (P=0.014). Patients with higher concentrations, both pre- and post-HD had an increased mortality rate compared to those with lower concentrations (P=0.007, P=0.002). We found age (P=0.009) and NT-proBNP (pre-HD P=0.007, post-HD P=0.001) predictive of death. Our findings demonstrate that CV disease in terms of LVH and reduced LVEF in addition to 24-h urine production and K(t)/V determine NT-proBNP levels. Post-HD levels of NT-proBNP were lower than pre-HD levels; both predictive of mortality.

Mendelian analysis of a metastasis-prone substrain of BALB/c nude mice using a subcutaneously inoculated human tumour.

Most nude mice do not allow the formation of metastases after heterotransplantation of human malignant tumours. Here we describe a substrain of BALB/c nude mice (BALB/c/AnNCr) that reproducibly allows some human cancers to metastasize. By Mendelian analysis of hybrids between this substrain and C57BL/6J +/+ mice we found that the ability to allow a human tumour (MDA-MB-435 BAG) to express its metastatic phenotype is determined by a recessively inheritable trait in the mouse host. We are presently working to identify the genetics responsible for development of metastases. The study also includes immunohistochemical and electron microscopic analysis of the test tumour, originally assumed to be a human mammary carcinoma, but shown to possess characteristics of a malignant melanoma (1). The ultimate aim of our ongoing study is to establish a substrain of nude mice that will allow metastasis in all recipients.

Bisphosphonate infusions: patient preference, safety and clinic use.

GOALS OF WORK: We set out to assess the preference of patients with common cancers involving bone receiving intravenous bisphosphonate therapy for either pamidronate (P) or zoledronic acid (Z) and their preference for the location of the infusion (clinic or home). We also aimed to monitor these patients' renal safety, and to compare their time in clinic to receive P and Z infusions. PATIENTS AND METHODS: Enrolled in the study were 184 patients, and all received initial infusions of Z (so any first infusion reactions did not confound preferences for P). For their second and third infusions, patients were randomized to receive Z then P or P then Z, and questioned on their preferences. For up to 1 year they continued on Z infusions every 3-4 weeks, while their renal safety was monitored. Where practical, later infusions were given at home (rather than in the clinic) and patients questioned on their preferred infusion location. In a convenience subset of 43 patients, clinic use for Z and P infusions was also measured by timing infusions and other procedures. MAIN RESULTS: Of 144 patients who received a third infusion, 138 responded to questions on bisphosphonate preference, and of these 138, 92% (127) preferred Z to P, because shorter infusions caused less disruption to their day. Only 12% of eligible patients (16/138) received home infusions, but 13/14 questioned preferred this location. Among 184 patients, 19 episodes of renal impairment were noted, mostly owing to disease progression (e.g. obstructive uropathy), with none linked to Z therapy. The mean clinic time taken to receive Z and any concomitant therapy was about half that for P (78 vs 161 min). CONCLUSIONS: Cancer patients prefer shorter bisphosphonate infusions-and at home, where practical. Regular Z 4 mg infusions appear to be safe in these patients, with routine monitoring of serum creatinine. Using Z rather than P could save busy cancer centres time and improve patient satisfaction.

Cardiovascular and neuroendocrine responses to left lateral position in non-obese young males.

Previous results from our laboratory indicate that the heart is distended by the left lateral position (LAT) compared to horizontal supine (SUP). We therefore tested the hypothesis that cardiac output is increased by LAT and that mean arterial pressure is maintained unchanged or even decreased through peripheral vasodilatation induced by cardiopulmonary low-pressure receptor stimulation. Twelve non-obese young males were investigated. The location of the mid-aorta between the aortic valves was used as the hydrostatic reference point for the arterial pressure measurements. It was determined by magnetic resonance (n=6) to be 7.0 +/- 0.2 cm below the sternum in SUP (1/3 of anteroposterior chest diameter below the sternum) and 2.5 +/- 0.2 cm below the midsternal level in LAT. Brachial mean (auscultation) and finger mean arterial pressures (infrared photoplethysmography), cardiac output (foreign gas rebreathing), heart rate, and plasma concentrations (n=6) of vasoactive hormones were unchanged by LAT. In conclusion, cardiac output, mean arterial pressures, and vasoactive hormone releases were unaffected by 30 min of LAT. Furthermore, the hydrostatic reference points for arterial pressure measurements is located one third of the antero-posterior chest diameter below the sternum in SUP and 2.5 cm below the midsternal level in LAT in non-obese young males.

Lithium treatment at 52.

The paper reviews briefly and comments in detail on selected events in the history of lithium treatment. The events include Cade's discovery of lithium's antimanic action, the discovery and establishment of its prophylactic action, the ensuing debate, amelioration and prevention of side effects and risks, use during pregnancy, non-compliance, selection of patients, information and instruction, the question whether new and better prophylactic agents are about to oust lithium, the use of combination treatment, the effect of lithium on suicidal behavior, the benefits of prophylactic lithium treatment, and the design of future comparative trials.

Suicidal behavior and prophylactic lithium treatment of major mood disorders: a review of reviews.

This paper briefly summarizes and discusses at length two recent reviews. Their main findings were the following: (1) During prophylactic lithium treatment the overall mortality of patients with major mood disorders was much lower than in such patients in general. (2) The frequency of suicidal acts was many times lower in patients on lithium than in patients not on lithium. The limitations of the studies reviewed and the difficulty of interpreting their findings are discussed. It is concluded that prophylactic lithium treatment is indicated in patients with major mood disorders who are at high risk of committing suicide, that is, those with severe depressions or depressions with persistent suicidal thoughts or with suicide attempts in the past.