Origin-Independent Dynamic Polarizability Density from Coupled Cluster Response Theory.

The calculation of the origin-independent density of the dynamic electric dipole polarizability, previously presented for uncorrelated and density functional theory (DFT)-based methods, has been developed and implemented at the coupled cluster singles and doubles (CCSD) level of theory. A pointwise analysis of polarizability densities calculated for a number of molecules at Hartree-Fock (HF) and CCSD clearly shows that the electron correlation effect is much larger than one would argue considering the integrated dipole electric polarizability alone. Large error compensations occur during the integration process, which hide fairly large deviations mainly located in the internuclear regions. The same is observed when calculated CCSD and B3LYP polarizability densities are compared, with the remarkable feature that positive/negative deviations between CCSD and HF reverse sign, becoming negative/positive when comparing CCSD to B3LYP.

The effect of oral dexamethasone on duration of analgesia after upper limb surgery under infraclavicular brachial plexus block: a randomised controlled trial.

The effects of oral dexamethasone on peripheral nerve blocks have not been investigated. We randomly allocated adults scheduled for forearm or hand surgery to oral placebo (n = 61), dexamethasone 12 mg (n = 61) or dexamethasone 24 mg (n = 57) about 45 min before lateral infraclavicular block. Mean (SD) time until first pain after block were: 841 (327) min; 1171 (318) min; and 1256 (395) min, respectively. Mean (98.3%CI) differences in time until first postoperative pain for dexamethasone 24 mg vs. placebo and vs. dexamethasone 12 mg were: 412 (248-577) min, p < 0.001; and 85 (-78 to 249) min, p = 0.21, respectively. Mean (98.3%CI) difference in time until first postoperative pain for dexamethasone 12 mg vs. placebo was 330 (186-474) min, p < 0.001. Both 24 mg and 12 mg of oral dexamethasone increased the time until first postoperative pain compared with placebo in patients having upper limb surgery under infraclavicular brachial plexus block.

Number of musculoskeletal pain sites leads to increased long-term healthcare contacts and healthcare related costs - a Danish population-based cohort study.

BACKGROUND: People with musculoskeletal pain seek more healthcare than the general population, however little is known about the long-term effect on healthcare use. The aim of this study was to examine the consequences of number of musculoskeletal pain sites on long-term care-seeking and healthcare-related costs and explore how health anxiety influences this relationship. METHODS: We conducted a Danish population-based longitudinal cohort study of 4883 participants combining self-reported survey data from 2008 with ten-year follow-up data from national health registers. Using a causal inference framework, we examined associations between number of pain sites (range 0-7)/level of health anxiety (high/low level) and face-to-face healthcare contacts/healthcare-related costs. Data were analyzed using negative binomial regression with generalized estimating equations. Regression models were adjusted for sex, age, duration of pain, level of education, comorbidity, personality traits, risk of depression, marital status, physical job exposure, and previous healthcare utilization. RESULTS: For each additional pain site general healthcare contacts (Incidence Rate Ratio (IRR): 1.04 (95% CI: 1.03-1.05)), healthcare-related costs (IRR: 1.06 (95% CI: 1.03-1.08) and musculoskeletal healthcare contacts (IRR: 1.11 (95% CI:1.09-1.14) increased. Those with high levels of health anxiety at baseline had a slightly higher number of general healthcare contacts (IRR 1.06 (1.01-1.11), independent of number of pain sites. However, level of anxiety did not influence the effect of number of pain sites on any healthcare use or cost outcomes. CONCLUSIONS: We found evidence for a causal association between increasing number of pain sites and greater healthcare use and cost, and high levels of health anxiety did not increase the strength of this association. This suggests that number of pain sites could be a potential target for biopsychosocial interventions in order to reduce the need for future care-seeking.

Use of antipsychotics in Denmark 1997-2018: a nation-wide drug utilisation study with focus on off-label use and associated diagnoses.

AIMS: Antipsychotics are primarily labelled for the treatment of severe mental illness and have documented clinical utility in certain neurological disorders or palliative care. However, off-label use of antipsychotics is common and increasing, and prior studies on antipsychotic utilisation have not specifically assessed users in neurology, palliative care or general practice. We aimed to explore diagnoses associated with antipsychotic use, treatment patterns and characteristics of users without diagnoses relevant to antipsychotic treatment. METHODS: Population-based study identifiying all users of antipsychotics in Denmark (pop 5.7 mio.) 1997-2018 in the Danish National Prescription Register (DNPR). Possible indications for antipsychotic therapy were evaluated using in- and outpatient contacts from the DNPR. Users were divided hierarchically into six groups: severe mental disorders (schizophrenia, bipolar-spectrum disorders), chronic mental disorders (dementias, mental retardation, autism), other mental disorders (depression-spectrum, anxiety and personality disorders, etc.), selected neurological diseases, cancer and antipsychotic users without any of these diagnoses. This last group was characterised regarding demographics, antipsychotic use, health care utilisation and likely antipsychotic treatment initiator in 2018. RESULTS: Altogether, 630 307 antipsychotic users were identified, of whom 127 649 had filled prescriptions during 2018. Users without diagnoses relevant to antipsychotic treatment comprised of the largest group (37%), followed by schizophrenia and bipolar-spectrum disorders (34%), other mental disorders (15%), dementia, autism and mental retardation (11%), cancer (2.2%) and neurological diagnoses (2.0%). Of 37 478 incident users in 2018, 39% had no diagnosis relevant to antipsychotic treatment, 7.9% had major depression, 7.7% neurotic/stress-related disorders and 7.5% dementia. Quetiapine was most commonly used, both overall (51%) and among users without diagnoses relevant to antipsychotic treatment (58%). Of 14 474 incident users in 2018 without diagnoses relevant to antipsychotic treatment, treatment was most likely initiated by a general practitioner (65%), with only 17% seeing a psychiatrist during the following year. As many as 18% of patients with adjustment disorders and 14% of those without relevant diagnoses for antipsychotic use, remained on antipsychotic treatment 5 years after their first prescription. CONCLUSIONS: Over one-third of antipsychotic users in Denmark did not have psychiatric, neurological or cancer diagnoses as possible indications for antipsychotic therapy. Many antipsychotics are initiated or prescribed in general practice, and a concerningly large subgroup without documented diagnoses relevant for antipsychotics continued to receive them. Rational prescribing, adequate side effect monitoring and further research into reasons for the observed antipsychotic use patterns and their risk-benefit ratio are needed.

Sensory distribution of the lateral femoral cutaneous nerve block - a randomised, blinded trial.

BACKGROUND: The lateral femoral cutaneous nerve (LFCN) block may be used for post-operative pain management in patients undergoing total hip arthroplasty. The aim of this trial was to investigate the sensory coverage of the posterior and the lateral incision lines and the involvement of the femoral nerve after an LFCN block. METHODS: The study was a randomised, blinded trial in 20 healthy volunteers. All subjects received a bilateral LFCN block randomised to 8 ml ropivacaine on the right side and 8 ml isotonic saline on the left side, or vice versa. An orthopaedic surgeon depicted the incision lines (invisible to the investigators) prior to block performance. The distribution of the blocked area and the coverage of the incision lines were assessed with temperature discrimination and pinprick test before unblinding the incision lines. Pain during tonic heat stimulation and involvement of the femoral nerve by measuring quadriceps strength were assessed. RESULTS: The mean difference in block coverage of the posterior (primary outcome) and the lateral incision lines tested with temperature discrimination were 5.8% (95% CI: -2.2 to 14.0%, P = 0.146) and 18.9% (95% CI: 6.5-31.4%, P = 0.005), respectively, comparing the active with the placebo side. A varying anatomic distribution area was observed. No clinically significant differences for experimental pain and quadriceps muscle strength were found. The block failure rate was 15%. CONCLUSION: An LFCN block consisting of 8 ml 0.75% ropivacaine had limited coverage of the posterior and lateral incision lines.

A Systematic Review of the Clinimetric Properties of the 6-Item Version of the Hamilton Depression Rating Scale (HAM-D6).

BACKGROUND: In a study aimed at identifying the items carrying information regarding the global severity of depression, the 6-item Hamilton Depression Rating Scale (HAM-D6) was derived from the original 17-item version of the scale (HAM-D17). Since then, the HAM-D6 has been used in a wide range of clinical studies. We now provide a systematic review of the clinimetric properties of HAM-D6 in comparison with those of HAM-D17 and the Montgomery Asberg Depression Rating Scale (MADRS). METHODS: We conducted a systematic search of the literature in PubMed, PsycInfo, and EMBASE databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Studies reporting data on the clinimetric validity of the HAM-D6 and either the HAM-D17 or MADRS in non-psychotic unipolar or bipolar depression were included in the synthesis. RESULTS: The search identified 681 unique records, of which 51 articles met the inclusion criteria. According to the published literature, HAM-D6 has proven to be superior to both HAM-D17 and MADRS in terms of scalability (each item contains unique information regarding syndrome severity), transferability (scalability is constant over time and irrespective of sex, age, and depressive subtypes), and responsiveness (sensitivity to change in severity during treatment). CONCLUSIONS: According to the published literature, the clinimetric properties of HAM-D6 are superior to those of both the HAM-D17 and MADRS. Since the validity of HAM-D6 has been demonstrated in both research and clinical practice, using the scale more consistently would facilitate translation of results from one setting to the other.

Sleep and delirium in unsedated patients in the intensive care unit.

BACKGROUND: Sleep deprivation and delirium are major problems in the ICU. We aimed to assess the sleep quality by polysomnography (PSG) in relation to delirium in mechanically ventilated non-sedated ICU patients. METHODS: Interpretation of 24-h PSG and clinical sleep assessment in 14 patients. Delirium assessment was done using the confusion assessment method for the intensive care unit (CAM-ICU). RESULTS: Of four patients who were delirium free, only one had identifiable sleep on PSG. Sleep was disrupted with loss of circadian rhythm, and diminished REM sleep. In the remaining three patients the PSGs were atypical, meaning that no sleep signs were found, and sleep could not be quantified from the PSGs. Clinical total sleep time (ClinTST) ranged from 2.0-13.1 h in patients without delirium. Six patients with delirium all had atypical PSGs, so sleep could not be quantified. Short periods of REM sleep were found. ClinTST was median 8.5 h (range 0.4-13.8 h). EEG reactivity and wakefulness was found in all but one PSG. Four patients were CAM-ICU "unassessable" (unresponsive to voice). PSGs were atypical without reactivity or wakefulness, even though clinical wakefulness was documented. ClinTST was median 18.3 h (range 3.7-19.8 h). Paroxystic EEG activity was found in this subgroup. CONCLUSIONS: The objective signs of sleep were absent in all but one PSG, so even though patients were not sedated, sleep could not be quantified. Even in patients without delirium, sleep could only be quantified in one of four patients. Paroxystic activity is frequent in unsedated patients, unresponsive to voice, but the implication is unknown.

The experience of demanding work environments in younger workers.

BACKGROUND: Investigating whether certain individual or background characteristics are associated with an increased risk of experiencing an excessively demanding work environment in younger workers may help to reduce future inequality in health and maximize their labour market participation. AIMS: To describe the work environment of Danish 20- to 21-year olds and to investigate the influence of family socioeconomic background and individual characteristics at age 14-15 on later experience of physical and psychosocial work environments. METHODS: We obtained information on subjects' school performance, vulnerability, health and parental socioeconomic status from registers and a questionnaire completed in 2004. A questionnaire concerning eight measures of subjects' psychosocial and physical work environment in 2010 was used to determine the outcomes of interest. RESULTS: The study population consisted of 679 younger workers aged 20-21. The psychosocial work environment was in general good but younger workers experienced more demanding physical work than the general working population. Overall, individual as well as family factors had a limited impact on their assessment of the work environment. Low self-esteem at age 14-15 was associated with experiencing high demands and lack of trust and fairness at work, whereas low parental socioeconomic status was associated with a demanding physical work environment. CONCLUSIONS: This study showed a social gradient in experiencing a demanding physical work environment at age 20-21. The psychosocial work environment experienced by younger workers was generally good, but vulnerable young people may need special attention to protect them from or prepare them for psychosocially demanding jobs later in life.

Individual and work-unit measures of psychological demands and decision latitude and the use of antihypertensive medication.

PURPOSE: To analyse whether psychological demands and decision latitude measured on individual and work-unit level were related to prescription of antihypertensive medication. METHODS: A total of 3,421 women and 897 men within 388 small work units completed a questionnaire concerning psychological working conditions according to the job strain model. Mean levels of psychological demands and decision latitude were computed for each work unit to obtain exposure measures that were less influenced by reporting bias. Dispensed antihypertensive medication prescriptions were identified in The Danish National Prescription Registry. Odds ratios (OR) comparing the highest and lowest third of the population at individual and work-unit level, respectively, were estimated by multilevel logistic regression adjusted for confounders. Psychological demands and decision latitude were tested for interaction. Supplementary analyses of 21 months follow-up were conducted. RESULTS: Among women, increasing psychological demands at individual (adjusted OR 1.54; 95 % CI 1.02-2.33) and work-unit level (adjusted OR 1.41; 95 % CI 1.04-1.90) was significantly associated with purchase of antihypertensive medication. No significant association was found for decision latitude. Follow-up results supported an association with psychological demands but they were not significant. All results for men showed no association. Psychological demands and decision latitude did not interact. CONCLUSION: High psychological work demands were associated with the purchase of prescribed antihypertensive medication among women. This effect was present on both the work-unit and the individual level. Among men there were no associations. The lack of interaction between psychological demands and decision latitude did not support the job strain model.

Sleep in the Intensive Care Unit measured by polysomnography.

BACKGROUND: Sleep deprivation has deleterious effects on most organ systems. Patients in the Intensive care unit (ICU) report sleep deprivation as the second worst experience during their stay only superseded by pain. The aim of the review is to provide the clinician with knowledge of the optimal sleep-friendly care and environment. METHODS: Pubmed was systematically searched. Studies regarding polysomnography in ICU populations or healthy volunteers exposed to ICU conditions were included. RESULTS: Thirty-eight studies were identified. The patients were qualitatively but not necessarily quantitatively sleep deprived with loss of circadian rhythm and extreme sleep fragmentation. Sedation, care interventions, noise, disease and mechanical ventilation are the most contributing factors to sleep deprivation. CONCLUSION: Sedation should be kept at a minimum and interrupted once daily. Care interventions should be clustered and noise reduced and/or masked with earplugs. NAVA, proportional assist+ or assist-control ventilation should be preferred to pressure support ventilation and adjusted to allow smaller tidal volumes, thus avoiding central apnoeas.

Computer use and ulnar neuropathy: results from a case-referent study.

We aimed to evaluate associations between vocational computer use and 1) ulnar neuropathy, and 2) ulnar neuropathy- like symptoms as distinguished by electroneurography. We identified all patients aged 18-65 years, examined at the Department of Neurophysiology on suspicion of ulnar neuropathy, 2001-2007. We mailed a questionnaire to 546 patients with ulnar neuropathy, 633 patients with ulnar neuropathy-like symptoms, and three community referents per case, matched on sex, age, and primary care centre. From a Job Exposure Matrix we extracted estimates of daily hours of computer use. The analysis was performed by conditional logistic regression.There were a negative association between daily hours of computer use and the two outcomes of interest. Participants who reported their elbow to be in contact with their working table for 2 hours or more during the workday had an elevated risk for ulnar neuropathy (OR=2.16, 95 % CI; 1.06-4.44).The two outcomes were not associated with daily hours of computer use. Findings suggested specific effects of pressure on the elbow, and might be an explanation for the overweight of left-sided outcomes in this primarily right-handed group. Preventive efforts would then be straightforward by providing appropriate arm support for the left arm and elbow.

The norepinephrine transporter gene is a candidate gene for panic disorder.

Panic disorder (PD) is an anxiety disorder characterized by recurrent panic attacks with a lifetime prevalence of 4.7%. Genetic factors are known to contribute to the development of the disorder. Several lines of evidence point towards a major role of the norepinephrine system in the pathogenesis of PD. The SLC6A2 gene is located on chromosome 16q12.2 and encodes the norepinephrine transporter (NET), responsible for the reuptake of norepinephrine into presynaptic nerve terminals. The aim of the present study was to analyze genetic variants located within the NET gene for association with PD. The case-control sample consisted of 449 patients with PD and 279 ethnically matched controls. All cases fulfilled the ICD-10 diagnostic criteria for PD. Genotyping was performed using the Sequenom platform (Sequenom, Inc, San Diego, USA). To test for allelic and haplotypic association, the PLINK software was used, and COMBASSOC was applied to test for gene-wise association. After quality control 29 single nucleotide polymorphisms (SNPs) spanning the gene-region were successfully analyzed. Seven SNPs located within the 5' end of the gene were significantly associated with PD. Furthermore, the NET gene showed overall evidence for association with the disease (P = 0.000035). In conclusion, the present study indicates that NET could be a susceptibility gene for PD.

Sick at work--a risk factor for long-term sickness absence at a later date?

BACKGROUND: Little is known about the long-term consequences of sickness presence (ie, going to work despite ill-health), although one study suggests an association with coronary heart disease. This study examined the effect of sickness presence on future long-term sickness absence. METHODS: Information from a random sample of 11 838 members of the Danish core workforce was collected from questionnaires, containing questions about work, family and attitudes towards sickness absence. Information on prospective sickness absence spells of at least 2 weeks was derived from an official register during a follow-up period of 1.5 years. RESULTS: Sickness presence is associated with long-term sickness absence of at least 2 weeks' duration as well as with spells lasting at least 2 months. Participants who had gone to work ill more than six times in the year prior to baseline had a 74% higher risk of becoming sick-listed for more than 2 months, even when controlling for a wide range of potential confounders as well as baseline health status and previous long-term sickness absence. The association was consistent for most subgroups of employees reporting various symptoms, but either disappeared or became insignificant when analysing subgroups of employees with specific chronic diseases. CONCLUSIONS: Going to work ill repeatedly is associated with long-term sickness absence at a later date. For this reason, researchers and policy-makers should consider this phenomenon more carefully when planning future studies of sickness absence or when laying out new policies.

Dietary exposure assessment of Danish consumers to dithiocarbamate residues in food: a comparison of the deterministic and probabilistic approach.

Probabilistic and deterministic estimates of the acute and chronic exposure of the Danish populations to dithiocarbamate residues were performed. The Monte Carlo Risk Assessment programme (MCRA 4.0) was used for the probabilistic risk assessment. Food consumption data were obtained from the nationwide dietary survey conducted in 2000--02. Residue data for 5721 samples from the monitoring programme conducted in the period 1998--2003 were used for dithiocarbamates, which had been determined as carbon disulphide. Contributions from 26 commodities were included in the calculations. Using the probabilistic approach, the daily acute intakes at the 99.9% percentile for adults and children were 11.2 and 28.2 microg kg(-1) body weight day(-1), representing 5.6% and 14.1% of the ARfD for maneb, respectively. When comparing the point estimate approach with the probabilistic approach, the outcome of the point estimate calculations was generally higher or comparable with the outcome of the probabilistic approach at the 99.9 percentile (consumers only). The chronic exposures for adults and children were 0.35 and 0.76 microg kg(-1) body weight day(-1) at the 99.9 percentile, representing 0.7% and 1.5%, respectively, of the acceptable daily intake for mancozeb and maneb at 50 microg kg(-1) body weight.

Computer mouse use predicts acute pain but not prolonged or chronic pain in the neck and shoulder.

BACKGROUND: Computer use may have an adverse effect on musculoskeletal outcomes. This study assessed the risk of neck and shoulder pain associated with objectively recorded professional computer use. METHODS: A computer programme was used to collect data on mouse and keyboard usage and weekly reports of neck and shoulder pain among 2146 technical assistants. Questionnaires were also completed at baseline and at 12 months. The three outcome measures were: (1) acute pain (measured as weekly pain); (2) prolonged pain (no or minor pain in the neck and shoulder region over four consecutive weeks followed by three consecutive weeks with a high pain score); and (3) chronic pain (reported pain or discomfort lasting more than 30 days and "quite a lot of trouble" during the past 12 months). RESULTS: Risk for acute neck pain and shoulder pain increased linearly by 4% and 10%, respectively, for each quartile increase in weekly mouse usage time. Mouse and keyboard usage time did not predict the onset of prolonged or chronic pain in the neck or shoulder. Women had higher risks for neck and shoulder pain. Number of keystrokes and mouse clicks, length of the average activity period, and micro-pauses did not influence reports of acute or prolonged pain. A few psychosocial factors predicted the risk of prolonged pain. CONCLUSIONS: Most computer workers have no or minor neck and shoulder pain, few experience prolonged pain, and even fewer, chronic neck and shoulder pain. Moreover, there seems to be no relationship between computer use and prolonged and chronic neck and shoulder pain.

Determination of chlormequat in pig serum and sow milk by LC-MS/MS.

Chlormequat is a plant growth regulator widely used on cereals, and there is general concern that it may impair human fertility. A LC-MS/MS method for the analysis of chlormequat in milk and serum was developed and validated in connection with an investigation on the effect of chlormequat on pig reproduction. Validation of the method was based on recovery tests at three spiking levels, determined as double determinations and repeated at least four times. Samples were extracted with methanol-water-acetic acid, centrifuged, filtrated and determined by LC-MS/MS. The mean recoveries were in the range 80-110%, and the LOD was 0.2 ng/g for serum and 0.3 ng/g for milk. The values for repeatability and reproducibility were within 2/3 of the limits given by the Horwitz equation. Samples of pig serum (59) and sow milk (27) were analyzed using the method. Chlormequat was determined in four milk samples in the range of 0.4 ng/g to 1.2 ng/g and in all serum samples in the range of 0.2 ng/g-4.0 ng/g.

Survey of pesticide residues in table grapes: determination of processing factors, intake and risk assessment.

The differences in residue pattern between Italy and South Africa, the main exporters of table grapes to the Danish market, were investigated. The results showed no major differences with respect to the number of samples with residues, with residues being found in 54-78% of the samples. Exceedances of the European Union maximum residue limit (MRL) were found in five samples from Italy. A number of samples were rinsed to study the possible reduction of residues. For copper, iprodione, procymidone and dithiocarbamates a significant effect of rinsing was found (20-49% reduction of residues). However, no significant effect was found for organophosphorus pesticides and pyrethroids, whereas the number of samples with residues of benzilates, phenylamids and triazoles was insufficient to demonstrate any significant effects. An intake calculation showed that the average intake from Italian grapes was 3.9 microg day(-1) for pesticides and 21 microg day(-1) for copper. Correspondingly, the intakes from South African grapes were 2.6 and 5.7 microg day(-1), respectively. When the total exposure of pesticides from grapes were related to acceptable daily intake, expressed as the sum of Hazard Quotients, the exposure were approximately 0.5% for Italian samples and 1% for South African samples.

Risk factors for hand-wrist disorders in repetitive work.

OBJECTIVES: To identify the risk of hand-wrist disorders related to repetitive movements, use of hand force and wrist position in repetitive monotonous work. METHODS: Using questionnaires and physical examinations, the prevalence and incidence of hand-wrist pain and possible extensor tendonitis (wrist pain and palpation tenderness) were determined in 3123 employees in 19 industrial settings. With the use of questionnaires and video recordings of homogenous work tasks number of wrist movements, hand force requirements and wrist position were analysed as risk factors for hand-wrist disorders, controlling for potential personal and psychosocial confounders. All participants were re-examined three times during a follow-up period of three years. RESULTS: Force but not repetition and position was related to hand-wrist pain and possible tendonitis in the baseline analyses showing an exposure-response pattern. Odds ratios for the risk of hand pain was 1.7 (95% CI 1.3 to 2.2) and for possible tendonitis 1.9 (95% CI 1.1 to 3.3). There was no significant interaction between the ergonomic factors. In the follow-up analyses force remained a risk factor for hand pain (OR 1.4, 95% CI 1.1 to 1.8) and for possible tendonitis (OR 2.9, 95% CI 1.3 to 6.8). Repetition was also a risk factor for the onset of hand-wrist pain (OR 1.6, 95% CI 1.2 to 2.3). CONCLUSIONS: Increasing levels of force were associated with prevalent and incident hand-wrist pain and possible extensor tendonitis. The results for repetition were less consistent. Working with the hand in a non-neutral position could not be identified as a risk factor.