The AE4 transporter mediates kidney acid-base sensing.

The kidney plays a key role in the correction of systemic acid-base imbalances. Central for this regulation are the intercalated cells in the distal nephron, which secrete acid or base into the urine. How these cells sense acid-base disturbances is a long-standing question. Intercalated cells exclusively express the Na+-dependent Cl-/HCO3- exchanger AE4 (Slc4a9). Here we show that AE4-deficient mice exhibit a major dysregulation of acid-base balance. By combining molecular, imaging, biochemical and integrative approaches, we demonstrate that AE4-deficient mice are unable to sense and appropriately correct metabolic alkalosis and acidosis. Mechanistically, a lack of adaptive base secretion via the Cl-/HCO3- exchanger pendrin (Slc26a4) is the key cellular cause of this derailment. Our findings identify AE4 as an essential part of the renal sensing mechanism for changes in acid-base status.

Acquired Brain Injury Among Adolescents and Young Adults: A Nationwide Study of Labor Market Attachment.

Purpose Young patients represent a particularly vulnerable group regarding vocational prognosis after an acquired brain injury (ABI). We aimed to investigate how sequelae and rehabilitation needs are associated with vocational prognosis up to 3 years after an ABI in 15-30-year-old patients. Methods An incidence cohort of 285 patients with ABI completed a questionnaire on sequelae and rehabilitation interventions and needs 3 months after the index hospital contact. They were followed-up for up to 3 years with respect to the primary outcome "stable return to education/work (sRTW)", which was defined using a national register of public transfer payments. Data were analyzed using cumulative incidence curves and cause-specific hazard ratios. Results Young individuals reported a high frequency of mainly pain-related (52%) and cognitive sequelae (46%) at 3 months. Motor problems were less frequent (18%), but negatively associated with sRTW within 3 years (adjusted HR 0.57, 95% CI 0.39-0.84). Rehabilitation interventions were received by 28% while 21% reported unmet rehabilitation needs, and both factors were negatively associated with sRTW (adjusted HR 0.66, 95% CI 0.48-0.91 and adjusted HR 0.72, 95% CI 0.51-1.01). Conclusions Young patients frequently experienced sequelae and rehabilitation needs 3 months post ABI, which was negatively associated with long-term labor market attachment. The low rate of sRTW among patients with sequelae and unmet rehabilitation needs indicates an untapped potential for ameliorated vocational and rehabilitating initiatives targeted at young patients.

Reducing Shoulder Complaints in Employees with High Occupational Shoulder Exposures: A Cluster-Randomised Controlled Study (The Shoulder-Café Study).

PURPOSE: To evaluate if a group-based Shoulder-Café intervention could reduce shoulder complaints more effectively than an individual-based control intervention in employees with shoulder complaints and high occupational shoulder exposures. METHODS: A cluster-randomised controlled study of 109 participants from 60 companies in Central Denmark Region. Companies were randomised and allocated to either Shoulder-Café or control intervention. Participants in both interventions received a pamphlet on home-based shoulder exercises and a pamphlet with general information on reducing occupational shoulder exposures. They also had their occupational shoulder exposures assessed. Shoulder-Café participants additionally received three café-meetings with casual discussion, clinical shoulder evaluation, education about shoulder anatomy and occupational shoulder exposures, supervised exercises, workplace-oriented counselling, and an optional workplace visit. The primary outcome measure was the Oxford Shoulder Score (OSS) at 6-month follow-up. Secondary outcome measures were the OSS at 12 months, Fear-Avoidance Beliefs Questionnaire - Physical Activity at 6 and 12 months, and Patients' Global Impression of Change at 6 months. The study also included seven supplementary outcome measures. RESULTS: Both groups improved from baseline to 6 months with respect to the primary outcome (P < 0.01). No group differences were found for the primary outcome (mean difference (MD) [95% confidence interval]: 0.3 [- 1.6; 2.2]) or secondary outcomes. The supplementary outcomes "felt informed about handling shoulder complaints" and "felt informed about reducing occupational exposures" at 6 months, and "Patients' Global Impression of Change" and "overall satisfaction" at 12 months favoured the Shoulder-Café intervention. CONCLUSION: The Shoulder-Café intervention did not reduce shoulder complaints more effectively than the control intervention. TRIAL REGISTRATION: The trial was registered at Clinicaltrials.gov on 19 May 2017 (ID: NCT03159910).

Vocational/educational prognosis in adolescents and young adults with acquired brain injury: a nationwide cohort study.

OBJECTIVE: To determine prognostic factors for work ability and employment/educational status among young patients referred to outpatient neurorehabilitation clinics after an acquired brain injury. METHODS: A nationwide cohort study of 471 15-30-year-old patients who attended an interdisciplinary clinical assessment and provided questionnaire data at baseline and after one year. The outcomes were the Work Ability Score (WAS, 0-10 (best)) and employment/educational status after one year. Prognostic performance was analyzed using univariable regression and multivariable Ridge regression in a five-fold cross-validated procedure. RESULTS: Preinjury, 86% of the patients were employed, while the percentage had decreased to 55% at baseline and 52% at follow-up. The model, which included clinical measures of function, showed moderate prognostic performance with respect to WAS (R2=0.29) and employment/educational status (area under the curve (AUC)=0.77). Glasgow Outcome Scale Extended (R2=0.15, AUC=0.68) and the cognitive subscale of the Functional Independence Measure (R2=0.09, AUC=0.64), along with fatigue measured with the Multidimensional Fatigue Inventory (R2=0.15, AUC=0.60) were the single predictors with the highest predictive performance. CONCLUSION: Despite generally high scores in motor and cognitive tests, only about half of the patients were employed at baseline and this proportion remained stable. Global disability, cognitive sequelae and fatigue had the highest prognostic performance.

Inguinal hernia repair among men: development and validation of a preoperative risk score for persistent postoperative pain.

PURPOSE: Persistent postoperative pain (PPP) is a prevalent complication after inguinal hernia repair. The aim of this study was to develop and validate a preoperative risk score for PPP. METHODS: We developed the risk score based on a cohort of 2,508 Danish men, who answered a questionnaire six months after inguinal hernia repair performed 2015-2016. PPP was defined as a numerical rating scale score ≥ 2 during activity six months postoperatively. Logistic regression analyses were undertaken to determine statistically significant predictors of PPP. Univariable analysis selected potential predictors with a p value ≤ 0.20, and a subsequent multivariable model was built using backward elimination with a criterion of p value < 0.10. We created a risk score based on the ß coefficients of the multivariable model. The risk score was validated internally using Hosmer-Lemeshow goodness of fit test, calibration belt test, and receiver operating characteristic curve analyses with 95% confidence intervals based on the bootstrap analysis. External validation was performed in a cohort of 293 men recruited preoperatively. RESULTS: Predictors of PPP were age 18-49 and 50-59 (versus ≥ 60) years (p < 0.001), total load lifted > 1,000 kg/day (p = 0.001), working in a bent-over position > 1 h/day (p < 0.001), leisure-time physical activity < 2 h/week (p = 0.009), increasing body mass index (per unit) (p < 0.003), and repair of recurrent hernia (p = 0.001).The preoperative risk score predicted risks of 6-61% in the development population. The model showed good internal and external validity. CONCLUSION: The results suggest that the risk of PPP after inguinal hernia repair can be predicted using a preoperative risk score.

Attachment and symptom reporting in adolescents and young adults after a concussion.

BACKGROUND: The incidence of hospital-treated concussion is 100-300/100,000 person years. Reporting of long-lasting post-concussion symptoms (PCS) is estimated at 5-15%. Attachment insecurity is a potential vulnerability factor for physical illness and poorer disease outcomes in general. This study aimed to explore associations between attachment insecurity and PCS in young people sustaining a concussion. METHODS: This cross-sectional study was embedded in a cohort of 15-30-year-old patients (n = 3080) 3 months after sustaining a concussion. Data were obtained from a database and questionnaires. PCS were measured by the Rivermead Post-Concussion Symptoms Questionnaire and attachment dimensions (anxiety and avoidance) by the Experiences in Close Relationships-Relationship Structures Questionnaire. Multiple linear regression models were performed to investigate the association between the attachment dimensions and PCS with adjustment for demographic, injury-related and psychological factors and with additional testing for interaction between the attachment dimensions. RESULTS: In the final study sample, comprising 973 patients (31.6%), we found an interaction between the attachment dimensions. Hence, the effect of attachment anxiety on PCS was statistically insignificant at low avoidance (25th percentile) but significant at high avoidance (75th percentile, ß = 0.64 (95%CI: 0.02; 1.26)), whereas the effect of attachment avoidance was significant regardless of level of attachment anxiety (25th percentile, ß = 1.09 (95%CI: 0.18; 2.01); 75th percentile, ß = 2.71 (95%CI: 1.80; 3.61)). CONCLUSION: Attachment insecurity, especially characterised by high avoidance in combination with high anxiety, also called fearful attachment, is associated with PCS. Considering the attachment perspective can potentially improve health care for this patient group.

Predictors of disability in adolescents and young adults with acquired brain injury after the acute phase.

AIM: To develop and validate a prediction model for disability among young patients with acquired brain injury (ABI) after the acute phase. METHODS: Within a nationwide cohort of 446 15-30-year-old ABI-patients, we predicted disability in terms of Glasgow Outcome Scale - Extended (GOS-E) <7 12 months after baseline assessment in outpatient neurorehabilitation clinics. We studied 22 potential predictors covering demographic and medical factors, clinical tests, and self-reported fatigue and alcohol/drug consumption. The model was developed using multivariable logistic regression analysis and validated by 5-fold cross-validation and geographical validation. The model's performance was assessed by receiver operating characteristic curves and calibration plots. RESULTS: Baseline assessment took place a median of 12 months post-ABI. Low GOS-E (range 1-8 (best)) and Functional Independence Measure (range 18-126 (best)) along with high mental fatigue (range 4-20 (worst)) predicted disability. The model showed high validity and performance with an area under the curve of 0.82 (95% confidence interval (CI) 0.77, 0.87) in the cross-validation and 0.81 (95% CI 0.73, 0.88) in the geographical validation. CONCLUSION: We developed and validated a parsimonious model which effectively predicted disability. The model may be useful to guide decision-making in outpatient neurorehabilitation clinics treating young patients with ABI.

Investigation of boron carbide and iridium thin films, an enabling technology for future x-ray telescopes.

We present an experimental examination of iridium and boron carbide thin-film coatings for the purpose of fabricating x-ray optics. We use a combination of x-ray reflectometry and x-ray photoelectron spectroscopy to model the structure, composition, density, thickness, and micro-roughness of the thin films. We demonstrate in our analyses how the two characterization techniques are complementary, and from this we derive that an overlayer originating from atmospheric contamination with a thickness between 1.0-1.6 nm is present on the surface. The magnetron sputtered iridium films are measured to have a density of 22.4g/cm3. The boron carbide film exhibits a change in chemical composition in the top ∼2nm of the film surface when exposed to the ambient atmosphere. The chemical reaction occurring on the surface is due to an incorporation of oxygen and hydrogen present in the ambient atmosphere. Lastly, we present a correlation between the absorption edges and the emission lines exhibited by the thin films in an energy range from 50-800 eV and the impact on the reflectivity performance due to contamination in thin films.

Occupational mechanical exposures and reoperation after first-time inguinal hernia repair: a prognosis study in a male cohort.

PURPOSE: The aim of this study was to evaluate exposure-response relationships between occupational mechanical exposures and risk of reoperation after inguinal hernia repair. METHODS: Using register information, we identified all men born in Denmark 1938-1988, who had their first inguinal hernia repair 1998-2008, and who were 18-65 years old and active in the labour market at the time of surgery. The Danish Hernia Database provided information on repairs and reoperations. We used registered occupational codes and a job exposure matrix based on experts' ratings to estimate total load lifted per day, frequency of heavy lifting, and number of hours per day spent standing/walking. We also obtained register information on sickness absence. Multivariable Cox regression analysis was used. RESULTS: The cohort comprised 34,822 patients. We did not reveal exposure-response relationships between occupational mechanical exposures and the hazard ratio (HR) of reoperation. The percentage of patients with >2 weeks of sickness absence within 8 weeks after surgery increased with total load lifted per day from 15 to 53%. Longer sickness absence was associated with an increased HR of reoperation, but within strata of sickness absence, we found no increase in the HR of reoperation with increasing exposures. CONCLUSION: We did not find indications that the HR of reoperation was related to occupational mechanical exposures, even after accounting for a potential protective effect of sickness absence. Hence, the exposure-related prolonged duration of sickness absence could not be explained by exposure-related complications that led to reoperation.

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.

Time trends in surgery for non-traumatic shoulder disorders and postoperative risk of permanent work disability: a nationwide cohort study.

OBJECTIVES: Three previous randomized controlled trials found no overall difference in the effect of surgery compared with non-surgical treatment including exercise for patients with non-traumatic shoulder disorders. We assessed Danish temporal trends in the incidence of surgery for rotator cuff-related shoulder disorders, frozen shoulder, and osteoarthritis (OA) of the acromioclavicular (AC) joint, and the subsequent risk of permanent work disability. METHODS: Based on registers, we calculated annual incidence rates for the Danish population aged 18-63 years between 1996 and 2008. For a cohort of 19 264 first-time shoulder-operated patients who were in the labour market on admission, we used Cox proportional hazards models to assess risk of permanent work disability within 2 years after surgery. RESULTS: The annual incidence increased from 3.5 to 14.8 per 10 000, and 9.8% of the patients became permanently work disabled. No time trend was observed in this percentage. Formal education level was an important prognostic factor. Using 'higher or medium-level education' as a reference, the hazard ratio (HR) was 1.5 [95% confidence interval (CI) 1.3-1.8] for 'vocational education and training' and 2.0 (95% CI 1.8-2.3) for 'low education level'. For 'missing information on education', the HR was 0.7 (95% CI 0.6-0.9). CONCLUSIONS: We found a fourfold increase in surgery rates and a substantial risk of postoperative permanent work disability that remained constant over time. The risk was related to education level. These findings suggest that indications for surgery may need to be revisited and that attention should be given to supporting return to work, especially for blue-collar workers.

Task based exposure assessment in ergonomic epidemiology: a study of upper arm elevation in the jobs of machinists, car mechanics, and house painters.

AIMS: To explore the precision of task based estimates of upper arm elevation in three occupational groups, compared to direct measurements of job exposure. METHODS: Male machinists (n = 26), car mechanics (n = 23), and house painters (n = 23) were studied. Whole day recordings of upper arm elevation were obtained for four consecutive working days, and associated task information was collected in diaries. For each individual, task based estimates of job exposure were calculated by weighting task exposures from a collective database by task proportions according to the diaries. These estimates were validated against directly measured job exposures using linear regression. The performance of the task based approach was expressed through the gain in precision of occupational group mean exposures that could be obtained by adding subjects with task based estimates to a group of subjects with measured job exposures in a "validation" design. RESULTS: In all three occupations, tasks differed in mean exposure, and task proportions varied between individuals. Task based estimation proved inefficient, with squared correlation coefficients only occasionally exceeding 0.2 for the relation between task based and measured job exposures. Consequently, it was not possible to substantially improve the precision of an estimated group mean by including subjects whose job exposures were based on task information. CONCLUSIONS: Task based estimates of mechanical job exposure can be very imprecise, and only marginally better than estimates based on occupation. It is recommended that investigators in ergonomic epidemiology consider the prospects of task based exposure assessment carefully before placing resources at obtaining task information. Strategies disregarding tasks may be preferable in many cases.

Understanding work related musculoskeletal pain: does repetitive work cause stress symptoms?

BACKGROUND: Pain in the neck and upper extremity is reported with high frequency in repetitive work. Mechanical overload of soft tissues seems a plausible mechanism, but psychological factors have received considerable attention during the past decade. If psychological factors are important for development of regional pain in repetitive work, stress symptoms would likely be on the causal path. AIMS: To examine whether objective measures of repetitive monotonous work are related to occurrence and development of stress symptoms. METHODS: In 1994-95, 2033 unskilled workers with continuous repetitive work and 813 workers with varied work were enrolled. Measures of repetitiveness and force requirements were quantified using video observations to obtain individual exposure estimates. Stress symptoms were recorded at baseline and after approximately one, two, and three years by the Setterlind Stress Profile Inventory. RESULTS: Repetitive work, task cycle time, and quantified measures of repetitive upper extremity movements including force requirements were not related to occurrence of stress symptoms at baseline or development of stress symptoms during three years of follow up. CONCLUSIONS: The findings do not indicate that repetitive work is associated with stress symptoms, but small effects cannot be ruled out. Thus the results question the importance of mental stress mechanisms in the causation of regional pain related to repetitive work. However, the findings should be interpreted with caution because the stress inventory has not been validated against a gold standard.

Work related shoulder disorders: quantitative exposure-response relations with reference to arm posture.

AIMS: To determine quantitative exposure-response relations between work with highly elevated arms and supraspinatus tendinitis, shoulder pain with disability, and shoulder pain without disability. METHODS: A cross sectional study was conducted in a historical cohort of 1886 males from three occupational groups. Exposure measurements were performed for four consecutive working days in a random sample of 72 currently employed subjects. Individual work histories were obtained by questionnaire and register data. Health status was ascertained by physical examination blinded towards exposure and symptoms. Data were analysed by generalised estimating equation and multiple logistic regression with adjustment for potential confounders. RESULTS: For current upper arm elevation above 90 degrees, a duration increment of 1% of the daily working hours was associated with odds ratios of 1.23 (95% CI 1.10 to 1.39) for supraspinatus tendinitis, 1.16 (95% CI 1.08 to 1.24) for shoulder pain with disability, and 1.08 (95% CI 1.04 to 1.13) for shoulder pain without disability. The outcomes were not related to duration of employment in one of the three trades. CONCLUSIONS: Quantitative exposure-response relations were established between current work with highly elevated arms and clinically verified shoulder disorders. Substantial long term cumulative effects were not shown. A potential for primary prevention was revealed.

Prognosis of shoulder tendonitis in repetitive work: a follow up study in a cohort of Danish industrial and service workers.

BACKGROUND: The physical and psychosocial work environment is expected to modify recovery from shoulder disorders, but knowledge is limited. METHODS: In a follow up study of musculoskeletal disorders in industrial and service workers, 113 employees were identified with a history of shoulder pain combined with clinical signs of shoulder tendonitis. The workers had yearly re-examinations up to three times. Quantitative estimates of duration, repetitiveness, and forcefulness of current tasks were obtained from video recordings. Perception of job demands, decision latitude, and social support was recorded by a job content questionnaire. Recovery of shoulder tendonitis was analysed by Kaplan-Meier survival technique and by logistic regression on exposure variables and individual characteristics in models, allowing for time varying exposures. RESULTS: Some 50% of workers recovered within 10 months (95% CI 6 to 14 months). Higher age was strongly related to slow recovery, while physical job exposures were not. Perception of demands, control, and social support at the time when the shoulder disorder was diagnosed, were associated with delayed recovery, but these psychosocial factors did not predict slow recovery in incident cases identified during follow up. CONCLUSION: The median duration of shoulder tendonitis in a cross sectional sample of industrial and service workers was in the order of 10 months. This estimate is most likely biased towards too high a value. Recovery was strongly reduced in higher age. Physical workplace exposures and perceived psychosocial job characteristics during the period preceding diagnosis seem not to be important prognostic factors.

Medical mistakes: a workshop on personal perspectives.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded the Kenneth B. Schwartz Center at MGH. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to caregivers, and sustenance to the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. Medical errors are difficult to discuss. Significant medical errors occur in approximately 3% of hospitalizations. Two-thirds are preventable. Despite an entrenched belief that doctors should be infallible, errors are inevitable. Dr. Wendy Levinson of the University of Chicago facilitated a discussion of the impact medical errors have on staff. Staff broke into small groups to share their personal experience and then discussed common themes: the sense of shame and guilt, the punitive culture, guidelines for disclosure to patients and colleagues, and changes in medical practice that can prevent future mistakes. Auditing and improving systems has led to considerable improvements in the field of aviation safety. However, in medicine people are more important than the process. While we should never cease to aim for the very best in delivered care, we must acknowledge how prone we all are to mistakes and that we can learn from and prevent errors. Openly sharing experiences in a confidential setting, such as the Schwartz Rounds, helps defuse feelings of guilt and challenges the culture of shame and isolation that often surrounds medical errors. The Oncologist 2001;6:92-99

[Regional variations in the incidence of manic-depressive psychoses in the Danish psychiatric hospital system 1977-1993]. / Regionale variationer i incidensen af maniodepressiv psykose i det danske psykiatriske hospitalsvaesen 1977-1993.

The aim of the present study was to investigate geographical variations in first ever admission rates for manic-depressive psychosis during the period 1977 to 1993 at a county level. The analyses were based on data obtained from the national Danish Psychiatric Case Register comprising inpatient contacts to Danish psychiatric hospitals and psychiatric units in general hospitals. The results showed that the national first ever admission rates for manic-depressive psychosis in the age-group 15-74 years declined by 44% from 25.3 per 100,000 in 1977-1979 to 14.2 per 100,000 in 1991-1993. For the older age-group the rates were slightly increasing. Comparison of the individual counties revealed significantly geographical variations with respect to incidence level and temporal trends over the years 1977-1993. The results may reflect local differences in the provision of outpatient services and primary care facilities. However, there is also the possibility that some patients might never be treated.