Outcome-based Definition of the Lower Limit of Normal in Spirometry: A Study of 26,000 Young Adult Men.

Rationale The definition of the lower limit of normal (LLN) of spirometric variables is not well established. Objectives To investigate the relationship between spirometric abnormalities defined with different thresholds of the LLN and clinical outcomes, and to explore the possibility of using different LLN thresholds according to the pre-test probability of disease. Methods We studied the associations between pre-bronchodilator spirometric abnormalities (FEV1 < LLN, FVC < LLN, airflow obstruction, spirometric restriction) defined with different thresholds of the LLN (10th, 5th, 2.5th, 1st percentile) and multiple outcomes (prevalence of spirometric abnormalities, respiratory symptoms, all-cause and respiratory mortality) in 26,091 30-46 years old men who participated in a general population survey in Norway in 1988-1990 and were followed for 26 years. Analyses were performed with both local and GLI-2012 reference equations, stratified by pre-test risk (presence or absence of respiratory symptoms), and adjusted for age, BMI, smoking, and education. Results In the total population, the prevalence of airflow obstruction was 11.6% with GLI-LLN10, 11.0% with Local-LLN5, 6.1% with GLI-LLN5, 7.6% with Local-LLN2.5, and 3.5% with GLI-LLN2.5. The prevalence of spirometric restriction was 5.9% with GLI-LLN10, 5.2% with Local-LLN5, and 2.8% with GLI-LLN5. Increasingly lower thresholds of the LLN were associated with increasingly higher odds of respiratory symptoms and hazard of mortality for all spirometric abnormalities with both reference equations. Spirometric abnormalities defined with Local-LLN2.5 in asymptomatic subjects were associated with lower hazard of all-cause mortality (hazard ratio 1.50 (1.15, 1.95, 95% confidence intervals) for FEV1 < LLN) than those defined with Local-LLN5 in the general population (1.67 (1.50, 1.87) for FEV1 < LLN) and symptomatic subjects (1.67 (1.46, 1.91) for FEV1 < LLN). Overall, prevalence of spirometric abnormalities and associations with outcomes obtained with Local-LLN5 were comparable to those obtained with GLI-LLN10, and those obtained with Local-LLN2.5 to GLI-LLN5. Conclusions There is a relationship between statistically-based thresholds of the LLN of spirometric variables and clinical outcomes. Different thresholds of the LLN may be used in different risk subgroups of subjects, but the choice of the threshold needs to be evaluated together with the choice of reference equations.

Case Report: Limbic encephalitis following treatment with durvalumab for small-cell lung cancer.

Background: Durvalumab is an immune checkpoint Inhibitor (ICIs) that is used in the treatment of malignant tumors, such as lung cancer and melanoma. ICIs are associated with immune-related adverse events including autoimmune encephalitis, although both paraneoplastic phenomena and ICI treatment may lead to autoimmunity. Case presentation: We describe a 72-year old male patient with small-cell lung cancer, who during adjuvant treatment with Durvalumab developed GABABR1 and GAD65 antibodies and both diabetes and autoimmune limbic encephalitis. Because he was followed prospectively as part of a treatment study, we had access to repeated serum samples and cognitive assessments over time prior to developing encephalitis and diabetes, in addition to later assessments. A high titer of GABABR1 antibodies appeared early, while GAD65 antibodies appeared later with a lower titer in parallel with the development of diabetes. As he subsequently developed clinical signs of encephalitis, verified by EEG and brain MRI, he also had CSF GABABR1 antibodies. Durvalumab was discontinued and steroid treatment with subsequent plasmapheresis were started, resulting in reduction of both CSF and serum antibody levels. Clinical signs of encephalitis gradually improved. Conclusion: This case illustrates the importance of being aware of possible serious autoimmune adverse reactions, including neurological syndromes such as encephalitis, when treating patients with high risk of para-neoplasia with ICIs. In addition, the case shows the development of autoantibodies over time.

Reduced lung function and cause-specific mortality: A population-based study of Norwegian men followed for 26 years.

BACKGROUND AND AIM: Reduced lung function is associated with increased mortality, but it is unclear how different spirometric patterns are related to specific deaths. Aim of this study was to investigate these associations in a large general population cohort. METHODS: The study population consisted of 26,091 men aged 30-46 years from the Pneumoconiosis Survey of Western Norway conducted in 1988-1990 with follow-up on date and cause of death for 26 years. Cox proportional hazard models were used to estimate the association between baseline FEV1, FVC, obstructive (OSP) and restrictive spirometric pattern (RSP) (z-scores calculated according to GLI-2012 equations) and mortality (European 2012 shortlist classification (E-2012)), after adjustment for age, body mass index, smoking habits, and education. RESULTS: In total, 2462 (9%) subjects died. A predominant reduction of FEV1 (and OSP) were associated with respiratory non-cancer (E-8) (HR for one unit FEV1 z-score decrease 2.29 (95% CI 1.90, 2.77) and lung cancer mortality (E-2.1.8) (1.27(1.12, 1.44)). A similar reduction of FEV1 and FVC (and RSP) were associated with diabetes (E-4.1) (FEV1 2.21(1.67, 2.92), FVC 2.41(1.75, 3.32)), cerebrovascular (E-7.3) (1.52(1.21, 1.91), 1.54(1.19, 1.98)), ischemic heart disease (E-7.1) (1.22(1.10, 1.35), 1.21(1.08, 1.36)), neurological (E-6.3) (1.56(1.21, 2.01), 1.61(1.22, 2.13)), suicide (E-17.2) (1.37(1.13, 1.65), 1.29(1.04, 1.59)) and hematological cancer mortality (E-2.1.19-21) (1.29(1.05, 1.58), (1.26(1.00, 1.58)). No association was found between reduced lung function and mortality due to accidents, alcohol abuse, digestive and genitourinary cancer. CONCLUSIONS: Spirometric obstruction was mainly related to pulmonary mortality. Spirometric restriction was mainly related to extra-pulmonary mortality.

Low diffusion capacity of the lung predicts pneumothorax and chest drainage after CT-guided lung biopsy.

OBJECTIVES: Complications after CT-guided lung biopsy is a burden both for the individual patient and for the overall healthcare. Pneumothorax is the most common complication. This study determined the association between lung function tests and pneumothorax and chest drainage following CT-guided lung biopsy in consecutive patients in a large university hospital. RESULTS: We prospectively registered 875 biopsy procedures from 786 patients in one institution from January 27th 2012 to March 1st 2017 and recorded complications including pneumothorax with or without chest drainage. Lung function data from 637 patients undergoing 710 of the procedures were available. The association of lung function measures with pneumothorax with or without chest drainage was assessed using multivariable logistic regression analyses. Diffusion capacity for carbon monoxide (DLCO) below 4.70 mmol/min/kPa was associated with increased occurrence of pneumothorax and chest drainage after CT guided lung biopsy. We found no association between FEV1, RV and occurrence of pneumothorax and chest drainage. We found low DLCO to be a risk factor of pneumothorax and chest drainage after CT-guided lung biopsy. This should be taken into account in planning and performing the procedure.

Respiratory symptoms and cardiovascular causes of deaths: A population-based study with 45 years of follow-up.

This study determined the association between respiratory symptoms and death from cardiovascular (CV) diseases during 45 years in a pooled sample of four cohorts of random samples of the Norwegian population with 95,704 participants. Respiratory symptoms were assessed using a modification of the MRC questionnaire on chronic bronchitis. We analyzed the association between respiratory symptoms and specific cardiovascular deaths by using Cox regression analysis with age as the time variable, accounting for cluster-specific random effects using shared frailty for study cohort. Hazard ratios (HR) for death were adjusted for sex, highest attained education, smoking habits, occupational air pollution, and birth cohort. Overall, 12,491 (13%) of participants died from CV diseases: 4,123 (33%) acute myocardial infarction, 2,326 (18%) other ischemic heart disease, 2,246 (18%) other heart diseases, 2,553 (20%) cerebrovascular diseases, and 1,120 (9%) other vascular diseases. The adjusted HR (95% confidence interval) for CV deaths was 1.9 (1.7-2.1) in men and 1.5 (1.2-1.9) in women for "yes" to the question "Are you breathless when you walk on level ground at an ordinary pace?". The same item response showed an adjusted HR for death from acute myocardial infarction of 1.8 (1.5-2.1), other ischemic heart disease 2.2 (1.8-2.7), other heart diseases 1.5 (1.1-1.9), cerebrovascular disease 1.8 (1.5-2.3), and other circulatory diseases 1.7 (1.2-2.4). The adjusted HR for CV death was 1.3 (1.2-1.4) when answering positive to the question" Are you more breathless than people of your own age when walking uphill?". However, positive answers to questions on cough, phlegm, wheezing and attacks of breathlessness were after adjustments not associated with early CV deaths. The associations between CV deaths and breathlessness were also present in never smokers. Self-reported breathlessness was associated with CV deaths and could be an early marker of CV deaths.

Comparison of EQ-5D-3L and 5L versions following operative fixation of closed ankle fractures.

PURPOSE: To undertake the first testing and comparison of measurement properties for the EuroQol EQ-5D-3L and 5L in patients with ankle problems. METHODS: The cross-sectional postal survey of 959 patients aged ≥ 18 years, who underwent surgical treatment (ORIF) for unstable and closed ankle fractures in Eastern Norway. Both the EQ-5D-3L and 5L were included in a postal questionnaire in 2015, 3-6 years post surgery. Missing data, floor and ceiling effects, and response consistency were assessed. Tests of validity included comparisons with scores for the SF-36 and widely used ankle-specific instruments. The 5L version was assessed for test-retest reliability. RESULTS: There were 567 (59%) respondents; 501 completed both versions and 182 (61%) the 5L retest questionnaire. The 5L outperformed the 3L in tests of data quality and classification efficiency. Correlations with scores for other instruments largely met expectations, those for the 5L being slightly higher. All 5L scores had acceptable levels of reliability. For the 5L index, the smallest detectable differences for group and individual comparisons were 0.02 and 0.20, respectively. CONCLUSION: The 5L outperformed the 3L in terms of data quality, number of health states assessed and tests of validity. The 5L is recommended in research and other applications following surgery for ankle fracture but further testing including responsiveness to change is recommended at clinically relevant follow-up periods.

Comparing the use of patient-reported outcomes in clinical studies in Europe in 2008 and 2018: a literature review.

PURPOSE: Several guidelines for the use of patient-reported outcomes (PROs) in clinical studies have been published in the past decade. This review primarily aimed to compare the number and compliance with selected PRO-specific criteria for reporting of clinical studies in Europe using PROs published in 2008 and 2018. Secondarily, to describe the study designs, PRO instruments used, patient groups studied, and countries where the clinical studies were conducted. METHODS: A literature search was conducted in MEDLINE to identify eligible publications. To assess the number of publications, all abstracts were screened for eligibility by pairs of reviewers. Compliance with PRO-specific criteria and other key characteristics was assessed in a random sample of 150 eligible full-text publications from each year. Randomized controlled trials (RCTs) were assessed according to the full CONSORT-PRO checklist. RESULTS: The search identified 1692 publications in 2008 and 4290 in 2018. After screening of abstracts, 1240 from 2008 and 2869 from 2018 were clinical studies using PROs. By full-text review, the proportion of studies discussing PRO-specific limitations and implications was higher in 2018 than in 2008, but there were no differences in the other selected PRO-specific criteria. In 2018, a higher proportion of studies were longitudinal/cohort studies, included ≥ 300 patients, and used electronic administration of PRO than in 2008. The most common patient groups studied were those with cancer or diseases of the musculoskeletal system or connective tissue. CONCLUSION: The number of clinical studies from Europe using PROs was higher in 2018 than in 2008, but there was little difference in compliance with the PRO-specific criteria. The studies varied in terms of study design and PRO instruments used in both publication years.

Period and cohort effects: consequences on spirometric lung function in Norway during the 20th century.

Background and aim: Several factors can influence measured lung function over time. The aim of this study was to investigate period and cohort effects on spirometric measures in a large general population sample in Norway during the 20th century, using Global Lung Function Initiative (GLI-2012) equations as a reference. Methods: 36 466 subjects (born 1894-1969) from four cross-sectional surveys conducted between 1965 and 1999 were included, with harmonised data on smoking habits, respiratory symptoms, lung diseases, education and spirometry. Changes in forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) z-scores in healthy subjects across surveys were explored to investigate period effects. Linear mixed-effects models of FEV1 and FVC z-scores on birth cohort, with survey as random effect, were used to investigate cohort effects, both in subjects of the total population and in healthy ones. Results: Relatively higher FEV1 and FVC z-scores in healthy subjects were found in the first survey (1965-1970) compared to the more recent ones (1988-1999), suggesting period effects. FEV1 and FVC z-scores increased significantly with birth cohort from 1894 to 1935, after adjustment for covariates. A more stable trend of FEV1 and FVC z-scores with birth cohort was evidenced for subjects born more recently (1945-1969). Conclusions: An increase of lung function with year of birth was observed in Norwegian subjects during the first half of the 20th century. The impact of period effects on lung function decreased from 1965 to 1999.

Respiratory symptoms and respiratory deaths: A multi-cohort study with 45 years observation time.

This study determined the association between respiratory symptoms and death from respiratory causes over a period of 45 years. In four cohorts of random samples of Norwegian populations with 103,881 participants, 43,731 persons had died per 31 December 2016. In total, 5,949 (14%) had died from respiratory diseases; 2,442 (41%) from lung cancer, 1,717 (29%) chronic obstructive pulmonary disease (COPD), 1,348 (23%) pneumonia, 119 (2%) asthma, 147 (2%) interstitial lung disease and 176 (3%) other pulmonary diseases. Compared with persons without respiratory symptoms the multivariable adjusted hazard ratio (HR) for lung cancer deaths increased with score of breathlessness on effort and cough and phlegm, being 2.6 (95% CI 2.1-3.2) for breathlessness score 3 and 2.1 (95% CI 1.7-2.5) for cough and phlegm score 5. The HR of COPD death was 6.4 (95% CI 5.4-7.7) for breathlessness score 3 and 3.0 (2.4-3.6) for cough and phlegm score 5. Attacks of breathlessness and wheeze score 2 had a HR of 1.6 (1.4-1.9) for COPD death. The risk of pneumonia deaths increased also with higher breathlessness on effort score, but not with higher cough and phlegm score, except for score 2 with HR 1.5 (1.2-1.8). In this study with >2.4 million person-years at risk, a positive association was observed between scores of respiratory symptoms and deaths due to COPD and lung cancer. Respiratory symptoms are thus important risk factors, which should be followed thoroughly by health care practitioners for the benefit of public health.

The Oslo Ischaemia Study: cohort profile.

PURPOSE: The Oslo Ischaemia Study was designed to investigate the prevalence and predictors of silent coronary disease in Norwegian middle-aged men, specifically validating exercise electrocardiography (ECG) findings compared with angiography. The study has been important in investigating long-term predictors of cardiovascular morbidity and mortality, as well as investigating a broad spectrum of epidemiological and public health perspectives. PARTICIPANTS: In 1972-1975, 2014 healthy men, 40-59 years old, were enrolled in the study. Comprehensive clinical examination included an ECG-monitored exercise test at baseline and follow-ups. The cohort has been re-examined four times during 20 years. Linkage to health records and national health registries has ensured complete endpoint registration of morbidity until the end of 2006, and cancer and mortality until the end of 2017. FINDINGS TO DATE: The early study results provided new evidence, as many participants with a positive exercise ECG, but no chest pain ('silent ischaemia'), did not have significant coronary artery stenosis after all. Still, they were over-represented with coronary disease after years of follow-up. Furthermore, participants with the highest physical fitness had lower risk of cardiovascular disease, and the magnitude of blood pressure responses to moderate exercise was shown to influence the risk of cardiovascular disease and mortality. With time, follow-up data allowed the scope of research to expand into other fields of medicine, with the aim of investigating predictors and the importance of lifestyle and risk factors. FUTURE PLANS: Recently, the Oslo Ischaemia Study has been found worthy, as the first scientific study, to be preserved by The National Archives of Norway. All the study material will be digitised, free to use and accessible for all. In 2030, the Oslo Ischaemia Study will be linked to the Norwegian Cause of Death Registry to obtain complete follow-up to death. Thus, a broad spectrum of additional opportunities opens.

Predictors of pneumothorax and chest drainage after percutaneous CT-guided lung biopsy: A prospective study.

OBJECTIVES: We present an analysis of predictors of pneumothorax, and pneumothorax requiring chest drainage after CT-guided lung biopsy, in one of the largest Scandinavian dataset presented. METHODS: We prospectively registered 875 biopsy procedures from 786 patients in one institution from January 27, 2012, to March 1, 2017, and recorded complications including pneumothorax with or without chest drainage, and multiple variables we assumed could be associated with complications. We performed multivariable logistic regression analysis to identify predictors of pneumothorax and pneumothorax requiring chest drainage. RESULTS: Of the biopsied lesions, 65% were malignant, 29% benign, and 6% inconclusive. Pneumothorax occurred in 39% of the procedures and chest drainage was performed in 10%. In multivariable analysis, significant predictors of pneumothorax were emphysema (OR 1.92), smaller lesion size (OR 0.83, per 1 cm increase in lesion size), lateral body position during procedure (OR 2.00), longer needle time (OR 1.09, per minute), repositioning of coaxial needle with new insertion through pleura (OR 3.04), insertion through interlobar fissure (OR 5.21), and shorter distance to pleura (OR 0.79, per 1 cm increase in distance). Predictors of chest drainage were emphysema (OR 4.01), lateral body position (OR 2.61), and needle insertion through interlobar fissure (OR 4.17). CONCLUSION: Predictors of pneumothorax were emphysema, lateral body position, needle insertion through interlobar fissure, repositioning of coaxial needle with new insertion through pleura, and shorter distance to pleura. The finding of lateral body position as a predictor of pneumothorax is not earlier described. Emphysema, lateral body position, and needle insertion through interlobar fissure were also predictors of chest drainage. KEY POINTS: • Pneumothorax is a frequent complication to CT-guided lung biopsy; a smaller fraction of these complications needs chest drainage. • Predictors for pneumothorax are emphysema, smaller lesion size, lateral body position, longer needle time, repositioning of coaxial needle with new insertion through pleura, needle insertion through the interlobar fissure, and shorter distance to pleura. • Predictors for requirement for chest drainage post CT-guided lung biopsy are emphysema, lateral body position, and needle insertion through the interlobar fissure.

Health-related quality of life in hospitalized older patients with versus without prolonged use of opioid analgesics, benzodiazepines, and z-hypnotics: a cross-sectional study.

BACKGROUND: Central nervous system depressant medications (CNSDs) such as opioid analgesics and sedative-hypnotics are commonly prescribed to older patients for the treatment of chronic pain, anxiety and insomnia. Yet, while many studies reported potential harms, it remains unknown whether persistent use of these medications is beneficial for older patients' self-reported health-related quality of life (HRQoL). The present study clarified this knowledge gap through comparing HRQoL of hospitalized older patients with versus without using CNSD drugs for ≥4 weeks. Moreover, we explored the relationship between such use and HRQoL, adjusting for the effects of polypharmacy, comorbidity burden and other clinically relevant covariates. METHODS: The study was cross-sectional and included 246 older patients recruited consecutively from somatic departments of a large regional university hospital in Norway. We defined prolonged CNSD use as using opioids, benzodiazepines and/or z-hypnotics for ≥4 weeks. Patients' self-reported HRQoL were measured with scales of the EuroQol EQ-5D-3L instrument. Data analyses were mainly descriptive statistics and regression models. RESULTS: Patients with prolonged use of CNSDs reported lower scores on both EQ-5D index and EQ VAS compared with those without such use (p < 0.001). They had higher odds of having more problems performing usual activities (OR = 3.37, 95% CI: 1.40 to 8.13), pain/discomfort (OR = 2.06, 95% CI: 1.05 to 4.04), and anxiety/depression (OR = 3.77, 95% CI: 1.82 to 7.82). In multivariable regression models, there was no significant association between prolonged CNSD use and HRQoL when including pain as a predictor variable. In models not including pain, CNSD use was strongly associated with HRQoL (adjusted for sociodemographic background, polypharmacy, comorbidity, anxiety and depressive symptoms, regression coefficient - 0.19 (95% CI, - 0.31 to - 0.06). CONCLUSIONS: Older patients with prolonged CNSD use reported poorer HRQoL. They also had more pain and higher depression scores. Prolonged use of CNSDs was not independently associated with higher HRQoL.

Respiratory symptoms and mortality in four general population cohorts over 45 years.

OBJECTIVE: This study assessed the association between respiratory symptoms and mortality in four cohorts of the general population in Norway aged 15-75 years and in selected subgroups in the pooled sample. METHODS: The study comprised 158,702 persons, who were drawn randomly from the Norwegian population register. All subjects received a standardized, self-administered questionnaire on 11 respiratory symptoms between 1972 and 1998, with follow-up of death until December 31, 2017. Analyses were performed on 114,380 respondents. RESULTS: The hazard of death was closely associated with sex, age, and education. The hazard ratios (HR) for death and the 95% confidence intervals (CI) by risk factors were similar in the four cohorts. After adjustment for demographic and environmental, modifiable factors, the HR for death was 1.90 (95% CI 1.80-2.00) for breathlessness score 3, 1.28 (1.21-1.37) for cough/phlegm score 5 and 1.09 (1.05-1.14) for attack of breathlessness/wheeze score 2 compared to the referent (no symptom), respectively. The cough/phlegm score was associated with death in current smokers but not in never smokers or ex-smokers. Breathlessness score was associated with death in men and women. CONCLUSION: Among persons aged 45-75 years, respiratory symptoms were significant predictors of all cause mortality. Education and smoking habits influenced only the associations between coughing and mortality. The associations were independent of study sites.

Functional outcome 3-6 years after operative treatment of closed Weber B ankle fractures with or without syndesmotic fixation.

BACKGROUND: To compare the long-term functional outcomes of patients surgically treated for Weber B ankle fractures with or without syndesmotic fixation. METHODS: In total, 959 adult patients with previous treatment with open reduction and internal fixation (ORIF) for closed ankle fractures were eligible for inclusion in a cross-sectional postal survey 3-6 years after surgery; 645 had Weber B fractures. The survey assessed functional outcomes with three validated ankle questionnaires. RESULTS: In total 365 (57%) patients responded at a median of 4.2 years after the trauma. After adjusting for age, sex, education, smoking status, body mass index, diabetes, physical status before surgery, fracture classification, and duration of surgery, patients with a syndesmotic fixation had no different OMAS score (p = 0.98), LEFS score (p = 0.61), and SEFAS score (p = 0.98) than those without a syndesmotic fixation. Trimalleolar fracture was associated with worse functional outcomes than unimalleolar on two of the scales, the OMAS (p = 0.028) and LEFS (p = 0.046). CONCLUSIONS: In multivariable analysis, patients with a syndesmotic fixation had no worse long-term functional outcomes than those without syndesmotic fixation.

Risk factors for symptomatic venous thromboembolism following surgery for closed ankle fractures: A case-control study.

BACKGROUND: We analyzed risk factors for venous thromboembolism (VTE) within 6 months after surgery for closed ankle fractures. METHODS: This was a case-control study based on data from chart review in a cohort of patients having open reduction and internal fixation (ORIF) for closed ankle fractures in two large general hospitals 2009-2011. Cases with symptomatic VTE (pulmonary embolism or deep venous thrombosis) were identified in the cohort, and additional cases of VTE were identified by computerized search of discharge diagnoses in the same hospitals in 2004-2008 and 2012-2016. In total, we identified 60 cases with VTE and compared with 240 randomly selected controls among 998 patients without VTE in the cohort. Risk factors were assessed using logistic regression analysis. RESULTS: Among cases, 27 (45%) had pulmonary embolism, 33 (55%) deep venous thrombosis. Those with VTE were older, had higher BMI, had more often a family history of VTE, and more often had antibiotic prophylaxis during surgery than controls. In multivariable logistic regression analysis age/10 (OR 25.75, 95%CI 3.52-188.44, p=0.001), (age/10)2 (OR 0.77, 95%CI 0.65-0.93, p=0.005), BMI (1.15 per kg/m2, 95%CI 1.07-1.24, p<0.001) and Charlson comorbidity index ≥2 vs.0 (OR 0.27, 95%CI 0.08-0.92, p=0.036) and 1 vs. 0 (OR 0.27, 95%CI 0.09-0.86, p=0.026) were associated with VTE within 6 months of surgery. CONCLUSIONS: The odds of symptomatic VTE within 6 months of ORIF increased with increasing age and BMI, but were lower with increasing comorbidity.

Effectiveness of using STOPP/START criteria to identify potentially inappropriate medication in people aged ≥ 65 years with chronic kidney disease: a randomized clinical trial.

PURPOSE: Polypharmacy and inappropriate prescribing are common in elderly with chronic kidney disease (CKD). This study identified potentially inappropriate prescriptions (PIPs) and potential prescribing omissions (PPOs) using the Screening Tool of Older Persons' Prescriptions (STOPP) and the Screening Tool to Alert doctors to the Right Treatment (START) criteria in elderly with advanced CKD and determined the effect of a medication review on medication adherence and health-related quality of life (HRQoL). METHODS: The intervention consisted of a medication review using STOPP/START criteria with a recommendation to a nephrologist or similar review without a recommendation. End points were prevalence of PIP and PPO, medication adherence, and HRQoL. Group differences in outcomes were assessed using a generalized linear mixed model. The trial was registered under www.clinicaltrial.gov (ID: NCT02424786). RESULTS: We randomized 180 patients with advanced CKD (mean age 77 years, 23% female). The prevalence of PIPs and PPOs in the intervention group was 54% and 50%, respectively. The odds of PPOs were lower in the intervention than the control group (OR 0.42, 95% CI 0.19-0.92, p = 0.032), while there was no intergroup difference in the number of PIPs (OR 0.57, CI 0.27-1.20, p = 0.14). There was no difference in changes in medication adherence or HRQoL from baseline to 6 months between the groups. CONCLUSIONS: The intervention with the STOPP/START criteria identified a high prevalence of inappropriate medications in the elderly with advanced CKD and reduced the number of PPOs. However, there was no detectable impact of the intervention on medication adherence or HRQoL.

Evaluation of three patient reported outcome measures following operative fixation of closed ankle fractures.

BACKGROUND: Several patient reported outcome measures (PROMs) are available for assessing the outcomes of ankle fracture but few have been compared for recommended measurement properties. This study compares the measurement properties of the Lower Extremity Function Scale (LEFS), Olerud Molander Ankle Score (OMAS) and Self-Reported Foot and Ankle Score (SEFAS) following ankle surgery. METHODS: The retrospective cohort study included 959 patients aged 18 years and over who underwent surgical treatment (ORIF) for unstable and closed ankle fractures in SE Norway. The PROMs were included in a postal questionnaire sent to patients' homes in 2015, three years after surgery. Missing data, structural validity, internal consistency, test-retest reliability and validity were assessed. RESULTS: Confirmatory factor analysis results showed model fit for the SEFAS and a bi-dimensional LEFS with scales of easy and difficult items. The OMAS performed less satisfactorily. Cronbach's alpha and test-retest correlations ranged from 0.82 to 0.96 and 0.91 to 0.93 respectively. The smallest detectable differences for group and individual comparisons were 14.1 to 20.6 and 0.93 to 1.55; SEFAS performed best. As hypothesised, instrument scores were highly correlated and with those for the EQ-5D and SF-36 physical functioning. Mean imputation where half or more items are completed increased usable scores by 1.4-15.7% without affecting measurement properties. CONCLUSIONS: The three instruments largely performed satisfactorily in relation to important measurement properties but the LEFS had evidence for two dimensions relating to easier and more difficult aspects of function. Mean imputation where half or more items are completed increased the number of usable responses for all three instruments. The three instruments represent different approaches to measuring outcomes and their content should be considered carefully when choosing between them. The SEFAS is designed for a range of foot disorders including ankle fractures and has the best measurement properties in this population.

Finasteride treatment and male breast cancer: a register-based cohort study in four Nordic countries.

A potential link has been suggested between dispensed finasteride and increased risk of male breast cancer (MBC). Due to the rare occurrence of MBC, it remains to be established if such a relationship exists. The purpose of this study was to combine nationwide registers in four countries to assess the potential association between dispensed finasteride and MBC. A cohort of all males with dispensed finasteride in Denmark, Finland, Norway, and Sweden (1,365,088 person years) was followed up for up to 15 years for breast cancer, and compared to a cohort of males unexposed to finasteride. Individual-level register data included country, dates of dispensed finasteride, MBC diagnosis, and death. Incidence rate ratios (IRRs) were estimated using a generalized linear model with a Poisson distribution. An increased risk of MBC was found among finasteride users (IRR = 1.44, 95% confidence interval [95% CI] = 1.11-1.88) compared to nonusers. The IRR increased to 1.60 (95% CI = 1.20-2.13) when users in Norway and Sweden with short follow-up time were excluded. The highest IRR was seen among men with medium duration of dispensed finasteride, medium accumulated consumption of finasteride, and among men with first dispensed finasteride prescription 1-3 years prior to diagnosis. The analyses suggested possible ascertainment bias and did not support a clear relationship between dispensed finasteride and MBC. In conclusion, a significant association between dispensed finasteride and MBC was identified. However, due to limited data for adjustment of potential confounding and surveillance bias in the present study, further research is needed to confirm these results.

Functional outcomes following surgical-site infections after operative fixation of closed ankle fractures.

BACKGROUND: To compare the functional outcomes between patients with and without postoperative surgical-site infection (SSI) after surgical treatment in closed ankle fractures. METHODS: Retrospective cohort study with prospective follow-up. Of 1011 treated patients, 959 were eligible for inclusion in a postal survey. Functional outcomes were assessed using three self-reported questionnaires. RESULTS: In total 567 patients responded a median of 4.3 years (range 3.1-6.2 years) after surgery. In total 29/567 had an SSI. The mean Olerud and Molander Ankle Score was 19.8 points lower for patients with a deep SSI (p=0.02), the Lower Extremity Functional Scale score was 10.2 points lower (p<0.01) and the Self-Reported Foot & Ankle Questionnaire score was 5.0 points higher (p=0.10) than for those without an SSI, after adjusting for age, sex, smoking status, diabetes, physical status, fracture classification and duration of surgery. CONCLUSIONS: Patients with a deep SSI had worse long-term functional outcomes than those without an SSI.

No associations established between single nucleotide polymorphisms in human Toll-like receptor 2 and Toll-interacting protein and Staphylococcus aureus bloodstream infections.

Staphylococcus aureus bloodstream infections (SABSI) are associated with high morbidity and mortality. The Toll-like receptor 2 (TLR2) and Toll-interacting protein (TOLLIP) are important in recognition and regulation of human innate immunity response to S. aureus. Single nucleotide polymorphisms (SNPs) in the TLR2 and TOLLIP encoding genes have been associated with disease, including BSI. The aim of this study was to examine potential associations between a selection of SNPs in the genes encoding TLR2 and TOLLIP, and predisposition, severity, and outcome of SABSI. All patients ≥18 years of age with at least one S. aureus positive blood culture collected from March 2011 through February 2014 at Akershus University Hospital, Lørenskog, Norway, were considered for inclusion. Patients attending elective orthopaedic surgery (total hip and knee replacements, lumbar surgery) served as a control group. The TLR2 Arg753Gln, TLR2 Pro631His, TOLLIP rs5743942, and rs5743867 polymorphisms were analysed using TaqMan SNP Genotyping Assays. A total of 209 SABSI patients and 295 controls were included. The TLR2 Arg753Gln and TLR2 Pro631His polymorphisms were infrequent with no homozygotes and <10% heterozygotes. The included TLR2 and TOLLIP polymorphisms were not associated with susceptibility to SABSI, severity, 30-day all-cause mortality, or SABSI caused by the clonal complex 30 (CC30) genotype.