BACKGROUND: The negative impact of maternal smoking during pregnancy on offspring semen quality is well established. Less is known about the impact of paternal smoking.

METHODS: We estimated differences in semen parameters and testicle size according to paternal smoking in 772 adult sons of women enrolled in the Danish National Birth Cohort when pregnant. Parents' smoking was reported around gestational week 16, and analyses were adjusted for parents' ages at conception, maternal pre-pregnancy body mass index, maternal alcohol and caffeine intake, family occupational status, ejaculatory abstinence time, clinic of semen analysis, and season.

RESULTS: Sons of smoking fathers and non-smoking mothers had a 10% (95% confidence interval: -24%, 7%) lower semen concentration and 11% (95% confidence interval: -27%, 8%) lower sperm count than sons of non-smoking parents. Having two smoking parents was associated with 19% reduction in sperm count (95% confidence interval: -37%, 3%). Paternal smoking was not associated with volume, motility, or morphology. Adjusting for maternal smoking, paternal smoking was associated with a 26% increased risk of small testicular volume (95% confidence interval: 0.89, 1.78).

DISCUSSION: Exclusion of sons with a history of testicular cancer, chemotherapy, orchiectomy, and with only one or no testicles may have caused us to underestimate associations if these men's reproductive health including semen quality are in fact more sensitive to paternal smoking.

CONCLUSION: The study provides limited support for slightly lower sperm concentration and total sperm concentration in sons of smoking fathers, but findings are also compatible with no association.

Therapeutic exercise for knee osteoarthritis is recommended globally, based on more than 100 randomised, controlled trials documenting beneficial effects on pain and function. There are adverse effects of exercise and symptom exacerbations may occur in the first 4-6 weeks of an exercise programme, but will most often decline with time. If pain and function do not improve after a structured exercise program, other treatments must be considered. The effects of exercise decline over time, if regular exercise is not implemented in the daily life of the patient.

OBJECTIVE: Randomized controlled trials (RCTs) are considered the gold standard in clinical research due to credible causality. Their results, however, may not be generalizable to real-world populations. While glucocorticoids (GCs) remain a mainstay of rheumatoid arthritis (RA) treatment, it is unclear whether the results of GC-RCTs are generalizable to current real-world RA patients.

METHODS: MEDLINE was searched for RCTs and, as comparators, cohort studies (CSs) in RA evaluating systemic GCs. Random-effects meta-analyses were performed for descriptive baseline characteristics (including general demographics, comorbidities, and disease activity) that have been shown to be able to modify the benefit-risk-ratio of various RA therapeutics. These meta-analyses were stratified by study type (RCT and CS). Stratified estimates were subsequently compared. Further sensitivity analyses were performed stratifying by disease duration.

RESULTS: 56 RCTs (7053 participants) and 10 CSs (14,688 participants) were included. 12 characteristics were reported frequently enough to allow for comparative analysis. In 10/12 characteristics (83%), RCT estimates did not appear to differ from CS estimates. However, RCT participants were younger (-4.7 years [95% CI -7.2 to -2.1]; p < 0.001) and had higher erythrocyte sedimentation rates (11.8 mm/h [5.7 to 17.8]; p < 0.001) than CS participants. Comorbidities could not be assessed due to insufficient reporting.

CONCLUSION: Our findings suggest that evidence from GC trials in RA is of acceptable generalizability to current real-world patients - especially compared to findings from biologic agents in RA. However, RCT participants were younger than real-world patients, potentially limiting the generalizability of trial results to elderly patients.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD42019134675).

BACKGROUND: Myocardial injury after non-cardiac surgery occurs in a high number of patients, resulting in increased mortality in the post-operative period. The use of high inspiratory oxygen concentrations may cause hyperoxia, which is associated with impairment of coronary blood flow. Furthermore, the surgical stress response increases reactive oxygen species, which is involved in several perioperative complications including myocardial injury and death. Avoidance of hyperoxia and substitution of reactive oxygen species scavengers may be beneficial. Our primary objective is to examine the effect of oxygen and added antioxidants for prevention of myocardial injury assessed by area under the curve for troponin measurements during the first three post-operative days.

METHODS: The VIXIE trial (VitamIn and oXygen Interventions and cardiovascular Events) is an investigator-initiated, blinded, 2 × 2 factorial multicentre clinical trial. We include 600 patients with cardiovascular risk factors undergoing major non-cardiac surgery. Participants are randomised to an inspiratory oxygen fraction of 0.80 or 0.30 during and for 2 hours after surgery and either an intravenous bolus of vitamin C and an infusion of N-acetylcysteine or matching placebo of both. The primary outcome is the area under the curve for high-sensitive cardiac troponin release during the first three post-operative days as a marker of the extent of myocardial injury. Secondary outcomes are mortality, non-fatal myocardial infarction and non-fatal serious adverse events within 30 days.

PERSPECTIVE: The current trial will provide further evidence for clinicians on optimal administration of perioperative oxygen in surgical patients with cardiovascular risks and the clinical effects of two common antioxidants.

OBJECTIVES: The main study aim was to examine the applicability of a novel method to assess the criterion of values and preferences within the Grading of Recommendation, Assessment, Development and Evaluation evidence to decision framework. The group concept mapping (GCM) approach was applied to identify, organise and prioritise values and preferences in the example of health professionals' choice of analgesia for patients with acute trauma pain.

SETTING: Prehospital and emergency care centres in the Nordic countries of Denmark, Norway, Sweden, Finland and Iceland.

PARTICIPANTS: Acute care health professionals with qualifications to administer analgesic agents to patients in emergency and prehospital settings, including advanced ambulance assistants, rescue officers, paramedics, emergency physicians and emergency nurses, participated in an online survey in which statements were generated (n=40) and structured (n=11) and finally analysed and interpreted in a validation meeting (n=4).

RESULTS: Using GCM, ideas were generated and structured through online participation. Results were interpreted at a validation meeting. In total, 111 unique ideas were identified and organised into seven clusters: drug profile, administration, context, health professionals' preferences and logistics, safety profile, patient's medical history and acute clinical situation.

CONCLUSIONS: Based on GCM, a conceptual model was developed, and values and preferences around choice of analgesia in emergency care were revealed. Health professionals within acute care can apply the conceptual model to support their decision-making when choosing the best available treatment for pain for their patients in emergency care.