Parous women perform less moderate to vigorous physical activity than their nulliparous peers: a population-based study in Denmark.

OBJECTIVES: The World Health Organization (WHO) highlights parous women as a key population for monitoring trends of physical activity (PA). We aimed to estimate the proportion of Danish women non-adhering to WHO PA guidelines in parous women compared with nulliparous women and to describe leisure-time PA intensity in each of these groups. STUDY DESIGN: Cross-sectional study. METHODS: This population-based study builds on a sample of 27,668 women aged 16-40 years from the Danish National Health Survey 2021. These data were linked with childbirth data from the Danish National Birth Registry. The primary outcome was self-reported weekly hours of moderate to vigorous leisure-time PA (MVPA) dichotomized into: (i) adhering to WHO guidelines for MVPA or (ii) not adhering to WHO guidelines for MVPA. Binomial regression analysis was used to calculate prevalence proportions (PP) and prevalence proportion ratios (PPR). RESULTS: Of the 27,668 women, a total of 20,022 were included; 9338 (46.6%) parous women and 10,684 (53.4%) nulliparous women. The PP of women non-adhering to WHO PA guidelines was 63.8% (95% CI 62.9-64.8) for parous and 51.3% (95% CI 50.4-52.3) for nulliparous women, corresponding to a PPR of 1.24 (95% CI 1.21; 1.27). CONCLUSIONS: The proportion of parous women who did not adhere to WHO PA guidelines for MVPA was 24% higher than that of nulliparous women. This highlights parous women as a subgroup of the adult population at increased risk of non-adherence to WHO PA guidelines. These findings call for future research to inform new strategies aiming to promote PA in parous women.

Effect of simulation-based team training in airway management: a systematic review.

Major complications associated with airway management are rare but often have serious consequences. Complications frequently result from failures in communication and teamwork. We performed a systematic review on the effect of simulation-based team training on patient outcomes, healthcare professionals' clinical performance and preparedness for airway management. We included studies with simulation-based team training in airway management as the educational intervention, using any comparator, outcome and design. Two authors independently selected articles and assessed risk of bias using the Medical Education Research Study Quality Instrument and Newcastle-Ottawa Scale-Education. We screened 1248 titles and evaluated 116 full-text articles. Twenty-two studies were included. The Kirkpatrick model for evaluation of training was used to organise outcomes. Four studies reported patient-centred outcomes (Kirkpatrick level 4), and three studies' outcomes related to healthcare professionals' clinical performance (Kirkpatrick level 3). The results were ambiguous and the studies had significant methodological limitations, making it difficult to draw conclusions on the effect of simulation-based team training. To describe preparedness for airway management, we used outcomes related to participants' attitudes or perceptions and outcomes related to knowledge or skills demonstrated in a test setting (Kirkpatrick level 2). Most studies reporting these outcomes were in favour of simulation-based team training, but were prone to bias. We consider the current evidence to be weak and recommend that future research should be based on randomised study designs and patient-centred outcomes.

Pain perception in patients with hidradenitis suppurativa.

BACKGROUND: Pain is a prominent symptom of hidradenitis suppurativa (HS) and has been defined as a domain in the Core Outcome Set for the disease. Quality and intensity of pain is influenced by depression and anxiety, both of which are associated with HS. OBJECTIVES: To describe HS-related pain quantitatively and qualitatively; and to investigate how disease severity, depression and anxiety correlate with self-reported pain quality. METHODS: Pain perception was investigated using the McGill Pain Questionnaire. Symptoms of depression and anxiety were examined using the Hospital Anxiety and Depression Scale. Statistical analyses investigated differences in number of words chosen (NWC) and pain-rating index rank [PRI(R)] in patients with severe disease and in patients with depression/anxiety. RESULTS: A total of 138 patients with HS were recruited in an outpatient clinic (October 2017-March 2018). Patients presented a median NWC of 11·5 and a PRI(R) of 59·0%. Most common descriptors were 'shooting' (83%), 'itchy' (79%) and 'blinding' (75%). Patients with depression or anxiety presented significantly higher PRI(R)s [depressed 65% vs. non-depressed 57% (P = 0·015); anxious 65% vs. nonanxious 57% (P = 0·004)]. Patients with involvement of three or more HS regions vs. those with fewer than three involved regions exhibited a significantly higher NWC (13 vs. 8; P = 0·048). CONCLUSIONS: HS-related pain includes nociceptive and neuropathic pain, and perception appears to be influenced by disease severity, anxiety and depression. A multimodal pain management strategy may be the most appropriate; however, more detailed studies are necessary to define recommendations on pain management. What's already known about this topic? Pain is a core outcome domain hidradenitis suppurativa. Few studies have addressed this significant clinical problem. What does this study add? This study suggests that HS pain comprises both nociceptive and neuropathic pain. Pain appears associated to depression, anxiety and severity of the disease.

The Impact of Exercise on Bone Health in Type 2 Diabetes Mellitus-a Systematic Review.

PURPOSE OF REVIEW: Type 2 diabetes mellitus (T2DM) is associated with an increased fracture risk. Weight loss in T2DM management may result in lowering of bone mass. In this systematic literature review, we aimed to investigate how exercise affects bone health in people with T2DM. Furthermore, we examined the types of exercise with the potential to prevent and treat bone fragility in people with T2DM. RECENT FINDINGS: Exercise differs in type, mechanical load, and intensity, as does the osteogenic response to exercise. Aerobic exercise improves metabolic health in people with T2DM. However, the weight-bearing component of exercise is essential to bone health. Weight loss interventions in T2DM induce a loss of bone mass that may be attenuated if accompanied by resistance or weight-bearing exercise. Combination of weight-bearing aerobic and resistance exercise seems to be preventive against excessive bone loss in people with T2DM. However, evidence is sparse and clinical trials investigating the effects of exercise on bone health in people with T2DM are warranted.

Glucose-Lowering Drugs and Fracture Risk-a Systematic Review.

PURPOSE OF REVIEW: Diabetes mellitus (DM) is associated with increased fracture risk. The aim of this systematic review was to examine the effects of different classes of glucose-lowering drugs on fracture risk in patients with type 2 DM. The heterogeneity of the included studies did not allow formal statistical analyses. RECENT FINDINGS: Sixty studies were included in the review. Metformin, dipeptidylpeptidase-IV inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose cotransporter 2-inhibitors do not appear to increase fracture risk. Results for insulin and sulphonylureas were more disparate, although there may be an increased fracture risk related to hypoglycemia and falls with these treatments. Glitazones were consistently associated with increased fracture risk in women, although the evidence was sparser in men. New glucose-lowering drugs are continuously being developed and better understanding of these is leading to changes in prescription patterns. Our findings warrant continued research on the effects of glucose-lowering drugs on fracture risk, elucidating the class-specific effects of these drugs.

Increased mortality from somatic multimorbidity in patients with schizophrenia: a Danish nationwide cohort study.

OBJECTIVE: To investigate the association of single- and multimorbidity with mortality rates in patients with schizophrenia compared to the general population. METHOD: A nationwide cohort study including residents in Denmark between 1995 and 2015. The cohort was dichotomously divided by a diagnosis of schizophrenia. Somatic diseases included infections, cancer, endocrine, neurologic, cardiovascular, respiratory, digestive, skin, musculoskeletal, and urogenital diseases. Hazard ratios (HRs) and population attributable fractions (PAFs) were calculated. RESULTS: The cohort included 30 210 patients with schizophrenia [mean age (SD) = 32.6 (11.4), males = 57.2%], and 5 402 611 from the general population [mean age (SD) = 33.0 (14.5), males = 50.4%]. All number of somatic diseases were associated with an increased mortality in schizophrenia [HR = 16.3 (95% CI = 15.4-17.3) for 1 disease to 21.0 (95% CI = 19.1-23.0) for ≥5 diseases], using the general population with no somatic disease as reference. Across all somatic diseases, patients with schizophrenia showed a HR > 2, compared to the general population, and respiratory (PAF = 9.3%), digestive (PAF = 8.2%), and cardiovascular (PAF = 7.9%) diseases showed largest contributions to death. CONCLUSIONS: Patients with schizophrenia showed higher mortality on all levels of multimorbidity, and a doubled mortality rate across all somatic diseases, compared to the general population. The findings suggest that the clusters and trajectories of symptoms associated with schizophrenia is the main driver of the excess mortality.

The association between eccentric hip abduction strength and hip and knee angular movements in recreational male runners: An explorative study.

Weak hip abductors may be related with increased hip adduction and knee abduction angular movement, which may be risk factors of lower extremity injuries. As the role of eccentric hip abduction strength (EHAS) on hip adduction angular movement and knee abduction angular movement (KABD) remains unclear, the purpose of this study was to explore the association between EHAS and hip and knee angular movement. In 100 healthy male recreational runners, EHAS was quantified using an isokinetic dynamometer, while hip and knee angular movements were collected using pressure-sensitive treadmill and Codamotion active marker system. Using multiple linear regression models (n=186 legs), no relationships between EHAS and hip and knee kinematics were found. A possible reason for the lack of relationship between EHAS and hip and knee kinematics may be owing to differences in the running kinematics. Some runners with weak EHAS may compensate the weakness by leaning toward the stance limb and thereby reduces the demand on the hip abductors with the consequence of increased knee abduction moment, which may lead to an increased knee abduction angular excursion. Possible, others mechanism as the quadriceps strength and activity in the hip and thigh muscles may also be able to explain the lack of relationship that may or may not exist. Despite the inconclusive results of this study, the findings may suggest that weak hip abductor muscles may be a relevant factor to focus on in future studies.

Risk of psychiatric disorders, self-harm behaviour and service use associated with bariatric surgery.

OBJECTIVE: To investigate psychiatric outcomes after bariatric surgery, including suicide, self-harm, psychiatric service use and substance misuse. METHOD: Retrospective study on a Danish nationwide register-based cohort of 22 451 patients followed for 1 029 736 person-years. Data were analysed utilizing single- and multi-event Cox regression with non-operated controls with obesity and mirror-image analyses with the operated patient serving as their own controls. RESULTS: We showed an increased ratio of self-harm (hazard ratio [HR] 3.23, P < 0.001; incidence rate ratio [IRR] 1.71, P < 0.001), psychiatric service use (admissions IRR 1.52, P < 0.001; emergency room visits IRR 1.70, P < 0.001), psychiatric diagnosis (organic psychiatric disorders HR 1.78, P < 0.001; substance use HR 2.06, P < 0.001; mood disorders HR 2.66, P < 0.001; neurotic, stress-related and somatoform disorders HR 2.48, P < 0.001; behavioural syndromes HR 3.15, P < 0.001; disorders of personality HR 2.68, P < 0.001; behavioural and emotional disorders HR 6.43, P < 0.001), as well as substance misuse utilizing Cox regression as well as mirror-image analyses, as compared to non-operated. We did not find an increased suicide rate (HR 1.35, P = 0.658) among operated as compared to non-operated. CONCLUSION: Our study shows that undergoing bariatric surgery is associated with increases in self-harm, psychiatric service use and occurrence of mental disorders.

A framework for the etiology of running-related injuries.

The etiology of running-related injury is important to consider as the effectiveness of a given running-related injury prevention intervention is dependent on whether etiologic factors are readily modifiable and consistent with a biologically plausible causal mechanism. Therefore, the purpose of the present article was to present an evidence-informed conceptual framework outlining the multifactorial nature of running-related injury etiology. In the framework, four mutually exclusive parts are presented: (a) Structure-specific capacity when entering a running session; (b) structure-specific cumulative load per running session; (c) reduction in the structure-specific capacity during a running session; and (d) exceeding the structure-specific capacity. The framework can then be used to inform the design of future running-related injury prevention studies, including the formation of research questions and hypotheses, as well as the monitoring of participation-related and non-participation-related exposures. In addition, future research applications should focus on addressing how changes in one or more exposures influence the risk of running-related injury. This necessitates the investigation of how different factors affect the structure-specific load and/or the load capacity, and the dose-response relationship between running participation and injury risk. Ultimately, this direction allows researchers to move beyond traditional risk factor identification to produce research findings that are not only reliably reported in terms of the observed cause-effect association, but also translatable in practice.

Handball load and shoulder injury rate: a 31-week cohort study of 679 elite youth handball players.

BACKGROUND: Knowledge of injury patterns, an essential step towards injury prevention, is lacking in youth handball. AIM: To investigate if an increase in handball load is associated with increased shoulder injury rates compared with a minor increase or decrease, and if an association is influenced by scapular control, isometric shoulder strength or glenohumeral range of motion (ROM). METHODS: 679 players (14-18 years) provided weekly reports on shoulder injury and handball load (training and competition hours) over 31 weeks using the SMS, phone and medical examination system. Handball load in a given week was categorised into (1) <20% increase or decrease (reference), (2) increase between 20% and 60% and (3) increase >60% relative to the weekly average amount of handball load the preceding 4 weeks. Assessment of shoulder isometric rotational and abduction strength, ROM and scapular control was performed at baseline and midseason. RESULTS: An increase in handball load by >60% was associated with greater shoulder injury rate (HR 1.91; 95% CI 1.00 to 3.70, p=0.05) compared with the reference group. The effect of an increase in handball load between 20% and 60% was exacerbated among players with reduced external rotational strength (HR 4.0; 95% CI 1.1 to 15.2, p=0.04) or scapular dyskinesis (HR 4.8; 95% CI 1.3 to 18.3, p=0.02). Reduced external rotational strength exacerbated the effect of an increase above 60% (HR 4.2; 95% CI 1.4 to 12.8, p=0.01). CONCLUSIONS: A large increase in weekly handball load increases the shoulder injury rate in elite youth handball players; particularly, in the presence of reduced external rotational strength or scapular dyskinesis.

Cumulative dosages of antipsychotic drugs are associated with increased mortality rate in patients with Alzheimer's dementia.

OBJECTIVE: We wished to investigate the effects of cumulative dosages of antipsychotic drug in Alzheimer's dementia, when controlling for known risk factors, including current antipsychotic exposure, on all-cause mortality. METHOD: We utilized a nationwide, population-based, retrospective cohort study design with mortality as outcome in individual patients diagnosed with Alzheimer's dementia. RESULTS: We included a total of 45 894 patients and followed them for 3 803 996 person-years in total, presenting 27 894 deaths in the study population. Cumulative antipsychotic exposure increased mortality: more than 0 Daily Defined Dosage (DDDs) but less than 90: HR 2.20, 95% CI (2.14-2.27), P < 0.001; more than or equal to 90 DDDs but less than 365: HR 1.81, 95% CI (1.74-1.89), P < 0.001; more than or equal to 365 DDDs but less than 730: HR 1.38, 95% CI (1.428-1.49), P < 0.001; and more than or equal to 730 DDDs: HR 1.06, 95% CI (0.95-1.18), P = 0.322, when controlling for proxy markers of severity, somatic and mental comorbid disorders. CONCLUSION: In this nationwide cohort study of 45 894 patients diagnosed with Alzheimer's dementia, we found that cumulative dosages of antipsychotic drugs were associated with increased mortality rates.

The effect of chlorzoxazone on acute pain after spine surgery. A randomized, blinded trial.

BACKGROUND: Chlorzoxazone is a muscle relaxant administered for musculoskeletal pain, and as an analgesic adjunct for post-operative pain. Chlorzoxazone for low back pain is currently not advised due to the lack of placebo-controlled trials. We explored the effect of chlorzoxazone on acute pain after spine surgery. METHODS: One hundred and ten patients were randomly assigned to 500 mg oral chlorzoxazone or placebo in this blinded study of patients having spine surgery under general anaesthesia. In the 4 h trial period analgesia consisted of IV patient-controlled analgesia (morphine bolus 2.5 mg). Primary outcome was pain during mobilization (visual analogue scale) 2 h after the intervention. Secondary outcomes were pain at rest, opioid consumption, nausea, vomiting, sedation and dizziness. RESULTS: For pain during mobilization 2 h after intervention, there was no significant difference between groups: 51 (21) vs. 54 (25) mm in the chlorzoxazone and placebo groups, respectively, mean difference 3 mm (95% CI -8 to 10), P = 0.59. For pain during mobilization and at rest (wAUC 1-4 h), there were no significant differences between groups. There was no significant difference in total IV morphine use 0-4 h: median 10 (7-21) vs. 13 (5-19) mg in the chlorzoxazone and placebo groups, respectively, P = 0.82. We found no significant difference in adverse effects. CONCLUSION: No analgesic effect of single-dose chlorzoxazone was demonstrated in patients with acute pain after spine surgery. Based on these findings, chlorzoxazone cannot be recommended for immediate treatment of acute pain after such procedures.

Do workplace interventions reduce disability rates?

BACKGROUND: Increasing life expectancy and decreasing fertility have led to a shift in the workforce age structure towards older age groups. Deteriorating health and reduced work capacity are among the challenges to retaining older workers in the labour force. AIMS: To examine whether workplace interventions to facilitate work among employees with health problems or reduced work capacity affect disability rates among employees aged 50 years and older. METHODS: Data from a survey of Norwegian companies (n = 713) were linked with registry data on their employees aged 50-61 years (n = 30771). By means of a difference-in-differences approach, we compared change in likelihood of receiving a full disability pension among employees in companies with and without workplace interventions. RESULTS: Employees in companies reporting to have workplace interventions in 2005 had a higher risk of receiving full disability pension during the period 2001-03 compared with employees in companies without such interventions [odds ratio (OR) 1.25, 95% confidence interval (CI) 1.07-1.45]. During the period 2005-07, there was an overall reduction in disability rates (OR 0.83, 95% CI 0.71-0.96) in both the intervention and control group. However, employees in companies reporting to have interventions in 2005 experienced an additional reduction in an employee's likelihood of receiving a full disability pension (OR 0.80, 95% CI 0.64-0.99) compared with employees in companies without interventions. CONCLUSIONS: Interventions to facilitate work among employees with health problems or reduced work capacity have reduced disability rates among employees aged 50-61. This suggests that companies' preventive interventions are an effective means to retain older workers with deteriorating health.

Use of psychotropic drugs during pregnancy and breast-feeding.

OBJECTIVE: To write clinical guidelines for the use of psychotropic drugs during pregnancy and breast-feeding for daily practice in psychiatry, obstetrics and paediatrics. METHOD: As we wanted a guideline with a high degree of consensus among health professionals treating pregnant women with a psychiatric disease, we asked the Danish Psychiatric Society, the Danish Society of Obstetrics and Gynecology, the Danish Paediatric Society and the Danish Society of Clinical Pharmacology to appoint members for the working group. A comprehensive review of the literature was hereafter conducted. RESULTS: Sertraline and citalopram are first-line treatment among selective serotonin reuptake inhibitor for depression. It is recommended to use lithium for bipolar disorders if an overall assessment finds an indication for mood-stabilizing treatment during pregnancy. Lamotrigine can be used. Valproate and carbamazepin are contraindicated. Olanzapine, risperidone, quetiapine and clozapine can be used for bipolar disorders and schizophrenia. CONCLUSION: It is important that health professionals treating fertile women with a psychiatric disease discuss whether psychotropic drugs are needed during pregnancy and how it has to be administered.

Second-generation antipsychotic effect on cognition in patients with schizophrenia--a meta-analysis of randomized clinical trials.

OBJECTIVE: To investigate the effect of second-generation antipsychotics on cognitive function in patients diagnosed with schizophrenia or schizoaffective disorder. METHOD: Multiple-treatments meta-analysis model. RESULTS: On cognitive composite score, sertindole was superior to clozapine, effect size (ES) 0.87; 95% CI: 0.12-1.63, quetiapine, ES 0.75; 95% CI: 0.00-1.49, and first-generation antipsychotics (FGAs), ES 0.89; 95% CI: 0.14-1.64. Analyses on each cognitive domain showed clozapine, ES 0.37; 95% CI: 0.00-0.74, olanzapine, ES 0.31; 95%CI: 0.02-0.59, quetiapine, ES 0.34; 95% CI: 0.03-0.64, and FGAs, ES 0.51; 95% CI: 0.18-0.83 performing poorer on verbal working memory than ziprasidone, as well as FGAs performing poorer than risperidone, ES 0.31; 95% CI: 0.04-0.58. On executive function, sertindole performed better than clozapine, ES 0.82; 95% CI: 0.06-1.58, olanzapine, ES 0.81; 95% CI: 0.07-1.55, quetiapine, ES 0.76; 95% CI: 0.02-1.51, ziprasidone, ES 0.90; 95% CI: 0.14-1.67, and FGAs, ES 0.83; 95% CI: 0.08-1.58. On processing speed, FGAs performed poorer than sertindole, ES 0.97; 95% CI: 0.02-1.91, and quetiapine, ES 0.36; 95% CI: 0.01-0.72. On long-term verbal working memory, clozapine performed poorer than olanzapine, ES 0.41; 95% CI: 0.06-0.76. On verbal fluency, FGAs performed poorer than olanzapine, ES 0.26; 95% CI: 0.01-0.50, and clozapine, ES 0.44; 95% CI: 0.06-0.81. Lastly, FGAs, ES 0.41; 95% CI: 0.04-0.78, and clozapine, ES 0.44; 95% CI: 0.05-0.83, performed poorer on visuospatial skill compared to olanzapine. CONCLUSION: The meta-analysis was able to detect some trends in the data analyzed, but did not show any drug having a uniform positive cognitive profile.

Pre-operative baroreflex sensitivity and efferent cardiac parasympathetic activity are correlated with post-operative pain.

BACKGROUND: A maladaptation of the autonomic nervous system may been seen in patients with chronic pain that includes persistent changes in the autonomic tone, increased heart rate, and reduced heart rate variability and baroreflex sensitivity. Baroreflex sensitivity and acute pain intensity have been reported to be inversely correlated. However, it is unknown whether the same correlation applies with regard to post-operative pain. In the present study, autonomic function was measured in patients scheduled for minor hand surgery and correlated with early and persistent pain after the procedure. Thus, the cause (autonomic imbalance) was present before the effect (post-operative pain). Our primary hypothesis was that a lower level of pre-operative baroreflex sensitivity is correlated with increased early post-operative pain. METHODS: There were 30 patients included and scheduled for open carpal tunnel surgery. Baroreflex sensitivity and heart rate variability were measured before surgery. Efferent cardiac parasympathetic activity was estimated by power spectral analysis of heart rate variability. Post-operative pain was recorded daily for 6 weeks (early post-operative pain) and for 1 week 1 year after surgery (persistent post-operative pain). RESULTS: Pre-operative baroreflex sensitivity correlated negatively with early (P=0.05) and persistent (P=0.04) post-operative pain. Efferent cardiac parasympathetic activity correlated negatively with early (P=0.03) but not persistent post-operative pain (P=0.12). CONCLUSIONS: The findings suggest that a low pre-operative level of baroreflex sensitivity is associated with higher post-operative pain intensity. To our knowledge, this is the first study to show the correlation between baroreflex sensitivity and post-operative pain.

The influence of physical activity during youth on structural and functional properties of the Achilles tendon.

Achilles tendinopathy is a highly prevalent sports injury. Animal studies show a growth response in tendons in response to loading in the immature phase but not after puberty maturation. The aim of this investigation was to examine the structural and material properties in long distance runners who were either physically active (HAY) or inactive (LAY) in young age. Twelve men in HAY group and eight men in LAY group participated. Structural, functional, and biochemical properties of Achilles tendon were estimated from magnetic resonance imaging, ultrasound video recordings, mechanical tests, and tendon biopsies, respectively. There was no difference between the groups with respect to tendon cross-sectional area or tendon free length. There was no difference between the groups with respect to maximal force or mechanical properties. The collagen content, enzymatic and nonenzymatic cross-link density did not differ between the groups, nor did collagen fibril density, diameter, and area. There was a correlation between age and pentosidine/collagen within the groups [(HAY: P < 0.05 and r(2) = 0.47) and (LAY: P < 0.05 and r(2) = 0.52)]. The data suggest that high or low activity during youth did not appreciably influence the mechanical, structural, or biochemical properties of the Achilles tendon in adult long distance runners.

Safety and efficacy of resistance training in germ cell cancer patients undergoing chemotherapy: a randomized controlled trial.

BACKGROUND: Bleomycin-etoposid-cisplatin (BEP) chemotherapy is curative in most patients with disseminated germ cell cancer (GCC) but also associated with toxic actions and dysfunction in non-targeted tissues. We investigated changes in muscle function during BEP and the safety and efficacy of resistance training to modulate these changes. METHODS: Thirty GCC patients were randomly assigned to resistance training (resistance training group (INT), n=15) or usual care (CON, n=15) during 9 weeks of BEP therapy. Resistance training consisted of thrice weekly sessions of four exercises, 3-4 sets/exercise of 10-15 repetitions at 12-15 repetition maximum load. The primary endpoint was muscle fibre size, assessed in muscle biopsies from musculus vastus lateralis. Secondary endpoints were fibre phenotype composition, body composition, strength, blood biochemistry and patient-reported endpoints. Healthy age-matched subjects (REF, n=19) performed the same RT-programme for comparison purposes. RESULTS: Muscle fibre size decreased by -322 µm(2) (95% confidence interval (CI): -899 to 255; P=0.473) in the CON-group and increased by +206 µm(2) (95% CI: -384 to 796; P=0.257) in the INT-group (adjusted mean difference (AMD), +625 µm(2), 95% CI: -253 to 1503, P=0.149). Mean differences in type II fibre size (AMD, +823 µm(2), P=0.09) and lean mass (AMD, +1.49 kg, P=0.07) in favour of the INT-group approached significance. The REF-group improved all muscular endpoints and had significantly superior changes compared with the INT-group (P<0.05). CONCLUSIONS: BEP was associated with significant reduction in lean mass and strength and trends toward unfavourable changes in muscle fibre size and phenotype composition. Resistance training was safe and attenuated dysfunction in selected endpoints, but BEP blunted several positive adaptations observed in healthy controls. Thus, our study does not support the general application of resistance training in this setting but larger-scaled trials are required to confirm this finding.

Post-operative analgesic effects of paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations: a topical review.

In contemporary post-operative pain management, patients are most often treated with combinations of non-opioid analgesics, to enhance pain relief and to reduce opioid requirements and opioid-related adverse effects. A diversity of combinations is currently employed in clinical practice, and no well-documented 'gold standards' exist. The aim of the present topical, narrative review is to provide an update of the evidence for post-operative analgesic efficacy with the most commonly used, systemic non-opioid drugs, paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs)/COX-2 antagonists, glucocorticoids, gabapentinoids, and combinations of these. The review is based on data from previous systematic reviews with meta-analyses, investigating effects of non-opioid analgesics on pain, opioid-requirements, and opioid-related adverse effects. Paracetamol, NSAIDs, COX-2 antagonists, and gabapentin reduced 24 h post-operative morphine requirements with 6.3 (95% confidence interval: 3.7 to 9.0) mg, 10.2 (8.7, 11.7) mg, 10.9 (9.1, 12.8) mg, and ≥ 13 mg, respectively, when administered as monotherapy. The opioid-sparing effect of glucocorticoids was less convincing, 2.33 (0.26, 4.39) mg morphine/24 h. Trials of pregabalin > 300 mg/day indicated a morphine-sparing effect of 13.4 (4, 22.8) mg morphine/24 h. Notably, though, the available evidence for additive or synergistic effects of most combination regimens was sparse or lacking. Paracetamol, NSAIDs, selective COX-2 antagonists, and gabapentin all seem to have well-documented, clinically relevant analgesic properties. The analgesic effects of glucocorticoids and pregabalin await further clarification. Combination regimens are sparsely documented and should be further investigated in future studies.

A phase IIa, randomized, double-blind, safety, immunogenicity and efficacy trial of Plasmodium falciparum vaccine antigens merozoite surface protein 1 and RTS,S formulated with AS02 adjuvant in healthy, malaria-naïve adults.

BACKGROUND: To improve the efficacy of Plasmodium falciparum malaria vaccine RTS,S/AS02, we conducted a study in 2001 in healthy, malaria-naïve adults administered RTS,S/AS02 in combination with FMP1, a recombinant merozoite surface-protein-1, C-terminal 42kD fragment. METHODS: A double-blind Phase I/IIa study randomized N = 60 subjects 1:1:1:1 to one of four groups, N = 15/group, to evaluate safety, immunogenicity, and efficacy of intra-deltoid half-doses of RTS,S/AS02 and FMP1/AS02 administered in the contralateral (RTS,S + FMP1-separate) or same (RTS,S + FMP1-same) sites, or FMP1/AS02 alone (FMP1-alone), or RTS,S/AS02 alone (RTS,S-alone) on a 0-, 1-, 3-month schedule. Subjects receiving three doses of vaccine and non-immunized controls (N = 11) were infected with homologous P. falciparum 3D7 sporozoites by Controlled Human Malaria Infection (CHMI). RESULTS: Subjects in all vaccination groups experienced mostly mild or moderate local and general adverse events that resolved within eight days. Anti-circumsporozoite antibody levels were lower when FMP1 and RTS,S were co-administered at the same site (35.0 µg/mL: 95 % CI 20.3-63), versus separate arms (57.4 µg/mL: 95 % CI 32.3-102) or RTS,S alone (62.0 µg/mL: 95 % CI: 37.8-101.8). RTS,S-specific lymphoproliferative responses and ex vivo ELISpot CSP-specific interferon-gamma (IFN-γ) responses were indistinguishable among groups receiving RTS,S/AS02. There was no difference in antibody to FMP1 among groups receiving FMP1/AS02. After CHMI, groups immunized with a RTS,S-containing regimen had âˆ¼ 30 % sterile protection against parasitemia, and equivalent delays in time-to-parasitemia. The FMP1/AS02 alone group showed no sterile immunity or delay in parasitemia. CONCLUSION: Co-administration of RTS,S and FMP1/AS02 reduced anti-RTS,S antibody, but did not affect tolerability, cellular immunity, or efficacy in a stringent CHMI model. Absence of efficacy or delay of patency in the sporozoite challenge model in the FMP1/AS02 group did not rule out efficacy of FMP1/AS02 in an endemic population. However, a Phase IIb trial of FMP1/AS02 in children in malaria-endemic Kenya did not demonstrate efficacy against natural infection. CLINICALTRIALS: gov identifier: NCT01556945.