Changes in Upper Limb Capacity and Performance in the Early and Late Subacute Phase After Stroke.

BACKGROUND: The course of spontaneous biological recovery indicates that no essential improvements in upper limb (UL) capacity should be expected 3 months after stroke. Likewise, UL performance as assessed with accelerometers does not seem to increase. However, this plateau may not apply to all patients with stroke. OBJECTIVES: This study aimed to investigate the changes in UL capacity and performance from 3 to 6 months post-stroke, and the association between patients' UL capacity and actual UL performance. METHODS: This study was a secondary analysis of a prospective longitudinal cohort study. Patients with UL impairment and first or recurrent stroke were included. Their UL capacity was assessed at 3 and 6 months with the Action Research Arm Test (ARAT) and UL performance was examined with accelerometry and expressed as a use ratio. The association between ARAT and use ratio was examined with multiple regression analyses. RESULTS: Data from 67 patients were analyzed. It was shown that UL capacity as assessed with ARAT still improved from 3 to 6 months. A clinically meaningful improvement (≥ 6 points on ARAT) was found in 16 (46%) of the 35 patients whose scores allowed for such an increase. Improvements were mainly observed for patients with ARAT scores in the range of 15-51 at 3 months. Conversely, UL performance did not change. Three and 6 months after stroke respectively 69% and 64% of the variation in use ratio was explained by ARAT. CONCLUSION: While a substantial part of patients improved their UL capacity, UL performance did not change from 3 to 6 months post-stroke. Strategies to remind patients of including their affected UL may encourage the transfer from better capacity to increased performance.

Efficacy and safety of oral semaglutide in Japanese patients with type 2 diabetes: A subgroup analysis by baseline variables in the PIONEER 9 and PIONEER 10 trials.

AIMS/INTRODUCTION: To assess the impact of baseline characteristics on the efficacy and safety of oral semaglutide in Japanese patients with type 2 diabetes. MATERIALS AND METHODS: In the Peptide InnOvatioN for Early diabEtes tReatment (PIONEER) 9 and 10 trials, Japanese patients were randomized to once-daily oral semaglutide (3, 7, or 14 mg) or a comparator (placebo or once-daily subcutaneous liraglutide 0.9 mg in PIONEER 9; once-weekly subcutaneous dulaglutide 0.75 mg in PIONEER 10) for 52 weeks, with 5 weeks of follow up. An exploratory analysis grouped patients in each trial according to baseline glycated hemoglobin (HbA1c ; ≤8.0, >8.0-≤9.0, or >9.0%), body mass index (<25, ≥25-<30, or ≥30 kg/m2 ) and, for PIONEER 10 only, by background medication (sulfonylurea, glinide, thiazolidinedione, α-glucosidase inhibitor, sodium-glucose cotransporter 2 inhibitor). Efficacy (changes from baseline to week 26 in HbA1c and bodyweight) and safety were assessed. RESULTS: Seven hundred and one patients were included (PIONEER 9: N = 243; PIONEER 10: N = 458). In both trials, HbA1c reductions increased as baseline HbA1c increased; there were no other apparent patterns between the variables investigated and HbA1c or bodyweight changes. There was one statistically significant subgroup interaction between baseline HbA1c and estimated treatment differences in bodyweight change for oral semaglutide 14 mg versus placebo in PIONEER 9 (P = 0.0286). Baseline HbA1c , baseline body mass index and background medication did not appear to affect the proportions of patients reporting adverse events. CONCLUSIONS: Oral semaglutide is effective across a range of baseline subgroups of Japanese patients with type 2 diabetes, with no unexpected safety findings.

Thromboembolic and bleeding complications following primary total knee arthroplasty : a Danish nationwide cohort study.

AIMS: The aim of this study is to compare the effectiveness and safety of thromboprophylactic treatments in patients undergoing primary total knee arthroplasty (TKA). METHODS: Using nationwide medical registries, we identified patients with a primary TKA performed in Denmark between 1 January 2013 and 31 December 2018 who received thromboprophylactic treatment. We examined the 90-day risk of venous thromboembolism (VTE), major bleeding, and all-cause mortality following surgery. We used a Cox regression model to compute hazard ratios (HRs) with 95% confidence intervals (CIs) for each outcome, pairwise comparing treatment with dalteparin or dabigatran with rivaroxaban as the reference. The HRs were both computed using a multivariable and a propensity score matched analysis. RESULTS: We identified 27,736 primary TKA patients who received thromboprophylactic treatment (rivaroxaban (n = 18,846); dalteparin (n = 5,767); dabigatran (n = 1,443); tinzaparin (n = 1,372); and enoxaparin (n = 308)). In the adjusted multivariable analysis and compared with rivaroxaban, treatment with dalteparin (HR 0.68 (95% CI 0.49 to 0.92)) or dabigatran (HR 0.31 (95% CI 0.13 to 0.70)) was associated with a decreased risk of VTE. No statistically significant differences were observed for major bleeding or all-cause mortality. The propensity score matched analysis yielded similar results. CONCLUSION: Treatment with dalteparin or dabigatran was associated with a decreased 90-day risk of VTE following primary TKA surgery compared with treatment with rivaroxaban. Cite this article: Bone Joint J 2021;103-B(10):1571-1577.

Comparison of one-stage direct-to-implant with acellular dermal matrix and two-stage immediate implant-based breast reconstruction-a cohort study.

BACKGROUND: The use of acellular dermal matrix (ADM) in one-stage immediate implant-based breast reconstruction (BR) may offer advantages over the two-stage expander-to-implant technique, but literature shows conflicting results. The aim of the present study was to compare these two techniques for immediate implant-based BR regarding postoperative complications, aesthetic correction procedures and aesthetic outcome. METHODS: The study was designed as an observational cohort study with 44 participants admitted for immediate implant-based BR at Department of Plastic Surgery, Aarhus University Hospital, Denmark. 21 patients underwent BR with a one-stage direct-to-implant technique using ADM and 23 patients underwent BR with a two-stage expander-to-implant technique. Follow-up time was 2 years. RESULTS: The risk of implant loss was equal between groups; one-stage group 16% and two-stage group 17% whereas the risk of implant exchange (but not loss of BR) was 13% in the one-stage group compared to 7% in the two-stage group. The risk of at least one major complication were equal between groups; 28% and 24% but the risk of at least one minor complication was significantly higher in the two-stage group (41%) compared to the one-stage group (3%). Number of aesthetic corrections were equally frequent in the two treatment groups (one-stage group 1.8, two-stage group 1.5). Patient and investigator assessed aesthetic outcome was very high in both groups as well as the degree of symmetry between breasts. No capsular contracture Baker grade 3 or 4 was observed. CONCLUSIONS: The present study design sets limitations for drawing wide conclusions. This study did not reveal any significant differences between the two breast reconstructive techniques besides a higher risk of minor complications in the two-stage group, that did, however, not lead to a higher risk of implant loss. With equally high satisfaction with the aesthetic result and no significant difference in number of aesthetic corrections between the two groups we suggest, that the one-stage approach using ADM may be feasible and allows the patient to achieve an implant-based BR with a minimum of surgeries and outpatient visits. The study was registered in ClinicalTrials.gov (NCT04209010).

Reinforcement of the abdominal wall with acellular dermal matrix or synthetic mesh after breast reconstruction with the pedicled transverse rectus abdominis musculocutaneous flap. A prospective double-blind randomized study.

INTRODUCTION: The pedicled transverse rectus abdominis musculocutaneous flap (p-TRAM) is a well-established option for autologous breast reconstruction (BR) but donor-site morbidity is still reported. The aim of the present study was to compare donor-site morbidity after reinforcement of the abdominal wall regarding development of bulging or hernia, abdominal muscle strength, complications, and abdominal pain hypothesizing, that reinforcement with acellular dermal matrix (Strattice™) is superior to reinforcement with synthetic mesh (Prolene®). MATERIALS AND METHODS: A randomized, prospective, double-blind study was conducted with 29 patients admitted for BR with the p-TRAM flap at Department of Plastic Surgery, AUH, Denmark, 2014-2016. Allocation rate 1:1. Follow-up at 4, 12, and 24 months. RESULTS: 24 months postoperatively the computerized tomography verified bulging frequency was 35.7% in the ADM group and 6.7% in the synthetic mesh group (p = 0.11). Two patients (14.3%) in the ADM group and no patients in the synthetic mesh group developed hernia. No significant difference between baseline and 2-year measurement of abdominal muscle strength was observed. CONCLUSION: The present study did not demonstrate any statistically significant differences between treatment groups regarding risk of bulging or hernia, abdominal muscle strength, complications, pain or pain related QoL within two years of follow-up. Although the small sample size sets limitations for drawing wide conclusions the hypothesis that reinforcement with ADM is superior to synthetic mesh cannot be confirmed. Further research into methods for decreasing donor-side morbidity related to the TRAM flap or other rectus abdominis muscle-based flaps is needed.

Validation of registration of pharmacological treatment in the Danish Hip and Knee Arthroplasty Registers.

The aim of this study was to validate registration of pharmacological treatment in the Danish Hip Arthroplasty Register (DHR) and Danish Knee Arthroplasty Register (DKR). We conducted a population-based study in the Capital Region of Denmark, January 2012 to April 2016. Positive predictive value (PPV) and sensitivity were calculated with 95% confidence intervals (CI) for antithrombotic, antihemorrhagic and antibiotic treatment registered in the DHR and DKR using electronic health records as the reference standard. For the DHR, the PPV and sensitivity were 77.9% (95% CI: 77.2-78.6) and 99.6% (95% CI: 99.4-99.7) for antithrombotic treatment, 70.9% (95% CI: 70.1-71.7) and 97.4% (95% CI: 97.1-97.7) for antihemorrhagic treatment, and 82.9% (95% CI: 82.2-83.5) and 99.4% (95% CI: 99.3-99.5) for antibiotic treatment, respectively. For the DKR, the PPV and sensitivity were 80.6% (95% CI: 79.8-81.4) and 99.6% (95% CI: 99.4-99.7) for antithrombotic treatment, and 84.4% (95% CI: 83.7-85.1) and 100.0% (95% CI: 99.9-100.0) for antibiotic treatment, respectively. The PPV and sensitivity for overall pharmacological treatment registered in the DHR and DKR were generally high and acceptable for use in research.

Glycemic control and use of glucose-lowering medications in hospital-admitted type 2 diabetes patients over 80 years.

Treatment guidelines for type 2 diabetes (T2D) recommend avoidance of hypoglycemia and less stringent glycemic control in older patients. We examined the relation of glycemic control to glucose-lowering medications use in a cohort of patients aged>80 years with a diagnosis of T2D and a hospital admission in the Capital Region of Denmark in 2012-2016. We extracted data on medication use, diagnoses, and biochemistry from the hospitals' records. We identified 5,172 T2D patients with high degree of co-morbidity and where 17% had an HbA1c in the range recommended for frail, comorbid, older patients with type 2 diabetes (58-75 mmol/mol (7.5-9%)). Half of the patients (n = 2,575) had an HbA1c <48 mmol/mol (<6.5%), and a majority of these (36% of all patients) did not meet the diagnostic criteria for T2D. Of patients treated with one or more glucose-lowering medications (n = 1,758), 20% had HbA1c-values <42 mmol/mol (<6%), and 1% had critically low Hba1c values <30 mmol/mol (<4.9%), In conclusion, among these hospitalized T2D patients, few had an HbA1c within the generally recommended glycemic targets. One third of patients did not meet the diagnostic criteria for T2D, and of the patients who were treated with glucose-lowering medications, one-fifth had HbA1c-values suggesting overtreatment.

Real-world effectiveness and safety of pharmacological thromboprophylaxis in patients undergoing primary total hip and knee arthroplasty: A narrative review.

In this narrative review of the real-world effectiveness and safety of pharmacological thromboprophylaxis following primary total hip and knee arthroplasty, a total of 12 non-interventional observational studies were included. Pharmacological thromboprophylaxis included warfarin, heparins, dabigatran, rivaroxaban, apixaban, acetylsalicylic acid, and fondaparinux. The absolute risks varied across the included studies. These variations can be explained by differences in patient populations, drug exposure, follow-up time, and definition of outcomes, which makes it a challenge to compare the risk estimates. These findings emphasize the need for a large population-based real-world study to provide comparable risk estimates associated with different pharmacological thromboprophylaxis.

Content and validation of the Electronic Patient Medication module (EPM)-the administrative in-hospital drug use database in the Capital Region of Denmark.

Aims: Registries on in-hospital drug use are sparse, especially those that can be linked to nationwide registries. In this study, we present and validate the Electronic Patient Medication module (EPM)-the electronic administrative database on in-hospital drug use covering the Capital Region of Denmark. Methods: The research database (EPM-research) is an adaptation of the database underlying the electronic administrative database for in-hospital drug use (EPM-clinic). The validation study was comprised of two sub-studies. Sub-study 1: Accordance of registration between EPM-clinic and EPM-research was investigated by analyzing randomly chosen retrospective patient records. Sub-study 2: Workflows and real-life registration practices were investigated through visits to three different (two medical and one emergency) departments. An observer followed a nurse while dispensing and administering drugs. This information was compared with EPM-research. The primary endpoint for both sub-studies was accordance of generic name between registrations. Secondary endpoints were exact brand name, dose, and time of each administration. Accordance (proportions) with 95% confidence intervals (CI) using the Clopper-Pearson method were calculated. The study was approved by the Danish Data Protection Agency (BFH-2016-058-04906) and the Danish Patient Safety Authority (3-3013-1884/1/). Results: In sub-study 1 227 retrospective drug administrations were reviewed. Accordance of generic name was 100.0% (CI 98.4%-100.0%). In sub-study 2 176 drug administrations were observed of which 173 were recorded with identical generic name, resulting in 98.3% (CI 95.1%-99.6%) accordance of data. Conclusions: Our validation of the EPM-research showed very high accordance. With detailed information on in-hospital drug use, the EPM-research may be a useful tool in pharmacoepidemiological research.

The Danish model for the quick and safe implementation of infliximab and etanercept biosimilars.

PURPOSE: A rapidly increasing use of biological drugs has led to substantial costs. Shift to biosimilars enables considerable reduction of these costs without jeopardizing the treatment of patients, but most countries have extensive possibilities of untapped cost-savings. The aim of this study was to describe the Danish quick and near-complete implementation of the two first TNF inhibitor biosimilars (infliximab and etanercept). METHODS: We shed light on the considerations and experiences made during the implementation, and present key figures from the implementation. RESULTS: The infliximab biosimilar constituted 90.6% of the total amount of infliximab four months following patent expiration of the biooriginator. Similar results were seen for etanercept biosimilar. Substantial cost reductions were experienced in the way that e.g. the infliximab-shift reduced cost by two thirds. CONCLUSION: We believe that a thorough preparation and an organizational setting supporting the implementation is crucial for the successful implementation. This same implementation model will be used for future biosimilars.

Successful Treatment of Antihypertensive Overdose Using Intravenous Angiotensin II.

BACKGROUND: Despite multiple treatment options, antihypertensive overdose remains a cause of significant morbidity and mortality. Intravenous angiotensin II (AG II) is approved for use in vasodilatory shock. We describe 2 cases of refractory shock from antihypertensive overdose that were successfully treated using AG II. CASE REPORTS: A 24-year-old female presented after an overdose of multiple antihypertensive medications, including an angiotensin converting enzyme inhibitor (ACEI). She developed hypotension that was refractory to norepinephrine, epinephrine, and vasopressin, with a mean arterial pressure (MAP) of 57 mm Hg 9 h after emergency department arrival. Fifteen minutes after starting AG II at 10 ng/kg/min, her heart rate and MAP rose by 7 beats/min and 12 mm Hg, respectively. Her hemodynamic parameters continued to improve thereafter. She developed acute kidney injury, which resolved prior to discharge. The second patient, a 65-year-old male, presented after an overdose of multiple antihypertensive medications, including an ACEI. Despite norepinephrine, epinephrine, and hyperinsulinemia-euglycemia, he remained bradycardic and hypotensive, with a heart rate of 47 beats/min and MAP of 59 mm Hg. Thirty minutes after starting AG II at 10 ng/kg/min, his heart rate was 61 beats/min and MAP was 66 mm Hg. He recovered without apparent sequelae. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Antihypertensive overdose can lead to shock refractory to catecholamine and vasopressin therapy. Our experience suggests that AG II is efficacious in antihypertensive overdose and may be particularly efficacious in instances of ACEI overdose. However, further study is required to confirm the appropriate indication(s).

Hemodynamic Effects of Intravenous, High-Dose Lipid Emulsion With and Without Metoprolol Infusion in Healthy Volunteers: A Randomized Clinical Trial.

In a double-blinded, randomized, crossover trial, we investigated the hemodynamic effects of high-dose intravenous lipid emulsion (ILE) with/without metoprolol. Ten healthy volunteers each completed 4 trial days (placebo + ILE; metoprolol + placebo; metoprolol + ILE; placebo + placebo) in random order. Metoprolol was administered as an initial bolus (10 mg), followed by an infusion (50 mg) from 5 to 30 minutes. ILE was administered as a bolus at 12.5 minutes (2.5 mL/kg), followed by a 15-minute infusion (0.25 mL/kg per minute). On metoprolol + ILE days (compared with metoprolol + placebo) after 120 minutes, mean heart rates were significantly higher (difference, 5.5 beats per minute (bpm); 95% confidence interval (CI), 3.0-8.1 bpm; P < 0.001), and average relative cardiac output was higher (difference, 10 percentage points; 95% CI, 5-15 percentage points; P < 0.001). The hemodynamic effect of ILE developed gradually. ILE had no effect on plasma metoprolol or major adverse events. In conclusion, high-dose ILE has relatively marginal and delayed hemodynamic effects that may have limited clinical relevance in the short-term clinical toxicological setting.

Motor function tests for 0-2-year-old children - a systematic review.

INTRODUCTION: There is no evidence on how motor function is best evaluated in children in a low-risk setting. The method used in the Danish Preventive Child Health Examination Programme (DPCHEP) in general practise has not been validated. The objective of this review was to identify existing motor function tests for 0-2-year-old children that were validated for use in the background population and which are suitable for use in the DPCHEP. METHODS: This systematic review was conducted in accordance with the PRISMA guidelines. A systematic literature search was performed in PubMed, Embase, SwedMed, PsycInfo and CINAHL in accordance with the inclusion and exclusion criteria. RESULTS: Five motor function tests were identified. The Alberta Infant Motor Scale (AIMS) exclusively assesses motor function, the Harris Infant Neuromotor Assessment also assesses cognition and the Early Motor Questionnaire (EMQ) additionally assesses perception-action integration skills. The Ages and Stages Questionnaire (ASQ) and The Brigance Infant and Toddler Screen include further aspects of development. All test methods, except for the AIMS, are based on parent involvement. CONCLUSIONS: For implementation in the DPCHEP, five motor function tests were potentially adequate. However, the time consumption and extensive use of tools render three of the five tests unsuitable for implementation in the existing programme. The two remaining tests, the ASQ and the EMQ, are parent questionnaires. We suggest that these should be pilot tested with a view to their subsequent implementation in the DPCHEP. It may be considered to present the test elements in a more manageable and systematic way, possibly with illustrations.

Changing Infliximab Prescription Patterns in Inflammatory Bowel Disease: A Population-Based Cohort Study, 1999-2014.

Background: Long-term data on real life use of infliximab (IFX) for inflammatory bowel disease (IBD) are lacking. We studied prescription patterns during the first 16 years following marketing authorization. Methods: In a population-based cohort from the North Denmark Region, all IBD patients exposed to IFX during 1999 to 2014 were identified. Results: A total of 623 patients (210 with ulcerative colitis [UC] and 413 with Crohn's disease [CD]) were exposed to IFX. In patients with UC, age at first exposure decreased by 10 months per calendar year (P < 0.05) during the study period. In patients with CD, disease duration at time of first IFX exposure decreased by 7 months per calendar year (P < 0.001). From 2005-2009 to 2010-2014, the proportion of IFX-exposed patients with pancolitis (40% vs 24%, P = 0.04) and the proportion of patients with extensive CD (P = 0.002) decreased. The mean time to discontinuation of IFX remained stable in patients with CD during the study period (2.5-3.0 years) and increased from 0.34 years (2005-2009) to 1.11 years (2010-2015) in patients with UC (P = 0.04). Conclusion: During the first 16 years postmarketing, age at first exposure to IFX decreased in patients with UC, whereas disease duration at time of first exposure decreased in patients with CD. Also, a significant change toward less extensive disease in both UC and CD patients exposed to IFX was observed. Treatment duration in patients with UC increased during the study period, but did not reach the more constant and longer duration of treatment observed in patients with CD.

Risk of Adverse Pregnancy Outcome After Paternal Exposure to Methotrexate Within 90 Days Before Pregnancy.

OBJECTIVE: To study the association between paternal exposure to methotrexate within the 90-day period before pregnancy and congenital malformations and stillbirth in the offspring. METHODS: We conducted a nationwide register study. Our cohort consisted of all live births in Denmark between 1997 and 2011 identified from the Medical Birth Registry. Methotrexate-exposed fathers were identified from the National Prescription Registry. From the national Hospital Registry we identified paternity, live births, and stillbirths as well as discharge diagnoses on congenital malformations. RESULTS: We identified 849,676 live births with known paternity. There were 127 live births of methotrexate-exposed fathers. Of these, four (3.2%) had major malformations compared with 28,814 (3.4%) of the unexposed. The odds ratio (OR) for major congenital malformation among exposed fathers compared with unexposed was 0.93 (95% confidence interval [CI] 0.34-2.51) and when adjusted for year of birth, maternal age, educational length, household income, and parity, the adjusted OR was 1.01 (95% CI 0.37-2.74). There were no stillbirths in the methotrexate-exposed group compared with 2,541 (0.3%) in the unexposed group and no increased risk of preterm birth (adjusted OR 1.31, 95% CI 0.66-2.59) among the children from exposed fathers. CONCLUSION: We found no association between paternal exposure to methotrexate within 90 days before pregnancy and congenital malformations, stillbirths, or preterm birth. Available data suggest that prepregnancy paternal methotrexate exposure should not be of major concern. Multinational recommendations should be changed accordingly.

Delayed total breast reconstruction with brava.

Several surgical procedures exist in regard to reconstruction of the breast after mastectomy. The use of Brava a vacuum-based external soft-tissue expansion system in combination with fat transplantation is a less documented but viable option in treating patients after mastectomy. We share our experience in treating a 57-year-old patient with mastectomy, describing the complications and pitfalls we experienced when using the Brava system in combination with fat transplantation.

[Hepato-pericardial fistula caused by radiofrequency ablation of colorectal liver metastases]. / Galdefistel til perikardiet efter radiofrekvensablation af levertumor

Radiofrequency ablation (RFA) of colorectal liver metastases is a well tolerated minimally invasive procedure. Various complications can occur but most of these are self-limiting if diagnosed and treated in time. This case report describes a serious and rare complication following RFA treatment: hepato-pericardial fistula caused by several RFA procedures aiming to cure colorectal liver metastases. Complications to RFA treatment vary and can be difficult to diagnose. We recommend that RFA procedures and management of complications take place in highly specialised multidisciplinary departments.