α2A Adrenoceptors Contribute to Feedback Inhibition of Capsaicin-induced Hyperalgesia

Background: Studies on receptor knockout mice have so far shown that of the three [alpha]2-adrenoceptor subtypes, the [alpha]2A adrenoceptor has a major role in mediating the powerful central analgesia induced by synthetic [alpha]2-adrenoceptor agonists. However, because a knockout of the gene for the [alpha]2A adrenoceptor has produced only little if any change in the pain sensitivity of control, nerve-injured, or inflamed animals, it has not been clear whether activation of [alpha]2A-adrenoceptors by endogenous ligands has a significant pain regulatory role.

Methods: The authors assessed spontaneous pain behavior and mechanical hypersensitivity induced by administration of capsaicin in the colon or paw of [alpha]2A-adrenoceptor knockout mice versus their wild-type controls.

Results: Enhanced pain hypersensitivity was observed in [alpha]2A-adrenoceptor knockout mice 20 min or more after administration of capsaicin, but before, hypersensitivity and spontaneous pain were of equal magnitude in [alpha]2A-adrenoceptor knockout and wild-type mice. When wild-type mice were pretreated with an [alpha]2-adrenoceptor antagonist, capsaicin-induced pain hypersensitivity increased to a level equal to that in [alpha]2A-adrenoceptor knockout mice. Capsaicin-induced hypersensitivity was suppressed in wild-type but not [alpha]2A-adrenoceptor knockout mice by a centrally acting [alpha]2-adrenoceptor agonist, whereas a peripherally acting [alpha]2-adrenoceptor agonist was without effect on hypersensitivity, although it attenuated capsaicin-induced spontaneous pain behavior in wild-type mice.     

Predictive factors of hemodynamic collapse after coronary artery bypass grafting: a case-control study

OBJECTIVE: Sudden hemodynamic collapse after coronary artery bypass graft (CABG) surgery is a complication with high morbidity and mortality. The aim of this study was to explore factors possibly predictive of this major complication. DESIGN: Retrospective case-control study. SETTING: University hospital, department of cardiothoracic surgery. PARTICIPANTS: Between 1988 and 1999, of 8,807 CABG patients, a total of 76 (0.9%) suffered hemodynamic collapse after CABG surgery unrelated to pericardial tamponade or bleeding. Preoperatively matched patients (by age, sex, New York Heart Association classification, number of diseased vessels, left ventricular ejection fraction, and diabetes) served as a control group (n = 76). INTERVENTIONS: Patients with sudden cardiovascular collapse underwent emergency reopening of the sternotomy and open cardiac massage (OCM group). Several pre-, intra-, and postoperative variables were compared, and significant parameters in match-pair analysis were further tested with regression techniques. MEASUREMENTS AND MAIN RESULTS: Of the 76 OCMs, 57 (75%) occurred during the first 5 postoperative hours. In-hospital mortality was 46% (35 of 76) versus 0% in controls; 5-year survival was 49% versus 95%. In the OCM group, cardiopulmonary bypass (CPB) time was significantly prolonged (p = 0.0024), and cardiac index (p = 0.05) and the first acid-base values after CPB were lower (pH, p = 0.0057; BE, p = 0.0014). Postoperative myocardial ischemia appeared in 33% of patients in the OCM group and in 8% of controls (p < 0.0001). OCM-group patients more frequently required postoperative inotropic (epinephrine, p = 0.0002) and mechanical support (intra-aortic balloon pump, p = 0.005). Regression analysis revealed a correlation between cardiopulmonary resuscitation risk and low cardiac index, postoperative ischemia, and low pH level. CONCLUSION: Inadequate tissue perfusion, postoperative myocardial ischemia, and increased need for inotropic and mechanical support preceded hemodynamic collapse. Interventions to improve tissue perfusion and to prevent and treat myocardial ischemia may result in a more favorable outcome.     

Clinical outcome and occurrence of uveitis in children with idiopathic tubulointerstitial nephritis

Acute idiopathic tubulointerstitial nephritis (TIN) is considered a condition with a good long-term prognosis. However, there is evidence that some patients develop permanent renal impairment. The aim of this study was to evaluate the clinical characteristics of TIN at the time of diagnosis in children and determine whether the findings upon presentation predict renal outcome. The clinical data and biopsy findings from 26 children with idiopathic TIN admitted to four Finnish university hospitals were analyzed retrospectively. Twenty-five patients (96%) manifested renal insufficiency. After the mean follow-up time of 2.75 years (SD 2.5; 0.9–13.5), 4 patients (15%) had permanent renal insufficiency and 8 patients (31%) had persistent low-molecular weight proteinuria. Uveitis was found in 12 patients (46%). Four of these patients (33%) developed chronic uveitis. Our analysis showed that none of the laboratory or biopsy findings upon presentation prognosticated renal outcome. No correlation between renal disease and uveitis could be found either. The occurrence of uveitis among TIN patients was higher than previously reported. Uveitis may develop late and without recurrence of renal dysfunction. Therefore, follow-up by a pediatrician and by an ophthalmologist is warranted in children with acute TIN for at least 12 months from diagnosis.     

Double‐lung versus heart‐lung transplantation for precapillary pulmonary arterial hypertension: a 24‐year single‐center retrospective study

Transplant type for end‐stage pulmonary vascular disease remains debatable. We compared recipient outcome after heart‐lung (HLT) versus double‐lung (DLT) transplantation. Single‐center analysis (38 HLT–30 DLT; 1991–2014) for different causes of precapillary pulmonary hypertension (PH): idiopathic (22); heritable (two); drug‐induced (nine); hepato‐portal (one); connective tissue disease (four); congenital heart disease (CHD) (24); chronic thromboembolic PH (six). HLT decreased from 91.7% [1991–1995] to 21.4% [2010–2014]. Re‐intervention for bleeding was higher after HLT; (P = 0.06) while primary graft dysfunction grades 2 and 3 occurred more after DLT; (P < 0.0001). Graft survival at 90 days, 1, 5, 10, and 15 years was 93%, 83%, 70%, 47%, and 35% for DLT vs. 82%, 74%, 61%, 48%, and 30% for HLT, respectively (log‐rank P = 0.89). Graft survival improved over time: 100%, 93%, 87%, 72%, and 72% in [2010–2014] vs. 75%, 58%, 42%, 33%, and 33% in [1991–1995], respectively; P = 0.03. No difference in chronic lung allograft dysfunction (CLAD)‐free survival was observed: 80% & 28% for DLT vs. 75% & 28% for HLT after 5 and 10 years, respectively; P = 0.49. Primary graft dysfunction in PH patients was lower after HLT compared to DLT. Nonetheless, overall graft and CLAD‐free survival were comparable and improved over time with growing experience. DLT remains our preferred procedure for all forms of precapillary PH, except in patients with complex CHD.     

Comparison of wound closure techniques in median sternotomy scars in children: subcuticular suture versus Steri-Strip™ S

Objectives: The aim of this retrospective study was to compare subcuticular sutures and Steri-Strip? S in closing median sternotomy incisions in children with regard to wound healing and scar formation.

Methods: Fifty-three children and adolescents were enrolled in this study who all underwent a median sternotomy at age 0–18?years and had their presternal cutaneous wounds closed with either a running subcuticular suture (Group 1) or Steri-Strip? S (Group 2). Their scars were assessed using the Patient and Observer Scar Assessment Scale (POSAS). Secondary outcome measures were the scar measurements and the incidence of wound problems post-surgery.

Results: A significant difference was found between both groups in median POSAS observer scale scores for the items thickness (p?=?.027), pliability (p?=?.045), surface area (p?=?.045) and the total score (p?=?.048). All in favor of the subcuticular suture group. There were no significant differences concerning the POSAS patient scale scores. Middle parts of scars of patients in Group 2 were significantly broader (p?=?.001) than scars of patients in Group 1. No significant differences concerning wound problems were found.

Conclusions: There are, according to our results, no significant differences in wound healing of median sternotomy incisions in children closed with either a subcuticular suture or Steri-Strip? S. Significant differences do exist regarding scar formation and final cosmetic results of the scars, in favor of subcuticular closure.     

Risks of thromboembolism and bleeding with thromboprophylaxis in patients with atrial fibrillation: A net clinical benefit analysis using a 'real world' nationwide cohort study

It was the aim of this study to determine the efficacy and safety of vitamin K antagonists (VKAs) and acetylsalicylic acid (ASA) in patients with non-valvular atrial fibrillation (AF), with separate analyses according to predicted thromboembolic and bleeding risk. By individual level-linkage of nationwide registries, we identified all patients discharged with non-valvular AF in Denmark (n=132,372). For every patient, the risk of stroke and bleeding was calculated by CHADS?, CHA?DS?-VASc, and HAS-BLED. During follow-up, treatment with VKA and ASA was determined time-dependently. VKA consistently lowered the risk of thromboembolism compared to ASA and no treatment; the combination of VKA+ASA did not yield any additional benefit. In patients at high thromboembolic risk, hazard ratios (95% confidence interval) for thromboembolism were: 1.81 (1.73-1.90), 1.14 (1.06-1.23), and 1.86 (1.78-1.95) for ASA, VKA+ASA, and no treatment, respectively, compared to VKA. The risk of bleeding was increased with VKA, ASA, and VKA+ASA compared to no treatment, the hazard ratios were: 1.0 (VKA; reference), 0.93 (ASA; 0.89-0.97), 1.64 (VKA+ASA; 1.55-1.74), and 0.84 (no treatment; 0.81-0.88), respectively. There was a neutral or positive net clinical benefit (ischaemic stroke vs. intracranial haemorrhage) with VKA alone in patients with a CHADS? score of ≥ 0, and CHA?DS?-VASc score of ≥ 1. This large cohort study confirms the efficacy of VKA and no effect of ASA treatment on the risk of stroke/thromboembolism. Also, the risk of bleeding was increased with both VKA and ASA treatment, but the net clinical benefit was clearly positive, in favour of VKA in patients with increased risk of stroke/thromboembolism.     

Prevalence of different parasomnias in the general population

ObjectiveTo estimate lifetime and current prevalence (defined as having experienced the specific parasomnia at least once during the last 3 months) of different parasomnias in the general population. In addition, to study the relationship between the different parasomnias and gender, depressive mood, and symptoms of sleep apnea, insomnia and restless legs, as well as estimating the prevalence of having multiple parasomnias.MethodsPopulation based cross-sectional study. One thousand randomly selected adults (51% female), 18 years and above, participated in a telephone interview in Norway.ResultsLifetime prevalence of the different parasomnias varied from about 4% to 67%. For sleep walking lifetime prevalence was 22.4% and current prevalence 1.7%. For the other parasomnias, lifetime and current prevalence were as follows: sleep talking 66.8% and 17.7%, confusional arousal 18.5% and 6.9%, sleep terror 10.4% and 2.7%, injured yourself during sleep 4.3% and 0.9%, injured somebody else during sleep 3.8% and 0.4%, sexual acts during sleep 7.1% and 2.7%, nightmare 66.2% and 19.4%, dream enactment 15.0% and 5.0%, sleep related groaning 31.3% and 13.5%, and sleep-related eating 4.5% and 2.2%. Depressive mood was associated with confusional arousal, sleep terror, sleep-related injury, and nightmare. There were few associations between the parasomnias and gender and symptoms of sleep apnea, insomnia, and restless legs, respectively. About 12% reported having five or more parasomnias.ConclusionsThis is one of few population based studies investigating the prevalence of parasomnias. Several parasomnias were highly prevalent in the general population. The data need to be interpreted with caution due to methodological issues, i.e., low response rate and single questions.     

Experiences of nursing home staff using the targeted interdisciplinary model for evaluation and treatment of neuropsychiatric symptoms (TIME) – a qualitative study

Background/Aims: Neuropsychiatric symptoms (NPS) in dementia pose great challenges for residents and staff in nursing homes. The Targeted Interdisciplinary Model for Evaluation and Treatment of Neuropsychiatric Symptoms (TIME) has recently in a randomized controlled trial demonstrated reductions in NPS. We explored the participating staff's experiences with the model and how it meets the challenges when dealing with the complexity of NPS.

Methods: Three to six months after the end of the intervention, we interviewed 32 of the caregivers, leaders, and physicians participating in the trial, in five focus groups. We used thematic content analysis.

Results: The analysis yielded two main themes: (1) a systematic reflection method enhanced learning at work; (2) the structure of the approach helped staff to cope with NPS in residents with dementia.

Conclusion: TIME shifts the way of learning for the staff from a traditional to a more innovative and reflection-based learning through a process of learning how to learn at work. The staff's experienced increased coping in their approach to complex problems. Our results emphasise the importance of a structured and biopsychosocial approach to NPS in clinical practice. Future research should explore models for integrating situated learning in daily routines in nursing homes.