A randomized, controlled trial of a multi-modal exercise intervention in Huntington's disease

Introduction This study aimed to evaluate the feasibility and benefit of a structured exercise intervention in people with Huntington’s Disease (HD). Methods This study was conducted at 6 sites, and participants were randomized into either exercise or control (usual care) groups, and were assessed at baseline, 13 and 26 weeks. The intervention was a 12 week, three times per week progressive exercise program, including aerobic (stationary cycling) and upper and lower body strengthening exercise with tapered 1:1 support for 20 of 36 sessions. Results 314 adults were assessed for eligibility: 248 did not meet inclusion criteria, 34 declined, and 32 were recruited and randomized. Three individuals in the intervention group were withdrawn within the first month due to concomitant medical conditions, resulting in 14 participants in intervention and 15 in control groups. There were two AEs in the intervention group, both related to previous medical conditions, and there were two SAEs, both in the control group. The intervention group had better fitness (predicted VO2 max difference: 492.3 ml min−1, 95% CI: [97.1, 887.6]), lower UHDRS mMS (difference 2.9 points, 95% [−5.42, −0.32]) and lower weight at Week 13 (difference 2.25 kg, 95% CI: [−4.47, −0.03]). Conclusion This study demonstrates that a short-term exercise intervention is safe and feasible. Individuals with HD may benefit from structured exercise, and intensity, monitoring and support may be key factors in optimizing response. Larger scale trials are now required to fully elucidate the extended clinical potential of exercise in HD

TNF deficiency causes alterations in the spatial organization of neurogenic zones and alters the number of microglia and neurons in the cerebral cortex

•TNF deficiency alters the spatial organization of neurogenic zones.•TNF deficiency decreases WNT signaling-related proteins.•TNF deficiency alters neuronal and microglial numbers.•Long-term use of non-selective TNF inhibitors impairs learning and memory.•Long-term use of the soluble TNF selective inhibitor XPro1595 does not affect neurogenesis, learning and memory. Although tumor necrosis factor (TNF) inhibitors are used to treat chronic inflammatory diseases, there is little information about how long-term inhibition of TNF affects the homeostatic functions that TNF maintains in the intact CNS. To assess whether developmental TNF deficiency causes alterations in the naïve CNS, we estimated the number of proliferating cells, microglia, and neurons in the developing neocortex of E13.5, P7 and adult TNF knock out (TNF−/−) mice and wildtype (WT) littermates. We also measured changes in gene and protein expression and monoamine levels in adult WT and TNF−/− mice. To evaluate long-term effects of TNF inhibitors, we treated healthy adult C57BL/6 mice with either saline, the selective soluble TNF inhibitor XPro1595, or the nonselective TNF inhibitor etanercept. We estimated changes in cell number and protein expression after two months of treatment. We assessed the effects of TNF deficiency on cognition by testing adult WT and TNF−/− mice and mice treated with saline, XPro1595, or etanercept with specific behavioral tasks. TNF deficiency decreased the number of proliferating cells and microglia and increased the number of neurons. At the same time, TNF deficiency decreased the expression of WNT signaling-related proteins, specifically Collagen Triple Helix Repeat Containing 1 (CTHRC1) and Frizzled receptor 6 (FZD6). In contrast to XPro1595, long-term inhibition of TNF with etanercept in adult C57BL/6 mice decreased the number of BrdU+ cells in the granule cell layer of the dentate gyrus. Etanercept, but not XPro1595, also impaired spatial learning and memory in the Barnes maze memory test. TNF deficiency impacts the organization of neurogenic zones and alters the cell composition in brain. Long-term inhibition of TNF with the nonselective TNF inhibitor etanercept, but not the soluble TNF inhibitor XPro1595, decreases neurogenesis in the adult mouse hippocampus and impairs learning and memory after two months of treatment

Use and feasibility of delayed prescribing for respiratory tract infections: A questionnaire survey

<p>Abstract</p> <p>Background</p> <p>Delayed prescribing of antibiotics for respiratory tract infections (RTIs) lowers the amount of antibiotics consumed. Several national treatment guidelines on RTIs recommend the strategy. When advocating treatment innovations, the feasibility and credibility of the innovation must be taken into account. The objective of this study was to explore GPs use and patients uptake of wait-and-see prescriptions for RTIs, and to investigate the feasibility of the strategy from GPs' and patients' perspectives.</p> <p>Methods</p> <p>Questionnaire survey among Norwegian GPs issuing and patients receiving a wait-and-see-prescription for RTIs. Patients reported symptoms, confidence and antibiotics consumption, GPs reported diagnoses, reason for issuing a wait-and-see-prescription and their opinion about the method.</p> <p>Results</p> <p>304 response pairs from consultations with 49 GPs were received. The patient response rate was 80%. The most common diagnosis for the GPs to issue a wait-and-see prescription was sinusitis (33%) and otitis (21%). 46% of the patients reported to consume the antibiotics. When adjusted for other factors, the diagnosis did not predict antibiotic consumption, but both being 16 years or more (p = 0,006) and reporting to have a fever (p = 0,012) doubled the odds of antibiotic consumption, while feeling very ill more than quadrupled the odds (p = 0,002). In 210 cases (69%), the GP found delayed prescribing a very reasonable strategy, and 270 patients (89%) would prefer to receive a wait-and-see prescription in a similar situation in the future. The GPs found delayed prescribing very reasonable most frequently in cases of sinusitis (79%, p = 0,007) and least frequently in cases of lower RTIs (49%, p = 0,002).</p> <p>Conclusion</p> <p>Most patients and GPs are satisfied with the delayed prescribing strategy. The patients' age, symptoms and malaise are more important than the diagnosis in predicting antibiotic consumption. The GP's view of the method as a reasonable approach depends on the patient's diagnosis. In our setting, delayed prescribing seems to be a feasible strategy, especially in cases of sinusitis and otitis. Educational efforts to promote delayed prescribing in similar settings should focus on these diagnoses.</p

In vitro measurement of temperature changes during implantation of cemented glenoid components

Background and purpose It is unclear whether the increase in temperature during cement curing may cause osteonecrosis, leading to loosening of the glenoid component in shoulder arthroplasty. We therefore analyzed the temperature during implantation of cemented glenoid implants

Medicines containing codeine: perspectives of medical professionals in the Republic of Ireland

Aims: The aim of the study was to examine prescribing professional's perceptions on prescribed and OTC medicines, containing codeine in the Republic of Ireland. A secondary aim was to examine perceptions on codeine dependence, screening and treatment. Methods: A cross sectional study of a nationally representative group of prescribing professionals was conducted using a questionnaire containing a number of open and closed ended items. Data were analysed using SPSS version 21 and content analysis techniques. Results: 398 medical professionals participated in the study giving a response rate of 18%. 77% of respondents agreed to routinely review patient prescribed codeine. 59% of respondents routinely asked patients about their use of OTC medicines and 50% documented use of OTC codeine in their patients' medical notes. 93% indicated concern about the potential to purchase codeine from multiple sources. 88% implied that patients did not fully understand the risks of taking OTC medicine containing codeine. Only 21% of respondents were confident in identifying codeine dependence without being informed by the patient and 11.4% agreed to having suitable screening methods in practice. 76% indicated that they would like more instruction on prescribing addictive medicines. Conclusion: Policy should examine the need for greater public health awareness on codeine use and should examine the role of OTC and internet sales in the development of dependence. Further consideration should be given to training and support for those who prescribe addictive medicines in practice

Lay beliefs of TB and TB/HIV co-infection in Addis Ababa, Ethiopia: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Knowledge about lay beliefs of etiology, transmission and treatment of TB, and lay perceptions of the relationship between TB and HIV is important for understanding patients' health seeking behavior and adherence to treatment. We conducted a study to explore lay beliefs about TB and TB/HIV co-infection in Addis Ababa, Ethiopia.</p> <p>Findings</p> <p>We conducted a qualitative study using in-depth interviews with 15 TB/HIV co-infected patients and 9 health professionals and focus group discussions with 14 co-infected patients in Addis-Ababa, Ethiopia. We found that a predominant lay belief was that TB was caused by exposure to cold. Excessive sun exposure, exposure to mud, smoking, alcohol, khat and inadequate food intake were also reported as causes for TB. Such beliefs initially led to self-treatment. The majority of patients were aware of an association between TB and HIV. Some reported that TB could transform into HIV, while others said that the body could be weakened by HIV and become more susceptible to illnesses such as TB. Some patients classified TB as either HIV-related or non-HIV-related, and weight loss was a hallmark for HIV-related TB. The majority of patients believed that people in the community knew that there was an association between TB and HIV, and some feared that this would predispose them to HIV-related stigma.</p> <p>Conclusion</p> <p>There is a need for culturally sensitive information and educational efforts to address misperceptions about TB and HIV. Health professionals should provide information about causes and treatment of TB and HIV to co-infected patients.</p

Patients’ Perceptions and Experiences of Familial Hypercholesterolemia, Cascade Genetic Screening and Treatment

Background: Familial hypercholesterolemia (FH) is a serious genetic disorder affecting approximately 1 in every 300 to 500 individuals and is characterised by excessively high low-density lipoprotein (LDL) cholesterol levels, substantially increased risk of early-onset coronary heart disease (CHD) and premature mortality. If FH is untreated, it leads to a greater than 50 % risk of CHD in men by the age of 50 and at least 30 % in women by the age of 60. FH can be diagnosed through genetic screening and effectively managed through pharmacological treatment and lifestyle changes. Purpose: Familial hypercholesterolemia (FH) is a genetic health condition that increases the risk of cardiovascular disease. Although FH can be effectively managed with appropriate pharmacological and dietary interventions, FH detection rate through genetic screening remains low. The present study explored perceptions and experiences of FH patients (N = 18) involved in a genetic cascade screening programme. Methods: Face-to-face interviews were conducted to assess patients’ knowledge and understanding of FH, explore factors linked to adherence to health-protective behaviours and examine perceptions of genetic screening. Results: Thematic analysis of interviews revealed four themes: disease knowledge, severity of FH, lifestyle behavioural change and barriers to cascade screening and treatment. Participants recognised FH as a permanent, genetic condition that increased their risk of CHD and premature mortality. Many participants dismissed the seriousness of FH and the importance of lifestyle changes because they perceived it to be effectively managed through medication. Despite positive attitudes toward screening, many participants reported that relatives were reluctant to attend screening due to their relatives’ ‘fatalistic’ outlook or low motivation. Participants believed that they had insufficient authority or control to persuade family members to attend screening and welcomed greater hospital assistance for contact with relatives. Conclusions: Findings support the adoption of direct methods of recruitment to cascade screening led by medical professionals, who were perceived as having greater authority. Other implications included the need for clinicians to provide clear information, particularly to those who are asymptomatic, related to the seriousness of FH and the necessity for adherence to medication and lifestyle changes

A summer heat wave decreases the immunocompetence of the mesograzer, Idotea baltica

Extreme events associated with global change will impose increasing stress on coastal organisms. How strong biological interactions such as the host–parasite arms-race are modulated by environmental change is largely unknown. The immune system of invertebrates, in particular phagocytosis and phenoloxidase activity response are key defence mechanisms against parasites, yet they may be sensitive to environmental perturbations. We here simulated an extreme event that mimicked the European heat wave in 2003 to investigate the effect of environmental change on the immunocompetence of the mesograzer Idotea baltica. Unlike earlier studies, our experiment aimed at simulation of the natural situation as closely as possible by using long acclimation, a slow increase in temperature and a natural community setting including the animals’ providence with natural food sources (Zostera marina and Fucus vesiculosus). Our results demonstrate that a simulated heat wave results in decreased immunocompetence of the mesograzer Idotea baltica, in particular a drop of phagocytosis by 50%. This suggests that global change has the potential to significantly affect host–parasite interactions