Non-invasive brain stimulation techniques for chronic pain

Copyright © 2014 The Cochrane Collaboration.Various devices are available that can electrically stimulate the brain without the need for surgery or any invasive treatment in order to manage chronic pain. There are four main treatment types: repetitive transcranial magnetic stimulation (rTMS) in which the brain is stimulated by a coil applied to the scalp, cranial electrotherapy stimulation (CES) in which electrodes are clipped to the ears or applied to the scalp, transcranial direct current stimulation (tDCS) and reduced impedance non-invasive cortical electrostimulation (RINCE) in which electrodes are applied to the scalp. These have been used to try to reduce pain by aiming to alter the activity of the brain, but the efficacy of these treatments is uncertain. This review update included 56 studies: 30 of rTMS, 11 of CES, 14 of tDCS and one of RINCE. We judged only three studies as having a low risk of bias. Low or very low-quality evidence suggests that low-frequency rTMS and rTMS applied to pre-frontal areas of the brain are not effective but that a single dose of high-frequency stimulation of the motor cortex area of the brain provides short-term pain relief. This effect appears to be small and may be exaggerated by a number of sources of bias. Studies that gave a course of multiple treatments of rTMS produced conflicting results with no overall effect seen when we pooled the results of these studies. Most studies of rTMS are small and there is substantial variation between studies in terms of the treatment methods used. Low-quality evidence does not suggest that CES or tDCS are effective treatments for chronic pain. A single small study of RINCE provided very low-quality evidence of a short-term effect on pain. For all forms of stimulation the evidence is not conclusive and uncertainty remains. The reporting of side effects varied across the studies. Of the studies that clearly reported side effects, short-lived and minor side effects such as headache, nausea and skin irritation were usually reported both after real and sham stimulation. There were two reports of seizure following real rTMS. While the broad conclusions for rTMS and CES have not changed substantially, the addition of this new evidence and the application of the GRADE system has modified some of our interpretation. Previous readers should re-read this update. More studies of rigorous design and adequate size are required to evaluate accurately all forms of non-invasive brain stimulation for the treatment of chronic pain

Non-invasive brain stimulation techniques for chronic pain

Background This is an updated version of the original Cochrane Review published in 2010, Issue 9, and last updated in 2014, Issue 4. Non-invasive brain stimulation techniques aim to induce an electrical stimulation of the brain in an attempt to reduce chronic pain by directly altering brain activity. They include repetitive transcranial magnetic stimulation (rTMS), cranial electrotherapy stimulation (CES), transcranial direct current stimulation (tDCS), transcranial random noise stimulation (tRNS) and reduced impedance non-invasive cortical electrostimulation (RINCE). Objectives To evaluate the efficacy of non-invasive cortical stimulation techniques in the treatment of chronic pain. Search methods For this update we searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, LILACS and clinical trials registers from July 2013 to October 2017. Selection criteria Randomised and quasi-randomised studies of rTMS, CES, tDCS, RINCE and tRNS if they employed a sham stimulation control group, recruited patients over the age of 18 years with pain of three months' duration or more, and measured pain as an outcome. Outcomes of interest were pain intensity measured using visual analogue scales or numerical rating scales, disability, quality of life and adverse events. Data collection and analysis Two review authors independently extracted and verified data. Where possible we entered data into meta-analyses, excluding studies judged as high risk of bias. We used the GRADE system to assess the quality of evidence for core comparisons, and created three 'Summary of findings' tables. Main results We included an additional 38 trials (involving 1225 randomised participants) in this update, making a total of 94 trials in the review (involving 2983 randomised participants). This update included a total of 42 rTMS studies, 11 CES, 36 tDCS, two RINCE and two tRNS. One study evaluated both rTMS and tDCS. We judged only four studies as low risk of bias across all key criteria. Using the GRADE criteria we judged the quality of evidence for each outcome, and for all comparisons as low or very low; in large part this was due to issues of blinding and of precision. rTMS Meta-analysis of rTMS studies versus sham for pain intensity at short-term follow-up (0 to < 1 week postintervention), (27 studies, involving 655 participants), demonstrated a small effect with heterogeneity (standardised mean difference (SMD) -0.22, 95% confidence interval (CI) -0.29 to -0.16, low-quality evidence). This equates to a 7% (95% CI 5% to 9%) reduction in pain, or a 0.40 (95% CI 0.53 to 0.32) point reduction on a 0 to 10 pain intensity scale, which does not meet the minimum clinically important difference threshold of 15% or greater. Pre-specified subgroup analyses did not find a difference between low-frequency stimulation (low-quality evidence) and rTMS applied to the prefrontal cortex compared to sham for reducing pain intensity at short-term follow-up (very low-quality evidence). High-frequency stimulation of the motor cortex in single-dose studies was associated with a small short-term reduction in pain intensity at short-term follow-up (low-quality evidence, pooled n = 249, SMD -0.38 95% CI -0.49 to -0.27). This equates to a 12% (95% CI 9% to 16%) reduction in pain, or a 0.77 (95% CI 0.55 to 0.99) point change on a 0 to 10 pain intensity scale, which does not achieve the minimum clinically important difference threshold of 15% or greater. The results from multiple-dose studies were heterogeneous and there was no evidence of an effect in this subgroup (very low-quality evidence). We did not find evidence that rTMS improved disability. Meta-analysis of studies of rTMS versus sham for quality of life (measured using the Fibromyalgia Impact Questionnaire (FIQ) at short-term follow-up demonstrated a positive effect (MD -10.80 95% CI -15.04 to -6.55, low-quality evidence). CES For CES (five studies, 270 participants) we found no evidence of a difference between active stimulation and sham (SMD -0.24, 95% CI -0.48 to 0.01, low-quality evidence) for pain intensity. We found no evidence relating to the effectiveness of CES on disability. One study (36 participants) of CES versus sham for quality of life (measured using the FIQ) at short-term follow-up demonstrated a positive effect (MD -25.05 95% CI -37.82 to -12.28, very low-quality evidence). tDCS Analysis of tDCS studies (27 studies, 747 participants) showed heterogeneity and a difference between active and sham stimulation (SMD -0.43 95% CI -0.63 to -0.22, very low-quality evidence) for pain intensity. This equates to a reduction of 0.82 (95% CI 0.42 to 1.2) points, or a percentage change of 17% (95% CI 9% to 25%) of the control group outcome. This point estimate meets our threshold for a minimum clinically important difference, though the lower confidence interval is substantially below that threshold. We found evidence of small study bias in the tDCS analyses. We did not find evidence that tDCS improved disability. Meta-analysis of studies of tDCS versus sham for quality of life (measured using different scales across studies) at short-term follow-up demonstrated a positive effect (SMD 0.66 95% CI 0.21 to 1.11, low-quality evidence). Adverse events All forms of non-invasive brain stimulation and sham stimulation appear to be frequently associated with minor or transient side effects and there were two reported incidences of seizure, both related to the active rTMS intervention in the included studies. However many studies did not adequately report adverse events. Authors' conclusions There is very low-quality evidence that single doses of high-frequency rTMS of the motor cortex and tDCS may have short-term effects on chronic pain and quality of life but multiple sources of bias exist that may have influenced the observed effects. We did not find evidence that low-frequency rTMS, rTMS applied to the dorsolateral prefrontal cortex and CES are effective for reducing pain intensity in chronic pain. The broad conclusions of this review have not changed substantially for this update. There remains a need for substantially larger, rigorously designed studies, particularly of longer courses of stimulation. Future evidence may substantially impact upon the presented results.Cochrane Pain, Palliative and Supportive Car

Demography and disorders of the French Bulldog population under primary veterinary care in the UK in 2013

Abstract Background Despite its Gallic name, the French Bulldog is a breed of both British and French origin that was first recognised by The Kennel Club in 1906. The French Bulldog has demonstrated recent rapid rises in Kennel Club registrations and is now (2017) the second most commonly registered pedigree breed in the UK. However, the breed has been reported to be predisposed to several disorders including ocular, respiratory, neurological and dermatological problems. The VetCompass™ Programme collates de-identified clinical data from primary-care veterinary practices in the UK for epidemiological research. Using VetCompass™ clinical data, this study aimed to characterise the demography and common disorders of the general population of French Bulldogs under veterinary care in the UK. Results French Bulldogs comprised 2228 (0.49%) of 445,557 study dogs under veterinary care during 2013. Annual proportional birth rates showed that the proportional ownership of French Bulldog puppies rose steeply from 0.02% of the annual birth cohort attending VetCompass™ practices in 2003 to 1.46% in 2013. The median age of the French Bulldogs overall was 1.3 years (IQR 0.6–2.5, range 0.0–13.0). The most common colours of French Bulldogs were brindle (solid or main) (32.36%) and fawn (solid or main) (29.9%). Of the 2228 French Bulldogs under veterinary care during 2013, 1612 (72.4%) had at least one disorder recorded. The most prevalent fine-level precision disorders recorded were otitis externa (14.0%, 95% CI: 12.6–15.5), diarrhoea (7.5%, 95% CI: 6.4–8.7), conjunctivitis (3.2%, 95% CI: 2.5–4.0), nails overlong (3.1%, 95% CI% 2.4–3.9) and skin fold dermatitis (3.0%, 95% CI% 2.3–3.8). The most prevalent disorder groups were cutaneous (17.9%, 95% CI: 16.3–19.6), enteropathy (16.7%, 95% CI: 15.2–18.3), aural (16.3%, 95% CI: 14.8–17.9), upper respiratory tract (12.7%, 95% CI: 11.3–14.1) and ophthalmological (10.5%, 95% CI: 9.3–11.9). Conclusions Ownership of French Bulldogs in the UK is rising steeply. This means that the disorder profiles reported in this study reflect a current young UK population and are likely to shift as this cohort ages. Otitis externa, diarrhoea and conjunctivitis were the most common disorders in French Bulldogs. Identification of health priorities based on VetCompass™ data can support evidence–based reforms to improve health and welfare within the breed

Investigating the impact of poverty on colonization and infection with drug-resistant organisms in humans: a systematic review

Background Poverty increases the risk of contracting infectious diseases and therefore exposure to antibiotics. Yet there is lacking evidence on the relationship between income and non-income dimensions of poverty and antimicrobial resistance. Investigating such relationship would strengthen antimicrobial stewardship interventions. Methods A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Ovid, MEDLINE, EMBASE, Scopus, CINAHL, PsychINFO, EBSCO, HMIC, and Web of Science databases were searched in October 2016. Prospective and retrospective studies reporting on income or non-income dimensions of poverty and their influence on colonisation or infection with antimicrobial-resistant organisms were retrieved. Study quality was assessed with the Integrated quality criteria for review of multiple study designs (ICROMS) tool. Results Nineteen articles were reviewed. Crowding and homelessness were associated with antimicrobial resistance in community and hospital patients. In high-income countries, low income was associated with Streptococcus pneumoniae and Acinetobacter baumannii resistance and a seven-fold higher infection rate. In low-income countries the findings on this relation were contradictory. Lack of education was linked to resistant S. pneumoniae and Escherichia coli. Two papers explored the relation between water and sanitation and antimicrobial resistance in low-income settings. Conclusions Despite methodological limitations, the results suggest that addressing social determinants of poverty worldwide remains a crucial yet neglected step towards preventing antimicrobial resistance

A Discrete Event Simulation model to evaluate the treatment pathways of patients with Cataract in the United Kingdom

Background The number of people affected by cataract in the United Kingdom (UK) is growing rapidly due to ageing population. As the only way to treat cataract is through surgery, there is a high demand for this type of surgery and figures indicate that it is the most performed type of surgery in the UK. The National Health Service (NHS), which provides free of charge care in the UK, is under huge financial pressure due to budget austerity in the last decade. As the number of people affected by the disease is expected to grow significantly in coming years, the aim of this study is to evaluate whether the introduction of new processes and medical technologies will enable cataract services to cope with the demand within the NHS funding constraints. Methods We developed a Discrete Event Simulation model representing the cataract services pathways at Leicester Royal Infirmary Hospital. The model was inputted with data from national and local sources as well as from a surgery demand forecasting model developed in the study. The model was verified and validated with the participation of the cataract services clinical and management teams. Results Four scenarios involving increased number of surgeries per half-day surgery theatre slot were simulated. Results indicate that the total number of surgeries per year could be increased by 40% at no extra cost. However, the rate of improvement decreases for increased number of surgeries per half-day surgery theatre slot due to a higher number of cancelled surgeries. Productivity is expected to improve as the total number of doctors and nurses hours will increase by 5 and 12% respectively. However, non-human resources such as pre-surgery rooms and post-surgery recovery chairs are under-utilized across all scenarios. Conclusions Using new processes and medical technologies for cataract surgery is a promising way to deal with the expected higher demand especially as this could be achieved with limited impact on costs. Non-human resources capacity need to be evenly levelled across the surgery pathway to improve their utilisation. The performance of cataract services could be improved by better communication with and proactive management of patients.Peer reviewedFinal Published versio

Transient peak-strain matching partially recovers the age-impaired mechanoadaptive cortical bone response

Mechanoadaptation maintains bone mass and architecture; its failure underlies age-related decline in bone strength. It is unclear whether this is due to failure of osteocytes to sense strain, osteoblasts to form bone or insufficient mechanical stimulus. Mechanoadaptation can be restored to aged bone by surgical neurectomy, suggesting that changes in loading history can rescue mechanoadaptation. We use non-biased, whole-bone tibial analyses, along with characterisation of surface strains and ensuing mechanoadaptive responses in mice at a range of ages, to explore whether sufficient load magnitude can activate mechanoadaptation in aged bone. We find that younger mice adapt when imposed strains are lower than in mature and aged bone. Intriguingly, imposition of short-term, high magnitude loading effectively primes cortical but not trabecular bone of aged mice to respond. This response was regionally-matched to highest strains measured by digital image correlation and to osteocytic mechanoactivation. These data indicate that aged bone’s loading response can be partially recovered, non-invasively by transient, focal high strain regions. Our results indicate that old murine bone does respond to load when the loading is of sufficient magnitude, and bones’ age-related adaptation failure may be due to insufficient mechanical stimulus to trigger mechanoadaptation

Terpenoid biotransformations by Mucor species

Terpenoids are natural products of great interest due to their widespread use in agrochemicals, drugs, fragrances, flavouring and pigments. Biocatalysts are increasingly being used in the search for new derivatives with improved properties especially to obtain structurally novel leads for new drugs which are difficult to obtain using conventional organic chemical methods. This review, covering up to the end of 2012, reports on the application of Mucor species as catalysts in terpenoid biotransformation to obtain new drug targets, enhance pharmacological activity or decrease the unwanted effects of starting material

Breastfeeding training for health professionals and resultant changes in breastfeeding duration

CONTEXT: Promotion of breastfeeding in Brazilian maternity hospitals. OBJECTIVE: To quantify changes in the breastfeeding duration among mothers served by hospitals exposed to the Wellstart-SLC course, comparing them with changes among mothers attended by institutions not exposed to this course. DESIGN: Randomized Institutional Trial. SETTING: The effects of training on breastfeeding duration was assessed in eight Brazilian hospitals assigned at random to either an exposed group (staff attending the Wellstart-SLC course) or a control group. SAMPLE: For each of the eight study hospitals, two cohorts of about 50 children were visited at home at one and six months after birth. The first cohort (n = 494) was composed of babies born in the month prior to exposure to the Wellstart-SLC course, and the second cohort (n = 476) was composed of babies born six months subsequent to this exposure. MAIN MEASUREMENTS: Kaplan-Meier curves were plotted to describe the weaning process and log-rank tests were used to assess statistical differences among survival curves. Hazard ratio (HR) estimates were calculated by fitting Cox proportional hazard regression models to the data. RESULTS: The increases in estimated, adjusted rates for children born in hospitals with trained personnel were 29% (HR = 0.71) and 20% (HR = 0.80) for exclusive and full breastfeeding, respectively. No changes were identified for total breastfeeding. CONCLUSION: This randomized trial supports a growing body of evidence that training hospital health professionals in breastfeeding promotion and protection results in an increase in breastfeeding duration.CONTEXTO: Promoção do aleitamento materno em maternidades brasileiras. OBJETIVO: Quantificar mudanças na duração do aleitamento materno de mães assistidas em maternidades expostas ao curso Wellstart-SLC, comparando-as com mudanças em mães assistidas por maternidades não expostas. TIPO DE ESTUDO: Ensaio institucional randomizado. LOCAL: Os efeitos do treinamento na duração do aleitamento materno foi avaliado em oito maternidades randomicamente alocadas ao grupo exposto (equipe freqüenta o curso Wellstart-SLC) ou controle. AMOSTRA: Em cada uma das oito maternidades, duas coortes de cerca de 50 crianças foram visitadas em suas casas ao completarem um e seis meses de vida. As primeiras coortes (n = 494) foram compostas de bebês nascidos no mês anterior ao treinamento, enquanto que as segundas coortes (n = 476) foram compostas por bebês nascidos seis meses após a exposição ao curso Weelstart-SLC. VARIÁVEIS ESTUDADAS: Para descrever o processo de desmame foram traçadas curvas de Kaplan-Meier. Para avaliar as diferenças estatísticas entre as curvas de sobrevivência foi utilizado o teste log-rank. Foram calculadas estimativas das razões de risco(HR) ajustando modelos de regressão de riscos proporcionais de Cox aos dados. RESULTADOS: O aumento estimado, a partir das razões ajustadas para crianças nascidas em hospitais com pessoal treinado, foi 29% (HR = 0,71) e 20% (HR = 0,80) para aleitamento exclusivo e pleno respectivamente. Não foram identificadas mudanças para o tempo de aleitamento total. CONCLUSÕES: Esse ensaio randomizado confirma evidências crescentes de que treinar profissionais de saúde em hospitais, na promoção e proteção do aleitamento materno, resulta em aumento do tempo de aleitamento materno.Universidade Federal de São Paulo (UNIFESP) Department of PediatricsUniversidade de Santo Amaro Maternal and Child Health Graduate ProgramUniversidade Federal de São Paulo (UNIFESP) School of Public HealthState of São Paulo State Health Secretariat Health InstituteUNIFESP, Department of PediatricsUNIFESP, School of Public HealthSciEL