IMPLEmenting a clinical practice guideline for acute low back pain evidence-based manageMENT in general practice (IMPLEMENT) : cluster randomised controlled trial study protocol

Background: Evidence generated from reliable research is not frequently implemented into clinical practice. Evidence-based clinical practice guidelines are a potential vehicle to achieve this. A recent systematic review of implementation strategies of guideline dissemination concluded that there was a lack of evidence regarding effective strategies to promote the uptake of guidelines. Recommendations from this review, and other studies, have suggested the use of interventions that are theoretically based because these may be more effective than those that are not. An evidencebased clinical practice guideline for the management of acute low back pain was recently developed in Australia. This provides an opportunity to develop and test a theory-based implementation intervention for a condition which is common, has a high burden, and for which there is an evidence-practice gap in the primary care setting. Aim: This study aims to test the effectiveness of a theory-based intervention for implementing a clinical practice guideline for acute low back pain in general practice in Victoria, Australia. Specifically, our primary objectives are to establish if the intervention is effective in reducing the percentage of patients who are referred for a plain x-ray, and improving mean level of disability for patients three months post-consultation. Methods/Design: This study protocol describes the details of a cluster randomised controlled trial. Ninety-two general practices (clusters), which include at least one consenting general practitioner, will be randomised to an intervention or control arm using restricted randomisation. Patients aged 18 years or older who visit a participating practitioner for acute non-specific low back pain of less than three months duration will be eligible for inclusion. An average of twenty-five patients per general practice will be recruited, providing a total of 2,300 patient participants. General practitioners in the control arm will receive access to the guideline using the existing dissemination strategy. Practitioners in the intervention arm will be invited to participate in facilitated face-to-face workshops that have been underpinned by behavioural theory. Investigators (not involved in the delivery of the intervention), patients, outcome assessors and the study statistician will be blinded to group allocation. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN012606000098538 (date registered 14/03/2006).The trial is funded by the NHMRC by way of a Primary Health Care Project Grant (334060). JF has 50% of her time funded by the Chief Scientist Office3/2006). of the Scottish Government Health Directorate and 50% by the University of Aberdeen. PK is supported by a NHMRC Health Professional Fellowship (384366) and RB by a NHMRC Practitioner Fellowship (334010). JG holds a Canada Research Chair in Health Knowledge Transfer and Uptake. All other authors are funded by their own institutions

Remote physiological monitoring: Clinical, financial, and behavioral outcomes in a heart failure population

This article reports on the outcomes associated with remote physiological monitoring (RPM) conducted as part of a heart failure disease management program. Claims data, medical records, data transmission records, and survey results for 91 individuals ages 50–92 (mean 74 years) successfully completing a heart failure RPM program were analyzed for time periods before, during, and after the monitoring intervention. The program was associated with significant reductions in per member per month costs and emergency room and hospital utilization. More detailed analyses were performed for specific gender and age subgroups. Participant surveys indicated high levels of satisfaction, and improvements in self-perceived health status, self-efficacy, and self-management behaviors. This study is the first to assess the impact of a RPM program following removal of the monitoring equipment. The results indicate that RPM, as a component of a traditional disease management program, has a sustained, beneficial effect on participants’ lifestyles after the monitoring period has ended

Assessing the Validity of Sexual Behaviour Reports in a Whole Population Survey in Rural Malawi

Background: Sexual behaviour surveys are widely used, but under-reporting of particular risk behaviours is common, especially by women. Surveys in whole populations provide an unusual opportunity to understand the extent and nature of such under-reporting.Methods: All consenting individuals aged between 15 and 59 within a demographic surveillance site in northern Malawi were interviewed about their sexual behaviour. Validity of responses was assessed by analysis of probing questions; by comparison of results with in-depth interviews and with Herpes simplex type-2 (HSV-2) seropositivity; by comparing reports to same sex and opposite sex interviewers; and by quantifying the partnerships within the local community reported by men and by women, adjusted for response rates.Results: 6,796 women and 5,253 men (83% and 72% of those eligible) consented and took part in sexual behaviour interviews. Probing questions and HSV-2 antibody tests in those who denied sexual activity identified under-reporting for both men and women. Reports varied little by sex or age of the interviewer. The number of marital partnerships reported was comparable for men and women, but men reported about 4 times as many non-marital partnerships. The discrepancy in reporting of non-marital partnerships was most marked for married women (men reported about 7 times as many non-marital partnerships with married women as were reported by married women themselves), but was only apparent in younger married women.Conclusions: We have shown that the under-reporting of non-marital partnerships by women was strongly age-dependent. The extent of under-reporting of sexual activity by young men was surprisingly high. The results emphasise the importance of triangulation, including biomarkers, and the advantages of considering a whole population

Complement is activated in progressive multiple sclerosis cortical grey matter lesions

The symptoms of multiple sclerosis (MS) are caused by damage to myelin and nerve cells in the brain and spinal cord. Inflammation is tightly linked with neurodegeneration, and it is the accumulation of neurodegeneration that underlies increasing neurological disability in progressive MS. Determining pathological mechanisms at play in MS grey matter is therefore a key to our understanding of disease progression

Misinformation as Immigration Control

It is wrong to force refugees to return to the countries they fled from. It is similarly wrong, many argue, to force migrants back to countries with life-threatening conditions. I argue that it is additionally wrong to help such refugees and migrants voluntarily return whilst failing to inform them of the risks. Drawing on existing data, and original data from East Africa, I describe distinct types of cases where such a wrong arises. In ‘Misinformation Cases’ officials tell refugees that it is safe to return, when it is not, and refugees return who would have otherwise stayed. In ‘Omission Cases’ officials do not provide any information on countries of origin, and this omission causes refugees to repatriate. In ‘Relevancy Cases’ refugees are misinformed or uninformed, but would have returned even if better informed. In all of these cases, at least some state officials are blameworthy for their failure to inform refugees, and are engaging in a form of wrongful immigration control

Not the End of the World? Post-Classical Decline and Recovery in Rural Anatolia

Between the foundation of Constantinople as capital of the eastern half of the Roman Empire in 330 CE and its sack by the Fourth Crusade in 1204 CE, the Byzantine Empire underwent a full cycle from political-economic stability, through rural insecurity and agrarian decline, and back to renewed prosperity. These stages plausibly correspond to the phases of over-extension (K), subsequent release (Ω) and recovery (α) of the Adaptive Cycle in Socio-Ecological Systems. Here we track and partly quantify the consequences of those changes in different regions of Anatolia, firstly for rural settlement (via regional archaeological surveys) and secondly for land cover (via pollen analysis). We also examine the impact of climate changes on the agrarian system. While individual histories vary, the archaeological record shows a major demographic decline between ca .650 and ca. 900 CE in central and southwestern Anatolia, which was then a frontier zone between Byzantine and Arab armies. In these regions, and also in northwest Anatolia, century-scale trends in pollen indicate a substantial decline in the production of cereal and tree crops, and a smaller decline in pastoral activity. During the subsequent recovery (α) phase after 900 CE there was strong regional differentiation, with central Anatolia moving to a new economic system based on agro-pastoralism, while lowland areas of northern and western Anatolia returned to the cultivation of commercial crops such as olive trees. The extent of recovery in the agrarian economy was broadly predictable by the magnitude of its preceding decline, but the trajectories of recovery varied between different regions

Evaluation of a Theory-Informed Implementation Intervention for the Management of Acute Low Back Pain in General Medical Practice: The IMPLEMENT Cluster Randomised Trial

Introduction: This cluster randomised trial evaluated an intervention to decrease x-ray referrals and increase giving advice to stay active for people with acute low back pain (LBP) in general practice. Methods: General practices were randomised to either access to a guideline for acute LBP (control) or facilitated interactive workshops (intervention). We measured behavioural predictors (e.g. knowledge, attitudes and intentions) and fear avoidance beliefs. We were unable to recruit sufficient patients to measure our original primary outcomes so we introduced other outcomes measured at the general practitioner (GP) level: behavioural simulation (clinical decision about vignettes) and rates of x-ray and CT-scan (medical administrative data). All those not involved in the delivery of the intervention were blinded to allocation. Results: 47 practices (53 GPs) were randomised to the control and 45 practices (59 GPs) to the intervention. The number of GPs available for analysis at 12 months varied by outcome due to missing confounder information; a minimum of 38 GPs were available from the intervention group, and a minimum of 40 GPs from the control group. For the behavioural constructs, although effect estimates were small, the intervention group GPs had greater intention of practising consistent with the guideline for the clinical behaviour of x-ray referral. For behavioural simulation, intervention group GPs were more likely to adhere to guideline recommendations about x-ray (OR 1.76, 95%CI 1.01, 3.05) and more likely to give advice to stay active (OR 4.49, 95%CI 1.90 to 10.60). Imaging referral was not statistically significantly different between groups and the potential importance of effects was unclear; rate ratio 0.87 (95%CI 0.68, 1.10) for x-ray or CT-scan. Conclusions: The intervention led to small changes in GP intention to practice in a manner that is consistent with an evidence-based guideline, but it did not result in statistically significant changes in actual behaviour. Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN01260600009853

Plant-symbiotic fungi as chemical engineers: multi-genome analysis of the Clavicipitaceae reveals dynamics of alkaloid Loci

The fungal family Clavicipitaceae includes plant symbionts and parasites that produce several psychoactive and bioprotective alkaloids. The family includes grass symbionts in the epichloae clade (Epichloë and Neotyphodium species), which are extraordinarily diverse both in their host interactions and in their alkaloid profiles. Epichloae produce alkaloids of four distinct classes, all of which deter insects, and some—including the infamous ergot alkaloids—have potent effects on mammals. The exceptional chemotypic diversity of the epichloae may relate to their broad range of host interactions, whereby some are pathogenic and contagious, others are mutualistic and vertically transmitted (seed-borne), and still others vary in pathogenic or mutualistic behavior. We profiled the alkaloids and sequenced the genomes of 10 epichloae, three ergot fungi (Claviceps species), a morning-glory symbiont (Periglandula ipomoeae), and a bamboo pathogen (Aciculosporium take), and compared the gene clusters for four classes of alkaloids. Results indicated a strong tendency for alkaloid loci to have conserved cores that specify the skeleton structures and peripheral genes that determine chemical variations that are known to affect their pharmacological specificities. Generally, gene locations in cluster peripheries positioned them near to transposon-derived, AT-rich repeat blocks, which were probably involved in gene losses, duplications, and neofunctionalizations. The alkaloid loci in the epichloae had unusual structures riddled with large, complex, and dynamic repeat blocks. This feature was not reflective of overall differences in repeat contents in the genomes, nor was it characteristic of most other specialized metabolism loci. The organization and dynamics of alkaloid loci and abundant repeat blocks in the epichloae suggested that these fungi are under selection for alkaloid diversification. We suggest that such selection is related to the variable life histories of the epichloae, their protective roles as symbionts, and their associations with the highly speciose and ecologically diverse cool-season grasses

Pilot Study For Using Fitbit Activity Trackers To Monitor And Predict Onset Of CAR-T Cell Immunotherapy Related Adverse Events Including Cytokine Release Syndrome

Introduction: Immunotherapy using T Cells with engineered chimeric antigen receptors (CAR) is a revolutionary modality for treating cancer, especially B cell malignancies. It also has specific toxicities. The most common toxicities observed are cytokine-release syndrome (CRS) and neurotoxicity. These therapy-related adverse events can range from mild to fatal. If appropriately and timely treated, they have a good prognosis. Thus, further insight into predictive biomarkers can help clinical management of patients and reduce morbidity and mortality. Objective: One of the constitutional symptoms associated with CRS is fatigue. With the advent of activity tracking digital technology, I propose a pilot study exploring the use of fitness trackers to quantify activity level as a potential predictive biomarker of CRS due to CAR T-Cell immunotherapy. Methods: The proposed study would be a single-arm trial. Patients who are receiving CAR-T Cell immunotherapy will be given a Fitbit Flex 2™ tracker. One week of activity data (measured as steps per day) prior to CAR-T Cell infusion will establish patient baseline activity. From the date of infusion, activity levels will continue to be tracked and analyzed through CRS onset. The patient data will be gathered from Fitbit’s server via a customized app built using Fitbit’s Web Application Programming Interface (API). Results: This is a proposed study. No results have been gathered. Discussion: If a correlation is established between activity levels and onset of CRS, it would enhance the current predictive algorithm, allow easier outpatient management and remote monitoring, decrease costs, and reduce morbidity and mortality