Genetic studies of body mass index yield new insights for obesity biology.

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Genome wide association identifies common variants at the SERPINA6/SERPINA1 locus influencing plasma cortisol and corticosteroid binding globulin.

Variation in plasma levels of cortisol, an essential hormone in the stress response, is associated in population-based studies with cardio-metabolic, inflammatory and neuro-cognitive traits and diseases. Heritability of plasma cortisol is estimated at 30-60% but no common genetic contribution has been identified. The CORtisol NETwork (CORNET) consortium undertook genome wide association meta-analysis for plasma cortisol in 12,597 Caucasian participants, replicated in 2,795 participants. The results indicate that <1% of variance in plasma cortisol is accounted for by genetic variation in a single region of chromosome 14. This locus spans SERPINA6, encoding corticosteroid binding globulin (CBG, the major cortisol-binding protein in plasma), and SERPINA1, encoding α1-antitrypsin (which inhibits cleavage of the reactive centre loop that releases cortisol from CBG). Three partially independent signals were identified within the region, represented by common SNPs; detailed biochemical investigation in a nested sub-cohort showed all these SNPs were associated with variation in total cortisol binding activity in plasma, but some variants influenced total CBG concentrations while the top hit (rs12589136) influenced the immunoreactivity of the reactive centre loop of CBG. Exome chip and 1000 Genomes imputation analysis of this locus in the CROATIA-Korcula cohort identified missense mutations in SERPINA6 and SERPINA1 that did not account for the effects of common variants. These findings reveal a novel common genetic source of variation in binding of cortisol by CBG, and reinforce the key role of CBG in determining plasma cortisol levels. In turn this genetic variation may contribute to cortisol-associated degenerative diseases.

Management of Back Pain-related Disorders in a Community With Limited Access to Health Care Services: A Description of Integration of Chiropractors as Service Providers.

OBJECTIVE: The purpose of this study was to evaluate a chiropractic service for back pain patients integrated within a publicly funded, multidisciplinary, primary care community health center in Cambridge, Ontario, Canada. METHODS: Patients consulting for back pain of any duration were referred by their medical doctor or nurse practitioner for chiropractic treatment at the community health center. Patients completed questionnaires at baseline and at discharge from the service. Data were collected prospectively on consecutive patients between January 2014 and January 2016. RESULTS: Questionnaire data were obtained from 93 patients. The mean age of the sample was 49.0 ± 16.27 years, and 66% were unemployed. More than three-quarters (77%) had had their back pain for more than a month, and 68% described it as constant. According to the Bournemouth Questionnaire, Bothersomeness, and global improvement scales, a majority (63%, 74%, and 93%, respectively) reported improvement at discharge, and most (82%) reported a significant reduction in pain medication. More than three-quarters (77%) did not visit their primary care provider while under chiropractic care, and almost all (93%) were satisfied with the service. According to the EuroQol 5 Domain questionnaire, more than one-third of patients (39%) also reported improvement in their general health state at discharge. CONCLUSION: Implementation of an integrated chiropractic service was associated with high levels of improvement and patient satisfaction in a sample of patients of low socioeconomic status with subacute and chronic back pain.

Are the presence of MODIC changes on MRI scans related to "improvement" in low back pain patients treated with lumbar facet joint injections?

BACKGROUND: Modic changes (MC) have been linked with low back pain (LBP) and worse outcomes from some treatments. No studies have investigated the impact that MCs may have on patient outcomes from lumbar facet injections. Therefore, the purpose of this study is to investigate whether the presence of Modic changes is related to 'improvement' in patients undergoing imaging-guided lumbar facet injection therapy. METHODS: Outcomes from 226 patients with MRI scans within 3 months of their imaging-guided lumbar facet injections were investigated to determine whether MCs are related to 'improvement' post injection. At 1 day, 1 week and 1 month post injection the Patients Global Impression of Change scale answers were collected by postal questionnaire. This was the primary outcome measure. The numerical rating scale for pain data was collected prior to treatment and at the same post injection time points. The MRI scans were independently evaluated by two examiners for the presence/absence of Modic changes and the type of Modic change if present. Kappa statistics were used for reliability of diagnosis analysis. Chi-squared test and logistic regression analysis tested MCs with 'improvement'. RESULTS: Intra- and inter-examiner reliability for the diagnosis of MCs was Kappa = 0.77 and 0.74. Intra- and inter-examiner reliability for categorizing MCs was K = 0.77 and K = 0.78. At 1 month post injection 45.2 % of patients without MCs reported clinically relevant 'improvement' compared to 34.2 % of patients with MC I and 32.1 % of patients with MC II. However, this did not reach statistical significance. Logistic regression found that Modic changes were not predictive of 'improvement'. CONCLUSIONS: There was a tendency for patients without MCs to have better outcomes but this did not reach statistical significance. The reliability of diagnosing MCs was substantial.

Evaluation of an FFQ to assess total energy and nutrient intakes in severely obese pregnant women.

OBJECTIVE: FFQ are popular instruments for assessing dietary intakes in epidemiological studies but have not been validated for use in severely obese pregnancy. The aim of the present study was to compare nutrient intakes assessed by an FFQ with those obtained from a food diary among severely obese pregnant women. DESIGN: Comparison of an FFQ containing 170 food items and a food diary for 4 d (three weekdays and one weekend day); absolute agreement was assessed using the paired t test and relative agreement by Pearson/Spearman correlation, crossclassification into tertiles and weighted kappa values. SETTING: Antenatal metabolic clinic for severely obese women. SUBJECTS: Thirty-one severely obese (BMI at booking ≥ 40.0 kg/m2) and thirty-two lean control (BMI520.0­24.9 kg/m2) pregnant women. RESULTS: The findings showed that nutrient intakes estimated by the FFQ were significantly higher than those from the food diary; average correlation was 0.32 in obese and 0.43 in lean women. A mean of 48.5% of obese and 47.3% of lean women were correctly classified, while 12.9% (obese) and 10.0% (lean) were grossly misclassified. Weighted k values ranged from 20.04 to 0.79 in obese women and from 0.16 to 0.78 in lean women. CONCLUSIONS: Overall, the relative agreement between the FFQ and food diary was lower in the obese group than in the lean group, but was comparable with earlier studies conducted in pregnant women. The validity assessments suggest that the FFQ is a useful tool for ranking severely obese pregnant women according to the levels of their dietary intake.

Development and pilot testing of the Baby-Feed web application for healthcare professionals and parents to improve infant diets.

BACKGROUND: Diet is key in preventing rapid infant weight gain but adherence to infant dietary recommendations is difficult to follow and low in adherence. OBJECTIVE: Develop and pilot test the "Baby-Feed" web application for parents and healthcare professionals to easily evaluate infant diets and provide immediate feedback to promote adherence to current infant dietary recommendations. METHODS: Baby-Feed was developed following the ADDIE (analysis, design, development, implementation, and evaluation) model. It was pilot tested among two clinicians and 25 parents of infants aged 4 to 12 months that had a scheduled well-child visit at a community health center in Miami. After 2 weeks of using Baby-Feed, parents completed a feasibility, acceptability, satisfaction, and usability questionnaire. Parents and clinicians were also asked to suggest improvements. Descriptive analysis included frequency and median (25th, 75th percentiles). One-sample binomial tests was used to evaluate if feasible, acceptable, satisfactory, and usable. RESULTS: Twenty-three parents completed the evaluation (all were mothers), 31.0 (26.0, 33.0) years-old, 96% Hispanic, 83% had ≥ high school education, with 1.5 (1.0, 2.0) children. Infants' age was 6.1 (4.0, 9.0) months and 57% were boys. Binomial tests indicated that most parents (greater than87%) agreed that Baby-Feed was easy to use, learn, quick, would use it again, rated it as 4/5 stars. They used it greater than 1 times per week (p < 0.001). Parents suggested improving the visuals (more icons, colors, and pictures) and images of portion sizes, highlighting missing fields, being able to view/open it on their phones, and adding recipes and more information. The two clinicians (a pediatrician and a physician assistant) suggested to be open-access and to add more infant nutrition information. CONCLUSION: Baby-Feed was feasible, usable, satisfactory, and acceptable. It could be used as a tool to easily evaluate infant diets in the healthcare setting to provide immediate feedback.

Fine-mapping the POLL locus in Brahman cattle yields the diagnostic marker CSAFG29.

The POLL locus has been mapped to the centromeric region of bovine chromosome 1 (BTA1) in both taurine breeds and taurine-indicine crosses in an interval of approximately 1 Mb. It has not yet been mapped in pure-bred zebu cattle. Despite several efforts, neither causative mutations in candidate genes nor a singular diagnostic DNA marker has been identified. In this study, we genotyped a total of 68 Brahman cattle and 20 Hereford cattle informative for the POLL locus for 33 DNA microsatellites, 16 of which we identified de novo from the bovine genome sequence, mapping the POLL locus to the region of the genes IFNAR2 and SYNJ1. The 303-bp allele of the new microsatellite, CSAFG29, showed strong association with the POLL allele. We then genotyped 855 Brahman cattle for CSAFG29 and confirmed the association between the 303-bp allele and POLL. To determine whether the same association was found in taurine breeds, we genotyped 334 animals of the Angus, Hereford and Limousin breeds and 376 animals of the Brangus, Droughtmaster and Santa Gertrudis composite taurine-zebu breeds. The association between the 303-bp allele and POLL was confirmed in these breeds; however, an additional allele (305 bp) was also associated but not fully predictive of POLL. Across the data, CSAFG29 was in sufficient linkage disequilibrium to the POLL allele in Australian Brahman cattle that it could potentially be used as a diagnostic marker in that breed, but this may not be the case in other breeds. Further, we provide confirmatory evidence that the scur phenotype generally occurs in animals that are heterozygous for the POLL allele.

Efficacy of chiropractic manual therapy on infant colic: a pragmatic single-blind, randomized controlled trial.

OBJECTIVE: The purpose of this study was to determine the efficacy of chiropractic manual therapy for infants with unexplained crying behavior and if there was any effect of parental reporting bias. METHODS: Infants with unexplained persistent crying (infant colic) were recruited between October 2007 and November 2009 at a chiropractic teaching clinic in the United Kingdom. Infants younger than 8 weeks were randomized to 1 of 3 groups: (i) infant treated, parent aware; (ii) infant treated, parent unaware; and (iii) infant not treated, parent unaware. The primary outcome was a daily crying diary completed by parents over a period of 10 days. Treatments were pragmatic, individualized to examination findings, and consisted of chiropractic manual therapy of the spine. Analysis of covariance was used to investigate differences between groups. RESULTS: One hundred four patients were randomized. In parents blinded to treatment allocation, using 2 or less hours of crying per day to determine a clinically significant improvement in crying time, the increased odds of improvement in treated infants compared with those not receiving treatment were statistically significant at day 8 (adjusted odds ratio [OR], 8.1; 95% confidence interval [CI], 1.4-45.0) and at day 10 (adjusted OR, 11.8; 95% CI, 2.1-68.3). The number needed to treat was 3. In contrast, the odds of improvement in treated infants were not significantly different in blinded compared with nonblinded parents (adjusted ORs, 0.7 [95% CI, 0.2-2.0] and 0.5 [95% CI, 0.1-1.6] at days 8 and 10, respectively). CONCLUSIONS: In this study, chiropractic manual therapy improved crying behavior in infants with colic. The findings showed that knowledge of treatment by the parent did not appear to contribute to the observed treatment effects in this study. Thus, it is unlikely that observed treatment effect is due to bias on the part of the reporting parent.

Predictors of improvement in patients with acute and chronic low back pain undergoing chiropractic treatment.

OBJECTIVES: The purpose of this study was to investigate outcomes and prognostic factors in patients with acute or chronic low back pain (LBP) undergoing chiropractic treatment. METHODS: This was a prognostic cohort study with medium-term outcomes. Adult patients with LBP of any duration who had not received chiropractic or manual therapy in the prior 3 months were recruited from multiple chiropractic practices in Switzerland. Participating doctors of chiropractic were allowed to use their typical treatment methods (such as chiropractic manipulation, soft tissue mobilization, or other methods) because the purpose of the study was to evaluate outcomes from routine chiropractic practice. Patients completed a numerical pain rating scale and Oswestry disability questionnaire immediately before treatment and at 1 week, 1 month, and 3 months after the start of treatment, together with self-reported improvement using the Patient Global Impression of Change. RESULTS: Patients with acute (<4 weeks; n = 523) and chronic (>3 months; n = 293) LBP were included. Baseline mean pain and disability scores were significantly (P < .001) higher in patients with acute LBP. In both groups of patients, there were significant (P < .0001) improvements in mean scores of pain and disability at 1 week, 1 month, and 3 months, although these change scores were significantly greater in the acute group. Similarly, a greater proportion of patients in the acute group reported improvement at each follow-up. The most consistent predictor was self-reported improvement at 1 week, which was independently associated with improvement at 1 month (adjusted odds ratio [OR], 2.4 [95% confidence interval, 1.3-4.5] and 5.0 [2.4-10.6]) and at 3 months (2.9 [1.3-6.6] and 3.3 [1.3-8.7]) in patients with acute and chronic pain, respectively. The presence of radiculopathy at baseline was not a predictor of outcome. CONCLUSIONS: Patients with chronic and acute pain reporting that they were "much better" or "better" on the Patient Global Impression of Change scale at 1 week after the first chiropractic visit were 4 to 5 times more likely to be improved at both 1 and 3 months compared with patients who were not improved at 1 week. Patients with acute pain reported more severe pain and disability initially but recovered faster. Patients with chronic and acute back pain both reported good outcomes, and most patients with radiculopathy also improved.

Association between polymorphisms of the dopamine receptor D2 and catechol-o-methyl transferase genes and cognitive function.

The dopaminergic neurotransmitter system of the brain is involved in working memory and other cognitive functions. Studies suggest an important role for dopamine synthesis and uptake in modulation of human cognitive processes. We studied the association between polymorphisms in the catechol-o-methyl transferase (COMT) and dopamine receptor D2 (DRD2) genes and general cognitive ability in a secondary analysis of 2091 men and women, aged 55-80 years living in Scotland. General cognitive ability 'g' was derived from five cognitive tests of different domains. COMT was not associated with cognitive ability in this population. The DRD2 C:C genotype of rs6277 was associated with decreased general cognitive ability 'g' (p = 0.003), and DRD2 rs1800497 heterozygotes had lowest mean general cognitive ability 'g' (p = 0.007). There was an indication of a potential interaction between the DRD2 SNPs.

Validity of weekly recall ratings of average pain intensity in neck pain patients.

OBJECTIVE: Ratings of usual pain over a period of 1 week are commonly used to rate a patient's usual level of pain intensity. This study investigated the validity of weekly recall pain ratings and biasing effects of pain levels on these ratings. METHODS: Seventy-eight patients presenting to a chiropractic outpatient clinic with nonspecific neck pain completed a 7-day diary rating their pain 4 times each day on an 11-point numerical rating scale. From these 28 ratings, the patients' "actual average" pain was computed. On day 8, patients were asked to rate their current pain, as well as recall their pain "on average," at its "worst," and at its "least" over the previous week. RESULTS: Recall of average pain over the previous week was shown to be a valid measure using ratings of actual pain as the criterion standard (Pearson r = 0.95). The error between actual and recall readings was random and consistent across all levels of actual pain. Patients were also able to accurately recall their pain at its worst (r = 0.93) and at its least (r = 0.92) over the preceding week. In regression analyses, there were no appreciable biasing effects on the recall of average pain of either current pain at the time of recall, or of pain at its worst or at its least during the recall period. CONCLUSION: These results suggest that recall ratings of pain intensity may be valid for use in clinical research and practice on patients with nonspecific neck pain.

Predictors for immediate and global responses to chiropractic manipulation of the cervical spine.

OBJECTIVE: Patients with nonspecific musculoskeletal disorders may vary in their response to treatment. This study set out to identify the predictors for either improvement or worsening in symptoms for which cervical spine manipulation is indicated. METHOD: A large prospective study recorded details on patients, their presenting symptoms, and type of treatment. At the end of the consultation, any immediate improvement or worsening in presenting symptoms was noted. At the follow-up visit, information was collected on the patients' self-reported improvement. RESULTS: Data were collected from 28,807 treatment consultations (in 19,722 patients) and 13,873 follow-up treatments. The presenting symptoms of "neck pain," "shoulder, arm pain," "reduced neck, shoulder, arm movement, stiffness," "headache," "upper, mid back pain," and "none or one presenting symptom" emerged in the final model as significant predictors for an immediate improvement. The presence of any 4 of these predictors raised the probability for an immediate improvement in presenting symptoms after treatment from 70% to approximately 95%. With regard to immediate worsening, "neck pain," "shoulder, arm pain, "headache," "numbness, tingling upper limbs," "upper, mid back pain," and "fainting, dizziness, light-headedness" emerged as predictors; and the presence of any 4 of these raised the probability for immediate worsening from 4.4% to approximately 12%. For global improvement, only 2 predictors were identified; but these did not enhance the postprediction probability. CONCLUSIONS: This study is the first attempt to identify variables that can predict immediate outcomes in terms of improvement and worsening of presenting symptoms, and global improvement, after cervical spine manipulation. The predictor variables were strongest for immediate improvement.

Synthetic cannabinoids: Variety is definitely not the spice of life.

Although the past few years have seen a significant increase in the use of synthetic cannabinoids, very few fatalities have been reported whereby synthetic cannabinoids have contributed or were solely responsible for the death of an individual. We report a rapid death of an individual following ingestion of 5 F-PB-22 and 5 F-AKB-48. Case information and autopsy findings are presented. Post-mortem blood samples were obtained and 5 F-PB-22 and 5 F-AKB-48 were detected along with 311 mg/100 ml alcohol. The cause of death was certified as the effects of a combination of alcohol and synthetic cannabinoids (5 F-PB-22 and 5 F-AKB-48).

Molecular Biomarkers for Weight Control in Obese Individuals Subjected to a Multiphase Dietary Intervention.

Context: Although calorie restriction has proven beneficial for weight loss, long-term weight control is variable between individuals. Objective: To identify biomarkers of successful weight control during a dietary intervention (DI). Design, Setting, and Participants: Adipose tissue (AT) transcriptomes were compared between 21 obese individuals who either maintained weight loss or regained weight during the DI. Results were validated on 310 individuals from the same study using quantitative reverse transcription polymerase chain reaction and protein levels of potential circulating biomarkers measured by enzyme-linked immunosorbent assay. Intervention: Individuals underwent 8 weeks of low-calorie diet, then 6 months of ad libitum diet. Outcome Measure: Weight changes at the end of the DI. Results: We evaluated six genes that had altered expression during DI, encode secreted proteins, and have not previously been implicated in weight control (EGFL6, FSTL3, CRYAB, TNMD, SPARC, IGFBP3), as well as genes for which baseline expression differed between those with good and poor weight control (ASPN, USP53). Changes in plasma concentrations of EGFL6, FSTL3, and CRYAB mirrored AT messenger RNA expression; all decreased during DI in individuals with good weight control. ASPN and USP53 had higher baseline expression in individuals who went on to have good weight control. Expression quantitative trait loci analysis found polymorphisms associated with expression levels of USP53 in AT. A regulatory network was identified in which transforming growth factor ß1 (TGF-ß1) was responsible for downregulation of certain genes during DI in good controllers. Interestingly, ASPN is a TGF-ß1 inhibitor. Conclusions: We found circulating biomarkers associated with weight control that could influence weight management strategies and genes that may be prognostic for successful weight control.

Transcriptome profiling from adipose tissue during a low-calorie diet reveals predictors of weight and glycemic outcomes in obese, nondiabetic subjects.

Background: A low-calorie diet (LCD) reduces fat mass excess, improves insulin sensitivity, and alters adipose tissue (AT) gene expression, yet the relation with clinical outcomes remains unclear.Objective: We evaluated AT transcriptome alterations during an LCD and the association with weight and glycemic outcomes both at LCD termination and 6 mo after the LCD.Design: Using RNA sequencing (RNAseq), we analyzed transcriptome changes in AT from 191 obese, nondiabetic patients within a multicenter, controlled dietary intervention. Expression changes were associated with outcomes after an 8-wk LCD (800-1000 kcal/d) and 6 mo after the LCD. Results were validated by using quantitative reverse transcriptase-polymerase chain reaction in 350 subjects from the same cohort. Statistical models were constructed to classify weight maintainers or glycemic improvers.Results: With RNAseq analyses, we identified 1173 genes that were differentially expressed after the LCD, of which 350 and 33 were associated with changes in body mass index (BMI; in kg/m2) and Matsuda index values, respectively, whereas 29 genes were associated with both endpoints. Pathway analyses highlighted enrichment in lipid and glucose metabolism. Classification models were constructed to identify weight maintainers. A model based on clinical baseline variables could not achieve any classification (validation AUC: 0.50; 95% CI: 0.36, 0.64). However, clinical changes during the LCD yielded better performance of the model (AUC: 0.73; 95% CI: 0.60, 0.87]). Adding baseline expression to this model improved the performance significantly (AUC: 0.87; 95% CI: 0.77, 0.96; Delong's P = 0.012). Similar analyses were performed to classify subjects with good glycemic improvements. Baseline- and LCD-based clinical models yielded similar performance (best AUC: 0.73; 95% CI: 0.60, 0.86). The addition of expression changes during the LCD improved the performance substantially (AUC: 0.80; 95% CI: 0.69, 0.92; P = 0.058).Conclusions: This study investigated AT transcriptome alterations after an LCD in a large cohort of obese, nondiabetic patients. Gene expression combined with clinical variables enabled us to distinguish weight and glycemic responders from nonresponders. These potential biomarkers may help clinicians understand intersubject variability and better predict the success of dietary interventions. This trial was registered at clinicaltrials.gov as NCT00390637.

The low single nucleotide polymorphism heritability of plasma and saliva cortisol levels.

Cortisol is an important stress hormone affected by a variety of biological and environmental factors, such as the circadian rhythm, exercise and psychological stress. Cortisol is mostly measured using blood or saliva samples. A number of genetic variants have been found to contribute to cortisol levels with these methods. While the effects of several specific single genetic variants is known, the joint genome-wide contribution to cortisol levels is unclear. Our aim was to estimate the amount of cortisol variance explained by common single nucleotide polymorphisms, i.e. the SNP heritability, using a variety of cortisol measures, cohorts and analysis approaches. We analyzed morning plasma (n=5705) and saliva levels (n=1717), as well as diurnal saliva levels (n=1541), in the Rotterdam Study using genomic restricted maximum likelihood estimation. Additionally, linkage disequilibrium score regression was fitted on the results of genome-wide association studies (GWAS) performed by the CORNET consortium on morning plasma cortisol (n=12,597) and saliva cortisol (n=7703). No significant SNP heritability was detected for any cortisol measure, sample or analysis approach. Point estimates ranged from 0% to 9%. Morning plasma cortisol in the CORNET cohorts, the sample with the most power, had a 6% [95%CI: 0-13%] SNP heritability. The results consistently suggest a low SNP heritability of these acute and short-term measures of cortisol. The low SNP heritability may reflect the substantial environmental and, in particular, situational component of these cortisol measures. Future GWAS will require very large sample sizes. Alternatively, more long-term cortisol measures such as hair cortisol samples are needed to discover further genetic pathways regulating cortisol concentrations.

Perceptions of the quality of the therapeutic alliance in chiropractic care in The Netherlands: a cross-sectional survey.

BACKGROUND: Research in various medical fields demonstrates a consistent and positive association between clinical outcomes and the quality of the therapeutic alliance between the patient and clinician. The aim of this study was to explore how well chiropractors and their patients in The Netherlands perceive the quality of their working relationship. METHODS: A nationwide survey of chiropractors and their patients was conducted in The Netherlands, using a validated Dutch translation of the Working Alliance Inventory (WAV-12). Data were collected over a 5-week period in September-October 2014. Both patients and chiropractors were requested to reflect on 12 statements about to how well they perceived their collaboration in reaching consensus on treatment goals and treatment strategies, and how well they perceived the existence of an affective bond in their working relationship. A 5-point Likert scale was used to answer each question. Higher ratings reflected a more positive perception of the therapeutic alliance. Furthermore, levels of agreement between patients' and chiropractors' perceptions of the quality of their therapeutic alliance were determined. RESULTS: In total, 207 working relationships between patients and their chiropractor were analysed. The quality of the therapeutic alliance was perceived as being very positive for both patients (n = 183, mean 49.14 ± 7.12) and chiropractors (n = 202, mean 50.48 ± 4.97). There was no difference in patients' perceptions whether treated by a male or female chiropractor, nor in relation to the chiropractor's years of experience. Nevertheless, poor agreement was found between perceptions of patients and chiropractors in the same relationship (ICC = 0.13). CONCLUSIONS: Both patients and chiropractors perceived the quality of the therapeutic alliance as being very positive. Despite these positive results, patient and chiropractor pairs perceived the level of collaboration in order to reach agreement on treatment goals and strategies and the quality of their affective bond very differently. Clinically, these results suggest that chiropractors should, during the course of treatment, continue to collaborate with their patient and frequently verify whether their patient continues to agree with the treatment goals and treatment plan applied to further develop, improve and maintain a positive therapeutic alliance.

Adult height, coronary heart disease and stroke: a multi-locus Mendelian randomization meta-analysis.

Background: We investigated causal effect of completed growth, measured by adult height, on coronary heart disease (CHD), stroke and cardiovascular traits, using instrumental variable (IV) Mendelian randomization meta-analysis. Methods: We developed an allele score based on 69 single nucleotide polymorphisms (SNPs) associated with adult height, identified by the IBCCardioChip, and used it for IV analysis against cardiovascular risk factors and events in 21 studies and 60 028 participants. IV analysis on CHD was supplemented by summary data from 180 height-SNPs from the GIANT consortium and their corresponding CHD estimates derived from CARDIoGRAMplusC4D. Results: IV estimates from IBCCardioChip and GIANT-CARDIoGRAMplusC4D showed that a 6.5-cm increase in height reduced the odds of CHD by 10% [odds ratios 0.90; 95% confidence intervals (CIs): 0.78 to 1.03 and 0.85 to 0.95, respectively],which agrees with the estimate from the Emerging Risk Factors Collaboration (hazard ratio 0.93; 95% CI: 0.91 to 0.94). IV analysis revealed no association with stroke (odds ratio 0.97; 95% CI: 0.79 to 1.19). IV analysis showed that a 6.5-cm increase in height resulted in lower levels of body mass index ( P < 0.001), triglycerides ( P < 0.001), non high-density (non-HDL) cholesterol ( P < 0.001), C-reactive protein ( P = 0.042), and systolic blood pressure ( P = 0.064) and higher levels of forced expiratory volume in 1 s and forced vital capacity ( P < 0.001 for both). Conclusions: Taller individuals have a lower risk of CHD with potential explanations being that taller people have a better lung function and lower levels of body mass index, cholesterol and blood pressure.

A cross-sectional study comparing pain and disability levels in patients with low back pain with and without transitional lumbosacral vertebrae.

OBJECTIVE: To determine whether patients with transitional lumbosacral vertebrae report more pain and disability compared with patients with normal lumbar vertebrae. METHODS: Radiographic and questionnaire data were collected from 353 patients with low back pain. Back pain severity was measured using 2 scales: one for pain over the entire episode and the other for pain during the previous week. All patients completed the Revised Oswestry Disability Questionnaire before radiography was performed. Patients were divided into 2 groups: those with and those without a transitional lumbosacral vertebra. Differences between patient groups were investigated using the unpaired t test. Multiple linear regression analysis was applied to investigate the effect of the transitional lumbosacral vertebrae on pain and disability controlling for the effects of age and sex. RESULTS: Forty-three patients (12.2%) had a transitional lumbosacral vertebra. There were no differences in pain or disability levels between the 2 groups on any of the pain scales or Revised Oswestry subscales. Older patients reported significantly more pain (P = .039) and disability (P = .002) than younger patients. CONCLUSIONS: The presence of a transitional lumbosacral vertebra in this group of patients was not related to an increased level of reported low back pain or disability.

Post-mortem toxicology: A pilot study to evaluate the use of a Bayesian network to assess the likelihood of fatality.

The challenge of interpreting post-mortem drug concentrations is well documented and relies on appropriate sample collection, knowledge of case circumstances as well as reference to published tables of data, whilst taking into account the known issues of post-mortem drug redistribution and tolerance. Existing published data has evolved from simple data tables to those now including sample origin and single to poly drug use, but additional information tends to be specific to those reported in individual case studies. We have developed a Bayesian network framework to assign a likelihood of fatality based on the contribution of drug concentrations whilst taking into account the pathological findings. This expert system has been tested against casework within the coronial jurisdiction of Sunderland, UK. We demonstrate in this pilot study that the Bayesian network can be used to proffer a degree of confidence in how deaths may be reported in cases when drugs are implicated. It has also highlighted the potential for deaths to be reported according to the pathological states at post-mortem when drugs have a significant contribution that may have an impact on mortality statistics. The Bayesian network could be used as complementary approach to assist in the interpretation of post-mortem drug concentrations.