A systematic review of gut microbiota composition in observational studies of major depressive disorder, bipolar disorder and schizophrenia.

The emerging understanding of gut microbiota as 'metabolic machinery' influencing many aspects of physiology has gained substantial attention in the field of psychiatry. This is largely due to the many overlapping pathophysiological mechanisms associated with both the potential functionality of the gut microbiota and the biological mechanisms thought to be underpinning mental disorders. In this systematic review, we synthesised the current literature investigating differences in gut microbiota composition in people with the major psychiatric disorders, major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SZ), compared to 'healthy' controls. We also explored gut microbiota composition across disorders in an attempt to elucidate potential commonalities in the microbial signatures associated with these mental disorders. Following the PRISMA guidelines, databases were searched from inception through to December 2021. We identified 44 studies (including a total of 2510 psychiatric cases and 2407 controls) that met inclusion criteria, of which 24 investigated gut microbiota composition in MDD, seven investigated gut microbiota composition in BD, and 15 investigated gut microbiota composition in SZ. Our syntheses provide no strong evidence for a difference in the number or distribution (α-diversity) of bacteria in those with a mental disorder compared to controls. However, studies were relatively consistent in reporting differences in overall community composition (ß-diversity) in people with and without mental disorders. Our syntheses also identified specific bacterial taxa commonly associated with mental disorders, including lower levels of bacterial genera that produce short-chain fatty acids (e.g. butyrate), higher levels of lactic acid-producing bacteria, and higher levels of bacteria associated with glutamate and GABA metabolism. We also observed substantial heterogeneity across studies with regards to methodologies and reporting. Further prospective and experimental research using new tools and robust guidelines hold promise for improving our understanding of the role of the gut microbiota in mental and brain health and the development of interventions based on modification of gut microbiota.

Associations Between Primary Residence and Mental Health in Global Marginalized Populations.

Scholars suggest that marginalized people in non-urban areas experience higher distress levels and fewer psychosocial resources than in urban areas. Researchers have yet to test whether precise proximity to urban centers is associated with mental health for marginalized populations. We recruited 1733 people who reported living in 45 different countries. Participants entered their home locations and completed measures of anxiety, depression, social support, and resilience. Regression and thematic analyses were used to determine what role distance from legislative and urban centers may play in mental health when marginalized people were disaggregated. Greater distance from legislative center predicted higher anxiety and resilience. Greater distance from urban center also predicted more resilience. Thematic analyses yielded five categories (e.g., safety, connection) that further illustrated the impact of geographic location on health. Implications for community mental health are discussed including the need to better understand and further expand resilience in rural areas.

The Impact of Parental Presence Restrictions on Canadian Parents in the NICU During COVID-19: A National Survey.

The purpose of this research was to explore parental perspectives on the impact of parent restrictions imposed in response to the COVID-19 pandemic across Canadian Neonatal Intensive Care Units (NICUs). A co-designed online survey was conducted targeting parents (n = 235) of infants admitted to a Canadian NICU from March 1, 2020, until March 5, 2021. Parents completed the survey from 38 Canadian NICUs. Large variation in the severity of policies regarding parental presence was reported. Most respondents (68.9%) were classified as experiencing high restrictions, with one or no support people allowed in the NICU, and felt that policies were less easy to understand, felt less valued and respected, and found it more challenging to access medicine or health care. Parents reported gaps in care related to self-care, accessibility, and mental health outcomes. There is significant variation in parental restrictions implemented across Canadian NICUs. National guidelines are needed to support consistent and equitable care practices.

Neurodevelopmental outcomes of very preterm infants who received cord milking at birth: a randomized controlled trial.

Umbilical cord milking improves postnatal adaptation and short-term outcomes of very preterm infants compared to early cord clamping. Little is known about the impact of umbilical cord milking on long-term neurodevelopmental outcomes. The objective of this study is to compare the effects of intact umbilical cord milking (UCM) vs. early cord clamping (ECC) at birth on neurodevelopmental outcomes at 36 months' corrected age. Preterm infants < 31 weeks' gestation who were randomized at birth to receive three time milking of their attached cord or ECC (< 10 s) were evaluated at 36 months' corrected age. Neurodevelopmental outcomes were assessed by blinded examiners using Bayley Scales of Infant and Toddler Development (version III). Analysis was by intention to treat. Out of the 73 infants included in the original trial, 2 died and 65 (92%) infants were evaluated at 36 months' corrected age. Patient characteristics and short-term outcomes were similar in both study groups. There were no significant differences in the median cognitive, motor or language scores or in the rates of cerebral palsy, developmental impairment, deafness, or blindness between study groups. CONCLUSION: Neurodevelopmental outcomes at 36 months' corrected age of very preterm infants who received UCM were not shown to be significantly different from those who received ECC at birth. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01487187 What is Known: • Compared to early cord clamping, umbilical cord milking improves postnatal adaptation and short-term outcomes of very preterm infants compared to early cord clamping. • Little is known about the impact of umbilical cord milking on neurodevelopmental outcomes. WHAT IS NEW: • Neurodevelopmental outcomes at 3 years of age were not significantly different in very preterm infants who received cord milking vs. those who received early cord clamping at birth.

Informing the public health response to COVID-19: a systematic review of risk factors for disease, severity, and mortality.

BACKGROUND: Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) has challenged public health agencies globally. In order to effectively target government responses, it is critical to identify the individuals most at risk of coronavirus disease-19 (COVID-19), developing severe clinical signs, and mortality. We undertook a systematic review of the literature to present the current status of scientific knowledge in these areas and describe the need for unified global approaches, moving forwards, as well as lessons learnt for future pandemics. METHODS: Medline, Embase and Global Health were searched to the end of April 2020, as well as the Web of Science. Search terms were specific to the SARS-CoV-2 virus and COVID-19. Comparative studies of risk factors from any setting, population group and in any language were included. Titles, abstracts and full texts were screened by two reviewers and extracted in duplicate into a standardised form. Data were extracted on risk factors for COVID-19 disease, severe disease, or death and were narratively and descriptively synthesised. RESULTS: One thousand two hundred and thirty-eight papers were identified post-deduplication. Thirty-three met our inclusion criteria, of which 26 were from China. Six assessed the risk of contracting the disease, 20 the risk of having severe disease and ten the risk of dying. Age, gender and co-morbidities were commonly assessed as risk factors. The weight of evidence showed increasing age to be associated with severe disease and mortality, and general comorbidities with mortality. Only seven studies presented multivariable analyses and power was generally limited. A wide range of definitions were used for disease severity. CONCLUSIONS: The volume of literature generated in the short time since the appearance of SARS-CoV-2 has been considerable. Many studies have sought to document the risk factors for COVID-19 disease, disease severity and mortality; age was the only risk factor based on robust studies and with a consistent body of evidence. Mechanistic studies are required to understand why age is such an important risk factor. At the start of pandemics, large, standardised, studies that use multivariable analyses are urgently needed so that the populations most at risk can be rapidly protected. REGISTRATION: This review was registered on PROSPERO as CRD42020177714 .

Bowel cancer screening in an English prison: a qualitative service evaluation.

OBJECTIVES: Bowel cancer screening home-testing kits are offered every two years to individuals aged 60-74 years in the United Kingdom (UK), with prisoners eligible for screening in the same way as the general population. There are currently major changes planned to the bowel cancer screening programme in England, with the transition to the single-sample faecal immunochemical test (FIT) and the planned lowering of the age limit from 60 to 50 years. In this project, we aimed to explore processes and beliefs around bowel cancer screening in an English prison. STUDY DESIGN: This is a qualitative study. METHODS: Semistructured qualitative interviews were conducted with eight prisoners and four staff members in a male prison in North West England. Data were analysed via thematic analysis. RESULTS: Promoting and impeding factors to screening were identified. There was high willingness amongst prisoners to be screened for bowel cancer, with screening seen as important and having benefits for the individual and healthcare system. However, there was often low awareness of screening and there were psychological challenges associated with screening. Prison healthcare staff were widely respected and were a motivator to accept screening, with prisoners viewing prison as a good opportunity to access health care. Despite this, prison life was characterised by competing priorities, with security taking precedence, and screening sometimes a low priority for staff and prisoners. There were also considerable logistical challenges to delivering bowel cancer screening in a prison, and the system was not comparable with that in the community. Providing good-quality understandable information, though challenging, was key. CONCLUSIONS: This is the first project to explore entering the bowel cancer screening programme in UK prisons, and promoting and impeding factors to the take-up of screening have been identified. This information could be practically used by local commissioners and policymakers to aid the design of staff and prisoner interventions to maximise uptake of bowel cancer screening in prisons. As the planned changes to bowel cancer screening in England are likely to increase the number of eligible prisoners, this work could also be used to inform any service reconfiguration required to accommodate these changes.

Standardized programming to reduce the burden of inappropriate therapies in implantable cardioverter defibrillators - Single centre follow up results.

BACKGROUND: Current algorithms and device morphology templates have been proposed in current Implantable Cardioverter-Defibrillators (ICDs) to minimize inappropriate therapies (ITS), but this has not been completely successful. AIM: Assess the impact of a deliberate strategy of using an atrial lead implant with standardized parameters; based on all current ICD discriminators and technologies, on the burden of ITS. METHOD: A retrospective single-centre analysis of 250 patients with either dual chamber (DR) ICDs or biventricular ICDs (CRTDs) over a (41.9 ± 27.3) month period was performed. The incidence of ITS on all ICD and CRTD patients was chronicled after the implementation of standardized programming. RESULTS: 39 events of anti-tachycardial pacing (ATP) and/or shocks were identified in 20 patients (8% incidence rate among patients). The total number of individual therapies was 120, of which 34% were inappropriate ATP, and 36% were inappropriate shocks. 11 patients of the 250 patients received ITS (4.4%). Of the 20 patients, four had ICDs for primary prevention and 16 for a secondary prevention. All the episodes in the primary indication group were inappropriate, while seven patients (43%) of the secondary indication group experienced inappropriate therapies. CONCLUSIONS: The burden of ITS in the population of patients receiving ICDs was 4.4% in the presence of atrial leads. The proposed rationalized programming criteria seems an effective strategy to minimize the burden of inappropriate therapies and will require further validation.

Development of a portable blood salvage and autotransfusion technology to enhance survivability of personnel requiring major medical interventions in austere or military environments.

INTRODUCTION: Uncontrolled haemorrhage is the leading cause of death on the battlefield, and two-thirds of these deaths result from non-compressible haemorrhage. Blood salvage and autotransfusion represent an alternative to conventional blood transfusion techniques for austere environments, potentially providing blood to the casualty at point of injury. The aim of this paper is to describe the design, development and initial proof-of-concept testing of a portable blood salvage and autotransfusion technology to enhance survivability of personnel requiring major medical interventions in austere or military environments. METHOD: A manually operable, dual-headed pump was developed that removes blood from site of injury to a collection reservoir (upper pump) and back to casualty (lower pump). Theoretical flow rate calculations determined pump configuration and a three-dimensionally printed peristaltic pump was manufactured. Flow rates were tested with fresh bovine blood under laboratory conditions representative of the predicted clinical environment. RESULTS: Mathematical modelling suggested flow rates of 3.6 L/min and 0.57 L/min for upper and lower pumps. Using fresh bovine blood, flow rates produced were 2.67 L/min and 0.43 L/min. To mimic expected battlefield conditions, upper suction pump flow rate was calculated using a blood/air mixture. CONCLUSION: The authors believe that this technology can potentially enhance survivability for casualties in austere and deployed military settings through autotransfusion and cell concentration. It reduces negative effects of blood donation on the conventional donor pool, and potentially negates the logistical constraints associated with allogenic transfusions.

Impact of gain-of-function mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) on glucose and lipid homeostasis.

LRP5 loss-of-function mutations have been shown to cause profound osteoporosis and have been associated with impaired insulin sensitivity and dysregulated lipid metabolism. We hypothesized that gain-of-function mutations in LRP5 would also affect these parameters. We therefore studied individuals with LRP5 gain-of-function mutations exhibiting high bone mass (HBM) phenotypes and found that while there was no detected change in insulin sensitivity, there was a significant reduction in serum LDL. INTRODUCTION: Wnt signaling through LRP5 represents a newly appreciated metabolic pathway, which potentially represents a target for drug discovery in type 2 diabetes and hyperlipidemia. Studies in animal models suggest a physiologic link between LRP5 and glucose and lipid homeostasis; however, whether it plays a similar role in humans is unclear. As current literature links loss-of-function LRP5 to impaired glucose and lipid metabolism, we hypothesized that individuals with an HBM-causing mutation in LRP5 would exhibit improved glucose and lipid homeostasis. Since studies in animal models have suggested that Wnt signaling augments insulin secretion, we also examined the effect of Wnt signaling on glucose-stimulated insulin secretion on human pancreatic islets. METHODS: This was a matched case-control study. We used several methods to assess glucose and lipid metabolism in 11 individuals with HBM-causing mutations in LRP5. Affected study participants were recruited from previously identified kindreds with HBM-causing LRP5 mutations and included 9 males and 2 females. Two subjects that were being treated with insulin for type 2 diabetes were excluded from our analysis, as this would have obscured our ability to determine the impact of gain-of-function LRP5 mutations on glucose metabolism. The mean age of the evaluated study subjects was 55 ± 7 with a mean BMI of 27.2 ± 2.0. Control subjects were matched and recruited from the general community at an equivalent ratio, with 18 males and 4 females (mean age 56 ± 4; mean BMI 27.2 ± 1.0). Study testing was conducted at an academic medical center. RESULTS: There were no statistically significant differences between affected and matched control populations for HbA1c (p = 0.06), eAG (p = 0.06), insulin (p = 0.82), HOMA-B (p = 0.34), or HOMA-IR (p = 0.66). The mean Insulin Sensitivity Index (ISI) was also similar between control and affected individuals. Total cholesterol (p = 0.43), triglycerides (TG) (p = 0.56), and HDL (p = 0.32) were not different between the same two groups. In a small subset of studied subjects, intramyocellular and hepatic lipid content were similar in the affected individuals and controls when quantified by proton magnetic resonance spectroscopy (MRS). However, the mean value for serum LDL was significantly lower (p = 0.04) in affected individuals. In primary human islets, there were no differences between control and Wnt treatment groups for insulin secretion measured as area under the curve (AUC) for first phase (p = 0.17) or second phase (p = 0.33) insulin secretion. CONCLUSIONS: Although our sample size was small, our data do not support the hypothesis that HBM-causing LRP5 mutations, associated with increased Wnt signaling, improve glucose metabolism in humans. However, it does appear that LRP5 variants may affect LDL metabolism, a major risk factor for coronary artery disease. The molecular mechanisms underpinning this effect warrant further study.

Stretch training induces unequal adaptation in muscle fascicles and thickness in medial and lateral gastrocnemii.

This study compared adaptations in fascicle lengths, pennation angles, and muscle thickness of the lateral and medial gastrocnemii in response to 6 weeks of stretch training. The nondominant plantar flexors of 11 males were stretched five times per week for 6 weeks and compared with the contralateral leg and a nonstretched control group of 10 males. During stretch training, instantaneous electromyography was utilized to ensure passive muscle stretch. At baseline, week three, week six and 1 week after the conclusion of stretch training, ultrasound was used to measure fascicle lengths, pennation angles, muscle thickness of the lateral gastrocnemius and medial gastrocnemius, and Achilles tendon thickness and length. Plantar flexion torque was measured, and voluntary activation was assessed. Muscle thickness increased 5.6% after 6 weeks of stretch training (P=.009). The fascicles in the lateral gastrocnemius lengthened to a greater extent than the medial. Overall, fascicles lengthened 25% (P<.001) in the muscle tendon junction and 5.1% (P<.001) in the muscle belly. Pennation angles were unchanged in the medial gastrocnemius but decreased in the lateral gastrocnemius 7.1% (P=.02). There was no change in maximal voluntary contraction, voluntary activation, tendon length, or thickness. This study demonstrates that stretch training is a viable modality to alter muscle architecture of the human gastrocnemius through lengthening of muscle fascicles, decreasing pennation angles, and increasing muscle thickness, albeit adaptations are unequal between the lateral and medial heads.

Usage of allergy codes in primary care electronic health records: a national evaluation in Scotland.

BACKGROUND: The UK's NHS intends to move from the current Read code system to the international, detailed Systematized Nomenclature of Medicine Clinical Terms (SNOMED-CT) to facilitate more clinically appropriate coding of conditions and associated risk factors and outcomes. Given concerns about coding behaviour of general practitioners, we sought to study the current coding patterns in allergies and identify lessons for the future migration to SNOMED-CT. METHODS: Data from 2 014 551 primary care consultations in over 100 000 patients with one or more of 11 potentially allergic diseases (anaphylaxis, angioedema, asthma, conjunctivitis, drug allergies, eczema, food allergy, rhinitis, urticaria, venom allergy and other probable allergic disorders) from the Scottish Primary Care Clinical Informatics Unit Research (PCCIU-R) database were descriptively analysed and visualized to understand Read code usage patterns. RESULTS: We identified 352 Read codes for these allergic diseases, but only 36 codes (10%) were used in 95% of consultations; 73 codes (21%) were never used. Half of all usage was for Quality and Outcomes Framework codes for asthma. Despite 149 detailed codes (42%) being available for allergic triggers, these were infrequently used. CONCLUSIONS: This analysis of Read codes use suggests that introduction of the more detailed SNOMED-CT, in isolation, will not improve the quality of allergy coding in Scottish primary care. The introduction of SNOMED-CT should be accompanied by initiatives aimed at improving coding quality, such as the definition of terms/codes, the availability of terminology browsers, a recommended list of codes and mechanisms to incentivize detailed coding of the condition and the underlying allergic trigger.

Duration of fascicle shortening is affected by muscle architecture and sex.

PURPOSE: The purpose of this study was to examine muscle fascicle properties of the gastrocnemius medialis (GM) during contraction and stretch between males and females. During contraction muscle fascicles shorten and pennation angles increase to generate force. Due to the elastic nature of the attached tendon, the fascicles continue to shorten when maximal force is achieved in order to sustain isometric force and this duration of fascicle shortening (DFS) can be observed with ultrasonography. Linear and curved muscle fascicles both display these kinetics; however, it is currently unknown if static stretch prior to a maximal voluntary contraction (MVC) alters the DFS and whether the effect differs between males and females. METHODS: Subjects performed an isometric MVC of the plantar flexors before and after a 2-min maximal dorsi-flexion stretch. Plantar flexor force was measured and ultrasound videography used to record GM and Achilles tendon architecture. RESULTS: Males were stronger than females (p = 0.004). The DFS was longer for females compared to males (p = 0.001) and the addition of a static stretch increased the DFS for curved (p = 0.002), but not linear, fascicles. Curved fascicles were longer (p = 0.05) with larger pennation angles (p = 0.04) for both males and females when compared to linear fascicles. Tendon excursion was greater (p = 0.05) post-stretch during contraction when compared to pre-stretch. CONCLUSIONS: This study provides evidence that regardless of sex, curved muscle fascicles behave differently than linear fascicles and should be considered separately when muscle architecture is examined.

Determination of the allelic frequency in Smith-Lemli-Opitz syndrome by analysis of massively parallel sequencing data sets.

Data from massively parallel sequencing or 'Next Generation Sequencing' of the human exome has reached a critical mass in both public and private databases, in that these collections now allow researchers to critically evaluate population genetics in a manner that was not feasible a decade ago. The ability to determine pathogenic allele frequencies by evaluation of the full coding sequences and not merely a single nucleotide polymorphism (SNP) or series of SNPs will lead to more accurate estimations of incidence. For demonstrative purposes, we analyzed the causative gene for the disorder Smith-Lemli-Opitz Syndrome (SLOS), the 7-dehydrocholesterol reductase (DHCR7) gene and determined both the carrier frequency for DHCR7 mutations, and predicted an expected incidence of the disorder. Estimations of the incidence of SLOS have ranged widely from 1:10,000 to 1:70,000 while the carrier frequency has been reported as high as 1 in 30. Using four exome data sets with a total of 17,836 chromosomes, we ascertained a carrier frequency of pathogenic DHRC7 mutations of 1.01%, and predict a SLOS disease incidence of 1/39,215 conceptions. This approach highlights yet another valuable aspect of the exome sequencing databases, to inform clinical and health policy decisions related to genetic counseling, prenatal testing and newborn screening.

Voice outcomes after endoscopic treatment of laryngotracheal stenosis.

OBJECTIVE: This study aimed to assess vocal disability in patients with laryngotracheal stenosis who are managed with endoscopic surgery, comparing patients with posterior glottic stenosis (PGS) to those with subglottic or tracheal stenosis (SGS/TS). METHODS: Patients who underwent endoscopic treatment for laryngotracheal stenosis with voice outcomes data from 2005 to 2013 were studied. The mean Voice Handicap Index-10 (VHI-10) was compared over the study period. Of those with SGS/TS, the distance from the vocal folds to the proximal portion of the stenosis was obtained and compared to VHI-10. RESULTS: Forty-four patients met inclusion criteria. The mean VHI-10 for all patients was 14.6. Fifty percent were dysphonic (VHI-10>11). The mean VHI-10 for PGS patients was 22.4, and for SGS/TS patients, 10.9 (P=.004). Of those with PGS, 78.6% were dysphonic compared to only 36.7% of those with SGS/TS. Voice Handicap Index-10 improved from 14.1 for those with proximal stenosis to 4 for those with stenosis more than 2 cm distal to the vocal folds. CONCLUSION: Following endoscopic management of stenosis, those with PGS have poorer voice outcomes compared to those with SGS/TS. The majority of those with SGS/TS are not dysphonic. Vocal outcomes are greatest for those with stenosis beginning at least 2 cm distal to the vocal folds.

Trivalent inactivated seasonal influenza vaccine effectiveness for the prevention of laboratory-confirmed influenza in a Scottish population 2000 to 2009.

To evaluate seasonal trivalent inactivated influenza vaccine effectiveness (VE) in Scotland, we performed a Scotland-wide linkage of patient-level primary care, hospital and virological swab data from 3,323 swabs (pooling data over nine influenza seasons: 2000/01 to 2008/09). We estimated the VE for reducing realtime RT-PCR-confirmed influenza using a test-negative study design. Vaccination was associated with a 57% (95% confidence interval (CI): 31­73) reduction in the risk of PCR-confirmed influenza. VE was 60% (95% CI:22­79) for patients younger than 65 years and clinically at risk of serious complications from influenza, and 19% (95% CI: −104 to 68) for any individual 65 years and older. Vaccination was associated with substantial, sustained reductions in laboratory-confirmed influenza in the general population and younger patients in clinical at-risk groups.

Crossability of Arachis valida and B genome Arachis species.

The peanut (Arachis hypogaea) is an important food crop in much of the tropical and semi-tropical parts of the world. The peanut is an allotetraploid with an AABB genome formula derived from diploids A. duranensis (A genome) and A. ipaënsis (B genome). The success of an introgression program that aims to improve cultivated varieties of the peanut depends on whether the chosen B genome species is homologous with the B genome of the peanut. While not directly involved in the origin of the peanut to the best of our knowledge, Arachis valida is a B genome species that could potentially be a bridge species or a source of new and different alleles, because of its resistance to diseases and pests. In this study, we investigated the crossability of A. valida with five other B genome species of section Arachis. Eight cross-combinations were made with A. valida and A. gregoryi, A. ipaënsis, A. magna, A. valida, and A. williamsii. Two hundred and forty pollinations were made yielding 61 fruit segments, 61 seeds, one abortion, and 24 hybrid plants. An analysis of the morphological characteristics and pollen viability confirmed that the plants were hybrids. Our results indicated that higher pollen viability of hybrid plants corresponded with higher affinity between parent plants used in crossings. This conclusion corroborates much of previous research carried out by many other authors in the past.

Improving medication adherence in rheumatoid arthritis (RA): a pilot study.

The aim of this exploratory pilot study was to adapt a psychological intervention to improve adherence to medication for patients with rheumatoid arthritis (RA). The approach draws on cognitive behavioural therapy (CBT) techniques, including motivational interviewing . The current study aimed to (i) adapt the intervention for patients with RA, (ii) assess its effectiveness in improving adherence to medication and (iii) evaluate patients' experience of the intervention. Participants were randomly allocated to either the 'intervention group' (N = 10), receiving up to six weekly sessions of 'Compliance Therapy', or to the 'wait-list control' group (N = 8), who received standard care. Data was collected pre intervention (baseline), post intervention and at six weeks post intervention (follow-up). Eighteen female participants with a mean age of 48.78 years (SD 15.12) took part in the study. Comparisons across the two time points for each group found that only those in the 'intervention' group demonstrated significant improvement in mean scores on adherence measures. Between-group comparisons were not significant. The pilot study suggests that an intervention based on CBT may improve adherence in patients with RA, but further research is required.

The effects of diabetes medications on post-operative long bone fracture healing.

PURPOSE: Diabetes has long been known to have an impact on bone repair. More recently, however, most diabetic patients receive medications to normalise this hyperglycaemic environment. To date, no studies have investigated the effects of diabetic medications on fracture healing in humans. METHOD: Patients were identified from two tertiary trauma centres. Inclusion criteria were adult patients having sustained a closed diaphyseal femoral or tibial fracture, treated surgically. Exclusion criteria were open, pathological or peri-prosthetic fractures, and patients having sustained polytrauma. Matched non-diabetic controls were identified, matched for age, sex, fracture classification and osteosynthesis. Output measures were: time to callus first appearance, bridging of involved cortices and time to union, along with the eventual outcome: union/non-union. RESULTS: A total of 36 (25 males) eligible patients were identified with a control group of 166 patients (138 males). ANOVA demonstrated class of medication to have a significant effect at two of the three time points and on the eventual outcome. Multiple regression analysis also demonstrated significant impact (p = 0.02). CONCLUSION: All classes of medication demonstrated anti-osteogenic effects compared to the control cohort. Biguanides demonstrated this in contrast to the in vitro evidence to date. Sulphonylureas demonstrated this to a greater extent; however, no in vitro evidence is available for comparison within this class. Clinicians should be aware of these delays in bone healing when treating diabetic patients and aim for optimal blood glucose control until such time as further research can be undertaken.

Serum levels of sclerostin, Dickkopf-1, and secreted frizzled-related protein-4 are not changed in individuals with high bone mass causing mutations in LRP5.

SUMMARY: We compared circulating levels of Wnt inhibitors among patients with high bone mass mutations in LRP5, unaffected kindred, and unrelated normal controls. Inhibitors were unchanged in affected and unaffected kindred. We saw no meaningful differences between controls and affected individuals. LRP5 signaling may not influence circulating levels of these inhibitors. INTRODUCTION: It is thought that gain-of-function mutations in LRP5 result in high bone mass syndromes because these allelic variants confer resistance to the actions of endogenous inhibitors of Wnt signaling. We therefore attempted to determine if circulating levels of Wnt inhibitors are altered in patients with gain-of-function mutations in LRP5. METHODS: This is a cross-sectional study in a university research center. Serum was collected from consented volunteers known to have either the G171V or N198S gain-of-function mutations in LRP5, kindred members affected with either mutation, unrelated kindred, and unrelated normal age-matched controls. BMD was provided or measured on site. RESULTS: There were no significant differences found in the serum levels of sclerostin (SOST), Dickkopf-1 (Dkk-1), or secreted frizzled-related protein-4 (SFRP-4) in affected vs. unaffected individuals from different kindreds or when compared to age-matched unrelated normal individuals. Mean serum SOST values in affected and unaffected kindred members and unrelated normal controls were 52.7 ± 6.1, 36.5 ± 9.6, and 54.8 ± 5.4, respectively. For Dkk-1, the values were 25.9 ± 3.4, 25.7 ± 3.0, and 17.3 ± 2.3 and for SFRP-4, 38.1 ± 2.3, 39.8 ± 3.6, and 28.5 ± 1.7. Serum levels of RANKL and osteoprotegerin (OPG) were not different in the three groups. CONCLUSIONS: Circulating levels of endogenous Wnt inhibitors do not change in patients with gain-of-function mutations in LRP5 including Dkk1, which is suppressed by Wnt signaling. It may be that circulating levels of Wnt inhibitors do not reflect changes in target tissues. It is also possible that other mechanisms besides or in addition to resistance in Wnt inhibitors explains the skeletal effects of these mutations.

Prevalence of polypharmacy in a Scottish primary care population.

PURPOSE: Polypharmacy-the use of multiple medications by a single patient-is an important issue associated with various adverse clinical outcomes and rising costs. It is also a topic rarely addressed by clinical guidelines. We used routine Scottish health records to address the lack of data on the prevalence of polypharmacy in the broader, adult primary care population, particularly in relation to long-term conditions. METHODS: We conducted a cross-sectional analysis of adult electronic primary healthcare records and used linear regression models to examine the association between the number of medicines prescribed regularly and both multimorbidity and specific clinical conditions, adjusting for age, gender and socioeconomic deprivation. RESULTS: Overall, 16.9 % of the adults assessed were receiving four to nine medications, and 4.6 % were receiving ten or more medications, increasing with age (28.6 and 7.4 %, respectively, in those aged 60-69 years; 51.8 and 18.6 %, respectively, in those aged ≥ 80 years), but relatively unaffected by gender or deprivation. Of those patients with two clinical conditions, 20.8 % were receiving four to nine medications, and 1.1 % were receiving ten or more medications; in those patients with six or more comorbidities, these values were 47.7 and 41.7 %, respectively. The number of medications varied considerably between clinical conditions, with cardiovascular conditions associated with the greatest number of additional medications. The accumulation of additional medicines was less with concordant conditions. CONCLUSIONS: Polypharmacy is common in UK primary care. The main factor associated with this is multimorbidity, although considerable variation exists between different conditions. The impact of clinical conditions on the number of medicines is generally less in the presence of co-existing concordant conditions.