Schizophrenia polygenic risk score and type 2 diabetes onset in older adults with no schizophrenia diagnosis.

OBJECTIVES: An association between type 2 diabetes (T2DM) and schizophrenia has long been observed, and recent research revealed presence of shared genetic factors. However, epidemiological evidence was inconsistent, some reported insignificant contribution of genetic factors to T2DM-schizophrenia comorbidity. Prior works studied people with schizophrenia, particularly, antipsychotic-naive patients, or those during the first psychotic experience to limit schizophrenia-related environmental factors. In contrast, we controlled such factors by utilizing a general population sample of individuals undiagnosed with schizophrenia. We hypothesized that if schizophrenia genetics impact T2DM development and such impact is not fully mediated by schizophrenia-related environment, people with high polygenic schizophrenia risk would exhibit elevated T2DM incidence. METHODS: Using a population-representative sample of adults aged ≥50 from English Longitudinal Study of Ageing ( n  = 5968, 493 T2DM cases, average follow-up 8.7 years), we investigated if schizophrenia polygenic risk score (PGS-SZ) is associated with T2DM onset. A proportional hazards model with interval censoring was adjusted for age and sex (Model 1), and age, sex, BMI, hypertension, cardiovascular diseases, exercise, smoking, depressive symptoms and T2DM polygenic risk score (Model 2). According to the power calculations, hazard rates > 1.14 per standard deviation in PGS-SZ could be detected. RESULTS: We did not observe a significant association between PGS-SZ and T2DM incidence (hazard ratio 1.04; 95% CI 0.93-1.15; and 1.01, 95% CI 0.94-1.09). CONCLUSION: Our results suggest low contribution of the intrinsic biological mechanisms driven by the polygenic risk of schizophrenia on future T2DM onset. Further research is needed.

Polygenic Propensity for Longevity, APOE-ε4 Status, Dementia Diagnosis, and Risk for Cause-Specific Mortality: A Large Population-Based Longitudinal Study of Older Adults.

To deepen the understanding of genetic mechanisms influencing mortality risk, we investigated the impact of genetic predisposition to longevity and APOE-ε4, on all-cause mortality and specific causes of mortality. We further investigated the mediating effects of dementia on these relationships. Using data on 7 131 adults aged ≥50 years (mean = 64.7 years, standard deviation [SD] = 9.5) from the English Longitudinal Study of Aging, genetic predisposition to longevity was calculated using the polygenic score approach (PGSlongevity). APOE-ε4 status was defined according to the absence or presence of ε4 alleles. The causes of death were ascertained from the National Health Service central register, which was classified into cardiovascular diseases, cancers, respiratory illness, and all other causes of mortality. Of the entire sample, 1 234 (17.3%) died during an average 10-year follow-up. One-SD increase in PGSlongevity was associated with a reduced risk for all-cause mortality (hazard ratio [HR] = 0.93, 95% confidence interval [CI]: 0.88-0.98, p = .010) and mortalities due to other causes (HR = 0.81, 95% CI: 0.71-0.93, p = .002) in the following 10 years. In gender-stratified analyses, APOE-ε4 status was associated with a reduced risk for all-cause mortality and mortalities related to cancers in women. Mediation analyses estimated that the percent excess risk of APOE-ε4 on other causes of mortality risk explained by the dementia diagnosis was 24%, which increased to 34% when the sample was restricted to adults who were aged ≤75 years old. To reduce the mortality rate in adults who are aged ≥50 years old, it is essential to prevent dementia onset in the general population.

Low rate of secondary surgery and implant removal following superior, precontoured plating of midshaft clavicle fractures.

Background: Surgical fixation of midshaft clavicle fractures with a single 3.5 mm superior clavicular plate has been associated with a high rate of hardware removal due to symptomatic hardware. Because of this, dual-plating techniques with lower-profile implants have been proposed. However, dual-plating systems have disadvantages, including increased cost and increased surgical morbidity. The aim of this study was to define the rate of symptomatic hardware removal for all midshaft clavicle fractures. Methods: We retrospectively reviewed information on all patients from 2014 to 2018 at a single level 1 trauma institution with surgeries performed by two fellowship-trained orthopedic trauma surgeons. Documented removal of hardware and the reason for removal were recorded. We then contacted all patients at their listed telephone number to confirm the hardware was still in place and to administer patient outcome questionnaires. If patients did not answer, attempts were made to contact them multiple times on multiple days. Those who were not reached but had documented hardware removal were included in the total number of patients with hardware removal. Results: The search revealed 158 patients, of whom 89 (61.8%) were included in the study. Average follow up was 4.09 years (range 2.02-6.50 years). Five patients (5.56%) underwent hardware removal. Removal was for symptomatic or irritating hardware in two of these patients (2.22%). Average abbreviated Disability of Arm, Shoulder, and Hand score was 6.27, and average American Society of Shoulder and Elbow Surgeons shoulder score was 93.6. Conclusion: In our series, the rate of symptomatic hardware removal was 2.22%, well below reported removal rates. Hardware removal rates for prominent symptomatic superior clavicular plates may be significantly lower than previously reported, and these fractures may be adequately treated with a single, superior plate.

Association of Brain Natriuretic Peptide Levels at Time of Injury with Morbidity and Mortality in Patients with Surgically Treated Hip Fractures.

An elevated brain natriuretic peptide (BNP) level has been shown to be associated with mortality and cardiac events in cardiac surgery, but its utility in the prediction of morbidity and mortality in hip fracture surgery is unknown. The primary aim of this study was to determine if there is a difference in BNP level at the time of injury between patients who do and do not develop complications after hip fracture surgery. The secondary aim was to determine if there is a predictive relationship between complications associated with the initial BNP level and mortality. Methods: A retrospective chart review of 455 hip fractures in patients ≥60 years old that were operatively treated between February 2014 and July 2018 was performed. Patients were included if they had a BNP level within 48 hours after injury (BNPi). Specific perioperative (≤7 days), 30-day, 1-year, and 2-year postoperative complications were recorded. Wilcoxon rank-sum tests were used to determine if higher BNPi values were associated with greater morbidity. The complications associated with higher BNPi values were further analyzed to assess if they were predictive of mortality, using univariate and multivariable analyses. Results: Higher BNPi was significantly associated with greater morbidity at all postoperative time points and with higher mortality at 1 and 2 years postoperatively. Furthermore, several complications including cardiac failure or exacerbation and altered mental status were associated with mortality at all time points in univariate analysis and at many time points in multivariable analysis. Conclusions: Patients with higher BNPi levels were more likely to develop complications up to 1 year postoperatively, and several of these complications were associated with increased mortality. Future studies to determine if delaying surgery until BNP levels are normalized or lowered may help guide management, and may be useful in determining the need for further medical optimization. Future studies aimed at defining a threshold BNP value at the time of injury may also help in better managing patients preoperatively. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Characterizing breast masses using an integrative framework of machine learning and CEUS-based radiomics.

AIMS: We evaluated the performance of contrast-enhanced ultrasound (CEUS) based on radiomics analysis to distinguish benign from malignant breast masses. METHODS: 131 women with suspicious breast masses (BI-RADS 4a, 4b, or 4c) who underwent CEUS examinations (using intravenous injection of perflutren lipid microsphere or sulfur hexafluoride lipid-type A microspheres) prior to ultrasound-guided biopsies were retrospectively identified. Post biopsy pathology showed 115 benign and 16 malignant masses. From the cine clip of the CEUS exams obtained using the built-in GE scanner software, breast masses and adjacent normal tissue were then manually segmented using the ImageJ software. One frame representing each of the four phases: precontrast, early, peak, and delay enhancement were selected post segmentation from each CEUS clip. 112 radiomic metrics were extracted from each segmented tissue normalized breast mass using custom Matlab® code. Linear and nonlinear machine learning (ML) methods were used to build the prediction model to distinguish benign from malignant masses. tenfold cross-validation evaluated model performance. Area under the curve (AUC) was used to quantify prediction accuracy. RESULTS: Univariate analysis found 35 (38.5%) radiomic variables with p < 0.05 in differentiating between benign from malignant masses. No feature selection was performed. Predictive models based on AdaBoost reported an AUC = 0.72 95% CI (0.56, 0.89), followed by Random Forest with an AUC = 0.71 95% CI (0.56, 0.87). CONCLUSIONS: CEUS based texture metrics can distinguish between benign and malignant breast masses, which can, in turn, lead to reduced unnecessary breast biopsies.

Accuracy of contrast-enhanced spectral mammography compared with MRI for invasive breast cancers: Prospective study in population of predominantly underrepresented minorities.

OBJECTIVES: This prospective study compares contrast-enhanced spectral mammography (CESM) with contrast-enhanced breast MRI in assessing the extent of newly diagnosed breast cancer in a multiethnic cohort. METHODS: This study includes 41 patients with invasive breast cancer detected by mammography or conventional ultrasound imaging from May 2017 to March 2020. CESM and MRI scans were performed prior to any treatment. Results are compared with each other and to histopathology. Detection of the malignant lesion was assessed by sensitivity, specificity, PPV, NPV. Consistency of malignant tumor size measurement was compared between modalities using Intraclass Correlation Coefficient (ICC). RESULTS: In a multiethnic cohort with over 65% Hispanic and African-American women, the sensitivity of detecting malignant lesions for CESM is 93.1% (77.23%, 99.15%) and MRI is 96.55% (82.24%, 99.91%). The PPV for CESM 96.43% (81.65%, 99.91%) is better compared to MRI 82.35% (65.47%, 93.24%). CESM is as effective as MRI in evaluating index cancers and multifocal/multicentric/contralateral disease. CESM has greater specificity and PPV since MRI tends to overcall benign lesions. There is a good agreement of tumor size between CESM to surgery and MRI to surgery with ICC of 0.85 (95% CI 0.69, 0.93) and 0.87 (95% CI 0.74, 0.94), respectively. There is good agreement of malignancy detection between CESM and MRI with Kappa of 0.74 (95% CI 0.52, 0.95). CONCLUSIONS: CESM is an effective imaging modality for evaluating the extent of disease in newly diagnosed invasive breast cancers and a good alternative to MRI in a multiethnic population.

Clinical Considerations to Reduce Saphenous Neurovascular Bundle Injury During Suture Button Fixation of Syndesmosis Injuries.

OBJECTIVE: To document angles, from 2 difference starting points, or danger zones that should be avoided to minimize risk of injury or irritation to the saphenous neurovascular bundle (SNVB) during suture button (SB) fixation for distal tibiofibular syndesmosis injuries. DESIGN: Retrospective imaging study. SETTING: Academic Level 1 trauma center. PATIENTS: Forty-eight randomly selected patients with healthy ankles and computed tomography scans for nonankle diagnoses. MAIN OUTCOME MEASURES: Computed tomography scans and 3D reconstructed images were used to define the angle between the SNVB and 2 different fibular starting points, using the direct lateral (DL) and the posterolateral (PL) starting points. Descriptive analyses were performed to identify angles that should be avoided during suture button fixation. Distances from the SNVB using preset angles of 0, 10, 20, and 30 degrees were analyzed. In addition, the width of the SNVB, the midsubstance angle of the SNVB, and the distance from the 30-degree point to the tibialis anterior were recorded. RESULTS: The mean angle between the SNVB and the standard DL starting point was 13.7 ± 5.0 degrees (P < 0.05), whereas the mean angle using the alternate PL starting point was 17.2 ± 5.3 degrees (P < 0.05). The SNVB width was 5.2 mm [range, 2.6-9.1 mm] (P < 0.05). The distances from the SNVB were greatest for the DL 30-degree group and the PL 0-degree group. CONCLUSIONS: The results document angles that should be avoided when using suture button fixation for syndesmosis injuries. Device characteristics and surgery-related variables may require intraoperative modifications, and knowledge of this anatomical relationship may reduce SNVB injury during those situations. Considering our results, we recommend that surgeons place suture buttons from the DL starting point with a 30-degree trajectory to avoid injuries to the SNVB.

Effect of lifestyle, medication and ethnicity on cardiometabolic risk in the year following the first episode of psychosis: prospective cohort study.

BACKGROUND: The first episode of psychosis is a critical period in the emergence of cardiometabolic risk. AIMS: We set out to explore the influence of individual and lifestyle factors on cardiometabolic outcomes in early psychosis. METHOD: This was a prospective cohort study of 293 UK adults presenting with first-episode psychosis investigating the influence of sociodemographics, lifestyle (physical activity, sedentary behaviour, nutrition, smoking, alcohol, substance use) and medication on cardiometabolic outcomes over the following 12 months. RESULTS: Rates of obesity and glucose dysregulation rose from 17.8% and 12%, respectively, at baseline to 23.7% and 23.7% at 1 year. Little change was seen over time in the 76.8% tobacco smoking rate or the quarter who were sedentary for over 10 h daily. We found no association between lifestyle at baseline or type of antipsychotic medication prescribed with either baseline or 1-year cardiometabolic outcomes. Median haemoglobin A1c (HbA1c) rose by 3.3 mmol/mol in participants from Black and minority ethnic (BME) groups, with little change observed in their White counterparts. At 12 months, one-third of those with BME heritage exceeded the threshold for prediabetes (HbA1c >39 mmol/mol). CONCLUSIONS: Unhealthy lifestyle choices are prevalent in early psychosis and cardiometabolic risk worsens over the next year, creating an important window for prevention. We found no evidence, however, that preventative strategies should be preferentially directed based on lifestyle habits. Further work is needed to determine whether clinical strategies should allow for differential patterns of emergence of cardiometabolic risk in people of different ethnicities.

Ischial tuberosity avulsion fracture nonunions in the adolescent population treated with a posterior column screw: A case series of two patients.

Various surgical techniques exist to approach an ischial tuberosity avulsion fracture, including open reduction and internal fixation with screws and suture anchors, augmentation with allograft tendon, and excision of the fragment. However, the majority of these techniques approached acute fractures, and nonunions were not addressed nor studied. This case series describes two adolescent patients treated for ischial tuberosity nonunions with a posterior column screw through a subgluteal approach. Both patients demonstrated radiographic healing of their nonunion sites at 6 months' follow-up. Each patient reported no pain during activity, had symmetric hamstring strength, and were able to return to pre-injury level of activity by final follow-up. In conclusion, the authors utilized a muscle-sparing approach to the ischial tuberosity nonunion site through a cosmetically appealing incision and introduced a novel approach to nonunion fixation without the use of bone graft, resulting in excellent clinical outcomes.

Development of a multivariable gene-expression signature targeting T-cell-mediated rejection in peripheral blood of kidney transplant recipients validated in cross-sectional and longitudinal samples.

BACKGROUND: Acute T-cell mediated rejection (TCMR) is usually indicated by alteration in serum-creatinine measurements when considerable transplant damage has already occurred. There is, therefore, a need for non-invasive early detection of immune signals that would precede the onset of rejection, prior to transplant damage. METHODS: We examined the RT-qPCR expression of 22 literature-based genes in peripheral blood samples from 248 patients in the Kidney Allograft Immune Biomarkers of Rejection Episodes (KALIBRE) study. To account for post-transplantation changes unrelated to rejection, we generated time-adjusted gene-expression residuals from linear mixed-effects models in stable patients. To select genes, we used penalised logistic regression based on 27 stable patients and 27 rejectors with biopsy-proven T-cell-mediated rejection, fulfilling strict inclusion/exclusion criteria. We validated this signature in i) an independent group of stable patients and patients with concomitant T-cell and antibody-mediated-rejection, ii) patients from an independent study, iii) cross-sectional pre-biopsy samples from non-rejectors and iv) longitudinal follow-up samples covering the first post-transplant year from rejectors, non-rejectors and stable patients. FINDINGS: A parsimonious TCMR-signature (IFNG, IP-10, ITGA4, MARCH8, RORc, SEMA7A, WDR40A) showed cross-validated area-under-ROC curve 0.84 (0.77-0.88) (median, 2.5th-97.5th centile of fifty cross-validation cycles), sensitivity 0.67 (0.59-0.74) and specificity 0.85 (0.75-0.89). The estimated probability of TCMR increased seven weeks prior to the diagnostic biopsy and decreased after treatment. Gene expression in all patients showed pronounced variability, with up to 24% of the longitudinal samples in stable patients being TCMR-signature positive. In patients with borderline changes, up to 40% of pre-biopsy samples were TCMR-signature positive. INTERPRETATION: Molecular marker alterations in blood emerge well ahead of the time of clinically overt TCMR. Monitoring a TCMR-signature in peripheral blood could unravel T-cell-related pro-inflammatory activity and hidden immunological processes. This additional information could support clinical management decisions in cases of patients with stable but poor kidney function or with inconclusive biopsy results.

Transdiagnostic Risk Calculator for the Automatic Detection of Individuals at Risk and the Prediction of Psychosis: Second Replication in an Independent National Health Service Trust.

BACKGROUND: The benefits of indicated primary prevention among individuals at Clinical High Risk for Psychosis (CHR-P) are limited by the difficulty in detecting these individuals. To overcome this problem, a transdiagnostic, clinically based, individualized risk calculator has recently been developed and subjected to a first external validation in 2 different catchment areas of the South London and Maudsley (SLaM) NHS Trust. METHODS: Second external validation of real world, real-time electronic clinical register-based cohort study. All individuals who received a first ICD-10 index diagnosis of nonorganic and nonpsychotic mental disorder within the Camden and Islington (C&I) NHS Trust between 2009 and 2016 were included. The model previously validated included age, gender, ethnicity, age by gender, and ICD-10 index diagnosis to predict the development of any ICD-10 nonorganic psychosis. The model's performance was measured using Harrell's C-index. RESULTS: This study included a total of 13702 patients with an average age of 40 (range 16-99), 52% were female, and most were of white ethnicity (64%). There were no CHR-P or child/adolescent services in the C&I Trust. The C&I and SLaM Trust samples also differed significantly in terms of age, gender, ethnicity, and distribution of index diagnosis. Despite these significant differences, the original model retained an acceptable predictive performance (Harrell's C of 0.73), which is comparable to that of CHR-P tools currently recommended for clinical use. CONCLUSIONS: This risk calculator may pragmatically support an improved transdiagnostic detection of at-risk individuals and psychosis prediction even in NHS Trusts in the United Kingdom where CHR-P services are not provided.

Association between depressive symptoms and objectively measured daily step count in individuals at high risk of cardiovascular disease in South London, UK: a cross-sectional study.

OBJECTIVES: Depressive symptoms are common but rarely considered a risk factor for unhealthy lifestyles associated with cardiovascular disease (CVD). This study investigates whether depressive symptoms are associated with reduced physical activity (PA) in individuals at high risk of developing CVD. DESIGN: Secondary analysis of the cross-sectional baseline data from a randomised controlled trial of an intensive lifestyle intervention. SETTING: 135 primary care practices in South London, UK. PARTICIPANTS: 1742 adults, 49-74 years, 86% male at high (≥20%) risk of developing CVD in the next 10 years as defined via QRISK2 score. OUTCOME MEASURES: The main explanatory variable was depressive symptoms measured via the Patient Health Questionnaire-9 (PHQ-9). The main outcome was daily step count measured with an accelerometer (ActiGraph GT3X) stratified by weekdays and weekend days. RESULTS: The median daily step count of the total sample was 6151 (IQR 3510) with significant differences (P<0.001) in mean daily step count between participants with low (PHQ-9 score: 0-4), mild (PHQ-9 score: 5-9) and moderate to severe depressive symptoms (PHQ-9 score: ≥10). Controlling for age, gender, ethnicity, education level, body mass index (BMI), smoking, consumption of alcohol, day of the week and season, individuals with mild depressive symptoms and those with moderate to severe depressive symptoms walked 13.3% (95% CI 18.8% to 7.9%) and 15.6% (95% CI 23.7% to 6.5%) less than non-depressed individuals, respectively. Furthermore, male gender, white ethnicity, higher education level, lower BMI, non-smoking, moderate alcohol intake, weekdays and summer season were independently associated with higher step count. CONCLUSIONS: People at high risk of CVD with depressive symptoms have lower levels of PA. TRIAL REGISTRATION: ISRCTN84864870; Pre-results.

A comparison of machine learning methods for classification using simulation with multiple real data examples from mental health studies.

BACKGROUND: Recent literature on the comparison of machine learning methods has raised questions about the neutrality, unbiasedness and utility of many comparative studies. Reporting of results on favourable datasets and sampling error in the estimated performance measures based on single samples are thought to be the major sources of bias in such comparisons. Better performance in one or a few instances does not necessarily imply so on an average or on a population level and simulation studies may be a better alternative for objectively comparing the performances of machine learning algorithms. METHODS: We compare the classification performance of a number of important and widely used machine learning algorithms, namely the Random Forests (RF), Support Vector Machines (SVM), Linear Discriminant Analysis (LDA) and k-Nearest Neighbour (kNN). Using massively parallel processing on high-performance supercomputers, we compare the generalisation errors at various combinations of levels of several factors: number of features, training sample size, biological variation, experimental variation, effect size, replication and correlation between features. RESULTS: For smaller number of correlated features, number of features not exceeding approximately half the sample size, LDA was found to be the method of choice in terms of average generalisation errors as well as stability (precision) of error estimates. SVM (with RBF kernel) outperforms LDA as well as RF and kNN by a clear margin as the feature set gets larger provided the sample size is not too small (at least 20). The performance of kNN also improves as the number of features grows and outplays that of LDA and RF unless the data variability is too high and/or effect sizes are too small. RF was found to outperform only kNN in some instances where the data are more variable and have smaller effect sizes, in which cases it also provide more stable error estimates than kNN and LDA. Applications to a number of real datasets supported the findings from the simulation study.

Healing Time and Complications in Operatively Treated Atypical Femur Fractures Associated With Bisphosphonate Use: A Multicenter Retrospective Cohort.

OBJECTIVES: The purpose of this study was to characterize demographics, healing time, and complications of a large series of operatively treated atypical femur fractures. DESIGN: Retrospective multicenter review. SETTING: Seventeen academic medical centers. PATIENTS: Bisphosphonate-related fractures as defined by American Society of Bone and Mineral Research. Fractures had to be followed for at least 6 months or to union or revision. INTERVENTION: Operative treatment of bisphosphonate-related fracture. MAIN OUTCOME MEASUREMENTS: Union time and complications of treatment, as well as information about the contralateral limb. RESULTS: There were 179 patients, average age 72, average body mass index 27.2. Average follow-up was 17 months. Twenty-one percent had a previous history of fragility fracture; 34% had prodromal pain. Most (88%) lived independently before injury. Thirty-one percent had radiographic changes suggesting stress reaction. Surgical fixation was with cephalomedullary nail (51%), IM nail (48%), or plate (1%). Complications included death (4), PE (3), and wound infection (6). Twenty (12%) patients underwent revision at an average of 11 months. Excluding revisions, average union time was 5.2 months. For revisions, union occurred at an average of 10.2 months after intervention. No association was identified between discontinuation of bisphosphonates and union time (P = 0.5) or need for revision (P = 0.7). Twenty-one percent sustained contralateral femur fractures; 32% of these had pain and 59% had stress reaction before contralateral fracture. CONCLUSIONS: In this series, surgery had a 12% failure rate and delayed average time to union. Twenty-one percent developed contralateral femur fractures within 2 years, underscoring the need to evaluate the contralateral extremity. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Operatively Treated Meniscal Tears Associated With Tibial Plateau Fractures: A Report on 661 Patients.

OBJECTIVE: To describe the incidence and common patterns of lateral meniscal tears detected intraoperatively and surgically treated based on tibial plateau fracture patterns. DESIGN: Retrospective analysis of a prospective database. SETTING: Level One Regional Trauma Center. METHODS: All tibial plateau fractures in skeletally mature patients treated operatively between 2002 and 2011 were included. All operative notes and radiographs were reviewed to determine type of tibial plateau fracture, mechanism of injury, intraoperative detection of a lateral meniscal tear, and operative repair/partial resection of the meniscus itself. Patients were excluded if there was no mention of a submeniscal arthrotomy, if fracture stabilization was performed percutaneously, or if the fracture was an isolated medial condyle fracture. Statistical analysis was performed using χ analysis and Fisher exact test to determine the overall incidence of lateral meniscal tears and any correlation between meniscal tear and fracture pattern. RESULTS: A total of 602 patients were included in the final analysis. Lateral meniscal tears requiring operative repair were detected intraoperatively in 179 patients (30%). This could be broken down into 12% for pure lateral split fractures, 45% for split depression fractures (P < 0.001), 18% for pure depression fractures, 22% for bicondylar fractures, and 26% for intraarticular plus shaft fractures. Lateral meniscal tears associated with a split depression fracture pattern were most commonly peripheral rim tears (83%). For all other fracture patterns, the type of meniscal injury was evenly distributed between peripheral and radial tear. Young males demonstrated a statistically higher rate of lateral meniscal tears (33%). CONCLUSIONS: In our series, the incidence of a lateral meniscal tear detected intraoperatively requiring repair was 30%. These tears occurred more frequently in young males, with peripheral rim tears most commonly associated with split depression fractures. Based on our data, we believe that preoperative imaging for meniscal injury overstates the true incidence of meniscal tears requiring operative intervention. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

The association between depressive symptoms and systemic inflammation in people with type 2 diabetes: findings from the South London Diabetes Study.

OBJECTIVE: The prevalence of depression and depressive symptoms is increased twofold in people with type 2 diabetes compared with the general population and is associated with worse biomedical outcomes and increased mortality. Type 2 diabetes, cardiovascular disease, and depression in nondiabetes subjects are independently associated with raised concentrations of circulating inflammatory markers, but it is not known if a similar association is observed in type 2 diabetes. We tested the hypothesis that higher depressive symptom scores in newly diagnosed type 2 diabetes patients were associated with higher concentrations of inflammatory markers. RESEARCH DESIGN AND METHODS: Depressive symptoms in adults with newly diagnosed type 2 diabetes recruited from primary care were assessed using the Patient Health Questionnaire-9. Twelve markers of inflammation (C-reactive protein [hs-CRP], interleukin-4 [IL-4], IL-6, IL-10, vascular endothelial growth factor [VEGF], tumor necrosis factor-α [TNF-α], IL-1ß, IL-1 receptor antagonist [IL-1RA], monocyte chemotactic protein-1 [MCP-1], white blood cell count [WBC], adiponectin, and triglyceride [TG]) were measured. Covariates included sociodemographic factors, adiposity, macrovascular disease, HbA1c, and prescribed medication. The association between each inflammatory marker and depressive symptom score was estimated by multiple linear regression. RESULTS: The baseline cohort consisted of 1,790 participants. After adjusting for covariates, CRP (B = 0.13, P < 0.001), IL-1ß (B = 0.06, P = 0.047), IL-1RA (B = 0.13, P < 0.001), MCP-1 (B = 0.11, P = 0.001), WBC (B = 0.13, P < 0.001), and TG (B = 0.10, P < 0.001) were associated with depressive symptoms. CONCLUSIONS: Increased inflammation may be involved in the pathogenesis of depressive symptoms in type 2 diabetes and contribute to the increased risk of complications and mortality in this group.

Improving physical health and reducing substance use in psychosis--randomised control trial (IMPACT RCT): study protocol for a cluster randomised controlled trial.

BACKGROUND: Cardiovascular morbidity and mortality is increased in individuals with severe mental illnesses.We set out to establish a multicentre, two arm, parallel cluster randomized controlled trial (RCT) of a health promotion intervention (HPI), IMPACT Therapy. The patient-tailored IMPACT Therapy aims to target one or more health behaviours from a pre-defined list that includes cannabis use; alcohol use; other substance use; cigarette smoking; exercise; diet and diabetic control, prioritising those identified as problematic by the patient, taking a motivational interviewing and CBT approach. METHODS: Impact therapy will be delivered by care coordinators in the community to the treatment group and will be compared to treatment as usual (TAU). The main hypothesis is that the addition of IMPACT Therapy (HPI) to TAU will be more effective than TAU alone in improving patients' quality of life as measured by the Short Form-36, including mental health and physical health subscales on completion of the intervention at 12 months post randomisation. A subsidiary hypothesis will be that addition of IMPACT Therapy (HPI) will be more cost-effective than TAU alone in improving health in people with SMI 12 months from baseline. The IMPACT therapy patient groups' improvement in quality of life, as well as its cost effectiveness, is hypothesised to be maintained at 15 months. Outcomes will be analyzed on an intention-to-treat (ITT) basis. DISCUSSION: The results of the trial will provide information about the effectiveness of the IMPACT therapy programme in supporting community mental health teams to address physical comorbidity in severe mental illness. TRIAL REGISTRATION: ISRCTN58667926.

Latent tuberculosis infection screening in Minnesota's critical access hospitals.

The prevalence of tuberculosis (TB) declined worldwide during most of the 20th century. However, between 1980 and 1990, the incidence rate rose. Subsequently, the United States, through the Centers for Disease Control and Prevention (CDC), and the United Nations increased efforts to control TB and reduce its burden on population health. One of those efforts has been offering guidance about screening health care workers. This article reports on the findings of an investigation into whether Critical Access Hospitals in Minnesota are following the CDC guidelines for screening and treatment for latent tuberculosis infection. Among the findings, 97% of the hospitals used the two-step tuberculosis skin test (TST) as their baseline test, 29% screened only on hire and 71% screened annually. Our study also found many hospitals do not follow CDC recommendations for TST administration or interpretation, nor do all hospitals refer individuals with positive test results for treatment.

The effects of hypothermia and L-arginine on skeletal muscle function in ischemia-reperfusion injury.

OBJECTIVES: Ischemia-reperfusion (I/R) injury can have detrimental effects on skeletal muscle. We have shown that vessel permeability can be minimized in a hypothermic setting and also by administering the nitric oxide synthase (NOS) stimulator, L-arginine, at physiologic temperatures. The purpose of this study was to examine and compare skeletal muscle contractility after an I/R insult during hypothermic conditions, warm conditions, and also with the administration of L-arginine at physiologic temperatures. We hypothesized that hypothermia and L-arginine administration will also demonstrate protective effects to skeletal muscle contractility. METHODS: Using Sprague-Dawley rats, the extensor digitorum longus muscle was rotated on its vascular pedicle to a thermo-controlled stage. Ischemia was established using an atraumatic femoral artery tourniquet. Reperfusion was performed under control and experimental conditions including local hypothermia and intravenous L-arginine. After harvesting experimental muscles, contractility was then quantified by using a tissue bath stimulator with force transducers. RESULTS: Warm reperfusion resulted in marked decrease in muscle contractility compared with sham animals. Local hypothermia showed statistically significant preservation of contractility compared with the sham group. This protective effect was recapitulated by the application of NOS inducers (L-arginine) at warm conditions. CONCLUSIONS: These findings demonstrate that hypothermia and L-arginine are protective of skeletal muscle contractility after an I/R injury. The results presented may have profound effects on future therapeutic recommendations and suggest possible pathways for clinical intervention to modulate I/R injury, which is commonplace in orthopaedic trauma and reconstructive surgery.

Therapist effects in routine psychotherapy practice: an account from chronic fatigue syndrome.

The effect of therapists in psychotherapy is a much debated topic, with a number of studies showing therapist variance being large while other studies show little or no variability in outcomes due to therapists. The aim of this study was to investigate therapist effects in a well-defined sample of patients and therapists from an outpatient service which specializes in providing cognitive behaviour therapy (CBT) for patients with chronic fatigue syndrome (CFS). Therapy was provided in a highly specialized clinical setting for CFS and was delivered by qualified CBT therapists with at least 2 years experience with this client group. Three hundred and seventy-four patients with CFS and 12 cognitive behavioural psychotherapists took part. Therapist effects on the primary outcomes of fatigue and disability were investigated with multilevel random effects models and variance component analysis. Different models were computed and compared. Results showed a reduction in fatigue and disability scores after therapy. Variance explained by therapists, when demographic covariates were accounted for, was 0% for fatigue and under 2% for disability. A number of important factors may have played a significant role in minimizing therapist effects in our study. These are: specialist setting, single centre, patients with the same primary diagnosis, therapists of the same orientation and training, shared environment and supervision. Future studies may stress the importance of these factors in the investigation of the therapist effect in psychotherapy.