tbuckley/cabot-search huggingface dataset:
Efficacy of foot orthoses for the treatment of plantar heel pain: a systematic review and meta-analysis
Authors: Nadine Rasenberg, Henrik Riel, Michael S Rathleff, Sita M A Bierma-Zeinstra, Marienke van Middelkoop
Journal: British Journal of Sports Medicine (2018)

Background Plantar heel pain (PHP) is common. Foot orthoses are often applied as treatment for PHP, even though there is little evidence to support this. Objective To investigate the effects of different orthoses on pain, function and self-reported recovery in patients with PHP and compare them with other conservative interventions. Design Systematic review and meta-analysis. Data sources A systematic literature search was conducted in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, CINAHL and Google Scholar up to January 2017. Eligibility criteria for selecting studies Randomised controlled trials comparing foot orthoses with a control (defined as no intervention, sham or other type of conservative treatment) reporting on pain, function or self-reported recovery in patients with PHP. Results Twenty studies investigating eight different types of foot orthoses were included in the review. Most studies were of high quality. Pooled data from six studies showed no difference between prefabricated orthoses and sham orthoses for pain at short term (mean difference (MD) of 0.26 (95% CI −0.09 to 0.60)). No difference was found between sham orthoses and custom orthoses for pain at short term (MD 0.22 (95% CI −0.05 to 0.50)), nor was there a difference between prefabricated orthoses and custom orthoses for pain at short term (MD 0.03 (95% CI −0.15 to 0.22)). For the majority of other interventions, no significant differences were found. Conclusions Foot orthoses are not superior for improving pain and function compared with sham or other conservative treatment in patients with PHP. PROSPERO registration number CRD42015029659.
Public Health England defends appointments of heads of public health without specialty training
Authors: Helen Jaques
Journal: BMJ (2013)

Public Health England has defended the process for appointing senior public health staff to local authorities, amid concern that some councils have appointed people without appropriate specialty training.

Lancashire County Council, Telford and Wrekin Council, and Bolton Council have appointed people who aren’t trained in public health to take charge of joint public health and social services departments.1 The Faculty of Public Health said that the appointments were a “disaster” and could undermine the recruitment and retention of public health doctors at local authorities.

Public Health England has clarified that these public health leads …
Is There Any Potential of FDG PET/CT in Monitoring Disease Activity in Familial Hemophagocytic Lymphohistiocytosis?
Authors: YongXiang Tang, HongPei Tan, Shuo Hu
Journal: Clinical Nuclear Medicine (2018)

Abstract FDG PET/CT was performed in a 30-year-old woman to detect the source of fever of unknown origin. The images showed widespread abnormal activity, consistent with lymphoma. However, lymph node biopsy revealed only inflammation, and a diagnosis of familial hemophagocytic lymphohistiocytosis was eventually made after familial hemophagocytic lymphohistiocytosis–specific gene was detected. After proper therapy, a follow-up FDG PET/CT examination 2 months later showed resolution of most of the previously seen lesions.
Activity holidays for children
Authors: Hannah Milton
Journal: BMJ (2006)

The 5-year survival of patients with pancreatic cancer is poor and, despite oncological advances over the past two decades, has not significantly improved. However, there have been several surgical and oncological advances which have improved morbidity and mortality in surgery and more efficacious chemotherapy regimens, resulting in a better patient experience and an increase in survival by a number of months. Most patients have a tumour at the head of the pancreas and those with resectable disease undergo a pancreaticoduodenectomy, which can be performed laparoscopically. Those who have a pancreatic resection have an increased survival in comparison with those receiving oncological treatment only; however, only a quarter of patients have resectable disease at diagnosis. Some centres are now performing venous resections and/or arterial resections in order to increase the number of patients eligible for curative surgery. Innovative techniques using ablation technologies to downstage tumours for resection are also being investigated. After surgery, all patients should be offered adjuvant gemcitabine-based chemotherapy. Those with locally advanced tumours not suitable for surgery should be offered FOLFIRINOX chemotherapy, after which the tumour may be suitable for surgical resection. The use of radiotherapy in this group of patients is controversial but offered by a few centres. Patients with metastatic disease at diagnosis should also be offered FOLFIRINOX chemotherapy, which can improve survival by a few months. As our knowledge of the tumour biology of pancreatic cancer progresses, a number of new agents targeting specific genes and proteins are under investigation and there is hope that median survival will continue to improve over the next decade.
Multivalent Binding and Biomimetic Cell Rolling Improves the Sensitivity and Specificity of Circulating Tumor Cell Capture
Authors: Ja Hye Myung, Michael J. Eblan, Joseph M. Caster, Sin-Jung Park, Michael J. Poellmann, Kyle Wang, Kevin A. Tam, Seth M. Miller, Colette Shen, Ronald C. Chen, Tian Zhang, Joel E. Tepper, Bhishamjit S. Chera, Andrew Z. Wang, Seungpyo Hong
Journal: Clinical Cancer Research (2018)

Abstract Purpose: We aimed to examine the effects of multivalent binding and biomimetic cell rolling on the sensitivity and specificity of circulating tumor cell (CTC) capture. We also investigated the clinical significance of CTCs and their kinetic profiles in patients with cancer undergoing radiotherapy treatment. Experimental Design: Patients with histologically confirmed primary carcinoma undergoing radiotherapy, with or without chemotherapy, were eligible for enrollment. Peripheral blood was collected prospectively at up to five time points, including before radiotherapy, at the first week, mid-point and final week of treatment, as well as 4 to 12 weeks after completion of radiotherapy. CTC capture was accomplished using a nanotechnology-based assay (CapioCyte) functionalized with aEpCAM, aHER-2, and aEGFR. Results: CapioCyte was able to detect CTCs in all 24 cancer patients enrolled. Multivalent binding via poly(amidoamine) dendrimers further improved capture sensitivity. We also showed that cell rolling effect can improve CTC capture specificity (% of captured cells that are CK+/CD45−/DAPI+) up to 38%. Among the 18 patients with sequential CTC measurements, the median CTC decreased from 113 CTCs/mL before radiotherapy to 32 CTCs/mL at completion of radiotherapy (P = 0.001). CTCs declined throughout radiotherapy in patients with complete clinical and/or radiographic response, in contrast with an elevation in CTCs at mid or post-radiotherapy in the two patients with known pathologic residual disease. Conclusions: Our study demonstrated that multivalent binding and cell rolling can improve the sensitivity and specificity of CTC capture compared with multivalent binding alone, allowing reliable monitoring of CTC changes during and after treatment. Clin Cancer Res; 24(11); 2539–47. ©2018 AACR.
Cotargeting AR signaling and cell cycle: A randomized phase II study of androgen deprivation therapy with or without palbociclib in RB-positive metastatic hormone sensitive prostate cancer (mHSPC).
Authors: Phillip Lee Palmbos, Scott A. Tomlins, Neeraj Agarwal, Przemyslaw Twardowski, Alicia K. Morgans, William Kevin Kelly, Vivek Arora, Emmanuel S. Antonarakis, Javed Siddiqui, Stephanie Daignault, Karen E. Knudsen, Felix Y Feng, Maha Hussain
Journal: Journal of Clinical Oncology (2018)

251 Background: Palbociclib, a CDK4/6 inhibitor, blocked proliferation and promoted G1 arrest in an Rb and Cyclin D dependent manner in preclinical models of HSPC. Alterations in this pathway contribute to the development of CRPC. We hypothesized that co-targeting AR (ADT) and cell cycle (palbociclib) would improve outcomes including PSA RR at 28 weeks in mHSPC pts. Methods: mHSPC pts with Rb intact tumors based on IHC of metastatic biopsy were stratified and randomized (1:2) to Arm A: ADT or Arm B: ADT+ palbociclib (125mg 3 weeks on, 1 week off). Primary endpoint is confirmed PSA RR (≤ 4 ng/mL) after 28 weeks of therapy. With 20 patients randomized to ADT and 40 to ADT + palbociclib there is a 64.2% power to detect a 20% difference in proportions with a one-sided type I error of 0.10 using the mid p-value method of the Fisher’s exact test. Secondary endpoints include safety/tolerability, biochemical and clinical PFS, PSA and radiographic RR and exploratory biomarkers (circulating DNA, tumor cells and transcriptome). Results: 72 eligible pts (median age 67, PSA 73ng/mL) with newly diagnosed mHSPC were registered and underwent biopsy (41 soft tissue, 31 bone). 64/72 (90%) had adequate tissue for RB assessment and 62/64 (97%) retained RB expression (IHC). 62 pts were stratified by disease extent and early initiation of ADT, and randomized. 60 pts initiated therapy (Arm A: 20; Arm B: 40). Neutropenia was the most common G3/4 AE (Arm A: 0% Arm B: 33%). 80% of pts (Arm A: 16/20, Arm B: 32/40; p = 0.87) on both arms met primary PSA endpoint (≤4ng/mL at 28 weeks). PSA undetectable rate at 28 weeks was Arm A: 50% (10/20) and Arm B: 43% (17/40; p = 0.5). Measurable disease RR: Arm A: 78% and Arm B: 74%. 12-month biochemical PFS was Arm A 69% (95%CI: 43-85%), Arm B 74% (95%CI: 56-85%). Clinical PFS is not mature and correlative biomarker studies are ongoing. Conclusions: Co-targeting of AR signaling and cell cycle in a tissue biomarker preselected trial is feasible in mHSPC. RB loss was rare in this population. PSA RR at 28 weeks was not impacted by addition of palbociclib to ADT. Important clinical PFS data will be reported when mature. Clinical trial information: NCT02059213.
Prevalence and Predictors of Cholesterol Screening, Awareness, and Statin Treatment Among US Adults With Familial Hypercholesterolemia or Other Forms of Severe Dyslipidemia (1999–2014)
Authors: Emily M. Bucholz, Angie Mae Rodday, Katherine Kolor, Muin J. Khoury, Sarah D. de Ferranti
Journal: Circulation (2018)

Familial hypercholesterolemia (FH) and other extreme elevations in low-density lipoprotein cholesterol significantly increase the risk of atherosclerotic cardiovascular disease; however, recent data suggest that prescription rates for statins remain low in these patients. National rates of screening, awareness, and treatment with statins among individuals with FH or severe dyslipidemia are unknown.Data from the 1999 to 2014 National Health and Nutrition Examination Survey were used to estimate prevalence rates of self-reported screening, awareness, and statin therapy among US adults (n=42 471 weighted to represent 212 million US adults) with FH (defined using the Dutch Lipid Clinic criteria) and with severe dyslipidemia (defined as low-density lipoprotein cholesterol levels ≥190 mg/dL). Logistic regression was used to identify sociodemographic and clinical correlates of hypercholesterolemia awareness and statin therapy.The estimated US prevalence of definite/probable FH was 0.47% (standard error, 0.03%) and of severe dyslipidemia was 6.6% (standard error, 0.2%). The frequency of cholesterol screening and awareness was high (>80%) among adults with definite/probable FH or severe dyslipidemia; however, statin use was uniformly low (52.3% [standard error, 8.2%] of adults with definite/probable FH and 37.6% [standard error, 1.2%] of adults with severe dyslipidemia). Only 30.3% of patients with definite/probable FH on statins were taking a high-intensity statin. The prevalence of statin use in adults with severe dyslipidemia increased over time (from 29.4% to 47.7%) but not faster than trends in the general population (from 5.7% to 17.6%). Older age, health insurance status, having a usual source of care, diabetes mellitus, hypertension, and having a personal history of early atherosclerotic cardiovascular disease were associated with higher statin use.Despite the high prevalence of cholesterol screening and awareness, only ≈50% of adults with FH are on statin therapy, with even fewer prescribed a high-intensity statin; young and uninsured patients are at the highest risk for lack of screening and for undertreatment. This study highlights an imperative to improve the frequency of cholesterol screening and statin prescription rates to better identify and treat this high-risk population. Additional studies are needed to better understand how to close these gaps in screening and treatment.
COMPARING MYOCARDIAL FIBROSIS QUANTIFICATION METHODS FOR RISK STRATIFICATION IN PATIENTS WITH SUSPECTED MYOCARDITIS USING CARDIAC MAGNETIC RESONANCE IMAGING
Authors: Christoph Gräni, Christian Eichhorn, Loïc Bière, Kyoichi Kaneko, Vikram Agarwal, Venkatesh Murthy, Ayaz Aghayev, Michael Steigner, Ron Blankstein, Michael Jerosch-Herold, Raymond Kwong
Journal: Journal of the American College of Cardiology (2018)
Critical Care in Obstetrics
Authors: Jaya S Dhulkotia
Journal: BMJ (2008)

The recent Safer Childbirth report indicated that labour wards should have provision for up to 10 high dependency unit admissions per 1000 deliveries—that is, about 1% of deliveries.1 In reality the rate is likely to be higher. Moreover, as recognised by the Confidential Enquiry into Maternal and Child Health it is challenging to detect life threatening illness early.2 Further detection alone is of little value; it is the subsequent management that will alter the outcome. Despite this, little training or funding is allocated to …
Abstract 9865: A Validated, Simplified Risk Model for Predicting 6-Month Mortality in Infective Endocarditis
Authors: Larry Park, Vivian Chu, Gail Peterson, Athanasios Skoutelis, Tatjana Lejko-Zupa, Emilio Bouza, Alessandro Tebini, Pierre Tattevin, Gilbert Habib, Ren Tan, Javier Gonzalez, Javier Altclas, Jameela Edathodu, Claudio Q Fortes, Rinaldo F Siciliano, Orathai Pachirat, Souha Kanj, Andrew Wang
Journal: Circulation (2015)

Introduction: Infective endocarditis (IE) is a disease with high in-hospital and longer term mortality. Hypothesis: A validated risk model of prognostic variables may improve clinical risk stratification. Methods: Using a large, multinational, prospective registry of definite IE (International Collaboration on Endocarditis-Prospective Cohort Study, 2000-2006, n=4066), a model to predict 6-month survival was developed by Cox proportional hazard modeling with inverse probability weighting for surgery treatment and internally validated by bootstrapping method. This model was externally validated in an independent prospective registry (ICE-PLUS, 2008-2012, n=1582). Results: Six-month mortality was 964/4066 (23.7%) in ICE-PCS and 346/1582 (21.9%) in ICE-PLUS cohorts. Surgery during the index hospitalization was performed in 49.5% and 56.0% of the cohorts, respectively. In the derivation model, variables related to host factors (age, dialysis), IE characteristics (prosthetic or nosocomial IE, causative organism, left-sided valve vegetation), and IE complications (severe heart failure, stroke, paravalvular complication, and persistent bacteremia) were independently associated with 6-month mortality, and surgery was associated with a lower risk of mortality (Harrell’s C statistic=0.715). In the validation model, these variables had similar hazard ratios (Harrell’s C statistic=0.682), with a similar, independent benefit of surgery (HR=0.74 [95% CI, 0.62-0.89]). Both models differentiated quintiles of risk for 6-month mortality. A simplified risk model was developed by weight-adjustment of these variables. Conclusions: Six-month mortality after IE is approximately 25% and predicted by host factors, IE characteristics, and IE complications. Surgery during the index hospitalization is associated with lower mortality. A simplified risk model may be used to identify specific risk sub-groups in IE.
Techniques and applications of molecular biology
Authors: Emily Shaw
Journal: BMJ (2009)

The techniques and applications of molecular biology course is a four day taught course held in Coventry for medical practitioners and covers recent developments in the field of molecular biology. Where possible, the techniques are illustrated with clinical examples. For an additional fee and some follow-up work, course delegates can register with the University of Warwick for a masters level postgraduate award in techniques and applications of molecular biology. The course is well established—I attended the 36th session, having received recommendations from colleagues who had been on it.

The course is suitable for any doctor who wishes to gain an understanding of molecular biology techniques. The one I attended had training, career, and …
BMA asks doctors to support colleagues in fitness to practise proceedings
Authors: Abi Rimmer
Journal: BMJ (2015)

The BMA is recruiting doctors to support colleagues who are going through fitness to practise investigations.

The doctors will work for the BMA’s Doctors for Doctors unit, which has been commissioned by the General Medical Council to provide independent, confidential, and free support to all doctors.

Last year a GMC report on doctors who died by suicide while under …
Out of hours services in England are improving, finds analysis
Authors: Helen Jaques
Journal: BMJ (2012)

The quality of out of hours services in England was better in 2011 than in previous years, research by the Primary Care Foundation has found.

On average, in 80% of potentially urgent cases a definitive clinical assessment was made within 20 minutes, down from 60% in 2009.

The analysis of out of hours services in …
OUTCOMES OF CHORDAE TENDINAE AND PAPILLARY MUSCLE RUPTURE: RARE BUT POTENTIALLY FATAL COMPLICATION IN ACUTE ST SEGMENT ELEVATION MYOCARDIAL INFARCTION
Authors: Mohit Pahuja, Manmohan Singh, Achint Patel, Kinsuk Chauhan, Emmanuel Akintoye, Tushar Mishra, Tomo Ando, Neha Debnath, Luis Afonso
Journal: Journal of the American College of Cardiology (2018)
Germline pathologic mutations and cancer family history in prostate cancer patients.
Authors: Marcus Marie Moses, Elisa Ledet, Emma M. Ernst, Patrick Cotogno, Joshua Schiff, Brian E. Lewis, A. Oliver Sartor
Journal: Journal of Clinical Oncology (2018)

378 Background: Prostate cancer (PCa) patients (pts) with metastases and/or strong family history (FH) of cancer (Ca) are at higher risk of a germline mutation. The identification of alterations in PCa pts may be important for risk stratification as well as personalizing treatment options. The goal of this study was characterization of FH and pathogenic variants (PV) detected in PCa pts, with both localized and metastatic disease. Methods: 300 PCa pts from Tulane Cancer Center underwent germline testing. 265 Caucasian (C) and 35 African-Americans (AA) were tested and met the NCCN criteria for testing and/or had distant metastases (mets). Germline genetic testing was done via commercial panels (30-80 genes) (Invitae. San Francisco, Ca). PCa pts had extensive FH screening. Clinical annotation included age at diagnosis (dx), race, and presence of mets at any time. Chi square tests were used to compare clinical correlates and PVs. Results: Of the 300 pts tested, 182 pts (60.6%) had mets and 118 (39.4%) did not. 41 pts (13.6%) had ≥ 1 germline pathogenic variant (PV) and 161 pts (53.6%) had ≥ 1 germline variant of uncertain significance (VUS). PVs were detected in BRCA2 (n = 10), MUTYH (n = 8), CHEK2 (n = 6), BRCA1 (n = 4), ATM (n = 4), TP53 (n = 3), PMS2 (n = 2), BLM (n = 2), MITF (n = 2), NBN (n = 1), and RAD51D (n = 1). MUTYH and MITF are not known to be linked to prostate cancer. There was no significant relationships in FH PCa and FH non-PCa in regard to likelihood of a PV (p = .86 and p = .18). Of the 300 pts tested, 136 pts (45.3%) had PCa FH, 131 pts (43.6%) had breast Ca FH, 61 pts (20.3%) had lung Ca FH, 61 pts (20.3%) had colon Ca FH, 37 pts (12.3%) had pancreatic Ca FH, and 32 pts (10.6%) had ovarian Ca FH. 45.6% of C men (n = 121) and 42.8% of AA men (n = 15) had PCa FH. Pts with a non-PCa FH (n = 255) were 1.37 times more likely to develop mets (p = .01168). The median age of dx were 61 for PV pts, 62 for VUS pts, and 61 for negative pts (non-significant). 21/182 pts with mets (11.5%) had a PV; 8/182 (4.4%) pts with mets had a BRCA2 PV. Conclusions: In metastatic patients, FH of prostate cancer alone cannot predict those with PV. The most common Cas observed in these pts were breast, lung, colon and pancreatic. A larger cohort is needed to fully characterize and understand the co-segregation of PCa with other Cas.
Phase 1 Study of Venetoclax in Combination with Dexamethasone As Targeted Therapy for t(11;14) Relapsed/Refractory Multiple Myeloma
Authors: Jonathan L. Kaufman, Cristina J. Gasparetto, Joseph Mikhael, Philippe Moreau, Cyrille Touzeau, Ravi Vij, Thierry Facon, Brigitte Pegourie, Lofti Benboubker, Lawrence H. Boise, Stefanie Alzate, Martin Dunbar, Jia Jia, Kevin J. Freise, Maria Verdugo, Jeremy Ross, Paulo Maciag, Shaji K Kumar
Journal: Blood (2017)
Ten year final results of the TROG 03.04 (RADAR) randomised phase 3 trial evaluating duration of androgen suppression ± zoledronate for locally advanced prostate cancer.
Authors: David John Joseph, David S Lamb, James William Denham, Christopher Oldmeadow, John Attia, Allison Steigler
Journal: Journal of Clinical Oncology (2018)

1 Background: We investigated whether 18 months of androgen suppression (AS) plus radiotherapy (RT) ± 18 months of zoledronate (Z) is more effective than 6 months of neoadjuvant AS plus RT ± Z. Methods: Eligible men with T2a-4, N0, M0 prostatic adenocarcinomas with PSA ≥10 and Gleason score (GS) ≥7 in T2a cases were randomly allocated in a 2x2 factorial trial design to 6 months neo-adjuvant AS using leuprolide (22.5mg i.m. 3 monthly) and radiation (control arm) or followed by treatment factor 1- 12 months AS (22.5mg i.m. 3 monthly), or accompanied by the second treatment factor 2- 18 months Z (4mg i.v. 3 monthly) starting at randomisation, or by both treatment factors. Patients were stratified by centre, baseline PSA, tumour stage, GS, and use of a brachytherapy boost. The primary endpoint was prostate cancer-specific mortality (PCSM). Secondary endpoints included time to PSA, local, distant, bone and soft tissue progressions (PSA, LP, DP, BP and STP) and time to secondary therapeutic intervention and all-cause mortality (STI and ACM). Endpoints were analysed by intention to treat using competing risks methodology. ACM was analysed using Cox regression. Results: Between October 2003 and August 2007 1071 men were randomised with median age 68.7 years. Median follow-up was 10.4 years (IQR 7.9-11.7). No significant interaction was observed between AS and Z. Significant reductions were observed favouring 12 months AS for the primary endpoint: PCSM sHR 0.70 (0.50-0.97), p = 0.035; and for the secondary endpoints: BP sHR 0.61 (0.45-0.83), p = 0.001; DP sHR 0.71 (0.56-0.90), p = 0.004; PSA sHR 0.65 (0.53-0.78), p &lt; 0.001; LP sHR 0.60 (0.39-0.92), p = 0.021; and STI sHR 0.66 (0.53-0.81), p &lt; 0.0001. There were also non-significant reductions favouring 12 months AS in STP (sHR 0.85 [0.62-1.16], p = 0.30) and ACM (HR 0.84 [0.69-1.03], p = 0.10). The addition of 18 months Z did not influence any outcome significantly. Conclusions: 18 months AS+RT is an effective option for locally advanced prostate cancer but the use of 18 months Z is not beneficial. Clinical trial information: NCT00193856.