tbuckley/cabot-search huggingface dataset:
Maharashtra government launches mental health programme to reduce suicide in farmers
Authors: Cheryl Travasso
Journal: BMJ (2015)

The Maharashtra government is set to launch a programme with a budget of 7.6 crore rupees (£760 000; €1.03m; $1.16m) to identify farmers with depression, to help stem the rising number of suicides among agricultural workers.1

The rainfall deficit this monsoon season in Marathwada, one of the state’s five regions, has been about 53%, meaning that many dams …
Post-exposure prophylaxis against rabies is still needed after a bite from a vaccinated animal
Authors: Florence Ribadeau Dumas, Nadia Haddad, Philippe Gautret
Journal: BMJ (2016)

Crowcroft and Thampi’s review on rabies reports that, according to 2013 WHO recommendations, risk assessment for post-exposure prophylaxis should take the biting animal’s vaccination status into account.1 This change—WHO previously recommended not normally considering the animal’s vaccination status in developing countries2—might have important consequences.3

Every year, worldwide, 15 million people receive post-exposure …
Randomized trials in oncology stopped early for benefit: A systematic review
Authors: R. A. Wilcox, G. H. Guyatt, V. M. Montori
Journal: Journal of Clinical Oncology (2007)

6513 Background: Investigators finding a large treatment effect in an interim analysis may terminate a randomized trial (RCT) earlier than planned. A systematic review (Montori et. al., JAMA 2005; 294: 2203–2209) found that RCTs stopped early for benefit are poorly reported and may overestimate the true treatment affect. The extent to which RCTs in oncology stopped early for benefit share similar concerns remains unclear. Methods: We selected RCTs in oncology which had been reported in the original systematic review and reviewed the study characteristics, features related to the decision to monitor and stop the study early (sample size, interim analyses, monitoring and stopping rules), and the number of events and the estimated treatment effects. Results: We found 29 RCTs in malignant hematology (n=6) and oncology (n=23), 52% published in 2000–2004 and 41% in 3 high-impact medical journals (New England Journal of Medicine, Lancet, JAMA). The majority (79%) of trials reported a planned sample size and, on average, recruited 67% of the planned sample size (SD 31%). RCTs reported (1) the planned sample size (n=20), (2) the interim analysis at which the study was terminated (n=16), and (3) whether the decision to stop the study prematurely was informed by a stopping rule (n=16); only 13 reported all three. There was a highly significant correlation between the number of events and the treatment effect (r=0.68, p=0.0007). The odds of finding a large treatment effect (a relative risk &lt; median of 0.54, IQR 0.3–0.7) when studies stopped after a few events (no. events &lt; median of 54 events, IQR 22–125) was 6.2 times greater than when studies stopped later. Conclusions: RCTs in oncology stopped early for benefit tend to report large treatment effects that may overestimate the true treatment effect, particularly when the number of events driving study termination is small. Also, information pertinent to the decision to stop early was inconsistently reported. Clinicians and policymakers should interpret such studies with caution, especially when information about the decision to stop early is not provided and few events occurred. No significant financial relationships to disclose.
Contraction without depolarization in the in vivo heart: Kinetic and electronmicroscopic studies
Authors: J. KEDEM, R. YAROM, Y. MAHLER, S. ROGEL
Journal: Cardiovascular Research (1972)

Contraction without depolarization was demonstrated in the in vivo heart after very rapid single or paired stimulation. This occurred when the restitution curves exhibited a descending phase. Electronmicroscopic studies indicated that during the high contractile states induced by rapid electrical heart rates the myofilaments were flooded by Ca++ from their intracellular storage sites.
1,25(OH)2-vitamin D3 reduces spontaneous and hypocalcemia-stimulated pulsatile component of parathyroid hormone secretion.
Authors: C P Schmitt, F Schaefer, D Huber, I Zahn, J D Veldhuis, E Ritz, O Mehls
Journal: Journal of the American Society of Nephrology (1998)

To investigate the effects of 1,25(OH)2-vitamin D3 (1,25(OH)2D3) on pulsatile parathyroid hormone (PTH) release, minute-to-minute intact PTH secretion was examined in nine healthy adults under baseline conditions and during hypocalcemia (sodium citrate clamp) before and after 5 d of oral 1,25(OH)2D3 treatment (1 microgram/d). In addition, acute effects of 1,25(OH)2D3 were examined by a single intravenous bolus of 2 micrograms of 1,25(OH)2D3. Pulsatile and tonic PTH secretion rates were calculated by the multiparameter deconvolution technique. During baseline, 68% of circulating PTH was attributable to tonic, and 32% to pulsatile, secretion. During induction of hypocalcemia, a selective increase in pulsatile secretion (+1100%), mediated by a combined increase in burst frequency and burst mass, was observed. During the subsequent steady-state hypocalcemic period, burst frequency and mass decreased and tonic secretion increased to 3 times the baseline level. Intravenous 1,25(OH)2D3 did not affect the temporal pattern of PTH secretion. In contrast, oral 1,25(OH)2D3 decreased baseline plasma PTH by 30% without a detectable change in Ca2+. This suppression was accounted for mainly by a decrease in PTH burst frequency. During hypocalcemia induction, a significantly lower (30%) increase in burst mass occurred compared with the pretreatment study. During steady-state hypocalcemia, PTH burst mass (-45%) and pulsatile (-50%) and total (-35%) secretion rate were lower than before treatment. In conclusion, acute hypocalcemia selectively increases pulsatile PTH release by stimulating both burst frequency and mass via a Ca2+ rate-sensitive mechanism. Oral 1,25-(OH)2D3 suppresses pulsatile baseline PTH release and reduces the pulsatile secretory capacity of the parathyroids during a hypocalcemic stimulus.
The Egyptian National Breast Screening Program: Priorities, challenges, and results of the pilot phase
Authors: D. S. Salem, R. Kamal, N. H. Said, I. Adel, S. Talaat, L. Adel, N. Abdel Razek, M. Helal, A. Selim
Journal: Journal of Clinical Oncology (2009)

1523 Background: According to the World Health Organization,the number of breast cancercases in developing countries will increase dramatically by the year 2050. Egypt is likely to see an increase in this disease burden unless effective programs for early detection and control are implemented. Many women, especially those who are medically underserved, still do not understand the importance of regular mammograms, or how and where to get one. Methods: Four mobile mammography vans were launched in October 2007, to screen women over 45 years old in the underserved areas of Cairo. Each van was equipped with a full field digital mammography (FFDM) machine, dedicated computer system linked to the National Breast Screening Center via video SAT &amp; ADSL, sphygmomanometer, blood glucose measuring kit, and spring scale and meter to measure weight and height. Based on positive findings, patients were directed to Cairo University Hospital to receive appropriate treatment. Mobile units continued to operate through October, 2008. Results: From October 2007 through October 2008, 11,414 women were screened for breast cancer, hypertension, diabetes, and obesity. Two hundred forty four (2.13%) women were radiologically positive for cancer; of these, only 112 (45.9%) women agreed to be recalled for assessment; of these, 49.1% were confirmed to be true positive with BI-RADS 4,5 (61% cases were mass, with 27.9 % 1–2 cm in size; 16.4% cases were microcalcifications alone; multicentricity in 6.6 %; bilaterality in 2.5% of cases). 36.6% were false positive, and 14.2% are under further investigation. Conclusions: Although Cairo is the most developed city in Egypt, there is lack of breast cancer awareness, especially in the underserved areas. Breast cancer is now a priority for the Ministry of Health, with four more vans and 10 fixed FFDM units to be implemented during the next year. A 5-year plan has been established to cover all 29 Egyptian Governorates. No significant financial relationships to disclose.
Fertility preservation cost and use: Results from the LIVESTRONG survey.
Authors: Ruth Rechis, Stephanie Nutt, Carla Bann
Journal: Journal of Clinical Oncology (2013)

59 Background: Each year nearly 70,000 adolescents and young adults (AYAs) are diagnosed with cancer. Recently, steps have been taken to address infertility, which is an important issue experienced by AYAs. For example, ASCO QOPI includes fertility standards and Walgreens and the LIVESTRONG Foundation provide financial assistance for fertility preservation medications. To better understand the current state of fertility preservation, eight questions on this topic were included on the LIVESTRONG Survey. Methods: From June to December 2012, LIVESTRONG conducted an online survey (N = 6,313). Analysis here includes the 1,333 AYA respondents who were diagnosed since 2002. Results: Only 24% of respondents (42% of males, 12% of females) indicated they took steps to preserve their fertility before beginning treatment. Top reasons for not preserving their fertility were not receiving information about options (19%) and/or information about the risks to their fertility (14%). For the AYAs who did preserve their fertility, the median amount spent on fertility expenses was between $1,000 and $2,499 (Table) with males spending significantly less than females (p &lt; 0.001). Mostly commonly, males used sperm banking (97%) while females used egg and embryo banking (each 35%). The majority all who attempted to become pregnant were successful (58% and 68% respectively). Conclusions: Results from this analysis indicate that few survivors took steps to preserve their fertility before starting treatment. Yet for those who were interested in preserving their fertility and starting a family, the majority of individuals were successful. Many individuals reported not preserving their fertility due to a lack of information or resources. While a relatively small number of survivors will have fertility concerns, this is an important quality of life issue for those who do. [Table: see text]
Hereditary diffuse gastric cancer: Natural history, pathology, screening limitations, and prophylactic total gastrectomy in <i>CDH1</i> mutation carriers
Authors: H. T. Lynch, C. Caldas, D. Wirtzfeld, C. Vaccaro, W. Rubinstein, S. Weissman, P. Kaurah, N. Boyd, R. Fitzgerald, D. Huntsman
Journal: Journal of Clinical Oncology (2007)

4500 Background: Hereditary diffuse gastric cancer (HDGC) is a potentially fatal disease that occurs due to mutations in the E- cadherin (CDH1) gene, as discovered in 1998. Its penetrance ranges between 70–80%. Its morbidity and mortality can be altered favorably through genetic counseling, germline mutation testing, and highly-targeted management that includes prophylactic total gastrectomy. Lobular breast cancer has been identified as an integral lesion in HDGC. Methods: This international collaborative group on HDGC is comprised of 56 mutation-positive families, which is the world’s largest resource of such families. Cancer diagnoses were verified with pathology slides/tissue block review when possible, or reports. Genetic counseling covering the pros and cons of mutation testing, screening and its limitations, and the option of prophylactic total gastrectomy was provided. Results: Findings on 56 HDGC mutation-positive families show carrier testing to have been performed on 267 individuals, of which 123 were CDH1 mutation positive. Prophylactic gastrectomies were performed on 14 families involving 50 individuals. Occult cancer was diagnosed in 31 (31/39=79.5%; results are pending on the remaining 11), based upon pathology and verbal reports. Five individuals underwent prophylactic gastrectomy prior to genetic counseling, 3 of whom later tested negative for mutations. In one of these remarkable HDGC families, 11 first cousins who tested positive for the CDH1 mutation underwent prophylactic total gastrectomy. On a post-surgery questionnaire, they each stated that the decision for the prophylactic procedure was the “right one” for them. In each case, a parent had died of HDGC sequelae, adding to the cousins’ acceptance of DNA testing and surgery. They considered their post-operative nutritional programs to have been acceptable. Conclusion: HDGC and its life-threatening sequelae were significantly ameliorated in CDH1 mutation carriers through total prophylactic gastrectomy in patients at enormous lifetime risk for HDGC. Decision for mutation testing and surgery may be more acceptable through intensive education in concert with a compassionate management team. No significant financial relationships to disclose.
Abstract 11511: Genetic Variation in Retinal Vascular Patterning Predicts Variation in Pial Collateral Extent and Infarct Volume After Middle Cerebral Artery Occlusion
Authors: Pranay Prabhakar, Hua Zhang, De Chen, Stephen Lockett, James E Faber
Journal: Circulation (2014)

Introduction: The presence of a native (pre-existing) collateral circulation in tissues lessens injury in stroke and other occlusive diseases. However, differences in genetic background are accompanied by wide variation in the number and diameter (extent) of native collaterals in mice, resulting in large variation in protection. Indirect evidence suggests a similar wide variation also exists in humans. However, methods of measurement in humans are indirect, invasive and not widely available. Hypothesis: We sought to determine if differences in genetic background in mice result in variation in branch-patterning of the retinal circulation, and if these differences predict differences in collateral extent and, in turn, differences in severity of ischemic stroke. Methods: Patterning metrics were obtained for the retinal arterial trees of 10 mouse strains (n=8 per strain) that differ widely in collateral extent in brain and other tissues. We also obtained pial collateral number and diameter, and infarct volume 24h after permanent middle cerebral artery occlusion. Forward- and reverse-stepwise multivariate regression analysis was conducted and model performance assessed using K-fold cross-validation. Results: Twenty-one metrics varied significantly with genetic strain (p&lt;0.01). Ten metrics (eg, vessel caliber, bifurcation angle, lacunarity, optimality, branch length) strongly predicted collateral number and diameter across 7 regression models. The best models closely predicted (p&lt;0.0001) collateral number (K-fold R 2 =0.83-0.98), diameter (0.73-0.88) and infarct volume (0.85-0.87). Conclusions: Differences in retinal tree patterning are specified by genetic background and closely predict genetic variation in pial collateral extent and, in turn, stroke severity. If these findings can be confirmed in humans, and given that genetic variation in cerebral collaterals extends to other tissues at least in mice, a similar “retinal predictor index” could be developed as a biomarker for collateral extent in brain and other tissues. This could aid prediction of the risk-severity of tissue injury in occlusive disease as well as stratification of patients for treatment options and enrollment in clinical studies.
Abstract 2727: Molecular markers and pathway analysis of Middle Eastern colorectal carcinoma
Authors: Shaham Beg, Sarita Prabhakaran, Rong Bu, Mohammed Al-Assiri, Rami Sairafi, Fouad Al-Dayel, Nasser Al-Sanea, Abdul K. Siraj, Shahab Uddin, Khawla Al-Kuraya
Journal: Cancer Research (2015)

Abstract Colorectal cancer (CRC) is one of the common cancers in the world. In Saudi Arabia CRC is the most common cancer in males and third most common in females. A newly proposed integrated pathways comprising traditional, alternate and serrated by genetic and epigenetic factors was defined recently and hypothesized to role in the pathogenesis of CRC; however there is a paucity of information about these proposed molecular pathways in different ethnic group. Hence we analyzed a large cohort of Saudi colorectal tumors to understand the role of these molecular pathways. 770 archival CRCs specimen were evaluated for Microsatellite Instability (MSI), BRAF, KRAS and 500 cases for CpG Island Methylator Phenotype (CIMP). Traditional pathway constituted 33.4% of CRC cases; the alternate pathway comprised 11.6% of cases. Strikingly, the serrated molecular pathway accounted for only 0.8% of Middle Eastern CRC that is extremely below compared to publish data. 54.2% CRC cases did not qualify to fit into any pathway and thus were designated an unassigned group. Molecular pathways were significantly associated with tumor site and grade. In our attempt to further classify unassigned group a subset of the uncategorized pathway showed a significant survival difference (p = 0.0079). The Unassigned group that accounted for the majority of our cases reflects the heterogeneity of colorectal cancers and warrants the need to unravel the molecular genetic basis of this disease to further subcategorize these CRC cases. It also identifies the need to do further studies on different populations for better understanding of their exact role and incidence. Keywords: colorectal; molecular pathways; serrated Citation Format: Shaham Beg, Sarita Prabhakaran, Rong Bu, Mohammed Al-Assiri, Rami Sairafi, Fouad Al-Dayel, Nasser Al-Sanea, Abdul K. Siraj, Shahab Uddin, Khawla Al-Kuraya. Molecular markers and pathway analysis of Middle Eastern colorectal carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2727. doi:10.1158/1538-7445.AM2015-2727
South West London Cancer Network (SWLCN) audit of patients with chemotherapy-induced febrile neutropenia (CIFN)
Authors: U. Dernedde, S. Chan, H. Sykes, C. Oakley, J. Larkin, S. Popat, D. Gilbert, L. Jones, S. Chowdhury
Journal: Journal of Clinical Oncology (2008)

20653 Background: We audited eligible episodes of CIFN to analyse the frequency and pattern of admissions across the SWLCN. Methods: CIFN was defined as temperature ≥38°C with neutrophils <1.0 × 109/l in patients on chemotherapy. Data was collected over three months between May and July 2007. Results: We documented 71 episodes. In 51 patients, this was the first episode of CIFN. The most frequent cancer diagnosis was hematological (33%), breast cancer (18%), sarcoma (12%) and lung cancer (11%). Most frequently encountered chemotherapy regimes: CHOP (9), Docetaxel (6), AC (5), FEC (3). Chemotherapy intent was palliative in 39, curative in 17, and adjuvant in 15. Most episodes occurred on days 9 and 10 (22%) and during cycles 1 or 2 (50%). 23% had received prophylactic G-CSF, 25% had prophylactic antibiotics. Mean time from arrival to initial assessment was 20 minutes and antibiotic therapy was started within an average of 2.6 hours. The mean neutrophil count was 0.5;average temperature was 38.3. Six patients were hypotensive (≤80 systolic). 35 patients presented with chest-, 33 with gastrointestinal-, symptoms and 13 with mucositis. Chemotherapy had to be delayed in 19 patients (26%). Dose reduction of subsequent chemotherapy was instigated in 10 patients. 4 patients died during the admission for CIFN. 2 deaths were felt to be directly related to the neutropenic episode. Patients were hospitalized for a median of 5 days (range 1 - 60). 22 patients required 2nd line antibiotics, 12 had additional antifungals; 45 received G-CSF. Conclusions: CIFN still poses significant risk of morbidity and mortality. Following this audit, it is envisaged that a network neutropenic admission pathway will be developed to reduce risks and improve patient outcome. No significant financial relationships to disclose.
PTH-128 The weekend effect: the impact of out-of-hours liver transplantation upon transplant survival
Authors: N Halliday, K Martin, E Allen, D Thorburn
Journal: Gut (2015)

<h3>Introduction</h3> There is an excess mortality associated with weekend medical admissions for many conditions and poorer surgical outcomes with night-time (NT) operating. Due to the time critical nature of organ retrieval for liver transplantation many transplants occur ‘out-of-hours’. We sought to identify if there was an impact upon transplant survival (a composite outcome of graft failure or death) with weekend (5pm Friday to 8am Monday) or NT (7 pm to 7 am) liver transplantation. <h3>Method</h3> Data on 8338 liver only transplants were obtained from the UK Transplant Registry, as at 04/01/2015. These included only those with adult NHS group 1 recipients (aged 17 or more) transplanted in the UK from solid organ deceased donors from 1 January 2000 to 31 December 2014. Cox proportional hazard models were created controlling for variables with a statistical impact on survival such as renal support, ventilation status, sepsis, graft appearance, CIT, donor type, split liver and transplant year. <h3>Results</h3> There was a significant reduction in the hazard of the composite outcome of graft failure or death at 30 days (adjusted hazard ratio: 0.79, 95% CI: 0.67–0.93, p-value: 0.01), 90 days (0.83, 0.72–0.95, 0.01), 1 year (0.87, 0.77–0.97, 0.02) and 3 years (0.89, 0.80–0.99, 0.03) associated with weekend transplantation but not with NT transplantation. However, when the analysis was conditioned to only those patients alive and with a functioning graft at 30 days post transplantation, the weekend effect was no longer significant at both 1 year (0.96, 0.81–1.133, 0.62) and 3 years (0.96, 0.85–1.10, 0.59). <h3>Conclusion</h3> We have demonstrated a significant reduction in death or graft failure associated with liver transplantation at weekends of 10–20%, which is pertinent only to the early post-operative transplant survival. American studies have shown no change in outcomes with weekend liver transplantation but a possible increase in early mortality with nighttime operating in one small study. The reasons for reduced adverse outcomes with weekend transplantation are unclear. It may represent a “lead-in” effect as patients transplanted at the weekend will be in intensive care for the first days following surgery, where service provision is similar 7 days a week, and step down to level one care during the week rather than at weekends. Other factors may include transplanting teams being risk adverse at weekends and more likely to decline marginal organs for grafting and prioritising less complex cases for weekend working. This is a novel and interesting finding that requires deeper analysis of the data set and prospective monitoring. <h3>Disclosure of interest</h3> None Declared.