tbuckley/cabot-search huggingface dataset:
Efficacy of Grass Pollen Allergen Sublingual Immunotherapy Tablets for Seasonal Allergic Rhinoconjunctivitis
Authors: Danilo Di Bona, Antonella Plaia, Maria Stefania Leto-Barone, Simona La Piana, Gabriele Di Lorenzo
Journal: JAMA Internal Medicine (2015)

Randomized clinical trials (RCTs) and meta-analyses of sublingual immunotherapy (SLIT) for the treatment of seasonal allergic rhinoconjunctivitis (SARC) have shown a modest clinical benefit compared with placebo. Furthermore, indirect comparison by meta-analyses showed that subcutaneous immunotherapy is more effective than SLIT. Despite these data, SLIT has become the most prescribed treatment of SARC in Europe in recent years, and it was approved by the US Food and Drug Administration for the treatment of SARC to grass pollen in the United States on April 1, 2014.To assess the efficacy and safety of the grass pollen sublingual tablets licensed as drugs in the treatment of patients with SARC to grass pollen.Computerized bibliographic searches of MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov (from inception to April 30, 2014) were supplemented with a manual search of reference lists.Randomized clinical trials were included if they compared the grass pollen SLIT tablets approved by regulatory authorities in the European Union and the United States for SARC with placebo.Data on populations, interventions, and outcomes were extracted from each RCT according to the intent-to-treat method by 2 independent observers and were combined using the method by DerSimonian and Laird.The primary end point was the difference in the symptom score and medication score between SLIT and placebo. We pooled data using random-effects meta-analysis, with standardized mean differences (SMDs) and 95% CIs reported.Data were available in 13 RCTs for the symptom score (4659 patients) and in 12 RCTs for the medication score (4558 patients). We found a small treatment benefit in the symptom score (SMD, -0.28; 95% CI, -0.37 to -0.19; P < .001) and in the medication score (SMD, -0.24; 95% CI, -0.31 to -0.17; P < .001). Adverse events were reported in 1384 of 2259 patients (61.3%) receiving SLIT and in 477 of 2279 patients (20.9%) receiving placebo. Seven patients in the SLIT group reported treatment-related adverse events requiring epinephrine.Findings show a small benefit of the grass pollen sublingual tablets in reducing symptoms and in decreasing the use of symptomatic medication (antihistamines and corticosteroids) in patients with SARC. Considering the low magnitude of the benefit, the convenience and easy administration do not seem to be sufficient reasons for the choice of SLIT.
Abstract 2291: Recapitulation of a Right Ventricular Phenotype in a Transgenic Mouse Model Overexpressing the Plakophilin-2 R413x Mutation That Causes Severe ARVC in a Large Family
Authors: Bernhard Unsoeld, Sylvia Gunkel, Josee Vouffo, Conny Pfeiffer, Andrea Kranz, Dirk Lossnitzer, Bernd Wollnik, Larissa Fabritz, Lisa Fortmueller, Matthias Paul, Eric Schulze-Bahr, Paulus Kirchhoff, Gerd Hasenfuss, Ralph Knoell
Journal: Circulation (2009)

Background: Mutations in desmosomal proteins, including plakophilin-2 (PKP2), have been identified recently as major causes of ARVC. Here we describe a large family (58 family members) with an inhe...
Two doctors sentenced in Canary Islands for failing to treat woman with hyponatraemia
Authors: Aser García Rada
Journal: BMJ (2015)

Two doctors in the Canary Islands have been convicted of grievous bodily harm and sentenced to jail for their role in the mismanagement of a woman with severe hyponatraemia who ended up in a vegetative state.

Both doctors have been disqualified from practising for three years, sentenced to two years and three months of imprisonment, and fined €807 700 (£568 000; $885 000) for hospital costs and for serious disability and permanent injuries caused to the woman. They have also been ordered to pay €100 000 to the patient’s mother for moral damages to the family.

The 31 year old patient, who has a history …
24-hour of physiotherapy assistance does not reduce frequency of postoperative pulmonary complications
Authors: Janete Maria Silva, Bruna Peruzzo Rotta, Caue Padovani, Michele Ramos, Carolina Fu, Clarice Tanaka
Journal: European Respiratory Journal (2013)

Background:  Physiotherapy assistance (PTA) is required for the management of postoperative (PO) patients. Some studies tried to demonstrate the effects of PTA of PO pulmonary complications (PPCs), however, their outcomes were controversial and the working shift of PTA was not considered.  Objective:  To verify the effect of PTA shift (24-hours, Physio-24;12-hours, Physio-12) on frequency of PPCs (presence of nosocomial pneumonia or ventilator-associated pneumonia) in abdominal PO patients.  Method:  Observational, prospective, cohort study in a public tertiary-teaching hospital; included 107 abdominal PO patients (N=42 on Physio-12; N=65 on Physio-24), PO routine on intensive care unit (ICU), aged ≥18 years old, underwent ≥24 hours of invasive mechanical ventilation (IMV). All data were collected from patient’s records (see  ). Mann Whitney and Qui-Square tests were applied to quantitative and qualitative variables, respectively. Statistical significance was considered when p Results:  Despite Physio-24 patients received more sessions of chest PTA (p=0.03), no differences were found in the length of ICU stay (ICU LOS) (p=0.85), length of IMV (p=0.90) and in frequency of PPCs between groups (p=0.74).  Conclusion:  There was no difference in frequency of PPCs when abdominal PO patients are admitted in ICUs with 12 or 24-hours of PTA.
American Psychological Association colluded with US officials to bolster CIA torture program, report alleges
Authors: M. McCarthy
Journal: BMJ (2015)

During the administration of President George W Bush, senior personnel of the American Psychological Association (APA) secretly colluded with US officials in the White House, the Department of Defense, and the Central Intelligence Agency to support the ethical justification of the spy agency’s “enhanced” interrogation program, while the APA misled the public about its involvement, says a report by human rights activists and critics of the association released on 30 April.1

After the terrorist attacks in the United States on 9 September 2001, the US government ruled that suspected terrorists captured in Afghanistan and elsewhere were “unlawful combatants” who did not qualify for the protection afforded to prisoners of war under the Geneva Conventions and could be subject to “enhanced” interrogation techniques that included stress positions, sleep deprivation, waterboarding, and other techniques generally viewed as torture.

“The APA’s complicity in the CIA torture program, by allowing psychologists to administer and calibrate permitted harm, undermines the fundamental ethical standards of the profession. If not carefully understood and rejected by the …
Patterns of recurrence in rectal cancer treated with neoadjuvant chemoradiotherapy and TME.
Authors: D. Liska, P. Ding, K. A. Goodman, L. Saltz, J. G. Guillem, P. Paty, L. K. Temple, G. M. Nash, W. D. Wong, M. R. Weiser
Journal: Journal of Clinical Oncology (2010)

3644 Background: The aim of this study is to characterize patterns of recurrence in locally advanced rectal cancer treated with combined modality therapy (CMT) including neoadjuvant chemoradiation followed by total mesorectal excision. Methods: From a prospectively maintained single institution database, we identified 593 consecutive locally advanced (uT3 or uN1) rectal cancer patients staged by endorectal ultrasound and treated with CMT from 1998-2007. Initial sites, signs or symptoms, time interval, and method of diagnosing recurrence were investigated. Results: After median follow-up of 44 months, 119 patients (20%) recurred: lung was the most common site of distant recurrence (69%), followed by liver (20%). 14 patients (2.4%) had local recurrence. Single site recurrence was noted in 96 patients, while multiple site recurrence was noted in 25 patients. Median time to radiographic or histologic confirmation of pulmonary recurrence was significantly longer than for extrapulmonary recurrence (12.6 vs. 2.6 weeks; p = 0.005). While elevated CEA level was the most common initial sign leading to diagnosis of extrapulmonary recurrence, pulmonary recurrence was most commonly diagnosed by CT scan. In addition to lower incidence of elevated CEA, pulmonary recurrence was also less likely to be diagnosed by PET compared to nonpulmonary recurrence (p<0.02). Conclusions: Unlike colon cancer patients, who most frequently recur in the liver, patients with locally advanced rectal cancer treated with CMT most frequently recur in the lung. These data reaffirm the importance of pulmonary surveillance, justifying current ASCO and NCCN recommendations for follow-up chest CT in this patient population. Sites of recurrence in all patients and those with single site relapse Site All sites of recurrence n (%) Single site recurrence n (%) Lung 77 (69) 59 (69) Liver 22 (20) 13 (15) NRLN 12 (11) 4 (5) Bone 8 (7) 4 (5) Brain 5 (4) 3 (3) Carcinomatosis 5 (4) 3 (3) Abbreviation: NRLN, nonregional lymph nodes including retroperitoneal, inguinal, supraclavicular. No significant financial relationships to disclose.
American Psychology Association colluded with Pentagon and CIA to protect interrogation program, report finds
Authors: Michael McCarthy
Journal: BMJ (2015)

Officials of the American Psychological Association colluded with the US Department of Defense, the Central Intelligence Agency, and other officials of George W Bush’s administration to permit psychologists to participate in “enhanced interrogations” that used techniques such as waterboarding, widely considered to be torture, a new report has found.1

The 542 page report, released on 10 July, was commissioned by the association and prepared by a team led by David H Hoffman, an attorney in the Chicago office of the Sidley Austin law firm and a former federal prosecutor.

At issue was whether association officials worked with US government officials to formulate ethical guidelines that were aligned with the Bush administration’s policies so that psychologists could participate in the harsh interrogations of detainees held at the US Guantanamo Bay military prison and at secret CIA “black sites” set up around the world after the terrorist attacks on 11 September 2001. The guidelines were drawn up in 2005 by a specially commissioned association task force, the Presidential Task Force on Ethics and National Security (“PENS”), and adopted shortly thereafter by the association’s board.2

Critics of the guidelines have …
Midostaurin: Review of pharmacokinetics (PK) and PK/pharmacodynamic (PD) relationship in AML/MDS patients
Authors: C. Dutreix, A. Huntsman Labed, J. Roesel, C. Lanza, Y. Wang
Journal: Journal of Clinical Oncology (2009)

e14540 Background: Midostaurin is a multi-tyrosine-kinases inhibitor targeting class III tyrosine-protein-kinases, including Fms-like tyrosine kinase-3 (FLT3), involved in hematopoiesis and leukemia. Oral midostaurin has been tested as a single agent and in combination therapy in &gt;800 subjects. Methods: The two studies presented here involved patients with wild-type or FLT3-mutated de novo (phase Ib) or relapsed (phase II) AML or MDS. They covered a wide range of doses, given as monotherapy or in combination. Results: PK studies demonstrated that midostaurin was rapidly absorbed and metabolized into two major active metabolites: the demethylated compound, CGP62221 and the hydroxylated compound, CGP52421 . The relative potency of these metabolites (Midostaurin: CGP62221 : CGP52421 ) is approximately 1 : 1.4 : 0.1 in FLT3-based cellular assays. Following multiple oral daily single-agent doses, midostaurin and CGP62221 concentrations accumulated significantly in the first 3–5 days then declined by 40- 80% prior to a new steady state 2–3 weeks post-dose. CGP52421 concentrations accumulated continuously through day 28 and remained stable thereafter, roughly 7-times higher than the parent drug or CGP62221 . The time-dependent kinetics of midostaurin may reflect an induction of CYP3A4 by midostaurin and/or its metabolites, as already demonstrated in vitro, or alternatively a protein binding displacement mechanism. The blast response with monotherapy appeared to be correlated both with midostaurin plasma levels alone and summed together with its two major metabolites, corrected for their in vitro potency differences. PK/PD analyses showed sustained reduction (&gt;90% from baseline) in peripheral blast (PB) counts in patients with a higher midostaurin plasma exposure at steady state (&gt;2–3 μg/mL). However, evaluation of available bone marrow blast (BM) response data revealed that a much higher midostaurin plasma would be needed for a satisfactory BM response. Conclusions: Additional chemotherapy was required to achieve a clinical response, with particularly promising results for the FLT3-mutated patients. These results support the ongoing phase III AML study in AML FLT3-mutated patients with midostaurin given in combination with chemotherapy. No significant financial relationships to disclose.
Qualitative and economical analysis of transbronchial lung biopsy with the cryoprobe
Authors: Beatriz Amat, Sandra Sapia, María Fernanda Sanchez, José Manuel León, Ana Camarasa, Juan Manuel Córcoles, Juan Jose Egea, María Ródenas, Silvia Coves
Journal: European Respiratory Journal (2012)

Objective : To analyze the histological quality of transbronchial lung cryobiopsy in patients with interstitial or malignant lung diseases in which a previous transbronchial lung biopsy (TBB) with conventional forceps was no diagnostic. A second objective was to analyze the cost of TBB with the flexible cryoprobe compared with surgical lung biopsy.

Patients and methods : From 01.02.2011 until 31.01.2012, 19 TBB with the flexible cryoprobe were performed. Afterwards, we analyze the cost of a TBB with the flexible cryosonde compared with surgical lung biopsy.

Results: We obtained representative material in 18/19 (95%) patients. Cryobiopsies total specimen area was 20-60 mm2 compared to TBB with forceps which was 0.5-8 mm2. Cryobiopsies did not show crush artifact in any case. In 15/19 (79%) patients we obtained a definitive diagnosis: 2 malignant tumors and 13 benign disease: 6 usual interstitial pneumonia, 1nonspecific interstitial pneumonia,1desquamative interstitial pneumonia, 1diffuse panbronchiolitis, 1 follicular bronchiolitis, 1 rheumatoid nodules, 1 respiratory bronchiolitis and 1 organizing pneumonia. In 3 patients we found some pathological findings but a definitive diagnosis was not achieved. The cost of TBB with cryobiopsy was 351€ against the cost of surgical lung biopsy which was 1189€.

Conclusions : Transbronchial cryobiopsies are larger than TBB with conventional forceps with a preserved sample because of the absence of crush artifact. Moreover, cryobiopsy is 3 times cheaper than surgical lung biopsy. Hence, transbronchial cryobiopsies could be considered as a prior step or a potentially replacing tool for the open lung biopsy.
Cost analysis of an initial observation approach in metastatic renal cell carcinoma from a prospective study.
Authors: Hiral D. Parekh
Journal: Journal of Clinical Oncology (2015)

439 Background: A prospective observational study of metastatic renal cell carcinoma (mRCC) prior to initiation of systemic therapy has been conducted. (Rini et al., ASCO 2014, abst 4520). A direct cost analysis was undertaken in mRCC patients from this trial matched to historical control mRCC patients treated with immediate systemic therapy. Methods: Histologically-confirmed, asymptomatic mRCC patients without prior systemic treatment were enrolled and followed until starting initial systemic treatment on a prospective trial. Patients underwent clinic visits and radiographic evaluation every 3 months for year 1, every 4 months for year 2, then every 6 months until treatment was initiated per physician discretion. Control mRCC patients who received immediate systemic therapy were matched for age, gender, Heng risk criteria and length of follow up. After clinical review, non mRCC-related encounters were excluded from final analysis. The direct cost of inpatient and outpatient visits plus associated laboratory analysis and imaging studies were compared between the 2 groups using the Wilcoxon signed rank test. Results: Seventeen matched pairs were included in the final analysis. The median (range) number of hospital admissions was 1 (range, 0-6) for the observation group and 1 (range, 0-5) for the immediate therapy group (p=1.0). The median (range) number of outpatient visits in the observation group was 17 (range, 6-39) and 19 (range, 4-59) in the immediate therapy group (p=0.47). In aggregate, the direct costs for the observation group were 30.6% less for outpatient visits and 21.9% less in total (outpatient plus inpatient visits) as compared to the immediate therapy group (p=0.19 for both). Conclusions: Initial observation as a management strategy for a subset of mRCC patients is associated with a non-significant aggregate decrease in direct costs compared to patients requiring immediate treatment. Further study is required to evaluate costs associated with different management strategies over the lifetime of mRCC patients.
Balance control in chronic obstructive pulmonary disease: Does breathing disturb balance?
Authors: Paul Hodges, Michelle Smith
Journal: European Respiratory Journal (2013)

Chest wall movement during respiration perturbs balance, but hip/back motion compensates for this disturbance in healthy individuals. It is unknown whether this compensation is adequate in chronic obstructive pulmonary disease (COPD). This study compared centre of pressure (CoP) displacement and angular motion of the hip/back in people with and without COPD at rest and after exercise. People with COPD (n=12) and age-matched controls stood on a force plate and angular motion of the hip/back was measured with inclinometers. Respiration related motion of CoP and hip/back, coherence between respiration and trunk/hip/CoP motion, and the general range of CoP displacement in the frontal and sagittal planes were measured. Respiratory rate was greater in COPD. CoP displacement in the frontal plane was greater in COPD, but not the sagittal plane where respiratory movements have their largest impact. Motion of CoP and hip/trunk related to respiration did not differ between groups. Coherence between respiratory movement and motion of CoP or hip/trunk did not differ between groups before or after exercise. These data show that although balance is compromised in COPD (in the frontal plane) this does not appear to be due to compromised ability to counteract the postural disturbance from augmented respiration. Other data show increased activation of abdominal muscles in COPD, which is likely to restrict trunk motion. This would have a greater impact on CoP in the frontal than sagittal plane as balance control in the frontal plane has greater dependence on trunk motion. Taken together these data imply that adaptation of trunk muscle activation rather than increased breathing underpins poor balance in COPD.
Sakhalin Island
Authors: Christopher Timmis
Journal: BMJ (2008)

This book is an account of the remarkable study that Chekhov made of the conditions in the Russian penal colony on the barren Sakhalin Island off the east coast of Siberia. In 1890 the 30 year old Chekhov was an emerging figure in Moscow literary circles who had just won the prestigious Pushkin prize. He was also a qualified doctor and was building up a medical practice in the city. He had also been beset by tragedy: his elder brother, his sister in law, and a close friend had all recently died of tuberculosis. Chekhov, too, had already recognised the haemoptysis caused by the tuberculosis that would kill him at the age of 44.

It was a surprise to family and friends when he announced his plan to travel nearly 10 000 km to Sakhalin. Among several motives, he wanted to produce a scientific work of substance, something that would “repay his debt to medicine” and be a serious academic study to set alongside what he had then come to regard as his more frivolous literary work.

The gruelling three month journey across Siberia included some 4800 km on a horsedrawn cart. On arriving at Sakhalin Island he set about interviewing almost all of the population and recording their details on 10 000 structured index cards. Chekhov took particular interest in the ability of the colony to reform convicts and to equip them with new skills. He assessed each settlement for its ability to sustain profitable farming. In sending prisoners to Sakhalin the state’s aim was that they would, after completing their sentence, remain as “settled exiles” and establish a colony that would secure the land as Russian territory. Unfortunately, the harsh climate and the parcelling out of inadequate areas of the infertile land meant that the efforts to make a living from farming were often hopeless. As well as the starving families in the poorer settlements, Chekhov observed the universal squalor, the backbreaking labour, and the brutality of many prison officials. As a doctor he recognised and condemned the lack of care in the infirmary, where he found neglected wounds, blunt and broken instruments, stocks of obsolete drugs, and ignorant staff.

The book is clearly based on scientific method. Chekhov carefully describes his data cards, the methods, and the difficulties of data collection. He presents his findings systematically, settlement by settlement. The second part of the book discusses his findings, laid out under the headings of the various aspects of Sakhalin life. Here are tables of figures and comparisons with data from other regions of Russia. At one point he analyses the paradox of the apparent longevity of Sakhalin’s residents and observes the misleading effect of a population that is low in numbers of vulnerable children and elderly people.

In 1885 a survey by an American of the mainland Siberian labour camps had been damning. When eventually published in 1895 Chekhov’s book drew more attention to the previously obscure Sakhalin colony and added to the growing pressure to reform the Russian penal system.
Moloney Murine Sarcoma Virus Tumors in CBA/J Mice: Chemopreventive and Chemotherapeutic Actions of Supplemental β-Carotene&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;,&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;,&lt;xref ref-type="fn" rid="fn4"&gt;4&lt;/xref&gt;
Authors: E Seifter, G Rettura, J Padawer, S M Levenson
Journal: JNCI Journal of the National Cancer Institute (1982)

Decreased tumor frequency, increased latent period, and increased rate of tumor regression were observed in male inbred CBA/J mice fed supplemental β-carotene before and/or after they were inoculated with the Moloney sarcoma virus. When β-carotene feeding was begun after tumors were already present, it markedly increased the rate of tumor regression. β-Carotene minimized the virusinduced thymus gland involution that accompanies tumor growth, and this action on the thymus gland was believed to underlie part of β-carotene's antitumor activity. The basal diet, a standard commercial mouse chow containing more vitamin A than the National Research Council recommends as a daily allowance for rodents, supported normal growth, reproduction, and longevity of normal mice. The work reported here is the first demonstration of the antitumor action of ,Bcarotene in mice inoculated with an oncogenic virus.