tbuckley/cabot-search huggingface dataset:
The Medical Consultant's Role in Caring for Patients with Hip Fracture
Authors: R. Sean Morrison
Journal: Annals of Internal Medicine (1998)

Background: Hip fractures are an important cause of death and functional dependence in the United States. Purpose: To review the evidence for clinical decisions that medical consultants make for patients with hip fracture and to develop recommendations for care. Data Sources: Published reports of clinical studies were found by searching MEDLINE and selected bibliographies. Study Selection: Studies were included if data were presented on clinical interventions to improve care of conditions typically encountered by medical consultants in the care of patients with hip fracture. Such conditions include timing of surgery, infection prophylaxis, thromboembolic prophylaxis, postoperative nutritional management, urinary tract management, prevention and management of delirium, application and timing of rehabilitation services, and prevention of subsequent falls. Meta-analyses; randomized, controlled trials; or other controlled studies were included if possible. If no such trials were identified, the best evidence from studies with other designs was included. Data Extraction: Interventions were selected on the basis of their efficacy or potential efficacy in improving functional outcome. Trials with positive and negative results were compared for differences in intervention and strength of study methods. Data Synthesis: Strong evidence supports medical recommendations for decisions about timing and duration of prophylactic antibiotics, selection of thromboembolic prophylaxis, urinary tract and nutritional management, and rehabilitative services. Many case series support early surgical repair, although patients who would benefit from delay and further medical work-up have not been well identified. Evidence for decisions about assessment of subsequent risk for fall and risk for and management of delirium is based largely on data from patients without hip fracture but is probably applicable. Future research should target optimal duration of thromboembolic prophylaxis, cost-effectiveness of low-molecular-weight heparin compared with that of other thromboembolic prophylactic regimens, management of delirium, rehabilitative services, and efficacy of assessment of risk for later falls. Conclusions: The data suggest that evidence-based medical care can improve hip fracture outcomes. The medical consultant has a key role in providing this care and managing the preoperative conditions and postoperative complications that may affect optimal functional recovery.
P179 Nebulised 7% Hypertonic Saline as an Adjunct to Airway Clearance Can Be Commenced Safely in a Supervised Environment Without the Need For a Formal Bronchoconstriction Trial: Abstract P179 Table 1
Authors: NG Mills, JR Willis, SP Range, CM Ohri
Journal: Thorax (2012)

<h3>Background</h3> Nebulised Hypertonic Saline (HTS) has been shown to increase water content of airway surface liquid, enhance mucociliary clearance, reduce exacerbation frequency and improve quality of life in Cystic Fibrosis (CF) and non-CF Bronchiectasis. Historically HTS was associated with bronchoconstriction, therefore formal first dose bronchoconstriction trials (BCT) were performed. Recent studies have shown better tolerance that improves over up to 10 doses (Elkins 2006). We have observed that a fall in FEV1 &gt;15% following nebulised HTS rarely correlates with adverse signs or symptoms, questioning the need for a BCT. This study aimed to assess our use of HTS, its safety and tolerance without BCT, and its positive effects. <h3>Methods</h3> A senior physiotherapist completed a proforma for all patients commencing HTS over 6 months. HTS was used for different respiratory conditions to aid mucociliary clearance. All patients were pre-dosed with a bronchodilator, and had a closely supervised 1st test dose, replacing formal BCT. <h3>Results</h3> 54 patients aged 19–87 years (mean 54, median 61) commenced 7% HTS. 35 were inpatients and 19 outpatients. The primary diagnoses were: non-CF Bronchiectasis (20), post thoracic surgery (17), CF (13), Pneumonia (2), long term tracheostomy (1), and COPD with Laryngectomy (1). All patients experienced positive effects, listed in table 1. HTS prescription was individualised: BD regime (42), TDS (8), QDS (4). 13 patients (24%) experienced adverse effects – increased cough (13), slight chest tightness (3), a 5% decrease in oxygen saturations (1). All 13 patients and physiotherapists considered the adverse effects sufficiently mild to continue HTS and they subsequently reduced significantly after up to 5 doses. If no adverse effects were experienced during the test dose, no further adverse effects occurred with continued use. <h3>Conclusion</h3> This observational study demonstrates that HTS has positive effects in a wide variety of respiratory conditions. We have replaced BCT with a supervised test dose as it was found to a be a safe and efficient evaluation. Over 6 months HTS was well tolerated, with only mild adverse effects, which reduced over subsequent doses. Importantly, there were no adverse effects in patients who had previously undergone an uneventful test dose.
Misrouted cell surface GnRH receptors as a disease aetiology for congenital isolated hypogonadotrophic hypogonadism
Authors: Alfredo Ulloa-Aguirre, Jo Ann Janovick, Alfredo Leaños-Miranda, P Michael Conn
Journal: Human Reproduction Update (2004)

GnRH plays an essential and central role in neuroendocrine control of reproductive function. The GnRH receptor is located on the plasma membrane of gonadotrophs, pituitary cells that synthesize the gonadotrophins LH and FSH. This receptor belongs to the superfamily of G protein‐coupled receptors, and is preferentially coupled to the Gq/11 protein; its activation by GnRH analogues stimulates the synthesis and release of LH and FSH. Resistance to GnRH by inactivating (loss‐of‐function) mutations of the human GnRH receptor leads to distinct forms of sporadic or inherited hypogonadotrophic hypogonadism. Although in vitro expression of a number of these mutated GnRH receptors in heterologous systems has shown that these mutations appear to alter several functions of the molecule, including ligand binding, receptor activation or interaction with coupled effectors, recent observations from our laboratory have challenged this view and indicated that protein misfolding and resultant misrouting is a mechanism that, by itself, may lead to loss of function of the human GnRH receptor. In this review we describe the experimental data that led us to this conclusion and how these studies revealed previously unsuspected features of the mutant human GnRH receptor.
Recognising and responding to victims of human trafficking
Authors: S. Doherty, R. Morley
Journal: BMJ (2013)

New guidance for health professionals in the UK

Recent data suggest that 2077 people, almost a quarter of whom were children, were victims of human trafficking in the United Kingdom in 2011.1 Because traffickers go to great lengths to maintain secrecy, these figures are probably an underestimate.1 The trafficking of human beings for sexual and labour exploitation is one of the most highly profitable illegal trades worldwide.2 Human traffickers prey on the vulnerable and use abduction, deception, threat, violence, and other abuses of power to control their victims. Victims are forced to work in the sex industry or in factories, agriculture, or domestic servitude, often over prolonged periods.3 Recognising the “gross violation of human rights” that trafficking represents,4 the UK government ratified the Council of Europe Convention on Action against Trafficking in Human Beings in 2009,4 and it opted in to the European Union Directive on Preventing and Combating Trafficking in Human Beings and Protecting its Victims in 2011.5 This EU directive, which becomes law in the UK in April 2013, requires that member states provide “necessary medical treatment [and] psychological assistance” to those who have been trafficked.

As outlined in a BMJ editorial …
Oxidatively modified proteins in bronchoalveolar lavage fluid of patients with ARDS and patients at‐risk for ARDS
Authors: A-G. Lenz, P.G. Jorens, B. Meyer, W. De Backer, F. Van Overveld, L. Bossaert, K.L. Maier
Journal: European Respiratory Journal (1999)

Oxidative stress in acute respiratory distress syndrome (ARDS) is considered as an important pathophysiological mechanism in acute impairment of lung function. The present study investigated whether a pulmonary oxidant-antioxidant imbalance is indicated by substantial oxidative modification of proteins in bronchoalveolar lavage (BAL) fluid. Oxidatively modified proteins in BAL fluid, as measured by the reduction of protein carbonyl groups with tritiated borohydride, were studied in control subjects, patients with clinically established ARDS, and patients considered at-risk for ARDS because they had had coronary bypass surgery. Subsets of these at-risk patients were pretreated either with methylprednisolone or N-acetylcysteine. The carbonyl content of BAL fluid proteins was greatly increased in ARDS patients (5.0+/-13 nmol carbonyl x mL(-1) BAL fluid; mean+/-SEM; p=0.0004; n=10) and moderately increased in the untreated patients at-risk for ARDS (1.3+/-0.2 nmol x mL(-1); p=0.027; n=19) compared with controls (0.8+/-0.2 nmol x mL(-1); n=12). The two other at-risk groups pretreated either with methylprednisolone or N-acetylcysteine showed carbonyl values that were statistically not different from the controls (1.2+/-0.2 nmol x mL(-1); p=0.13; n=13, and 1.1+/-0.3 nmol x mL(-1); p=0.40; n=8, respectively). These results show that oxidatively modified proteins clearly accumulated in bronchoalveolar lavage fluid of acute respiratory distress syndrome patients, and to a minor extent in untreated at-risk patients. These data suggest a severe oxidant-antioxidant imbalance in acute respiratory distress syndrome.
High frequency chest wall oscillation in cystic fibrosis
Authors: J. M Bradley
Journal: Thorax (2010)

Airway clearance is considered an integral component of the management of cystic fibrosis (CF). Recent CF pulmonary guidelines made recommendations using the US Prentative Service task Force (USPSTF) grading scheme (a system which provides a mechanism to weigh the quality of evidence and the potential harms and benefits) on airway clearance.1 2 These guidelines recommended that airway clearance should be provided to all patients with CF (grade B recommendation: high certainty that the net benefit is moderate and at least moderate certainty that the net benefit is moderate to substantial).1 They also summarise the evidence for the efficacy of one airway clearance regime versus another and recommend (grade B) that no airway clearance regime has been shown to be superior to others although they recognise that, for any individual, one airway clearance regime may be superior. They advocate that patients should be able to choose, in collaboration with the therapist, which airway clearance regime/regimes they wish to use. Other guidelines and systematic reviews as well as many primary trials agree that there is no clear advantage of one particular airway clearance regime over another.3

The active cycle of breathing techniques (ACBT) is the standard airway clearance regime in the UK, although in the last few years other forms of airway clearance (eg, autogenic drainage) as well as a range of adjuncts have become popular (eg, positive expiratory pressure (PEP) mask, flutter and Acapella). These adjuncts are often provided “free” at the point of delivery to the patient within the current healthcare system. In the USA, high frequency chest wall oscillation (HFCWO; known as the Vest) is widely used and is purchased for patients under various insurance schemes. HFCWO is not widely provided to patients with CF in the UK or the Republic of Ireland, and patients who …
Cross-Sectional Study of Imatinib Plasma Trough Levels in Patients With Advanced Gastrointestinal Stromal Tumors: Impact of Gastrointestinal Resection on Exposure to Imatinib
Authors: Changhoon Yoo, Min-Hee Ryu, Byung Woog Kang, Shin-Kyo Yoon, Baek-Yeol Ryoo, Heung-Moon Chang, Jae-Lyun Lee, Mo Youl Beck, Tae Won Kim, Yoon-Koo Kang
Journal: Journal of Clinical Oncology (2010)

Imatinib plasma trough levels (C(min)) have been reported to correlate with treatment outcomes in patients with gastrointestinal stromal tumors (GISTs). We therefore have evaluated the correlation between imatinib C(min) and the clinical characteristics of patients with GIST.Steady-state imatinib C(min) in 107 patients with GIST who were taking imatinib 300 to 800 mg/d was measured.In patients treated with imatinib 400 (n = 92), 300 (n = 7), 600 (n = 2), or 800 (n = 11) mg/d, imatinib C(min) was 1,305 +/- 633 ng/mL, 1,452 +/- 830 ng/mL, 1,698 +/- 725 ng/mL, and 3,330 +/- 1,592 ng/mL, respectively. Of the 92 patients treated with 400 mg/d imatinib, 59 patients (63%) were men; the median age was 55 years (range, 28 to 76 years), and the median duration of imatinib use before sampling was 8.8 months (range, 0.5 to 67.6 months). The mean inter- and intrapatient variability rates were 44.7% and 26.5%, respectively. In univariate analyses, high C(min) was correlated with advanced age (P = .02), low creatinine clearance (P = .001), low hemoglobin (P = .03), and low albumin (P < .001) concentrations. Imatinib C(min) was also significantly lower in patients with (n = 18; 942 +/- 330 ng/mL) than without (n = 74; 1,393 +/- 659 ng/mL) major (ie, total or subtotal) gastrectomy (P = .002). In multivariate analysis, albumin (P = .001) concentrations, creatinine clearance (P = .002), and major gastrectomy (P = .003) were significantly correlated with C(min).In patients with GIST, imatinib C(min) at steady state was significantly associated with albumin concentration, creatinine clearance, and previous major gastrectomy. Although its clinical impact is unclear at present time, monitoring of imatinib C(min) might be particularly important for optimal treatment with imatinib in patients who have undergone major gastrectomy.
A Synoptic Evaluation of Asthma Hospital Admissions in New York City
Authors: PAUL F. JAMASON, LAURENCE S. KALKSTEIN, PETER J. GERGEN
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

An evaluation of weather/asthma relationships in the New York City Standard Metropolitan Statistical Area (SMSA) is developed using a synoptic climatological methodology. This procedure isolates "air masses," or bodies of air that are homogeneous in meteorological character, and relates them to daily counts of overnight asthma hospital admissions. The synoptic procedure used here, known as the temporal synoptic index (TSI), can identify air masses in automated fashion for every day over many years. It is apparent that certain air masses are related to statistically significant increases in asthma hospital admissions. The impact varies seasonally, with weather having a particularly important impact on asthma admissions during fall and winter. It appears that air pollution has little impact on asthma during these two seasons, and the air masses associated with the highest admissions are not distinguished by high concentrations of pollutants. However, during spring and summer, the air masses associated with highest admissions are among those with high pollution concentrations. There is a strong interseasonal differential response to weather and air pollution by asthmatics in New York City. If these results can be replicated at other locations in future studies, it may be possible to develop an asthma/weather watch-warning system, based on the expected arrival of high-admissions air masses.
Phase II Trial (BREAK-2) of the BRAF Inhibitor Dabrafenib (GSK2118436) in Patients With Metastatic Melanoma
Authors: Paolo A. Ascierto, David Minor, Antoni Ribas, Celeste Lebbe, Anne O'Hagan, Niki Arya, Mary Guckert, Dirk Schadendorf, Richard F. Kefford, Jean-Jacques Grob, Omid Hamid, Ravi Amaravadi, Ester Simeone, Tabea Wilhelm, Kevin B. Kim, Georgina V. Long, Anne-Marie Martin, Jolly Mazumdar, Vicki L. Goodman, Uwe Trefzer
Journal: Journal of Clinical Oncology (2013)

Purpose Dabrafenib (GSK2118436) is a potent inhibitor of mutated BRAF kinase. Our multicenter, single-arm, phase II study assessed the safety and clinical activity of dabrafenib in BRAF V600E/K mutation–positive metastatic melanoma (mut + MM). Patients and Methods Histologically confirmed patients with stage IV BRAF V600E/K mut + MM received oral dabrafenib 150 mg twice daily until disease progression, death, or unacceptable adverse events (AEs). The primary end point was investigator-assessed overall response rate in BRAF V600E mut + MM patients. Secondary end points included progression-free survival (PFS) and overall survival (OS). Exploratory objectives included the comparison of BRAF mutation status between tumor-specific circulating cell-free DNA (cfDNA) and tumor tissue, and the evaluation of cfDNA as a predictor of clinical outcome. Results Seventy-six patients with BRAF V600E and 16 patients with BRAF V600K mut + MM were enrolled onto the study. In the BRAF V600E group, 45 patients (59%) had a confirmed response (95% CI, 48.2 to 70.3), including five patients (7%) with complete responses. Two patients (13%) with BRAF V600K mut + MM had a confirmed partial response (95% CI, 0 to 28.7). In the BRAF V600E and BRAF V600K groups, median PFS was 6.3 months and 4.5 months, and median OS was 13.1 months and 12.9 months, respectively. The most common AEs were arthralgia (33%), hyperkeratosis (27%), and pyrexia (24%). Overall, 25 patients (27%) experienced a serious AE and nine patients (10%) had squamous cell carcinoma. Baseline cfDNA levels predicted response rate and PFS in BRAF V600E mut + MM patients. Conclusion Dabrafenib was well tolerated and clinically active in patients with BRAF V600E/K mut + MM. cfDNA may be a useful prognostic and response marker in future studies.
Constructing agents: Rethinking the how and what in developmental theories of social understanding
Authors: Victoria McGeer
Journal: Behavioral and Brain Sciences (2004)

Although I am broadly in sympathy with Carpendale &amp; Lewis's (C&amp;L's) version of social constructivism, I raise two issues they might address. One bears on the question of how social understanding develops: Is their resistance to individualism inappropriately combined with a resistance to internalism? A second question concerns a more radical implication of their view for what social understanding is.
Diffuse alveolar damage in a patient treated with gemcitabine
Authors: A Marruchella, G Fiorenzano, A Merizzi, G Rossi, PL Chiodera
Journal: European Respiratory Journal (1998)

We present a case of diffuse alveolar damage (DAD) that occurred in a male aged 68 yrs treated with gemcitabine, a novel antineoplastic agent, that was given for hepatic relapse of a previously resected non-small cell lung cancer. The patient developed acute respiratory failure after the sixth drug dose, and died 4 days after admission. Autopsy revealed a pattern of DAD. No evidence of infection or other specific aetiologies could be found. To our knowledge, only three cases of pulmonary toxicity resulting from treatment with gemcitabine have been published; two of them were fatal and postmortem examination revealed a pattern consistent with acute respiratory distress syndrome. A careful survey may determine the incidence of pulmonary toxicity of this new drug in the future.
Indirect comparisons of the efficacy of biological antirheumatic agents in rheumatoid arthritis in patients with an inadequate response to conventional disease-modifying antirheumatic drugs or to an anti-tumour necrosis factor agent: a meta-analysis
Authors: C. Salliot, A. Finckh, W. Katchamart, Y. Lu, Y. Sun, C. Bombardier, E. Keystone
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Background</h3> The availability of increasing numbers of biological agents for the treatment of rheumatoid arthritis (RA) offers several therapeutic options. While all biologicals have proven effective in trials, very limited direct comparisons are available. The objective of the present work was to compare the efficacy of biologicals (anti-tumour necrosis factor (TNF) agents, rituximab, abatacept, tocilizumab) in patients with RA with active disease and (i) an inadequate response (IR) to methotrexate (IR-MTX), (ii) an IR to anti-TNF agents (IR-anti-TNFs) using indirect comparisons. <h3>Methods</h3> Randomised clinical trials were identified examining the efficacy of a biological agent in RA at 6 months in patients with an IR-MTX or with an IR-anti-TNF. To compare the relative efficacy of biologicals, adjusted indirect comparison meta-analytic methods to estimate the ORs of achieving a 50% improvement according to American College of Rheumatology criteria (ACR50) response at 6 months were used. <h3>Results</h3> A total of 18 published trials and 1 abstract were included in the analyses. In IR-MTX, anti-TNFs had the same probability of reaching an ACR50 compared to ‘non-anti-TNF biologicals’ taken together (OR 1.30, 95 % CI 0.91 to 1.86). However, when compared to specific biological agents, anti-TNFs demonstrated a higher probability of reaching an ACR50 than abatacept (OR 1.52, 95 % CI 1.0 to 2.28), but not in comparison to rituximab and tocilizumab. In IR-anti-TNF, rituximab demonstrated a higher probability of achieving an ACR50 than tocilizumab (OR 2.61, 95% CI 1.10 to 6.37), but no significant differences existed between rituximab, tocilizumab, abatacept and golimumab. <h3>Conclusions</h3> In a meta-analysis of randomised clinical trials of patients with IR-MTX, anti-TNFs demonstrated a higher probability of achieving an ACR50 response than abatacept. In IR-anti-TNF, no difference was found between rituximab, tocimizumab, abatacept and golimumab.
A small amount of inhaled nitric oxide does not increase lung diffusing capacity
Authors: G. S. Zavorsky, J. M. Murias
Journal: European Respiratory Journal (2006)

The aim of the present study was to determine: 1) whether 40–50 ppm nitric oxide (NO) increases diffusing capacity of the lung for NO ( D L,NO ) and carbon monoxide ( D L,CO ), membrane diffusing capacity for CO ( D m,CO ) and pulmonary capillary blood volume ( V c ); 2) the actual number of tests required to provide a reasonable estimate of D L,NO , D L,CO , D m,CO and V c ; and 3) repeatability of these parameters using the single-breath D L,NO – D L,CO method. In total, 31 subjects performed five single-breath hold manoeuvres at rest, inhaling 43±3 ppm NO together with a standard diffusion mixture. D L,NO ( D m,CO ) remained unchanged from the first to fifth trial. However, compared with the first trial, D L,CO and V c had decreased by the fourth (−4±5%; 95% confidence interval (CI) = −5– −2%) and third trial (−5±7%; 95% CI = −7– −2%), respectively. Repeatability over five trials was 17, 3 and 7 mL·min −1 ·mmHg −1 for D L,NO , D L,CO and D m,CO , respectively, and 13 mL for V c when D m,CO = D L,NO /2.42. In conclusion, nitric oxide inhaled during sequential single-breath manoeuvres has no effect on diffusing capacity of the lung for nitric oxide and, thus, membrane diffusing capacity for carbon monoxide. Since more than two and three trials will lower pulmonary capillary blood volume and diffusing capacity of the lung for carbon monoxide, respectively, the average value of only two properly performed trials is suggested.