tbuckley/cabot-search huggingface dataset:
Rational, cost effective use of investigations
Authors: S. Bulusu
Journal: BMJ (2002)

Editor—Winkens and Dinant have highlighted some issues regarding the rising workload in pathology.1 In 1985 the workload in most diagnostic departments in the United Kingdom was reported to have been rising 10% a year whereas the number of inpatients and outpatients increased by less than 2% a year2; it is roughly similar now. A review of laboratory audits showed that the number of inappropriate tests requested by clinicians varies from 5% to 95%.3

The common perception among physicians is that these tests are cheap. Their unit cost may be low, but they have a high cumulative cost.3 The annual bill for operating laboratory tests is greater than the annual cost of operating computed tomographic scanners.3

Several methods to modify clinicians' use of diagnostic tests have been reported. The most potent interventions are methods that facilitate the preferred behaviour through blocking inappropriate requests or defaulting to the intended practice.4 In a study in the United States several characteristics were associated with a low level of laboratory use: being a leader, being part of a service group whose leader was a low user, clinical experience, being board certified, and being a graduate from “established” medical schools in the north east of America, Chicago, or California.5

The two most important reasons for the rising workload and costs in laboratories is the ease with which tests can be requested and lack of ownership by clinicians, as the problem is viewed largely as a laboratory problem. Good leadership and medical training are important. Thus consultants should play a key part as leaders, and a course on cost containment should be made compulsory in the medical curriculum.

The concepts of “profile” and “routine” should be abolished and investigations tailored to individual needs. It must be made mandatory for all junior doctors to get a certificate of competence in laboratory use from their consultants based on the information produced by the laboratory.

The question we have to grapple with is how we want to use our resources: whether to have more investigations or to fund more nurses, doctors, or such like to improve patient care. I suspect that the response would be similar to that of those people who say that they would prefer higher taxes to fund public services but vote otherwise in the polling booth. The decision we make will dictate the quality of NHS we have. Let's have more doctors and nurses.
Abstract 13496: Aortic Regurgitation Index Defines Severity of Periprosthetic Regurgitation and Predicts Outcome in Patients after Tavi: A Two-Centre Experience
Authors: Jan-Malte Sinning, Mariuca Vasa-Nicotera, Christoph Hammerstingl, Derek Chin, Alexander Ghanem, Robert Schueler, Alexander Sedaghat, Eberhard Grube, Jan Kovac, Georg Nickenig, Nikos Werner
Journal: Circulation (2012)

Background: More-than-mild peri-prosthetic aortic regurgitation (periAR) after TAVI is associated with adverse outcome. We hypothesized that periprocedural measurement of hemodynamic parameters all...
UK must improve its defences against biological weapons
Authors: Mark Silvert
Journal: BMJ (2000)

The United Kingdom must improve its defences against biological weapons, says a new Royal Society report on controlling the threat from biological weapons. The report was released last week as the Biological Weapons Convention reconvened in Geneva.

To prepare for the consequences of a biological weapons attack on Britain, plans need to be worked out now, the report says. In the past only naturally occurring micro-organisms and toxins, such as anthrax, Ebola virus, and botulinum, have been considered …
Abstract 5857: Oligofructose Supplementation Decreases Blood Pressure and Improves Lipid Metabolism in Hypertensive People: A Randomized Controlled Trial
Authors: Dan Qu, Hao Zhang, Xiang Cao, Jie Wang, Zhiyun Xu, Donglian Cai
Journal: Circulation (2009)

Background: Oligofructose (OFS), as a kind of prebiotics, apparent potential benefits for obesity and cardiovascular diseases. However, the effect of OFS on blood pressure is unknown.

Methods: A total of 96 adults (aged 47±12 yrs) with mild or borderline primary hypertension were enrolled in a prospective, randomized, double-blinded, placebo-controlled trial. A manual based self-management programme was performed in all participants for the homogenization in lifestyle. Compliance was monitored using serial contemporaneous food and lifestyle trackers. None of subjects received anti-hypertension drug therapy during the study period. Forty-eight subjects were randomly assigned to receive 20 g OFS per day (OFS group) or placebo (control group) for 12 weeks. Five subjects did not complete the trial. Primary study outcomes were changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP). Secondary outcomes included plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) and body weight.

Results: The measured outcomes showed more beneficial changes in OFS group. At the end of treatment, the decrease of SBP was 6.9±2.5 mmHg in OFS group and 3.5±1.2 mmHg in control group ( p  0.05).

Conclusion: Oligofructose supplementation leads to a significant reduction in blood pressure and improvement in lipid metabolism in subjects with mild or borderline primary hypertension.
Abstract P190: Teleconsultation Does Not Prolong Time Intervals in a Simulated Prehospital Cardiac Emergency Scenario
Authors: Max Skorning, Sebastian Bergrath, Daniel Rortgen, Stefan K Beckers, Jorg C Brokmann, Benjamin Gillmann, Joran Herding, Michael Protogerakis, Christina Mutscher, Rolf Rossaint
Journal: Circulation (2009)
Abstract 1947: Chymase Inhibition Reduces the Incidence of Intraplaque Hemorrhage and Induces a Stable Atherosclerotic Plaque Phenotype in ApoE Deficient Mice
Authors: Ilze Bot, Marijke M Westra, Sandra H van Heiningen, Hans Hilpert, Inge M Lankhuizen, Theo J van Berkel, Jürgen Fingerle, Erik A Biessen
Journal: Circulation (2008)

Mast cells are abundantly present in perivascular tissue during atherosclerotic plaque progression and were previously demonstrated to contribute significantly to plaque destabilization. In this study, we aimed to investigate to what extent inhibition of chymase, one of the mast cell proteases, could enhance plaque stability. We demonstrated earlier that the specific chymase inhibitor RO501 (1 μM) was able to quench mast cell activation in vitro , as illustrated by a decreased β-hexosaminidase (−41% and −80%, respectively; P&lt;0.05) as well as chymase activity in the releasate of activated MC/9 and peritoneal mast cells (−71% and −65%, respectively; P&lt;0.05). Next, we assessed whether chymase inhibition was also effective in vivo. Atherosclerotic carotid artery lesions were induced in ApoE −/− mice by perivascular collar placement and mast cells were activated by DNP challenge systemically during lesion development. RO501 (50 mg/kg/day) was administered as diet supplement, leading to serum concentrations of ~2 μM. While plaque size after 6 weeks of treatment did not differ, collagen content of the lesions was 2-fold enhanced in mice treated with RO501 compared to controls (1.4 ± 0.5% and 0.7 ± 0.2%, respectively). This was accompanied by a significant decrease in necrotic core size of the plaques (controls: 52 ± 3% versus RO501: 41 ± 4%, P&lt;0.05). To determine the effects of chymase inhibition after acute mast cell activation in advanced plaques, perivascular mast cells were focally activated in the adventitia of advanced lesions in ApoE −/− mice, which were treated with RO501 as described above. At three days after focal mast cell challenge, the incidence of intraplaque hemorrhage (IPH) was inhibited from 23% in control mice to 4.5% in RO501 treated mice, while also the plaque erythrocyte area was reduced by &gt;90% from 1.2 ± 0.6*10 3 to 0.1 ± 0.08*10 3 μm 2 (P&lt;0.05). Also, we observed a reduction in apoptotic cells (RO501: 0.68 ± 0.20% vs. 1.01 ± 0.36% for IPH negative controls and 1.23 ± 0.42% for IPH + plaques). In conclusion, our data suggest that chymase inhibition at least partly prevents the detrimental effects of perivascular mast cells on plaque stability, identifying chymase inhibition as a new therapeutic approach in the prevention of acute coronary syndromes.
Determinants of outcome in elderly patients with positive sentinel lymph nodes
Authors: M. Gemignani, A. Karam, M. Hsu, S. Patil, M. Stempel, T. Traina, A. Ho, H. Cody, M. Morrow
Journal: Journal of Clinical Oncology (2009)

614 Background: Older women are less likely to receive standard of care treatment for breast cancer. This undertreatment may be linked to the perception that elderly patients (pts) may not tolerate or derive benefit from treatment that is often viewed as “too toxic.” Methods: From July 1997 to July 2003, 1,470 pts with invasive cancer with positive sentinel lymph nodes (PSLN) by intraoperative frozen section or final pathologic exam by hematoxylin-eosin and/or immunohistochemistry (IHC). We examined sociodemographic, pathologic, and therapeutic variables that affected the outcome of elderly pts ≥70 years old. A comorbidity score was assigned using Adult Comorbidity Evaluation-27 system. Chi-square, Fisher's exact Wilcoxon tests, and multivariate logistic regression analysis were used. Results: The median age was 53 years (range 21–89) and median tumor size 1.6 cm (range 0.1–11). 1,265 (86.1%) pts were &lt;70 years old and 205 (13.9%) pts were ≥70 years old. 183 (12.5%) pts had IHC only PSLN, 1,021 (69.5%) had 1–3 PSLN, and 266 (18%) ≥4 PSLN. Breast conservation therapy (BCT) was performed in 59.7% of pts. Elderly pts were more likely to have moderate to severe comorbidities (46% vs. 11%, p &lt; 0.0001) and BCT (67% vs. 59%, p = 0.026), compared to pts &lt;70 years old. Elderly pts were less likely to undergo completion ALND (73% vs. 89%, p &lt; 0.0001), adjuvant chemotherapy (43% vs. 90%, p &lt; 0.0001) and radiotherapy following BCT (82% vs. 90%) compared to pts &lt;70 years old. The 5-year disease-free survival (DFS) was not significantly different for elderly pts compared to non-elderly pts (87.7% vs. 91.9%, p = 0.21), on the other hand the 5-year overall survival was significantly worse for elderly pts (80.4% vs. 93.2%, p &lt; 0.0001), a difference that was mainly due to a significantly higher 5-year cumulative incidence of death due to other causes (13.2% vs. 1.9%, p &lt; 0.0001). On multivariate analysis, ER or PR positive status, IHC only PSLN and T1 tumors were the only factors independently associated with improved odds of 5-year DFS. Conclusions: Tumor rather than patient factors were the primary determinants of breast cancer outcomes in our cohort of node positive breast cancer pts. Elderly breast cancer pts with an estimated life expectancy beyond 5 years should receive the same standard of care therapy as their younger counterparts. No significant financial relationships to disclose.
Abstract 1492: Molecular Imaging Of Occult Kidney Inflammation In ApoE −/− Mice Using <sup>19</sup> F MRI Nanobeacons For VCAM-1
Authors: Megan Kaneda, Richard Southworth, Junjie Chen, Lei Zhang, Huiying Zhang, Gregory Lanza, Samuel Wickline
Journal: Circulation (2008)

Although renal disease has been identified as a comorbidity for late-stage atherosclerosis, the early involvement of renal inflammation in the pathophysiology of progressive atherosclerosis has not yet been defined. To elucidate the impact of hyperlipidemia on incipient kidney disease, we deployed a VCAM-1-specific nanobeacon for magnetic resonance molecular imaging that emits a unique fluorine ( 19 F) signature without any background signal (Figure ). A dose of 1ml/kg was given intravenously to 6 cholesterol-fed ApoE −/− and 6 C57BL/6 mice, and VCAM -1 expression was measured after 2 hours at 11.7T ex vivo . Marked diffuse expression of VCAM-1 and macrophage infiltration was observed by immunocytochemistry in glomerular structures, especially in efferent and afferent arterioles. 19 F imaging confirmed widespread involvement in the renal cortex (Figure ). Magnetic resonance spectroscopic quantification of renal VCAM-1 expression in control (C57BL/6) mice was significantly lower (36.5±8.8 vs. 9.3±2.2x10 8 NP/g kidney) than that of ApoE−/− mice (p&lt;0.05). These data indicate that 19 F-based molecular MRI nanobeacons can detect and quantify renovascular disease in its earliest preclinical stages, and serve as a tool for both prognosis and management of generalized atherosclerosis. This research has received full or partial funding support from the American Heart Association, AHA Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota &amp; Wisconsin).
Abstract P55: Survival From Out-of-Hospital Cardiac Arrest Among Patients Receiving AHA 2000 ACLS Guidelines, AHA 2005 ACLS Guidelines, or Cardiocerebral Resuscitation: A Statewide Analysis
Authors: Bentley J Bobrow, Daniel W Spaite, Arthur B Sanders, Gordon A Ewy, Karl B Kern, Tyler F Vadeboncoeur, Lani L Clark, Vatsal Chikani, Robert A Berg
Journal: Circulation (2008)

Objective: Survival of patients with out-of-hospital cardiac arrest (OHCA) receiving standard ACLS before and after the transition from AHA 2000 to 2005 guidelines in EMS systems across Arizona was...
Abstract 4921: Differential Healing in Paclitaxel and Sirolimus-Eluting Stents in Combination with Oral PPAR Gamma Agents: The Role of Drug Interaction in Delayed Healing
Authors: Aloke Finn, Michael C John, Gaku Nakazawa, Chitra Raghunathan, Tucker Ezell, Scott Lajoie, Xin Xu, Qi Cheng, Frank Kolodgie, Renu Virmani, Herman K Gold
Journal: Circulation (2008)

Drug eluting stents (DES) contain different pharmacologic agents, yet the clinical relevance of this is unknown. Overlap exists between the molecular targets of sirolimus (SRL) (i.e. PI3K/mTOR) and many agents used to treat diabetes (DM). Because paclitaxel (PAC) works through other mechanisms, it might avoid this issue. The impact of interactions between eluted drug and commonly used DM meds on healing remains unknown. In rabbits receiving bare (BMS), PAC, and SRL DES, we investigated the effect of oral PPAR gamma agents, rosiglitazone (RSG) and pioglitazone (Pio), on stent endothelialization (ENDO). Rabbits were randomized to SRL, PAC or BMS and to placebo (PLC) versus RSG(3mg/kg/day) or Pio(10mg/kg/day). Animals were sacrificed at 28 days and arteries evaluated by scanning electron microscopy (SEM). 14day organ culture (OC) was also conducted. Cell culture experiments used human aortic endothelial cells (HAEC). RSG significantly reduced ENDO of the stent by SEM in animals receiving SRL vs. PLC, but no differences were seen in animals receiving PAC or BMS (table ). OC studies revealed significantly reduced VEGF levels in animals received SRL +RSG versus SRL +PLC, whereas animals receiving BMS and PAC demonstrated increased VEGF versus PLC. Similar results were seen in animals randomized to Pio vs. PLC. RSG +SRL additively inhibited p70s6k and SRL significantly blocked phosphorylation of Akt by RSG in HAEC. QRT-PCR revealed that SRL inhibited transcriptional upregulation of VEGF and heme oxygenase, a PPAR target gene, by RSG and suggests that in addition translational regulation, sirolimus may inhibit PPAR activity. RSG +SRL inhibits endothelialization because of significant drug interaction. No effect of PPAR gamma agonists is seen in animals receiving BMS or PAC. Our data suggest that SRL DES should be avoided in DM receiving PPAR gamma agonists and that investigation of other DM agents in combination with SRL is needed. 28 Day Endothelialization by SEM
Restoration of Voice after Laryngectomy
Authors: P Jassar, R J A England, N D Stafford
Journal: Journal of the Royal Society of Medicine (1999)

The importance of speech is not fully appreciated until the voice is lost. Speech is more than verbal communication; in addition, vocal intonation displays our emotional state. Cancer of the larynx is the most common head and neck malignancy in the western world1 and for a long time the only available treatment was major laryngeal surgery, (Billroth did the first total laryngectomy in 1873). Fortunately, since the advent of cobalt-60 in the 1950s and the improvement in endoscopic techniques, many patients with early disease can now be cured with radiotherapy alone or with minor surgical interventions that preserve the voice2-5. For some, however-those who do not respond and have residual disease or recurrence, and those who present with advanced diseasea major laryngeal resection provides the only hope of cure6'7. In a minority of cases partial laryngeal surgery, avoiding a permanent tracheostome, is feasible. However, the resulting voice is often poor and swallowing problems, especially aspiration, can be debilitating. In the UK, most patients who proceed to surgery still undergo a total laryngectomy. This involves the permanent separation of the respiratory tract from the upper digestive tract and the removal of the most important anatomical unit involved in voice production. It is a mutilating operation with lifelong functional and psychological consequences. Laryngectomized patients have a relatively favourable prognosis, with a 5-year survival rate of 65-75%8. Although this survival rate has changed little over the past 25 years, developments in post-laryngectomy speech rehabilitation have led to substantial improvements in quality of life. Here we offer a review of voice rehabilitation techniques.
Abstract 9925: Association between Resting Heart Rate, Chronotropic Index and Long-term Outcomes in Patients with Heart Failure Receiving Beta-blocker Therapy. Data from the HF-ACTION Trial
Authors: Daniela Dobre, Faiez Zannad, Steven J Keteyian, Susanna R Stevens, Patrick Rossignol, Delane K Kitzman, Joel Landzberg, Jonathan Howlett, William E Kraus, Stephen J Ellis
Journal: Circulation (2012)

Aim s: To assess the association between resting heart rate (HR), chronotropic index (CI) and clinical outcomes in patients with chronic heart failure (HF) on optimized β-blocker therapy. Methods: We performed a sub-study in 1118 patients with chronic HF and reduced ejection fraction (EF &lt;35%) who were enrolled in the HF-ACTION trial. We included patients in sinus rhythm who received a β-blocker and who performed an adequate symptom-limited maximum exercise test. Chronotropic Index was calculated as a percentage of predicted maximum HR reserve achieved, by using the equation (220-age) for estimating maximum HR. A sensitivity analysis using an equation estimating maximum HR for patients with HF taking β-blockers [(119 + (resting HR/2) - (age/2) - (5 * bike)] was also performed. Cox proportional hazards models were fit to assess the association between CI and clinical outcomes. Results: Median (25 th , 75 th percentiles) follow-up was 32 (21, 44) months. In a multivariable model including resting HR and CI as continuous variables, neither was associated with the primary outcome of all-cause mortality or hospitalization. However, in multivariable analysis, each 0.1 unit decrease in CI below 0.6 was associated with 17% increased risk of all-cause mortality (Hazard Ratio 1.17, 95% Confidence Interval 1.01-1.36; p=0.036) (figure), and 13% increased risk of cardiovascular mortality or HF hospitalization (Hazard ratio 1.13, 95% Confidence Interval 1.02-1.26; p=0.025). CI did not retain statistical significance when dichotomized at a value ≤0.62 as opposed to analysis of CI as a continuous variable. Sensitivity analysis showed a similar relationship between CI and outcomes. Conclusion: In patients with chronic HF receiving optimal medical therapy, a decrease in CI below 0.6 was associated with the risk of adverse clinical outcomes. These data support a strategy of including improved heart rate response to exercise, as a therapeutic target in the chronic HF population.
Administrative demands of care programme approach
Authors: C. Easton, F. Oyebode
Journal: BMJ (1996)

EDITOR,—Max Marshall makes the point that the care programme approach has never been fully evaluated, and that its American counterpart, case management, has not proved to be a particularly successful approach.1 In Britain, some studies have claimed that the approach is successful—for example, in tailoring care to individual needs—whereas others have shown that care programme approach fails to improve outcome and has no effect on rates of suicide or reoffending.2 3

We investigated the …
Biweekly (BW) chemotherapy (CHT) with oxaliplatin (OHP), irinotecan (CPT11), infusional 5-fluorouracil/folinic acid (FU/FA) in patients (pts) with metastatic colorectal cancer (MCRC) pretreated with CPT11- or OHP-based CHT
Authors: E. Mini, S. Nobili, S. Del Buono, V. Mazzocchi, F. Filippelli, B. Giglioni, T. Mazzei
Journal: Journal of Clinical Oncology (2004)

3751 Background:CPT11 or OHP in combination with infusional FU/FA induce objective responses (OR) in MCRC pts treated with the opposite combination. However, second-line response rates are still low. Preclinical studies show synergism or additivity between CPT11, OHP and FU in a ternary combination. This combination was associated with marked antitumor activity in MCRC pts at doses comparable to those used in binary combinations. Toxicities included frequent grade (G)4 neutropenia, G3 diarrhea, stomatitis and G2–3 neurotoxicity. We assessed the efficacy and tolerability of a ternary BW CPT11–OHP–infusional FU/FA combination in MCRC pts pretreated with CPT11 and/or OHP-based CHT using lower and potentially more tolerable doses.Methods:MCRC pts were given CPT11 followed by OHP (85mg/m2), FA (200mg/m2) and FU (48h infusion). CPT11 and FU dose escalation was planned.Results:22 pts were recruited: 15/7 males/females, median (m) age 63 yrs, m Karnofsky PS 100, primary tumor site: colon 14, rectum 8. 14 pts had received prior CPT11-, 6 prior OHP-based CHT and 2 both regimens. 3 dose levels were investigated: CPT11 at 100, 120 and 140mg/m2; FU at 1500, 1800 and 2100mg/m2 in 7, 10 and 5 pts, respectively. 22 pts are presently evaluable for toxicity, 18 for antitumor activity. All dose levels (144 cycles) were well tolerated with acceptable toxicity. Major toxicity included: one case G4 WHO stomatitis and G3 diarrhea, G3 nausea/vomiting (7pts,31.8%), neuromotor (6pts,27.3%) and neurosensory (2pts,9.1%). G2 toxicities were nausea/vomiting (4pts,18.2%), neuromotor (4pts,18.2%), diarrhea (3pts,13.6%), stomatitis (3pts,13.6%), leukopenia (3pts,13.6%) and neurosensory (1pt,4.5%). 2 pts experienced CR and 5 PR (OR 38.9%), 7 pts SD (38.9%), 4 pts PD (28.2%). M time-to-progression was 4.9 months. M survival has not yet been reached with 16 pts still alive after a m follow-up of 10.5 months.Conclusions:These preliminary data show that this combination has promising antitumor activity in CPT11- or OHP-pretreated MCRC pts and limited toxicity. No significant financial relationships to disclose.
Antiphosphatidylserine antibodies in human immunodeficiency virus-1 patients with evidence of T-cell apoptosis and mediate antibody- dependent cellular cytotoxicity [see comments]
Authors: F Silvestris, MA Frassanito, P Cafforio, D Potenza, M Di Loreto, M Tucci, MA Grizzuti, B Nico, F Dammacco
Journal: Blood (1996)
Abstract 14501: Power Training Blunt the Decline in Systolic Ventricular Function in Elderly
Authors: Luiz A Riani Costa, Andreia C Queiroz, Carlos E Suaide Silva, Luiz D Ferreira, Hélcio Kanegusuku, Alexandre Murad Neto, Marco T Mello, Carlos Ugrinowitsch, Cláudia L Forjaz
Journal: Circulation (2011)

Introduction: Few longitudinal interventional studies were designed to evaluate the impact of resistance training on cardiovascular system, and they reported that classical strength training did no...