tbuckley/cabot-search huggingface dataset:
Randomised, double blind, placebo controlled comparison of ginkgo biloba and acetazolamide for prevention of acute mountain sickness among Himalayan trekkers: the prevention of high altitude illness trial (PHAIT)
Authors: Jeffrey H Gertsch, Buddha Basnyat, E William Johnson, Janet Onopa, Peter S Holck
Journal: BMJ (2004)

Abstract Objective To evaluate the efficacy of ginkgo biloba, acetazolamide, and their combination as prophylaxis against acute mountain sickness. Design Prospective, double blind, randomised, placebo controlled trial. Setting Approach to Mount Everest base camp in the Nepal Himalayas at 4280 m or 4358 m and study end point at 4928 m during October and November 2002. Participants 614 healthy western trekkers (487 completed the trial) assigned to receive ginkgo, acetazolamide, combined acetazolamide and ginkgo, or placebo, initially taking at least three or four doses before continued ascent. Main outcome measures Incidence measured by Lake Louise acute mountain sickness score ≥ 3 with headache and one other symptom. Secondary outcome measures included blood oxygen content, severity of syndrome (Lake Louise scores ≥ 5), incidence of headache, and severity of headache. Results Ginkgo was not significantly different from placebo for any outcome; however participants in the acetazolamide group showed significant levels of protection. The incidence of acute mountain sickness was 34% for placebo, 12% for acetazolamide (odds ratio 3.76, 95% confidence interval 1.91 to 7.39, number needed to treat 4), 35% for ginkgo (0.95, 0.56 to 1.62), and 14% for combined ginkgo and acetazolamide (3.04, 1.62 to 5.69). The proportion of patients with increased severity of acute mountain sickness was 18% for placebo, 3% for acetazoalmide (6.46, 2.15 to 19.40, number needed to treat 7), 18% for ginkgo (1, 0.52 to 1.90), and 7% for combined ginkgo and acetazolamide (2.95, 1.30 to 6.70). Conclusions When compared with placebo, ginkgo is not effective at preventing acute mountain sickness. Acetazolamide 250 mg twice daily afforded robust protection against symptoms of acute mountain sickness.
Osteonecrosis of the jaws in newly diagnosed multiple myeloma patients treated with zoledronic acid and thalidomide-dexamethasone
Authors: Patrizia Tosi, Elena Zamagni, Delia Cangini, Paola Tacchetti, Francesco Di Raimondo, Lucio Catalano, Alfonso D'Arco, Sonia Ronconi, Claudia Cellini, Massimo Offidani, Giulia Perrone, Michela Ceccolini, Annamaria Brioli, Sante Tura, Michele Baccarani, Michele Cavo
Journal: Blood (2006)
Anticancer Agents Targeting Signaling Molecules and Cancer Cell Environment: Challenges for Drug Development?
Authors: K. A. Gelmon, E. A. Eisenhauer, A. L. Harris, M. J. Ratain, P. Workman
Journal: JNCI Journal of the National Cancer Institute (1999)

The focus of drug development has moved from cytotoxiccompounds identified by screening to therapies that act at spe-cific molecular targets. Although some of these agents maycause visible tumor reduction and may be adequately evaluatedby standard oncology drug development methods, other noveltherapies may not be amenable to our current practices. Conse-quently, our concepts of drug development must evolve andaddress various questions. How should we approach the pre-clinical development of these agents? Which laboratory experi-ments are critical prior to studying these new agents in theclinic? What phase I design strategies are appropriate? Agentsthat target specific molecules may not cause toxicity at effectivedoses and, therefore, phase I concepts such as maximum toler-ated dose (MTD) may not be relevant. What phase II designs suitthese agents? Drugs that have a cytostatic effect may be over-looked if tumor response is required as a selection criteria. PhaseII studies may not be necessary if the relevant end point issurvival, which cannot be fully addressed without a large ran-domized phase III trial. What can we learn from other areas ofmedicine? Many nononcology drugs target specific end pointsand are developed in a pattern quite different from the formulaused in oncology. Should we be adopting their methods of drugdevelopment?At the 10th National Cancer Institute–European Organizationfor Research and Treatment of Cancer Symposium on NewDrugs in Cancer Therapy, a workshop discussed these issues. Inthis commentary, we summarize some of the presentations. Al-though many new agents are entering or are already in clinicaltrials, it is imperative that we continue this dialogue with scien-tists, clinical researchers, cooperative groups, and industry andregulatory authorities because there is not yet an internationalconsensus on how to approach the challenges that lie ahead.
Significance of targeted therapy and genetic alterations in EGFR, ALK, or KRAS on survival in patients with non-small cell lung cancer treated with radiotherapy for brain metastases
Authors: K. S. Mak, J. F. Gainor, A. Niemierko, K. S. Oh, H. Willers, N. C. Choi, J. S. Loeffler, L. V. Sequist, A. T. Shaw, H. A. Shih
Journal: Neuro-Oncology (2014)

We determined the impact of genetic alterations in EGFR, ALK, or KRAS on survival after radiotherapy for brain metastases in non–small cell lung cancer (NSCLC). Of 172 genotyped NSCLC patients treated with radiotherapy for brain metastases in 2005–2012, 54 had cancers with EGFR mutations, 12 had ALK rearrangements, 38 had KRAS mutations, and 68 were wild-type (WT). Overall survival (OS) was determined. Median follow-up was 8.6 months. Median OS was 13.6 months for patients with EGFR mutations and 26.3 months for patients with ALK rearrangements, in contrast to 5.7 months for KRAS-mutant patients and 5.5 months for WT patients (P = .001). On multivariate analysis, adjusting for receipt of targeted therapy after cranial radiotherapy, ALK rearrangements were associated with improved OS (HR, 0.31; 95% CI, 0.13–0.74; P = .008). EGFR mutations were not significantly associated with improved OS on multivariate analysis (HR, 0.71; 95% CI, 0.37–1.38; P = .3). KRAS mutations were also not associated with improved OS (HR, 0.93; 95% CI, 0.59–1.47; P = .8). Receipt of targeted therapy after cranial radiotherapy was independently associated with improved OS (HR, 0.30; 95% CI, 0.17–0.54; P < .001). Receipt of chemotherapy after cranial radiotherapy, number of brain metastases, extracranial metastases, age, and performance status were also associated with OS. NSCLC patients with genetic alterations in ALK have improved survival outcomes after radiotherapy for brain metastases compared with EGFR, KRAS, or WT. Subsequent receipt of targeted therapy was associated with additional improvement in OS.
Validation of the AJCC TNM Substaging of pT2 Bladder Cancer: Deep Muscle Invasion Is Associated with Significantly Worse Outcome
Authors: Derya Tilki, Oliver Reich, Pierre I. Karakiewicz, Giacomo Novara, Wassim Kassouf, Süleyman Ergün, Yves Fradet, Vincenzo Ficarra, Guru Sonpavde, Christian G. Stief, Eila Skinner, Robert S. Svatek, Yair Lotan, Arthur I. Sagalowsky, Shahrokh F. Shariat
Journal: European Urology (2010)
Influence of Caffeine on Heart Rate Variability in Patients With Long-Standing Type 1 Diabetes
Authors: Tristan Richardson, Adrian Rozkovec, Peter Thomas, Jacqueline Ryder, Candy Meckes, David Kerr
Journal: Diabetes Care (2004)

OBJECTIVE—The effect of caffeine on cardiovascular health remains controversial. Patients with long-standing type 1 diabetes are at risk of autonomic failure and sudden cardiac death. We investigated the effects of caffeine on autonomic dysfunction (as assessed by heart rate variability [HRV]) in this high-risk group and in a control population. RESEARCH DESIGN AND METHODS—Using a randomized blinded, placebo-controlled, crossover design trial, we examined 2 weeks of caffeine consumption (250 mg twice daily) on HRV in 20 type 1 diabetic patients and 10 matched healthy volunteers. RESULTS—Baseline HRV was blunted in the diabetic patients (P &amp;lt; 0.0005 vs. control subjects) and markedly increased by caffeine in both groups (+103% in the group with diabetes [P = 0.009] and +38% in control subjects [P = 0.002]). The caffeine-associated increase in HRV was not statistically different between the control and the type 1 diabetes groups (P = 0.16). CONCLUSIONS—Modest amounts of caffeine improved autonomic function in diabetic patients and healthy volunteers. For individuals with abnormal HRV, regular caffeine use may have the potential to reduce the risk of cardiovascular events.
Impact of Systemic Treatment on Local Control for Patients With Lymph Node–Negative Breast Cancer Treated With Breast-Conservation Therapy
Authors: Thomas A. Buchholz, Susan L. Tucker, Jessica Erwin, Daniel Mathur, Eric A. Strom, Marsha D. McNeese, Gabriel N. Hortobagyi, Massimo Cristofanilli, Francisco J. Esteva, Lisa Newman, S. Eva Singletary, Aman U. Buzdar, Kelly K. Hunt
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To determine the impact of tamoxifen and chemotherapy on local control for breast cancer patients treated with breast-conservation therapy. PATIENTS AND METHODS: The data from 484 breast cancer patients who were treated with breast-conserving surgery and radiation were analyzed. Only patients with lymph node–negative disease were studied to provide comparative groups with a similar stage of disease and a similar competing risk for distant metastases. Actuarial local control rates of the 277 patients treated with systemic therapy (128, chemotherapy with or without tamoxifen; 149, tamoxifen alone) were compared with the rates for the 207 patients who received no systemic treatment. Only 10% of the patients had positive (2%), close (3%), or unknown margin status (5%). RESULTS: Patients treated with systemic therapy had improved 5-year (97.5% v 89.8%) and 8-year (95.6% v 85.2%) local control rates compared with those that did not receive systemic treatment (P = .004, log-rank test). There was no statistical difference in local control between patients treated with chemotherapy and patients treated with tamoxifen alone (P = .219). Systemic treatment, margin status, young patient age, estrogen and progesterone receptor status, and primary tumor size were analyzed in a Cox regression analysis. The use of systemic treatment was the most powerful predictor of local control: patients who did not receive systemic treatment had a relative risk of local recurrence of 3.3 (95% confidence interval, 1.5 to 7.5; P = .004). CONCLUSION: In this retrospective analysis, systemic therapy appears to contribute to long-term local control in patients with lymph node–negative breast cancer treated with breast-conservation therapy.
Association between lipid peroxidation and inflammation in obstructive sleep apnoea
Authors: K. Minoguchi, T. Yokoe, A. Tanaka, S. Ohta, T. Hirano, G. Yoshino, C. P. O’Donnell, M. Adachi
Journal: European Respiratory Journal (2006)

In the present study, the authors examined the relationship between lipid peroxidation and inflammation in patients with obstructive sleep apnoea (OSA). A total of 40 obese patients with OSA were studied, along with 18 obese and 12 lean subjects without OSA. Overnight excretion of 8-isoprostane in urine and serum levels of high-sensitivity C-reactive protein (hsCRP) were measured. In addition, the effects of 3 months’ treatment with nasal continuous positive airway pressure (nCPAP) were studied in 20 obese patients with moderate-to-severe OSA. Overnight urinary excretion of 8-isoprostane and serum levels of hsCRP were significantly higher in patients with moderate-to-severe OSA compared with patients with mild OSA and obese or lean subjects without OSA. Overnight urinary excretion of 8-isoprostane significantly correlated with apnoea–hypopnoea index, duration of hypoxia during sleep, body mass index, and serum levels of hsCRP in patients with OSA. The severity of OSA was an independent factor predicting the urinary excretion of 8-isoprostane. nCPAP significantly decreased urinary excretion of 8-isoprostane and serum levels of hsCRP. In conclusion, these results suggest that both obstructive sleep apnoea severity and obesity can independently contribute to elevations in urinary excretion of 8-isoprostane. Therefore, obstructive sleep apnoea may increase the risks of cardiovascular morbidity in obese patients.
Pharmacokinetically Guided Phase 1 Trial of the IGF-1 Receptor Antagonist RG1507 in Children with Recurrent or Refractory Solid Tumors
Authors: R. Bagatell, C.E. Herzog, T.M Trippett, J.F. Grippo, G. Cirrincione-Dall, E. Fox, M. Macy, J. Bish, P. Whitcomb, A. Aikin, G. Wright, S. Yurasov, F.M. Balis, L. Gore
Journal: Clinical Cancer Research (2010)

This pediatric phase I study was designed to identify the doses of RG1507, a monoclonal antibody against the Type 1 Insulin-like Growth Factor Receptor (IGF1R), that achieves exposures equivalent to those achieved in adults at recommended doses.Children with relapsed or refractory solid tumors were treated using the same doses and administration schedules of RG1507 (3 and 9 mg/kg/wk, and 16 mg/kg every 3 weeks [q3W]) as those studied in adults. Detailed pharmacokinetic (PK) sampling was performed after the first dose; selected peak and trough levels were subsequently obtained. Target exposures were ≥85% of mean areas under concentration x time curves (AUCs) in adults at doses of 9 mg/kg/wk and 16 mg/kg q3W. A maximum tolerated dose could be identified if dose-limiting toxicities (DLT) occurred.Thirty-one evaluable patients aged 3-17 years were enrolled at 3 mg/kg/wk (n = 3), 9 mg/kg/wk (n = 18), or 16 mg/kg q3W (n = 10). There were no DLTs. At 9 mg/kg/wk the mean AUC(0-7d) (21,000 μg h/mL) exceeded the target (16,000 μg h/mL). At 16 mg/kg q3W, the mean AUC(021d) (70,000 μg h/mL) exceeded the target (59,400 μg h/mL). Clearance normalized to body weight was age dependent. There were no objective responses. Seven patients had stable disease for >12 weeks, including two patients with osteosarcoma with stable disease for 52+ and 78+ weeks.The recommended doses of RG1507 in children with solid tumors are 9 mg/kg/wk and 16 mg/kg q3W. This flexible design is well suited for trials of agents associated with limited toxicity.
Monitoring the quality of laboratories and the prevalence of resistance to antituberculosis drugs: Italy, 1998–2000
Authors: G.B. Migliori, R. Centis, L. Fattorini, G. Besozzi, C. Saltini, G. Orefici, C. Piersimoni, A. Gori, A. Cassone
Journal: European Respiratory Journal (2003)

In 1998 a network of 20 regional tuberculosis (TB) laboratories (the Italian Multicentre Study on Resistance to Antituberculosis drugs (SMIRA) network) was established in Italy to implement proficiency testing and to monitor the prevalence of drug resistance nationwide. The network managed 30% of all TB cases reported in Italy each year. The aim of the present report is to describe: 1) the accuracy of drug-susceptibility testing in the network; 2) the prevalence of drug resistance for the period 1998–2000. Data were collected from the network laboratories. Sensitivity to streptomycin and ethambutol increased from the first survey (1998–1999) to the second survey (2000) from 87.7 to 91.9%. Specificity, predictive values for resistance and susceptibility, efficiency and reproducibility were consistent in both surveys. In previously untreated cases, the prevalence of multidrug-resistance was the same in both surveys (1.2%), while a slight decrease from the first to the second survey was observed for monoresistance to rifampicin (from 0.8 to 0.4%) and isoniazid (from 2.9 to 2%). The significant association found between isoniazid resistance and immigration is a useful indicator for both clinicians managing individual tuberculosis cases and public health services planning control strategies.
Spirometric screening: does it work?
Authors: D M Mannino
Journal: Thorax (2006)

Role of spirometric testing in smoking cessation

Pulmonary function testing offers an easy, inexpensive, and non-invasive means of diagnosing and staging chronic lung disease.1,2 It provides information on both the presence of obstructive lung disease and restrictive lung disease and can provide insights on how patients might respond to treatment.3,4 Spirometric testing also provides prognostic information, with lung function measures predicting mortality and the development of lung cancer.5,6

Despite the valuable information that spirometric testing provides, it is underused in medical practices in much of the world. There are several reasons for this, including (1) problems with doing the procedure,7 (2) problems related to compensation, and (3) …
Effect of Potassium Citrate on Calcium Phosphate Stones in a Model of Hypercalciuria
Authors: Nancy S. Krieger, John R. Asplin, Kevin K. Frick, Ignacio Granja, Christopher D. Culbertson, Adeline Ng, Marc D. Grynpas, David A. Bushinsky
Journal: Journal of the American Society of Nephrology (2015)

Potassium citrate is prescribed to decrease stone recurrence in patients with calcium nephrolithiasis. Citrate binds intestinal and urine calcium and increases urine pH. Citrate, metabolized to bicarbonate, should decrease calcium excretion by reducing bone resorption and increasing renal calcium reabsorption. However, citrate binding to intestinal calcium may increase absorption and renal excretion of both phosphate and oxalate. Thus, the effect of potassium citrate on urine calcium oxalate and calcium phosphate supersaturation and stone formation is complex and difficult to predict. To study the effects of potassium citrate on urine supersaturation and stone formation, we utilized 95th-generation inbred genetic hypercalciuric stone-forming rats. Rats were fed a fixed amount of a normal calcium (1.2%) diet supplemented with potassium citrate or potassium chloride (each 4 mmol/d) for 18 weeks. Urine was collected at 6, 12, and 18 weeks. At 18 weeks, stone formation was visualized by radiography. Urine citrate, phosphate, oxalate, and pH levels were higher and urine calcium level was lower in rats fed potassium citrate. Furthermore, calcium oxalate and calcium phosphate supersaturation were higher with potassium citrate; however, uric acid supersaturation was lower. Both groups had similar numbers of exclusively calcium phosphate stones. Thus, potassium citrate effectively raises urine citrate levels and lowers urine calcium levels; however, the increases in urine pH, oxalate, and phosphate levels lead to increased calcium oxalate and calcium phosphate supersaturation. Potassium citrate induces complex changes in urine chemistries and resultant supersaturation, which may not be beneficial in preventing calcium phosphate stone formation.
N-Terminal Pro–B-Type Natriuretic Peptide Testing Improves the Management of Patients With Suspected Acute Heart Failure
Authors: Gordon W. Moe, Jonathan Howlett, James L. Januzzi, Hanna Zowall
Journal: Circulation (2007)

The diagnostic utility of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure has been documented. However, most of the data were derived from countries with high healthcare resource use, and randomized evidence for utility of NT-proBNP was lacking.We tested the hypothesis that NT-proBNP testing improves the management of patients presenting with dyspnea to emergency departments in Canada by prospectively comparing the clinical and economic impact of a randomized management strategy either guided by NT-proBNP results or without knowledge of NT-proBNP concentrations. Five hundred patients presenting with dyspnea to 7 emergency departments were studied. The median NT-proBNP level among the 230 subjects with a final diagnosis of heart failure was 3697 compared with 212 pg/mL in those without heart failure (P<0.00001). Knowledge of NT-proBNP results reduced the duration of ED visit by 21% (6.3 to 5.6 hours; P=0.031), the number of patients rehospitalized over 60 days by 35% (51 to 33; P=0.046), and direct medical costs of all ED visits, hospitalizations, and subsequent outpatient services (US $6129 to US $5180 per patient; P=0.023) over 60 days from enrollment. Adding NT-proBNP to clinical judgment enhanced the accuracy of a diagnosis; the area under the receiver-operating characteristic curve increased from 0.83 to 0.90 (P<0.00001).In a universal health coverage system mandating judicious use of healthcare resources, inclusion of NT-proBNP testing improves the management of patients presenting to emergency departments with dyspnea through improved diagnosis, cost savings, and improvement in selected outcomes.
Maintenance of remission with human recombinant interferon alfa-2a in patients with stages III and IV low-grade malignant non-Hodgkin's lymphoma. European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group.
Authors: A Hagenbeek, P Carde, J H Meerwaldt, R Somers, J Thomas, R De Bock, J M Raemaekers, A van Hoof, C De Wolf-Peeters, M van Glabbeke
Journal: Journal of Clinical Oncology (1998)

PURPOSE Interferon alfa has shown significant activity in patients with low-grade malignant non-Hodgkin's lymphoma (NHL). In 1985, we initiated a prospective randomized study in which the potential benefit of interferon alfa given as maintenance treatment was investigated after tumor load reduction was achieved with chemoradiotherapy in patients with advanced low-grade malignant non-Hodgkin's lymphoma. PATIENTS AND METHODS The study involved 347 patients with stage III or IV disease, 315 satisfying the eligibility criteria. All were treated with a regimen of cyclophosphamide, vincristine, and prednisone (CVP) given every 3 weeks for eight cycles. Thereafter, patients were eligible for iceberg irradiation. Finally, all patients were completely restaged, and responding and stable-disease patients were then randomized, 122 to interferon alfa-2a maintenance, 3 million U three times weekly for 1 year; and 120 to no further treatment. RESULTS Seventy-nine percent of the patients response to CVP, ie, 45% complete remissions (CR) and 34% partial remissions (PR). In the group of randomized patients, the response rate after CVP plus or minus radiotherapy was 90%. As compared with control patients, patients in the interferon (IFN) maintenance group had a tendency toward a prolonged time to progression (TTP) (median, 132 v 87 weeks; P = .054, adjusted for response to CVP). However, overall survival was similar in both groups. Interferon was well tolerated. The median dose of IFN actually received corresponded to 90% of the planned cumulative dose. The treatment had to be stopped because of toxicity in 16 patients (15% of the patients in whom IFN was started). CONCLUSION Interferon maintenance treatment in the phase of minimal residual disease of patients with advanced low-grade malignant NHL increased TTP at the borderline of statistical significance, without remarkable toxicity. However, overall survival was not influenced.
Behavioral Treatment of Insomnia in Bipolar Disorder
Authors: Katherine A. Kaplan, Allison G. Harvey
Journal: American Journal of Psychiatry (2013)

Sleep disturbance is common in bipolar disorder. Stimulus control and sleep restriction are powerful, clinically useful behavioral interventions for insomnia, typically delivered as part of cognitive-behavioral therapy for insomnia (CBT-I). Both involve short-term sleep deprivation. The potential for manic or hypomanic symptoms to emerge after sleep deprivation in bipolar disorder raises questions about the appropriateness of these methods for treating insomnia. In a series of patients with bipolar disorder who underwent behavioral treatment for insomnia, the authors found that regularizing bedtimes and rise times was often sufficient to bring about improvements in sleep. Two patients in a total group of 15 patients reported mild increases in hypomanic symptoms the week following instruction on stimulus control. Total sleep time did not change for these individuals. Two of five patients who underwent sleep restriction reported mild hypomania that was unrelated to weekly sleep duration. Sleep restriction and stimulus control appear to be safe and efficacious procedures for treating insomnia in patients with bipolar disorder. Practitioners should encourage regularity in bedtimes and rise times as a first step in treatment, and carefully monitor changes in mood and daytime sleepiness throughout the intervention.