Tracking apex marine predator movements in a dynamic ocean.

Pelagic marine predators face unprecedented challenges and uncertain futures. Overexploitation and climate variability impact the abundance and distribution of top predators in ocean ecosystems. Improved understanding of ecological patterns, evolutionary constraints and ecosystem function is critical for preventing extinctions, loss of biodiversity and disruption of ecosystem services. Recent advances in electronic tagging techniques have provided the capacity to observe the movements and long-distance migrations of animals in relation to ocean processes across a range of ecological scales. Tagging of Pacific Predators, a field programme of the Census of Marine Life, deployed 4,306 tags on 23 species in the North Pacific Ocean, resulting in a tracking data set of unprecedented scale and species diversity that covers 265,386 tracking days from 2000 to 2009. Here we report migration pathways, link ocean features to multispecies hotspots and illustrate niche partitioning within and among congener guilds. Our results indicate that the California Current large marine ecosystem and the North Pacific transition zone attract and retain a diverse assemblage of marine vertebrates. Within the California Current large marine ecosystem, several predator guilds seasonally undertake north-south migrations that may be driven by oceanic processes, species-specific thermal tolerances and shifts in prey distributions. We identify critical habitats across multinational boundaries and show that top predators exploit their environment in predictable ways, providing the foundation for spatial management of large marine ecosystems.

Ultrasound is now better than mammography for the detection of invasive breast cancer.

OBJECTIVE: This study investigated the use of ultrasound (US) as a first-line diagnostic tool. METHODS: All women attending our breast center underwent bilateral whole-breast US in addition to all other investigations, and results were documented prospectively and preoperatively. RESULTS: Of 796 patients with breast cancer, US was positive in 710 (89%) and mammography in 706 (89%) (P = not significant). Either US or mammogram was positive in 770 (97%). Of 537 (67%) symptomatic patients, US was positive in 497 (93%) and mammography in 465 (87%). Either US or mammography was positive in 515 (96%). Of 259 (33%) screening patients, 220 (85%) had invasive cancer. US was positive in 195 (89%) and mammography in 203 (92%) (P = not significant). Either US or mammography was positive in 217 (99%). Of 39 screening patients with ductal carcinoma in situ (5% of all patients), US was positive in 18 (46%) and mammography in 38 (97%). CONCLUSIONS: US is significantly better than mammography for detecting invasive breast cancer (92% patients). The combination of US and mammography is significantly better than either modality used alone, together resulting in 9% more breast cancers detected.

Combined image guidance excision of non-palpable breast lesions.

When mammogramography detects a non-palpable lesion the surgeons may be called upon to establish a diagnosis. Various techniques are currently employed. We describe a technique, which can be used both for diagnostic and for therapeutic procedures. The technique essentially involves localising the tip of a guide-wire, placed under mammographic guidance, with ultrasound scanning. This minimises many of the problems encountered with wire guided excision. We conducted a prospective non-randomised study using our combined image guidance technique (CIG) for patients undergoing diagnostic (n = 24) and therapeutic biopsy (n = 13). We found that significantly smaller diagnostic biopsy weights were achievable using CIG, compared to non-CIG techniques. Reduced biopsy weights are recommended by current guidelines.

Immediate-release oxybutynin versus tolterodine in detrusor overactivity: a population analysis.

We evaluated adherence to treatment with immediate-release (IR) oxybutynin (515 patients) and tolterodine (505 patients) for detrusor overactivity through retrospective analysis of a pharmacy claims database. Outcomes included percentage of patients continuing therapy for 6 months, medication possession ratios, and time to discontinuation of therapy. The proportion of patients continuing therapy for 6 months was statistically superior for tolterodine (32%) compared with IR oxybutynin (22%, p<0.001). Medication possession ratios were also superior for patients in the tolterodine group (medians 0.83 and 0.64, ranges 0.11-1.15 and 0.07-1.13, respectively, p<0.001). Oxybutynin was discontinued significantly earlier (mean 45 days) than tolterodine (mean 59 days, p<0.001) and was switched to another therapy more commonly than tolterodine (19% and 14%, respectively). Tolterodine was favored over oxybutynin for several measurements of patient adherence. However, less than one-third of patients continued therapy with either agent for 6 months. The clinical relevance of these differences is unknown.

Patient self-reporting of compliance does not correspond with electronic monitoring: an evaluation using isosorbide dinitrate as a model drug.

STUDY OBJECTIVE: To assess the accuracy of patient-kept diaries relative to electronic monitoring of compliance with isosorbide dinitrate prescribed 3 times/day for ischemic heart disease. DESIGN: Unblinded, prospective, three-phase study. METHODS: Patients with coronary artery disease prescribed isosorbide dinitrate 3 times/day were asked to record the time of administration of each dose in a pocket diary while being monitored for compliance with a computerized Medication-Event Monitoring System (MEMS-4) vial that electronically recorded the date and time the vial was opened. RESULTS: Sixty-eight stable outpatients with documented coronary artery disease who were prescribed isosorbide dinitrate 3 times/day were evaluated. Based on a prospectively chosen definition including a nitrate-free period, the mean (+/-SD) overall compliance rates were 71% (+/-30) versus 55% (+/-32) for the patient-kept diaries and the MEMS vials respectively (p = 0.001). The concordance between patient-kept diaries and MEMS data indicate that 67% of patients overestimate their compliance when using a self-recording tool. An average of 30% of diary entries were in error compared with the MEMS vial recordings. CONCLUSIONS: Patient-kept diaries statistically overestimate actual compliance relative to that determined by MEMS devices. Given the prevalence of the use of diaries as the predominant tool on which researchers depend to document compliance with study drugs, our findings suggest that this practice should be reevaluated specifically when the time of the dose and documentation of administration are critical to qualifying the outcome of drug therapy. Such is the case with isosorbide dinitrate use in patients with ischemic heart disease. Furthermore, the overall poor compliance documented in this study suggests that the utility of isosorbide dinitrate prescribed 3 times/day be reevaluated as a clinically effective antianginal drug.

Chronopharmacologic considerations when treating the patient with hypertension: a review.

Recognition of the existence of circadian variation in exacerbation of cardiovascular disease may have relevance to clinical use of cardioactive agents. Physiologic rational for the chronobiology of cardiac disease exists and can provide a basis on which to examine the efficacy of agents to manage cardiac disease. The use of 24-hour ambulatory blood pressure monitoring (ABPM) devices have advanced our ability to describe the interplay of chronobiologic rhythms and pharmacodynamic response to antihypertensive medications. This review summarizes the studies evaluating the use of various antihypertensive medications in the context of using 24-hour blood pressure monitoring devices. The studies are described in an attempt to increase awareness of chronobiology and potential implications of designing chronotherapeutic regimens.

Predominance of slow acetylators of N-acetyltransferase in a Hmong population residing in the United States.

Pharmacogenetics can be an important determinant of pharmacologic response. To learn more about interpopulation differences in drug metabolism between ethnically diverse populations of subjects cared for by an International Clinic, a study was conducted to describe the prevalence of fast or slow acetylators of N-acetyltransferase (NAT2) in a population of Hmong residing in Minnesota. Ninety-eight healthy Hmong refugees from Laos volunteered to take caffeine as an oral probe drug to establish acetylator phenotype. Participants were classified as either rapid or slow acetylators based on the urinary molar ratio of select metabolites of caffeine. Assignment of phenotype was based on results from analysis of urine collected subsequent to ingestion of caffeine. The ratio of 5-acetylamino-6-formylamino-3-methyluracil (AFMU) to the combined products of the 7-demethylation pathway of paraxanthine (AFMU, 1-methylxanthine (1X), and 1-methylurate (1U)] formed the basis for this determination. A probit plot of the data collected in our subjects qualified a metabolic ratio of 0.34 as an acceptable cut point for phenotype assignment. Participants with an AFMU/(AFMU + 1X + 1U) ratio of < 0.34 were classified as slow acetylators and all others as rapid acetylators. Analysis of the data suggested a bimodal distribution with an excess (74.5%) of slow acetylators in the population. The predominance of slow acetylators found in the Hmong contrast with the prevalence of slow acetylators seen in other ethnic groups. These findings may have important clinical implications given the large number of Hmong treated each year in our International Clinic and the increasing use of medications metabolized by NAT2 in this population.

Magnitude and nature of noncompliance with treatment using isosorbide dinitrate in patients with ischemic heart disease.

Isosorbide dinitrate is one of the most commonly prescribed medications for the treatment of ischemic heart disease. It has been demonstrated to be ineffective relative to placebo when taken inappropriately. This study objectively documents the magnitude and nature of compliance in 68 ambulatory patients who were prescribed isosorbide dinitrate three times a day. Each patient received a 9-week supply of medication in a vial equipped with a computerized monitor (MEMS-4 cap; APREX Corporation, Fremont, CA) and were informed as to the purpose of the study. Of the patients, 74% were classified into the low and 16% into the high compliance category, defined as compliant < 70% and > or = 85% of study days, respectively. The mean (+/- SD) percent days in which isosorbide dinitrate was taken three times was 66% (+/- 29), and the mean number of days in which it was taken three times with a 10-hour "nitrate free period" was 53% (+/- 31). It is concluded that the magnitude of noncompliance in patients prescribed isosorbide dinitrate three times daily is substantial (74%). The nature of this noncompliance is often due to failure to observe a 10- to 12-hour nitrate free period. Given the need to take isosorbide dinitrate appropriately and given the demonstrated magnitude of noncompliance, physicians should take these factors into consideration when selecting this agent for the management of coronary artery disease relative to other pharmacologic options.