Capsule Counts Research Articles

Distribution of chironomid subfossil assemblages in sediments of an Irish lake: controls and potential for paleoenvironmental applications

ABSTRACTA survey of chironomid subfossil remains was carried out in Lough Muckno, a lake system located in northeast Ireland. The dataset provides new insights into chironomid ecology and subfossil taphonomy in the Irish Ecoregion. A significant degree of homogeneity in subfossil assemblages and presence of efficient offshore redeposition mechanisms was evident. The potential role of the thermocline and river discharge in determining subfossil assemblage composition was also explored. Redundancy analysis indicated that sample (spatial) location and water depth are governing and intertwined controls on chironomid assemblage composition. Profundal habitats at a sensible distance from the littoral best integrated basin-wide remains representing suitable locations for paleoecological reconstructions based on a single-core approach. However, assemblages in deep mid-lake habitats characterized by advanced diagenesis and low head capsule counts were deemed unsuitable for paleoecological applications. The results highlight the importance of accounting for both lake depth and distance metrics in the design of paleolimnological investigations in systems with a complex basin morphology.

Fish oil supplementation in chronic obstructive pulmonary disease: feasibility of conducting a randomised controlled trial

BackgroundLong-chain omega-3 polyunsaturated fatty acids (LCn-3PUFAs) may act as an effective adjunct therapy for chronic obstructive pulmonary disease (COPD), a condition characterised by persistent airflow limitation and inflammation. However, the nature of this illness presents challenges for evaluating potential benefits. The aim of this study was to determine the feasibility of undertaking a randomised controlled trial of LCn-3PUFA supplementation in adults with COPD.MethodsA 16-week parallel, double-blind, randomised, placebo-controlled dietary supplementation trial was conducted. Participants diagnosed with COPD were randomly allocated to take six 1-g capsules of fish oil (3.6 g LCn-3PUFA) or corn oil (placebo) daily for 16 weeks. Key outcomes used to determine the feasibility of the trial included recruitment rate, participant retention rate and supplement adherence (blood biomarker and returned capsule count). An estimate of the effect size for clinical outcomes such as pulmonary function and functional exercise capacity was calculated.ResultsNone of the key feasibility criteria were met. The enrolment target was 40 participants in 52 weeks; however, only 13 were finally enrolled, with just seven in the first 52 weeks. Eight participants completed the study (retention rate 62%). Targets for compliance were not achieved; red blood cell LCn-3PUFA content (expressed as percentage of total fatty acids) did not increase by more than 2% in the fish oil group; capsule counts were unreliable. As the target sample size was not achieved and only a small number of participants completed the study, it was not possible to use the variance in clinical outcomes to estimate a sample size for a future study.ConclusionsThis study highlights major difficulties, especially with recruitment, in conducting this LCn-3PUFA supplementation trial in people with COPD, rendering the protocol unfeasible by predetermined criteria. A modified approach is needed to investigate potential health benefits of fish oil in people with COPD. A multicentre study with changes to inclusion and exclusion criteria is recommended.Trial registrationAustralia and New Zealand Clinical Trials Register (ANZCTR), ACTRN12612000158864

Evolution of pain at 3 months by oral resveratrol in knee osteoarthritis (ARTHROL): protocol for a multicentre randomised double-blind placebo-controlled trial

IntroductionOsteoarthritis (OA) pathophysiology is driven in part by joint inflammation. Resveratrol has in vitro anti-inflammatory properties. We aim to assess the efficacy of oral resveratrol for knee pain at 3...

Reconstructing terrestrial temperatures in the Australian sub-tropics and tropics: A chironomid based transfer function approach

This paper presents chironomid-based transfer functions for temperature reconstructions intended for use in the Australian tropics and sub-tropics. Temperature was the primary independent control of chironomid assemblages. Two transfer functions were created to infer mean annual (MAT) and mean summer temperature as represented by February temperatures (MFT) as it was not reasonable to automatically assume that chironomid populations in the tropics are controlled by summer temperatures. Weighted average partial least square (WA-PLS) models were the most robust. For MAT they produced a coefficient of determination (r2jack) of 0.83, a maximum bias of 1.74 °C and a root mean squared error of prediction (RMSEP) of 2.35 °C while for MFT an r2jack of 0.76, maximum bias of 2.43 °C, and RMSEP of 2.43 °C was achieved. Based on the statistics we recommend that the MAT model is used for chironomid work in tropical regions.Though chironomid head capsule counts were low, we tentatively applied the MAT function to published Holocene chironomid data from Lake Barrine, northeast Queensland. The results suggest only minor temperature change through the last 9000 years. Based on other proxies, this appears to result in realistic temperature reconstructions. Consequently we highlight that sub-fossil chironomids have the potential to provide high quality temperature records for the Australian tropics.

Four-Year Placebo-Controlled Trial of Docosahexaenoic Acid in X-Linked Retinitis Pigmentosa (DHAX Trial)

X-linked retinitis pigmentosa is a severe inherited retinal degenerative disease with a frequency of 1 in 100,000 persons. Because no cure is available for this orphan disease and treatment options are limited, slowing of disease progression would be a meaningful outcome. To determine whether high-dose docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid, slows progression of X-linked retinitis pigmentosa measured by cone electroretinography (ERG). A 4-year, single-site, randomized, placebo-controlled, double-masked phase 2 clinical trial at a research center specializing in medical retina. Seventy-eight male patients diagnosed as having X-linked retinitis pigmentosa were randomized to DHA or placebo. Data were omitted for 2 patients with non-X-linked retinitis pigmentosa and 16 patients who were unable to follow protocol during the first year. The remaining participants were tested annually and composed a modified intent-to-treat cohort (DHA group, n = 33; placebo group, n = 27). All participants received a multivitamin and were randomly assigned to oral DHA (30 mg/kg/d) or placebo. The primary outcome was the rate of loss of cone ERG function. Secondary outcomes were rod and maximal ERG amplitudes and cone ERG implicit times. Capsule counts and red blood cell DHA levels were assessed to monitor adherence. Average (6-month to 4-year) red blood cell DHA levels were 4-fold higher in the DHA group than in the placebo group (P < .001). There was no difference between the DHA and placebo groups in the rate of cone ERG functional loss (0.028 vs 0.022 log µV/y, respectively; P = .30). No group differences were evident for change in rod ERG (P = .27), maximal ERG (P = .65), or cone implicit time (no change over 4 years). The rate of cone loss (ie, event rate) was markedly reduced compared with rates in previous studies. No severe treatment-emergent adverse events were found. Long-term DHA supplementation was not effective in slowing the loss of cone or rod ERG function associated with X-linked retinitis pigmentosa. Participant dropout and lower-than-expected disease event rate limited power to detect statistical significance. A larger sample size, longer trial, and attainment of a target blood DHA level (13%) would be desirable. While DHA supplementation at 30 mg/kg/d does not present serious adverse effects, routine monitoring of gastrointestinal tolerance is prudent. clinicaltrials.gov Identifier: NCT00100230.

Safety and efficacy of long-term esomeprazole 20 mg in Japanese patients with a history of peptic ulcer receiving daily non-steroidal anti-inflammatory drugs

BackgroundNon-steroidal anti-inflammatory drugs (NSAIDs) are an effective and common treatment for chronic pain disorders, but long-term use is associated with risk of potentially life-threatening gastrointestinal adverse events (AEs). The proton pump inhibitor esomeprazole has been found to be effective for gastroprotection in NSAID users, but few long-term studies have been conducted in Japan.MethodsThis was an open-label, multicentre, single-arm, prospective 1-year study of treatment with esomeprazole (20 mg once daily) in Japanese patients (aged ≥20 years) with endoscopic evidence of previous peptic ulcer and receiving daily oral NSAID therapy (at a stable dose) for a chronic condition. Eligibility was not dictated by type of oral NSAID. The primary objective was to determine long-term safety and tolerability of esomeprazole. Efficacy for prevention of peptic ulcers was also determined (Kaplan-Meier method). All statistical analyses were descriptive.ResultsA total of 130 patients (73.1% women, mean age 62.1 years, 43.8% Helicobacter pylori-positive) received treatment with esomeprazole in addition to long-term NSAID therapy (most commonly for rheumatoid arthritis [n=42] and osteoarthritis [n=34]). Loxoprofen, meloxicam and diclofenac were the most commonly used NSAIDs; cyclo-oxygenase (COX)-2 selective agents were used by 16.2% of patients (n=21). Long-term compliance with esomeprazole (capsule counts) was >75% for the majority of patients. Although 16.9% of patients (n=22) experienced AEs judged to be possibly related to treatment with esomeprazole, they were mostly mild and transient. The most commonly reported possibly treatment-related AEs were abnormal hepatic function, headache, increased γ-glutamyltransferase levels and muscle spasms (2 patients each). Overall, 95.9% (95% confidence interval: 92.3, 99.4) of patients remained ulcer free at 1 year.ConclusionLong-term treatment with esomeprazole (20 mg once daily) is well tolerated and efficacious for preventing ulcer recurrence in Japanese NSAID users with a history of peptic ulcer.Trial registrationClinicalTrials.gov identifier NCT00595517.

Systematics and Biology ofCremastobombycia chromolaenae, New Species (Gracillariidae), a Natural Enemy ofChromolaena odorata(L.) King and H. Robinson (Asteraceae)

ABSTRACT. A new species, Cremastobombycia chromolaenae, is described from Florida and Texas, USA. The larva is a leaf miner on Chromolaena odorata (L.) King and H. Robinson, a 2–3 m tall perennial shrub of the family Asteraceae, whose native range extends from southern Florida south to northern Argentina (Fig. 1). The plant is also known to occur in Africa, Asia, and Australia where it is considered exotic and in some countries has become a major weed. The larvae of C. chromolaenae are hypometamorphic and possess two distinct larval body forms and feeding behaviors—an early stage sap-feeding form with a flattened body and prognathous mouthparts and a later stage tissue-feeding form with a more cylindrical body and possessing hypognathous mouthparts. Based on head capsule counts and measurements, the larvae undergo five instars, with the first three instars being of the sap-feeding form and the last two tissue-feeding instars. The larval mine begins as a short, serpentine track which enlarges to a rounded,...

Medication adherence assessment in a clinical trial with centralized follow-up and direct-to-patient drug shipments

Assessment of adherence to study medications is a common challenge in clinical research. Counting unused study medication is the predominant method by which adherence is assessed in outpatient clinical trials but it has limitations that include questionable validity and burdens on research personnel. To compare capsule counts, patient questionnaire responses, and plasma drug levels as methods of determining adherence in a clinical trial that had 2056 participants and used centralized drug distribution and patient follow-up. Capsule counts from study medication bottles returned by participants and responses to questions regarding adherence during quarterly telephone interviews were averaged and compared. Both measures were compared to plasma drug levels obtained at the 3-month study visit of patients in the treatment group. Counts and questionnaire responses were converted to adherence rates (doses taken divided by days elapsed) and were categorized by stringent (≥85.7%) and liberal (≥71.4%) definitions. We calculated the prevalence-adjusted bias-adjusted kappa to assess agreement between the two measures. Using a pre-paid mailer, participants returned 76.0% of study medication bottles to the central pharmacy. Both capsule counts and questionnaire responses were available for 65.8% of participants and were used to assess adherence. Capsule counts identified more patients who were under-adherent (18.8% by the stringent definition and 7.5% by the liberal definition) than self-reports did (10.4% by the stringent definition and 2.1% by the liberal definition). The prevalence-adjusted bias-adjusted kappa was 0.58 (stringent) and 0.83 (liberal), indicating fair and very good agreement, respectively. Both measures were also in agreement with plasma drug levels determined at the 3-month visit (capsule counts: p = 0.005 for the stringent and p = 0.003 for the liberal definition; questionnaire: p = 0.002 for both adherence definitions). Inconsistent bottle returns and incomplete notations of medication start and stop dates resulted in missing data but exploratory missing data analyses showed no reason to believe that the missing data resulted in systematic bias. Depending upon the definition of adherence, there was fair to very good agreement between questionnaire results and capsule counts among returned study bottles, confirmed by plasma drug levels. We conclude that a self-report of medication adherence is potentially comparable to capsule counts as a method of assessing adherence in a clinical trial, if a relatively low adherence threshold is acceptable, but adherence should be confirmed by other measures if a high adherence threshold is required.

An automatic counter for aerial images of aggregations of large birds

Capsule Counts with precision comparable to those of an expert observer can be achieved automatically. Aims To develop an open-source freeware program that automatically extracts and counts the number of birds in aerial images of dense aggregations. Methods Software was developed and validated using aerial photographs of Greater Flamingo colonies from France, Turkey and Mauritania. We used a stochastic approach based on object processes. The objects representing flamingos were defined as ellipses, and the software detected these and produced a count. Details of the procedure are provided in electronic supplementary material. The energy is extracted by a birth-and-death algorithm, leading to the total number of birds. Results This procedure gave counts with precision comparable to manual counts of the aerial photographs by an expert (<5% difference). The procedure does not need any supervision of the extraction by an operator, thus reducing the processing time required to get the estimate of bird numbers in the image from >4 h to 20 min on average. Conclusion This open-source freeware should be useful for ornithologists and wildlife managers.

Sustained 24-h efficacy of NVA237, a once-daily long-acting muscarinic antagonist, in COPD patients

NVA237 is a once-daily inhaled long-acting muscarinic antagonist in development for the treatment of COPD. This randomized, double-blind, placebo-controlled, four-period, incomplete block crossover study, with open-label active comparator (tiotropium), assessed the efficacy and safety of NVA237. Patients (>or=40 years; smoking history >or=10 pack-years) with stable moderate-to-severe COPD (post-bronchodilator FEV(1) >or= 30% and <80% predicted, FEV(1)/FVC < 0.7) received NVA237 12.5, 25, 50 or 100 microg, placebo, or tiotropium 18 microg once-daily for 7 days. The primary endpoint was mean trough (23-24 h post-dose) FEV(1) on Day 7. Secondary endpoints included mean trough FEV(1) on Day 1, and FEV(1) and FVC at individual time points post-dose on Days 1 and 7. 83 patients (mean age 64.4 years; male 83.1%; mean COPD duration 6.7 years; mean post-bronchodilator FEV(1) 1.5 L/52.7% predicted) were randomized; 78 completed. Mean trough FEV(1) on Day 7 and Day 1 was significantly higher with all active treatments versus placebo (p < 0.05). NVA237 50 microg, 100 microg and tiotropium showed clinically relevant improvements versus placebo on Day 7 (differences of 131, 142 and 127 mL, respectively; p < 0.0001) and 1 (differences of 121, 135 and 112 mL, respectively; p < 0.0001). On Day 1, but not Day 7, FEV(1) was significantly higher (p < 0.05) with NVA237 50 and 100 microg versus tiotropium from 5 min up to 2 and 4 h post-dose, respectively. All doses of NVA237 and tiotropium were well tolerated. NVA237 once-daily was effective and well tolerated versus placebo, and demonstrated rapid and sustained 24-h bronchodilation. (ClinicalTrials.gov Identifier: NCT00501852).

Palaeolimnology of Lake Hess (Patagonia, Argentina): multi-proxy analyses of short sediment cores

In contrast with the extensive palaeolimnological studies carried out in North America and Europe, relatively few studies have described the anthropogenic and/or climate impacts in Patagonian lakes. We addressed these issues by analysing geochemistry, lithology, pigments and chironomid remains from sediment cores collected from Lake Hess (41°22′20″S, 71°44′0″W) located in the Nahuel Huapi National Park in northern Patagonia. The aim of this study is to provide a palaeoenvironmental and climate reconstruction of the past ca. three centuries for this cold oligotrophic, quasi-pristine lake which receives meltwaters from the Tronador ice cap. Chronology was based on 137Cs and 210Pb measurements of the upper sediments, and the inferred sedimentation rate of 23.2 mg cm−2 y−1 (0.15 cm y−1) was consistent with both sets of measurements. The sediment from Lake Hess was rich in tephra deposits particularly evident in the lower part of the cores. Tephras are valuable to use for core correlation and can be traced through peaks in the magnetic susceptibility (MS) profiles. Results from the multiproxy analyses in the longest core (83 cm) identify three main phases of change. From the bottom up to 42 cm (ca. ad 1800), the sediment is composed of light-grey organically rich clays. Both pigments and chironomids suggest variable trends in productivity and precipitation regime. At the end of the Little Ice Age chronozone (ad 1770–1850), pigment concentrations were very low. From 42 cm to ca. 25 cm (ad 1800–1940), the sedimentary record is composed of alternating black and dark organic-matter rich mud with variable amounts of macrophyte remains. Pigment concentrations and chironomid head capsule counts were also very low. These facies are composed of very fine plastic sediments with some faintly laminated intervals and an organic matter composition gradually decreasing towards the top of the zone. A sharp change occurs at 25 cm (ca. ad 1940) showing a strong increase in organic matter content, algal nutrients and plant pigments together with a change in the chironomid assemblages. This might document a change in the trophic condition of the lake associated with changes in erosion/deposition rates. Although there are records of human impact in the area studied, involving the use of fires, most of the observed chemical and biological changes in Lake Hess sediment sequence were interpreted in terms of climate changes, especially to changes in moisture balance brought about by variations in the strength of the westerlies.

Compliance with Proton Pump Inhibitor Therapy Impacts Resolution of GERD Symptoms – Preliminary Results

Purpose: While the efficacy of Proton Pump Inhibitor (PPI) therapy for healing erosive reflux esophagitis is well known from randomized controlled trials, how patients take their medications in the real world, and if they stop once symptoms are relieved and start their own “on demand” regimen, is not known. The primary aim of this study was to assess the correlation between GERD symptom resolution with compliance in taking a daily PPI for 8 weeks in patients with Los Angeles (LA) grade B, C or D esophagitis. Methods: In this prospective descriptive cohort study, symptomatic outpatients with LA grades B-D esophagitis were placed on esomeprazole 40 mg once daily for 8 weeks. GERD symptoms were recorded using the validated Mayo Dysphagia Questionnaire-30 at baseline and 8 weeks. To meet criteria for GERD symptoms patients had to report experiencing heartburn at least once per week that also radiated to the neck, awoke them at night, or improved with antacids, or report weekly acid regurgitation. Medication compliance was monitored using a Medication Event Monitoring System® (MEMS) bottle cap and by capsule counting. The MEMS cap contains a microchip that records the date and time the bottle is opened. By convention, compliance was defined as taking greater than 80% of the medication over the 8 weeks (≥ 45/56 capsules). Results: 173 patients with LA grades B-D esophagitis were screened between 1/30/2008 and 6/6/2008 of which 56 were eligible to participate. The majority of screen failures were inpatients (N = 54) and patients without sufficient GERD symptoms (N = 30). Of the 56 eligible patients, 29 (52%) enrolled in the study [15 males (52%), mean age 48.7 years; LA grade B = 23, C = 3, D = 3] and 12 (21%) declined. Evaluating physicians did not allow contact with 12 patients due to a plan for twice daily dosing. Three potential subjects were identified after they had left the Clinic. To date, 11 subjects have completed the trial of whom 6 (55%) were compliant and 5 (45%) non-compliant in taking their prescribed daily PPI. The mean number of capsules taken by the compliant group was 54 compared to 27 capsules by the non-compliant group (P < 0.05). GERD symptoms resolved in 5 (83%) compliant subjects and 1 (20%) non-compliant subject. Despite lack of compliance, very few capsules were returned after completing the study. Conclusion: Preliminary results indicate a large percentage of patients taking PPI's for symptomatic grade B, C or D erosive esophagitis are non-compliant in the short-term. The resolution of GERD symptoms appears to correlate with compliance. Capsule counts are a poor proxy for compliance with prescribed PPI use in patients with erosive esophagitis. This project was supported by an AstraZeneca Investigator-Initiated Award.

Observer variation in estimates of Meadow Pipit Anthus pratensis and Skylark Alauda arvensis abundance on moorland

Capsule Counts least susceptible to observer effects were those within 25 m of a transect and the total number along a transect, with observer effects greater for distance sampling.

Thyroid uptake error in four different gamma camera systems

The thyroid uptake of (123)I and (131)I is generally measured by a gamma camera system. We evaluated the error in determining thyroid uptake caused by different methods of calculation among four gamma camera systems with various collimators. We first designed an original thyroid phantom that consisted of the thyroid and a body containing various levels of radioiodine activity. The applications for thyroid uptake equipped in two gamma camera systems performed calculations by the automatic method with background counts not subtracted from the capsule counts. When the size of the rectangular region of interest (ROI) for the capsule was set at 10x8 cm (a typical ROI size for the thyroid), percentages of thyroid uptake as calculated by the manual method with background counts subtracted from the capsule counts and thyroid counts were 52% to 57% when the value was set at 55% for (123)I; and 54.2% and 58.7%, respectively, when the value was set at 60% for (131)I. On the other hand, the percentages of thyroid uptake calculated by the automatic method with the application using two gamma camera systems with non-subtraction of background counts from the capsule counts were 46% and 50.5% when the value was set at 55%; and 49.6% when the value was set at 60%. The values calculated by the automatic method were underestimated as a result of background counts that were not subtracted from the capsule counts. When ROI size for the capsule was set at 4x4 cm, which is slightly larger than the capsule size, even thyroid uptake as determined by the automatic method using the application showed a difference of less 2% from the set values. There was no difference in thyroid uptake among the various kinds of collimators, high-resolution collimators, all-purpose collimators, and a suitable collimator for gamma-ray energy of (123)I.

Plant monoterpenes do not raise plasma high-density-lipoprotein concentrations in humans

BackgroundLow plasma concentrations of HDLs are associated with an increased risk of coronary artery disease. Two uncontrolled studies suggested that plant monoterpenes may have substantial HDL-cholesterol-elevating activity in humans. Each study used a proprietary mixture of 6 monoterpenesin olive oil. ObjectiveThe present study was undertaken to test more rigorously the hypothesis that monoterpenes raise HDL concentrations in men with hypoalphalipoproteinemia. DesignA double-blind, placebo-controlled crossover design was used. Twenty-four men aged 58–68 y (x –: 62.3 y) with plasma HDL cholesterol < 1.1 mmol/L, plasma triacylglycerols <3.5 mmol/L, and plasma total cholesterol < 5.5 mmol/L at recruitment were randomly assigned to 6 capsules daily of a proprietary mixture of 6 monoterpenes in olive oil or 6 capsules daily of olive oil alone for 24 wk, followed by a washout period of 8 wk, and then the alternative capsules for 24 wk. ResultsFive men dropped out. In the others, compliance was excellent as judged by capsule counts and urinary menthol glucuronide concentrations. No significant effects were observed on plasma HDL-cholesterol or apolipoprotein A-I concentrations, nor on plasma triacylglycerol, LDL-cholesterol, or apolipoprotein B concentrations. ConclusionsPlant monoterpenes have no HDL-elevating activity of potential value for coronary artery disease prevention. Am J Clin Nutr 1998;68:1042–5.

Lipid Level Alterations in the Helsinki Heart Study

To the Editor. — The Helsinki Heart Study 1 demonstrated a significant decrease in coronary heart disease morbidity and mortality in middle-aged dyslipidemic men treated with gemfibrozil vs a placebo. Unfortunately, overall mortality was unchanged because of an increase in violence, accidents, and intracranial hemorrhage in the treated group. Further analysis 2 of that study published in the Aug 5 issue of JAMA revealed that the reduction in coronary heart disease incidence over the placebo group was largest in the Fredrickson type IIB and smallest in the type IIA dyslipidemic men, despite the fact that the largest reductions in low-density lipoprotein cholesterol levels were in the type IIA group. Also, changes in lipoprotein levels in the gemfibrozil group were related to medication compliance—subjects were arbitrarily divided into quartiles based on average capsule counts. Data comparing overall mortality in each of the gemfibrozil-treated IIA, IIB, and IV Fredrickson types would be

Effect of Obtrusive Measures on Antibiotic Compliance

The influence of compliance measurement activities on patient behavior was studied. The project measured the relationship among physical capsule counts, patient interviews, and the amounts of excreted ampicillin. The capsule counts and patient interviews were conducted in a manner that disguised their intent. Sixty college-age patients were assigned to one of three experimental groups: a telephone interview, a personal interview and capsule count, or a control group. Stimulation (interviews) occurred on the 2nd day of the prescribed regimen, and urine was collected on random days thereafter. Results indicated that both stimulation types were associated with more positive compliance rates. The influence diminished rapidly. The reactive influence of experimenter intervention associated with personal and phone communication was demonstrated.