Miracle-dz/UniFAR-FTUs huggingface dataset:
Iron supplementation in the non-dialysis chronic kidney disease (ND-CKD) patient: oral or intravenous?

Abstract Background: The management of iron-deficiency anaemia in patients with non-dialysis chronic kidney disease (ND-CKD) remains controversial, particularly regarding the use of oral versus intravenous iron supplementation. Methods: A PubMed search from 1970 to February 2009 was conducted to identify relevant research articles. Findings: Iron supplementation is advisable for all iron-deficient CKD patients receiving erythropoiesis stimulating agents (ESAs), and intravenous iron may be preferable to oral iron. However, there is also a growing body of data indicating that iron supplementation may avoid or delay the need for ESA therapy in some ND-CKD patients. In each of four randomised trials that included ND-CKD patients without ESA, the haemoglobin response was greater with i.v. versus oral iron. Moreover, some ND-CKD patients who remain anaemic on oral iron may subsequently respond to i.v. iron. Newer preparations (ferric carboxymaltose and ferumoxytol) permit rapid, high-dose administration. In a randomised study, a single 15-minute injection of ferric carboxymaltose, with up to two additional doses as required, resulted in 53.2% of ND-CKD patients achieving ≥1 g/dL increase in haemoglobin by day 56 without ESA, compared to 29.9% of patients given oral iron supplements. Two large, randomised, ongoing trials will address the important question of whether i.v. or oral iron supplementation affects the progression of renal dysfunction. While i.v. iron is more costly than oral iron, the cost differential over time may be lower than widely believed, and i.v. therapy avoids the poor absorption, gastrointestinal intolerance and non-compliance associated with oral preparations. In terms of safety, true anaphylaxis does not occur with modern preparations such as iron sucrose and iron gluconate. The novel preparations ferric carboxymaltose and ferumoxytol do not require a test dose and appear to offer a good safety profile, but long-term safety monitoring is mandatory. Conclusions: Intravenous iron offers an effective, feasible route towards reducing the heavy burden of iron-deficiency anaemia in the non-dialysis CKD patient, even in the absence of ESA therapy.
Abstract P6-14-01: Effect of Denosumab Versus Zoledronic Acid Treatment in Patients with Breast Cancer and Bone Metastases: Results from the Extended Blinded Treatment Phase

Background: Denosumab is a fully human monoclonal antibody which inhibits RANKL, a key mediator of osteoclast activity. Results from the primary analysis of this pivotal phase 3 trial showed that denosumab was superior to zoledronic acid (ZA) in delaying the time to first on-study skeletal-related events (SRE) in patients with breast cancer and bone metastases. We now report results including an additional 4 months of blinded treatment. Methods: Randomized patients received either subcutaneous (SC) denosumab (120 mg) and intravenous (IV) placebo or IV ZA (4 mg, adjusted for renal function) and SC placebo every 4 weeks. No dose adjustments were made for SC denosumab. All patients were advised to take daily calcium (≥500 mg) and vitamin D (≥400 IU) supplements. The primary endpoint was time to first on-study SRE (predefined as pathologic fracture, radiation or surgery to bone, or spinal cord compression). Time to first and subsequent SRE (multiple event analysis) and safety endpoints were also evaluated. Analyses for the extended treatment phase are considered exploratory. Results: Overall, 2046 patients enrolled: 1026 were randomized to denosumab and 1020 were randomized to ZA. Denosumab was superior to ZA in delaying the time to first on-study SRE by 18%, and the time to first and subsequent on-study SRE by 22% (Table). The median time to first on-study SRE was 5 months longer for the denosumab group (32.4 months) than the ZA group (27.4 months). Overall survival and disease progression were similar for both treatment groups. Similar percentages of subjects reported adverse events (AEs; 96.2% denosumab, 97.4% ZA) and serious AEs (47.9% denosumab, 50.2% ZA). Positively adjudicated cases of osteonecrosis of the jaw were reported in 2.5% (n=26) of denosumab-treated patients and 1.8% (n=18) of ZA-treated patients (P=0.29). Hypocalcemia was reported by 62 (6.1 %) patients in the denosumab group and 37 (3.7%) patients in the ZA group. Conclusion: Among patients with breast cancer and bone metastases, denosumab was superior to ZA in delaying or preventing SREs, and continued treatment with denosumab resulted in a median time to first SRE that was 5 months longer than treatment with ZA. Denosumab, with its novel mode of action, may represent a potential treatment option for patients with breast cancer and bone metastases without the need for dose adjustment or renal monitoring. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-14-01.
Dosing accuracy of commonly used disposable insulin pens

Abstract Objective: The present study aimed to assess the dosing accuracy of commonly used disposable insulin pens including SoloStar (SR)*, FlexPen (FP)†, Next Generation FlexPen (NGFP)†, and KwikPen (KP)‡. It is the first comparative study covering the whole dosing range from 1 U to 60 U. It also covers the accuracy of SR at 80 U. * SoloStar (SR) is a registered trademark of sanofi-aventis. † FlexPen (FP) and Next Generation FlexPen (NGFP) are registered trademarks of Novo Nordisk A/S. ‡ KwikPen (KP) is a registered trademark of Eli Lilly. Research design and method: A total of sixty insulin pens from two lots of each pen type were used. From each pen 1 U, 10 U, 30 U, 40 U, 60 U and 80 U were dispensed in random order. The 80 U dose was only evaluated for the SR as the other insulin pens do not deliver this dose in one injection. The actual doses were determined gravimetrically taking density of the different insulin preparations into account. The evaluation of dose accuracy was based on the regulations of the International Organization for Standardization (DIN EN ISO 11608-1:2000). Results: All tested insulin pens met the requirements for accuracy with none of the single values at all dose levels being outside the defined range of the ISO recommendations (1 ± 1 U, 10 ± 1 U, 30 ± 1.5 U, 40 ± 2 U, 60 ± 3 U and 80 ± 4 U). For the investigated dosage levels the absolute average deviation of all insulin pens ranged between 0.09 and 0.81 U. Conclusion: The present study demonstrates an excellent dosing accuracy for all tested insulin pens, with no clinically relevant differences between the products.
Association between HDL-C concentration and risk for a major cardiovascular event

Abstract Objective: To determine the association between baseline HDL-C concentrations and risk of a major cardiovascular event (within 5 years) in a large US claims database. Methods: A retrospective longitudinal analysis using claims data from the i3 Ingenix LabRx database was conducted. Patients were included if they had complete lipid panel lab results, were continuously enrolled for ≥6 months prior to and ≥12 months following the lab test (index date), and were ≥50 years of age. Cox proportional hazards analysis assessed the association between HDL-C concentrations and risk of a major cardiovascular event within 5 years of the index date, after adjusting for covariates. Results: There was a statistically significant association between HDL-C and risk of a major cardiovascular event. A 0.026 mmol/L (1 mg/dL) increase in HDL-C from baseline was associated with a 1.3% decreased risk of a major cardiovascular event (e.g., a 0.13 mmol/L [5 mg/dL] increase in HDL-C above baseline concentrations was associated with a 6.5% decrease). This association became evident within 1 year of follow-up. Conclusions: HDL-C concentrations were inversely associated with the occurrence of cardiovascular events within 5 years. Women who were ≥0.26 mmol/L (10 mg/dL) below their target concentrations had cardiovascular risk similar to that of women with baseline ischemic heart disease and hypertension, and men who were ≥0.26 mmol/L (10 mg/dL) below their target concentrations had cardiovascular risk similar to that of men with baseline cardiovascular disease, diabetes, or cerebrovascular disease. Limitations inherent to claims-based analyses must be considered when interpreting these findings, such as the potential for miscoding or incomplete data, and the fact that the presence of a diagnosis code on a medical claim is not positive presence of disease. Furthermore, patients who suffered a fatal cardiovascular event at home during the study period, and therefore did not receive treatment, were not captured in this analysis.
Effects of infections on severely malnourished children in Kilifi-Mombasa and Dar es Salaam: a comparative study.

Objective: To determine the e ects of infections on severely malnourished children. Study design: Descriptive, cross-sectional hospital based study. Results: There is little di erence in the prevalence of severe malnutrition between the two hospitals. 55% of all malnourished children were boys. Nonoedematous Protein Energy Malnutrition was more prevalent at Muhimbili National Hospital than at Kili District Hospital. More than 75% of all severe Protein Energy Malnutrition patients were below two years of age, 36% of all severe Protein Energy Malnutrition patients admitted also had malaria, 45% of all admitted patients with severe Protein Energy Malnutrition at Kili District Hospital also had diarrhoea. More than 25% of severely malnourished patients died, oedematous type having a higher case fatality rate than non-oedematous one. 86% of the patients who died at MNH had other co-morbidities. Septicaemic malnourished children succumbed more deaths than other co infections. Conlusion: Infections cause most deaths and complicate the management of severe malnutrition. Severe malnutrition is still a big problem among these countries.
Efficacy of a comprehensive program for reducing stress in women: A prospective, randomized trial

Abstract Objective: This study evaluated the efficacy of a comprehensive stress management program in reducing perceived stress among women who reported moderate-to-high stress levels. Methods: A total of 562 highly motivated females, aged 25–45, with moderate to high stress levels, were enrolled in a 14-week study. Participants were randomized into one of three groups: Group 1 included Internet-based coaching focusing on behavior modification, daily use of proprietary olfactive-based personal care products, and periodic feedback reports; Group 2 consisted of only online coaching; and Group 3 had no active stress management program. Participants in the three groups filled out validated psychometric assessments at baseline and throughout the study period. Several outcomes including Perceived Stress Scale (PSS), Profile of Mood States (POMS), St Mary’s Hospital Sleep Questionnaire (SMS), the Trier Inventory of Chronic Stress (TICS), Spielberger State-Trait Anxiety Inventory (STAI), Short-Form-36 (SF-36) and the Work Productivity and Activity Impairment (WPAI), were measured periodically to assess changes in subject-perceived stress, stress-related comorbidities, and sleep quality and to evaluate overall program efficacy. Ethical approval of protocols was conducted by the Allendale Investigational Review Board (AIRB). Voluntary informed consent was obtained from each subject. Results: At the end of the 14-week study period, subjects in Group 1 had statistically significant improvement in the PSS score vs. Group 3 (p < 0.01). There were statistically significant improvements in other efficacy outcomes such as POMS total mood disturbance, TICS work overload and social responsibility subscales, STAI and in the number of night awakenings, assessed by the SMS questionnaire (p < 0.05). Self-reported program efficacy was also significantly higher for Group 1 (p < 0.001). Conclusion: Despite study limitations, including reduction of stress in Group 3, this study demonstrates that this comprehensive stress management program is effective in reducing stress among women with moderate to high stress levels.
Effects of rivastigmine on common symptomatology of Alzheimer’s disease (EXPLORE)

Abstract Objective: To evaluate, in a real-world clinical setting, the efficacy of rivastigmine in the management of six symptoms commonly associated with Alzheimer's disease (AD). Methods: This was a naturalistic, prospective, open-label, multi-centre, post-marketing, observational study. Data were collected by the participating study physicians at their practices across Canada. Subjects had a clinical diagnosis of mild-to-moderate AD and were prescribed rivastigmine by their treating physician. Efficacy was primarily evaluated by a physician-assessed, abbreviated Clinical Global Impression of Change (CGI-C) scale, focusing on six symptoms: attention, apathy, anxiety, agitation, irritability and sleep disturbance. Changes were assessed at months 3, 6 and 12. Several other patient-, physician- and caregiver-related assessments were also included. Results: A total of 4460 patients were recruited by 353 study physicians; 3800 were deemed evaluable, having taken at least one dose of rivastigmine and with at least one post-baseline assessment. At baseline, attention problems were present in 86.0% of evaluable patients, anxiety in 77.3%, apathy in 68.3%, irritability in 64.0%, agitation in 54.6% and sleep disturbance in 54.5%. At both month 6 and month 12, for each symptom, the percentage of patients experiencing an improvement was considerably larger than the percentage of patients who experienced symptom worsening. Among evaluable patients, the proportions improving vs. deteriorating at month 6 were 46.4 vs. 8.8% for attention; 42.8 vs. 7.2% for apathy; 41.1 vs. 9.4% for anxiety; 33.8 vs. 7.7% for agitation; 35.1 vs. 10.1% for irritability; and 30.8 vs. 5.4% for sleep disturbance. Limitations: Open-label studies have an inherent potential for bias by both the caregiver and the physician. Conclusions: This study demonstrates that a considerable proportion of rivastigmine-treated patients experience improvements on each of the six symptoms studied. These findings add further support to previous randomised, clinical studies showing benefit of rivastigmine in AD.
A 26-week, placebo- and pioglitazone-controlled, dose-ranging study of rivoglitazone, a novel thiazolidinedione for the treatment of type 2 diabetes

Abstract Objective: To examine the efficacy and general safety of rivoglitazone, a novel thiazolidinedione, as a treatment for type 2 diabetes in a dose-ranging study over a period of up to 6 months. Research design and methods: A 26-week, randomized, double-blind, double-dummy, placebo- and active comparator (pioglitazone 45 mg)-controlled study designed to evaluate the efficacy and safety of once-daily rivoglitazone 1, 2, or 3 mg in subjects with type 2 diabetes. The study was conducted in adults with type 2 diabetes (glycated hemoglobin [HbA1c] ≥7.0% and <10.5%) who were either naïve to prior antidiabetes drug treatment or discontinued pre-study antidiabetes medications and were switched to study medication. A total of 441 subjects were randomized, using an equal allocation schedule to one of five treatment arms, including placebo. The primary efficacy measurement was the change in HbA1c from baseline to week 26 in the intent-to-treat population (last observation carried forward), for drug treatments minus placebo (placebo-subtracted). Clinical Trial Registration: Trial registration: ClinicalTrials.gov identifier: NCT00143520. Results: The incidence of early discontinuations was >50%, with most cases being related to a lack of efficacy (highest on placebo) or adverse experiences (highest on rivoglitazone 3 mg). Rivoglitazone 1, 2, and 3 mg and pioglitazone 45 mg were more effective than placebo in reducing HbA1c from baseline to week 26 (placebo-subtracted change from baseline: −0.55% [p = 0.0034], −0.99% [p < 0.0001], −1.10% [p < 0.0001], and −0.59% [p = 0.0016], respectively). In general, all treatments were safe. The most common drug-related adverse events reported with rivoglitazone were peripheral edema and weight gain; incidences increased with dose and were higher with rivoglitazone 2 and 3 mg than with pioglitazone or rivoglitazone 1 mg. Conclusions: Rivoglitazone is a potent thiazolidinedione agent with demonstrated glycemic benefits over a 6-month period in subjects with type 2 diabetes. Once-daily doses of 1, 2, and 3 mg rivoglitazone demonstrated HbA1c reduction similar or superior to those observed for pioglitazone 45 mg. Limitations in generalizing from this study include a modest sample size and a high rate of discontinuation prior to the last scheduled visit.
Study of levocetirizine in seasonal allergic rhinitis

Abstract Objective: To evaluate the efficacy of levocetirizine 5 mg once daily in reducing seasonal allergic rhinitis (SAR) symptoms in US adults. Research design and methods: This multicenter, randomized, double-blind, placebo-controlled, parallel-group study enrolled adults aged 18 to 65 years with SAR symptoms in the spring in the US. After a single-blind placebo run-in period, subjects received levocetirizine 5 mg or placebo once daily over 14 days. ClinicalTrials.gov registry no.: Trial registration: ClinicalTrials.gov identifier: NCT00621959. Main outcome measures: Primary efficacy variable was the Total 5-Symptom Score (T5SS). Secondary variables included Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), Work Productivity and Activity Impairment–Allergy Specific (WPAI-AS) questionnaire, and Epworth Sleepiness Scale (ESS). Safety assessments were based on adverse events (AEs). Results: The intent-to-treat population comprised 596 subjects (levocetirizine, n = 301; placebo, n = 295). Comparison of mean T5SS over the total treatment period showed a nonsignificant between-group difference (levocetirizine, 8.90 ± 0.19; placebo, 9.04 ± 0.19; adjusted mean difference, −0.14; p = 0.546). Levocetirizine showed numerical (mean RQLQ, WPAI-AS, ESS) and statistically superior differences (two domains within WPAI-AS) compared with placebo upon analysis of secondary efficacy variables. The incidence of treatment-emergent AEs was similar (levocetirizine, 23.9%; placebo, 24.4%). As the lack of efficacy was inconsistent with all previous levocetirizine studies, post hoc analyses were performed to assess the influence of pollen counts, geography, and other factors; however, no conclusive explanation could be identified. Conclusions: In this study, levocetirizine 5 mg QD was well tolerated but failed to show significant efficacy compared with placebo in a US adult population with SAR. This finding is inconsistent with all previous studies with levocetirizine and in contrast to a concurrently run, similarly designed US study. It reflects the importance of conducting duplicate studies as there is always a small but real risk of false negative results in clinical studies, irrespective of the methodologic quality.
A comparative effectiveness trial of two faecal immunochemical tests for haemoglobin (FIT). Assessment of test performance and adherence in a single round of a population-based screening programme for colorectal cancer

Aim To compare acceptability and diagnostic accuracy of a recently available faecal immunochemical test (FIT) system (HM-JACKarc) with the FIT routinely used in an established screening programme (OC-Sensor). Design Randomised controlled trial (ISRCTN20086618) within a population-based colorectal cancer (CRC) screening programme. Subjects eligible for invitation in the Umbria Region (Italy) programme were randomised (ratio 1:1) to be screened using one of the FIT systems. Results Screening uptake among the 48 888 invitees was the same for both systems among subjects invited in the first round and higher with OC-Sensor than with HM-JACKarc (relative risk (RR): 1.03; 95% CI 1.02 to 1.04) among those invited in subsequent rounds. Positivity rate (PR) was similar with OC-Sensor (6.5%) as with HM-JACKarc (6.2%) among subjects performing their first FIT screening and higher with OC-Sensor (5.6%, RR: 1.25, 95% CI 1.12 to 1.40) than with HM-JACKarc (4.4%) among those screened in previous rounds. Positive predictive value (PPV) (OC-Sensor: 25.9%, HM-JACKarc: 25.6%) and detection rate (DR) (OC-Sensor: 1.40%; HM-JACKarc: 1.42%) for advanced neoplasia (AN: CRC + advanced adenoma) were similar among subjects performing their first FIT screening. The differences in the AN PPV (OC-Sensor: 20.3%, HM-JACKarc: 22.6%) and DR (OC-Sensor: 0.96%, HM-JACKarc: 0.83%) among those screened in previous rounds were not statistically significant. The number needed to scope to detect one AN was 3.9 (95% CI 5.8 to 2.9) and 3.9 (95% CI 5.5 to 2.9) at first and 4.9 (95% CI 5.8 to 4.2) and 4.4 (95% CI 5.3 to 3.7) at subsequent screening, with OC-Sensor and HM-JACKarc, respectively. Conclusions Our results suggest that acceptability and diagnostic performance of HM-JACKarc and of OC-Sensor systems are similar in a screening setting. Trial registration number ISRCTN20086618; Results.
Quantitation of faecal Fusobacterium improves faecal immunochemical test in detecting advanced colorectal neoplasia

Objective There is a need for an improved biomarker for colorectal cancer (CRC) and advanced adenoma. We evaluated faecal microbial markers for clinical use in detecting CRC and advanced adenoma. Design We measured relative abundance of Fusobacterium nucleatum (Fn), Peptostreptococcus anaerobius (Pa) and Parvimonas micra (Pm) by quantitative PCR in 309 subjects, including 104 patients with CRC, 103 patients with advanced adenoma and 102 controls. We evaluated the diagnostic performance of these biomarkers with respect to faecal immunochemical test (FIT), and validated the results in an independent cohort of 181 subjects. Results The abundance was higher for all three individual markers in patients with CRC than controls (p<0.001), and for marker Fn in patients with advanced adenoma than controls (p=0.022). The marker Fn, when combined with FIT, showed superior sensitivity (92.3% vs 73.1%, p<0.001) and area under the receiver-operating characteristic curve (AUC) (0.95 vs 0.86, p<0.001) than stand-alone FIT in detecting CRC in the same patient cohort. This combined test also increased the sensitivity (38.6% vs 15.5%, p<0.001) and AUC (0.65 vs 0.57, p=0.007) for detecting advanced adenoma. The performance gain for both CRC and advanced adenoma was confirmed in the validation cohort (p=0.0014 and p=0.031, respectively). Conclusions This study identified marker Fn as a valuable marker to improve diagnostic performance of FIT, providing a complementary role to detect lesions missed by FIT alone. This simple approach may improve the clinical utility of the current FIT, and takes one step further towards a non-invasive, potentially more accurate and affordable diagnosis of advanced colorectal neoplasia.