Highlights • First known systematic review reporting the impact of pharmacist immunizers on vaccination rates. • Limited number of randomized controlled trials and high quality studies. • Pharmacist ...involvement in immunization services increased vaccine coverage rates.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Objectives The aim of this study was to assess the lipid-altering efficacy and safety of ETC-1002 in subjects with hypercholesterolemia. Background ETC-1002 is a small molecule that modulates ...pathways of cholesterol, fatty acid, and carbohydrate metabolism and may have therapeutic benefits in treating hypercholesterolemia and other cardiometabolic risk factors. Methods This multicenter, randomized, double-blind, placebo-controlled, parallel-group trial evaluated patients (n = 177) with elevated low-density lipoprotein cholesterol (LDL-C) (130 to 220 mg/dl), who were stratified by baseline triglycerides (not elevated <150 mg/dl or elevated 150–<400 mg/dl) and randomized to receive 40, 80, or 120 mg of ETC-1002 or placebo once daily for 12 weeks. Outcomes included changes in LDL-C (primary endpoint), other lipids, and cardiometabolic risk factors; and safety. Results ETC-1002 40, 80, and 120 mg lowered least-squares mean ± SE LDL-C levels by 17.9 ± 2.2%, 25.0 ± 2.1%, and 26.6 ± 2.2%, respectively, versus a reduction of 2.1 ± 2.2% with placebo (all, p < 0.0001); LDL-C lowering was similar between the subgroups with nonelevated and elevated triglycerides. ETC-1002 also lowered non–high-density lipoprotein cholesterol (non–HDL-C), apolipoprotein B, and LDL particle number (all, p < 0.0001) in a dose-dependent manner; HDL-C and triglyceride levels were relatively unchanged. Post-hoc analyses suggest that ETC-1002 may have favorable effects on other cardiometabolic risk factors. The ETC-1002 and placebo groups did not demonstrate clinically meaningful differences in adverse events or other safety assessments. Conclusions ETC-1002 significantly lowered LDL-C levels up to 27% across a broad range of baseline triglycerides and was generally safe and well tolerated. ETC-1002 has a novel mechanism of action and may be useful for reducing LDL-C. (A Study to Assess the Efficacy and Safety of ETC-1002 in Subjects With Elevated Blood Cholesterol and Either Normal or Elevated Triglycerides; NCT01262638 )
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background Exercise capacity, which is predictive of all-cause mortality and cardiovascular disease risk, is reduced significantly in patients with non–dialysis-dependent chronic kidney disease. This ...pilot study examined the effect of moderate-intensity exercise training on kidney function and indexes of cardiovascular risk in patients with progressive chronic kidney disease stages 3 to 4. Study Design Single-blind, randomized, controlled, parallel trial. Setting & Participants 20 patients (aged 18-80 years; 17 men) randomly assigned to rehabilitation (n = 10) or usual care (n = 10). Participants were included if they were 18 years or older and had evidence of rate of decline in creatinine-based estimated glomerular filtration rate (eGFRcr ) ≥ 2.9 mL/min/1.73 m2 per year for 12 months preintervention. Patients were excluded if they had unstable medical conditions or had recently started regular exercise. Intervention The rehabilitation group received resistance and aerobic training (3 days per week) for a 12-month period. The usual care group received standard care. Outcomes Kidney function assessed by comparing mean rate of change in eGFRcr (mL/min/1.73 m2 per year) from a 12-month preintervention period against the 12-month intervention period. Pulse wave velocity (PWV), peak oxygen uptake (V o2peak ), and waist circumference assessed at 0, 6, and 12 months. Measurements eGFR assessed using creatinine, cystatin C (eGFRcys ), and a combination of both values (eGFRcr-cys ). Results 18 participants (rehabilitation, 8; usual care, 10) completed the study. A significant mean difference in rate of change in eGFRcr (+7.8 ± 3.0 95% CI, 1.1-13.5 mL/min/1.73 m2 per year; P = 0.02) was observed between the rehabilitation and usual care groups, with the rehabilitation group demonstrating a slower decline. No significant between-group mean differences existed in absolute eGFRcr , eGFRcr-cys , or eGFRcys at 12 months of study intervention. Significant between-group mean differences existed in PWV (−2.30 95% CI, −3.02 to −1.59 m/s), waist circumference (−7.1 ± 12.8 95% CI, −12.4 to −3.2 cm), and V o2peak (5.7 95% CI, 1.34-10.10 mL/kg/min). Change in eGFRcr was correlated inversely with PWV ( r = −0.5; P = 0.04) at 12 months. Limitations Small sample size, inconsistency between primary and secondary measures of kidney function. Conclusions The effect of a 1-year exercise intervention on progression of kidney disease is inconclusive. A larger study with longer follow-up may be necessary.
We present an approach to estimate the feedback from large-scale thawing of permafrost soils using a simplified, data-constrained model that combines three elements: soil carbon (C) maps and profiles ...to identify the distribution and type of C in permafrost soils; incubation experiments to quantify the rates of C lost after thaw; and models of soil thermal dynamics in response to climate warming. We call the approach the Permafrost Carbon Network Incubation-Panarctic Thermal scaling approach (PInc-PanTher). The approach assumes that C stocks do not decompose at all when frozen, but once thawed follow set decomposition trajectories as a function of soil temperature. The trajectories are determined according to a three-pool decomposition model fitted to incubation data using parameters specific to soil horizon types. We calculate litterfall C inputs required to maintain steady-state C balance for the current climate, and hold those inputs constant. Soil temperatures are taken from the soil thermal modules of ecosystem model simulations forced by a common set of future climate change anomalies under two warming scenarios over the period 2010 to 2100. Under a medium warming scenario (RCP4.5), the approach projects permafrost soil C losses of 12.2-33.4 Pg C; under a high warming scenario (RCP8.5), the approach projects C losses of 27.9-112.6 Pg C. Projected C losses are roughly linearly proportional to global temperature changes across the two scenarios. These results indicate a global sensitivity of frozen soil C to climate change (γ sensitivity) of −14 to −19 Pg C °C−1 on a 100 year time scale. For CH4 emissions, our approach assumes a fixed saturated area and that increases in CH4 emissions are related to increased heterotrophic respiration in anoxic soil, yielding CH4 emission increases of 7% and 35% for the RCP4.5 and RCP8.5 scenarios, respectively, which add an additional greenhouse gas forcing of approximately 10-18%. The simplified approach presented here neglects many important processes that may amplify or mitigate C release from permafrost soils, but serves as a data-constrained estimate on the forced, large-scale permafrost C response to warming.
Full text
Available for:
BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Background ETC-1002 is an oral, once-daily, first-in-class medication being developed to treat hypercholesterolemia. Objectives To compare 2 doses of ETC-1002, alone or combined with ezetimibe 10 mg ...(EZE), vs EZE monotherapy for lowering low-density lipoprotein cholesterol (LDL-C). Methods This phase 2b, multicenter, double-blind trial-evaluated hypercholesterolemic patients (LDL-C, 130 to 220 mg/dL) with (n = 177) or without (n = 171) muscle-related intolerance to ≥2 statins; 1 at lowest approved dose. Subjects were randomized to 12-week treatment with ETC-1002 120 mg or ETC-1002 180 mg alone, EZE alone, ETC-1002 120 mg plus EZE, or ETC-1002 180 mg plus EZE. Results EZE alone lowered LDL-C by 21%, whereas ETC-1002 monotherapy with 120 mg or 180 mg reduced LDL-C by 27% ( P = .0008 vs EZE) and 30% ( P < .0001 vs EZE), respectively. The combination of ETC-1002, 120 mg or 180 mg plus EZE reduced LDL-C by 43% and 48%, respectively (both P < .0001 vs EZE). ETC-1002 alone or combined with EZE also reduced non–high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, LDL particle number, and high-sensitivity C-reactive protein compared with EZE alone. Across all treatment groups, statin-intolerant patients reported more muscle-related adverse events than did statin-tolerant patients. ETC-1002 was safe and well tolerated, and rates of muscle-related adverse events were similar in all treatment groups. Conclusions In patients with and without statin intolerance, daily treatment with ETC-1002 120 mg and 180 mg alone or with EZE reduced LDL-C more than EZE alone and had a similar tolerability profile (NCT01941836).
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
In songbirds, developmental stress affects song learning and production. Altered hypothalamic–pituitary–adrenal (HPA) axis function resulting in elevated corticosterone (CORT) may contribute to this ...effect. We examined whether developmental conditions affected the association between adult song and HPA axis function, and whether nutritional stress before and after nutritional independence has distinct effects on song learning and/or vocal performance. Zebra finches (Taeniopygia guttata) were raised in consistently high (HH) or low (LL) food conditions until post-hatch day (PHD) 62, or were switched from high to low conditions (HL) or vice versa (LH) at PHD 34. Song was recorded in adulthood. We assessed the response of CORT to handling during development and to dexamethasone (DEX) and adrenocorticotropic hormone (ACTH) challenges during adulthood. Song learning and vocal performance were not affected by nutritional stress at either developmental stage. Nutritional stress elevated baseline CORT during development. Nutritional stress also increased rate of CORT secretion in birds that experienced stress only in the juvenile phase (HL group). Birds in the LL group had lower CORT levels after injection of ACTH compared to the other groups, however there was no effect of nutritional stress on the response to DEX. Thus, our findings indicate that developmental stress can affect HPA function without concurrently affecting song.
•We investigate effects of developmental stress on adult song and HPA axis.•Song learning and vocal performance were not affected by nutritional stress.•Nutritional stress elevated baseline and rate of CORT secretion during development.•Nutritional stress until post-hatch day 60 reduced adult CORT after ACTH injection.•Nutritional stress that affects HPA axis does not always affect song development.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background Once-daily, oral ETC-1002 reduces low-density lipoprotein cholesterol (LDL-C) and has beneficial effects on other cardiometabolic risk factors but has not been examined in statin ...intolerant patients. Objectives To study the efficacy and safety of ETC-1002 (a novel LDL-C–lowering agent) in patients with hypercholesterolemia and a history of statin intolerance. Methods Patients intolerant to at least 1 statin were entered into this multicenter, double-blind, 8-week trial. Participants were required to have a history of muscle complaints that developed during statin treatment and resolved within 4 weeks of statin discontinuation. Patients (n = 56) were randomized in a 2:1 ratio to ETC-1002 60 mg daily or placebo. The ETC-1002 dose was increased at 2-week intervals to 120 mg, 180 mg, and 240 mg. The primary end point was the percentage change from baseline to week 8 in calculated LDL-C. Results ETC-1002 reduced LDL-C 28.7% more than placebo (95% confidence interval, −35.4 to −22.1; P < .0001). ETC-1002 significantly reduced non–high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, and high-sensitivity C-reactive protein. Triglycerides and high-density lipoprotein cholesterol did not change with ETC-1002 treatment. Sixty-two percent of patients receiving ETC-1002 and none in the placebo group achieved the 2004 National Cholesterol Education Program Adult Treatment Panel III LDL-C goal ( P < .0001). Muscle-related adverse events occurred with similar frequency in the placebo and ETC-1002 treatment groups, causing no discontinuations in ETC-1002–treated patients. Conclusions ETC-1002 appears to be effective at reducing LDL-C and was well tolerated in patients with statin-associated muscle complaints. Longer and larger studies are required to confirm the absence of muscle side effects.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Prophylactic ureteric stenting in renal transplantation reduces major urological complications; however, morbidity is related to the indwelling duration of a stent. We aimed to determine the optimal ...duration for stents in this clinical setting. Patients (aged 2–75 years) from six UK hospitals who were undergoing renal transplantation were recruited and randomly assigned to either early stent removal at 5 days (without cystoscopy) or late removal at 6 weeks after transplantation (with cystoscopy). The primary outcome was a composite of stent‐related complications defined as pain, visible hematuria, migration, fragmentation, and urinary tract infections (UTIs) within 3 mo of transplantation. Between May 2010 and Nov 2013, we randomly assigned 227 participants, with 205 included in the final analysis of the primary outcome. Stent‐related complications were significantly higher in the late versus early stent removal groups (36 of 126 28.6% vs. 6 of 79 7.6%; p < 0.001). The majority of stent complications consisted of UTIs, with an incidence of 31 of 126 (24.6%) in the late group compared with 6 of 79 (7.6%) in the early group (p = 0.004). We found early stent removal on day 5 significantly reduced stent‐related complications and improved quality of life in the first 3 mo after transplantation (ISRCTN09184595).
In this randomized controlled trial, the authors determine that early prophylactic stent removal in renal transplant recipients at 5 days is beneficial, in terms of stent‐related complications and quality of life, compared to stent removal at 6 weeks.
Full text
Available for:
BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
As a result of the COVID-19 pandemic first wave, reductions in ST-elevation myocardial infarction (STEMI) invasive care, ranging from 23% to 76%, have been reported from various countries. Whether ...this change had any impact on coronary angiography (CA) volume or on mechanical support device use for STEMI and post-STEMI mechanical complications in Canada is unknown.
We administered a Canada-wide survey to all cardiac catheterization laboratory directors, seeking the volume of CA use for STEMI performed during the period from March 1 2020 to May 31, 2020 (pandemic period), and during 2 control periods (March 1, 2019 to May 31, 2019 and March 1, 2018 to May 31, 2018). The number of left ventricular support devices used, as well as the number of ventricular septal defects and papillary muscle rupture cases diagnosed, was also recorded. We also assessed whether the number of COVID-19 cases recorded in each province was associated with STEMI-related CA volume.
A total of 41 of 42 Canadian catheterization laboratories (98%) provided data. There was a modest but statistically significant 16% reduction (incidence rate ratio IRR 0.84; 95% confidence interval 0.80-0.87) in CA for STEMI during the first wave of the pandemic, compared to control periods. IRR was not associated with provincial COVID-19 caseload. We observed a 26% reduction (IRR 0.74; 95% confidence interval 0.61-0.89) in the use of intra-aortic balloon pump use for STEMI. Use of an Impella pump and mechanical complications from STEMI were exceedingly rare.
We observed a modest 16% decrease in use of CA for STEMI during the pandemic first wave in Canada, lower than the level reported in other countries. Provincial COVID-19 caseload did not influence this reduction.
Après la première vague de la pandémie de COVID-19, de nombreux pays ont déclaré une réduction de 23 % à 76 % des soins invasifs de l'infarctus du myocarde avec élévation du segment ST (STEMI). On ignore si ce changement a entraîné des répercussions sur le volume d'angiographies coronariennes (AC) ou sur l'utilisation des dispositifs d'assistance mécanique lors de STEMI et des complications mécaniques post-STEMI au Canada.
Nous avons réalisé un sondage pancanadien auprès de tous les directeurs de laboratoire de cathétérisme cardiaque pour obtenir le volume d'utilisation des AC lors des STEMI réalisées durant la période du 1er mars 2020 au 31 mai 2020 (période de pandémie) et durant 2 périodes témoins (1er mars 2019 au 31 mai 2019 et 1er mars 2018 au 31 mai 2018). Le nombre de dispositifs d'assistance ventriculaire gauche utilisés et le nombre de cas de communications interventriculaires et de ruptures du muscle papillaire diagnostiqués ont également été enregistrés. Nous avons aussi évalué si le nombre de cas de COVID-19 enregistrés dans chaque province était associé au volume d'AC liées aux STEMI.
Au total, 41 des 42 laboratoires canadiens de cathétérisme (98 %) ont fourni des données. Lors de la comparaison de la première vague de la pandémie aux périodes témoins, nous avons noté une réduction modeste, mais significative, sur le plan statistique de 16 % (ratio du taux d'incidence RTI 0,84; intervalle de confiance à 95 % 0,80-0,87) des AC lors de STEMI. Le RTI n’était pas associé au nombre provincial de cas de COVID-19. Nous avons observé une réduction de 26 % (RTI 0,74; intervalle de confiance à 95 % 0,61-0,89) de l'utilisation de pompes à ballonnet intra-aortique lors de STEMI. L'utilisation d'une pompe Impella et les complications mécaniques après les STEMI étaient extrêmement rares.
Nous avons observé une diminution modeste de 16 % de l'utilisation des AC lors de STEMI durant la première vague de la pandémie au Canada, soit une diminution plus faible que ce que les autres pays ont signalé. Le nombre provincial de cas de COVID-19 n'a pas influencé cette réduction.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary Biological oncology products are integral to cancer treatment, but their high costs pose challenges to patients, families, providers, and insurers. The introduction of biosimilar ...agents—molecules that are similar in structure, function, activity, immunogenicity, and safety to the original biological drugs—provide opportunities both to improve health-care access and outcomes, and to reduce costs. Several international regulatory pathways have been developed to expedite entry of biosimilars into global marketplaces. The first wave of oncology biosimilar use was in Europe and India in 2007. Oncology biosimilars are now widely marketed in several countries in Europe, and in Australia, Japan, China, Russia, India, and South Korea. Their use is emerging worldwide, with the notable exception of the USA, where several regulatory and cost barriers to biosimilar approval exist. In this Review, we discuss oncology biosimilars and summarise their regulatory frameworks, clinical experiences, and safety concerns.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
PDF
