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1.
Purpose
The American College of Physicians (ACP) published a set of guidelines on how to prevent fractures in men and women with low bone density or osteoporosis. As the population ages, the overall risk of fractures increases, thus burdening the health care system. These guidelines review current evidence for osteoporosis management, providing an update to the previous 2008 ACP’s guidelines.Methods
The ACP put forth 6 recommendations addressing the complexities in osteoporosis management based on evidence available through October 2016 with a focus on bisphosphonates, calcium, vitamin D, and estrogen. Evidence was graded according to recommended strength by using the ACP standard methods.Findings
The ACP recommends anti-osteoporosis therapy with 1 of 3 bisphosphonates (alendronate, risedronate, or zoledronic acid) or denosumab in patients with osteoporosis, while excluding anabolic therapies, and recommends against raloxifene. Although bisphosphonates are the mainstay of treatment, anabolic therapy and raloxifene may be used in specific situations. Pharmacologic therapy is recommended for 5 years, oversimplifying length of therapy and failing to promote an individualized patient-centered care approach. Moreover, abrupt discontinuation of denosumab is associated with a decline in bone mineral density (BMD), which must be addressed. Routine monitoring of BMD by dual x-ray absorptiometry is not endorsed during treatment, which leads to underrecognition of management issues. Pharmacologic treatment with bisphosphonates for male osteoporosis is recommended, although therapies such as denosumab and teriparatide are excluded. Finally, the ACP recommends treatment for women aged ≥65 years at high risk for fracture with osteopenia after a discussion of patient preferences, fracture risk profile, and medications.Implications
Osteoporosis management is complex. The 2017 ACP guidelines address challenges faced by clinicians but oversimplify more complex issues. These are among a number of guidelines that are available for osteoporosis management, which may be used in combination with other sources to assist clinicians with diagnostic and management strategies. 相似文献2.
Diana Gritsenko Marianna Fedorenko Jorg J. Ruhe Jerry Altshuler 《Clinical therapeutics》2017,39(1):212-218
Purpose
Although vancomycin has been the mainstay of therapy for methicillin-resistant Staphylococcus aureus (MRSA) infections, its effectiveness has been challenged. Combination therapy may be used for patients with persistent MRSA bacteremia refractory to initial therapy. Studies have reported in vitro synergy between vancomycin and ceftaroline; however, clinical experience with this therapy is limited. Here, we report our experience with 5 cases of vancomycin-refractory MRSA bacteremia treated with the combination of vancomycin and ceftaroline.Methods
Between January 2014 and August 2016, 5 patients were identified who received vancomycin and ceftaroline combination therapy due to persistent bacteremia or deterioration of their clinical status on vancomycin alone (despite a vancomycin MIC within the susceptible range).Findings
Five patients presented with MRSA bacteremia secondary to endocarditis (n = 2), epidural abscess (n = 2), or left iliopsoas abscess (n = 1). Four of the 5 patients experienced microbiologic cure, and 1 patient transitioned to palliative care.Implications
This case series serves to describe additional clinical experience with vancomycin and ceftaroline combination therapy. This combination may be considered when vancomycin monotherapy does not lead to microbiological and/or clinical improvement in patients with metastatic MRSA bacteremia. Additional studies are warranted to further define its role in salvage therapy for persistent MRSA bacteremia. 相似文献3.
4.
Roger von Moos Jean-Jacques Body Blair Egerdie Alison Stopeck Janet E. Brown Danail Damyanov Lesley J. Fallowfield Gavin Marx Charles S. Cleeland Donald L. Patrick Felipe G. Palazzo Yi Qian Ada Braun Karen Chung 《Supportive care in cancer》2013,21(12):3497-3507
Purpose
This analysis evaluated patient-reported outcomes and analgesic use in patients with bone metastases from solid tumours across three comparative studies of denosumab and zoledronic acid.Methods
Pooled data were analysed from three identically designed double-blind phase III studies comparing subcutaneous denosumab 120 mg with intravenous zoledronic acid 4 mg monthly in patients with bone metastases from breast cancer (n?=?2,046), castration-resistant prostate cancer (n?=?1,901) or other solid tumours (n?=?1,597). Pain severity, pain interference, health-related quality of life and analgesic use were quantified.Results
At baseline, approximately half of patients had no/mild pain (53 % [1,386/2,620] denosumab; 50 % [1,297/2,578] zoledronic acid). Denosumab delayed onset of moderate/severe pain by 1.8 months (median, 6.5 vs 4.7 months; hazard ratio, 0.83; 95 % CI, 0.76–0.92; p?<?0.001; 17 % risk reduction) and clinically meaningful increases in overall pain interference by 2.6 months (median, 10.3 vs 7.7 months; hazard ratio, 0.83; 95 % CI, 0.75–0.92; p?<?0.001; 17 % risk reduction) compared with zoledronic acid. Strong opioid use and worsening of health-related quality of life were less common with denosumab.Conclusions
Across three large studies of patients with advanced solid tumours and bone metastases, denosumab prevented progression of pain severity and pain interference more effectively than zoledronic acid. 相似文献5.
Naomi C. Sacks Philip L. Cyr Arthur C. Louie Yanmei Liu Michael T. Chiarella Abhishek Sharma Karen C. Chung 《Clinical therapeutics》2018,40(5):692-703.e2
Purpose
Acute myeloid leukemia (AML) disproportionately affects older adults; the prognosis in this subpopulation is generally poor, with variable use of inpatient chemotherapy. This study characterizes treatment patterns, hospitalizations, and outcomes among older patients with AML.Methods
Using the Centers for Medicare & Medicaid Services' 2010–2012 100% Limited Data Set (LDS), data from all hospital claims from fee-for-service Medicare beneficiaries between 60 and 75 years of age with newly diagnosed AML and ≥1 hospitalization were analyzed.Findings
Among 3700 identified patients with AML, 1979 (53.5%) received chemotherapy. Hospitalization rates were highest initially and then declined over time, irrespective of chemotherapy use. The mean length of initial hospital stay was longer in patients receiving chemotherapy. Intensive care unit admissions occurred in 33% of initial hospitalizations. Factors associated with receiving chemotherapy included younger age, fewer comorbidities, and the absence of prior hematologic disorders. Chemotherapy was associated with significantly increased survival compared with no chemotherapy (P < 0.0001).Implications
AML in older patients is associated with frequent hospitalizations and intensive care unit admissions. New treatment options with more favorable risk-to-benefit profiles are needed in this population. 相似文献6.
Young-June Yang Sang-Hak Lee Byung Soo Kim Yun-Kyeong Cho Hyun-Jai Cho Kyoung Im Cho Seok-Yeon Kim Jae Kean Ryu Jin-Man Cho Joong-Il Park Jong-Seon Park Chang Gyu Park Woo Jung Chun Myung-A Kim Dong-Kyu Jin Namho Lee Byung Jin Kim Kwang Kon Koh Yangsoo Jang 《Clinical therapeutics》2017,39(1):107-117
Purpose
The aim of this study was to evaluate the efficacy and tolerability of rosuvastatin/ezetimibe combination therapy in Korean patients with high cardiovascular risk.Methods
This was a 12-week, randomized, double-blind, placebo-controlled, multicenter study. A total of 337 patients were screened. After a 4-week run-in period, 245 of these patients with high or moderately high risk as defined by the National Cholesterol Education Program Adult Treatment Panel III guidelines were randomly assigned. Patients received 1 of 6 regimens for 8 weeks as follows: (1) rosuvastatin 5 mg, (2) rosuvastatin 5 mg/ezetimibe 10 mg, (3) rosuvastatin 10 mg, (4) rosuvastatin 10 mg/ezetimibe 10 mg, (5) rosuvastatin 20 mg, or (6) rosuvastatin 20 mg/ezetimibe 10 mg. The primary outcome variable was percentage change in the level of LDL-C at week 8 of drug treatment. Secondary outcome variables included percentage changes of other lipid variables and achievement rates of LDL-C targets. Tolerability analyses were also performed.Findings
The percentage change of LDL-C ranged from –45% to –56% (mean, –51%) in the monotherapy groups and from –58% to –63% (mean, –60%) in the combination therapy groups. The percentage change was greater in the pooled combination therapy group than in the counterpart (P < 0.001 for the pooled groups); this difference was more obvious for regimens with a lower statin dose. The percentage reductions of total cholesterol and triglycerides were greater in the combination groups than in the monotherapy groups. The LDL-C target achievement rates were 64% to 87% (mean, 73%) in the monotherapy groups and 87% to 95% (mean, 91%) in the combination groups (P = 0.01 for the pooled groups). The rates were significantly greater in patients receiving the combination therapy than in the monotherapy at lower doses of rosuvastatin. The proportions of patients with various adverse events were not significantly different between the groups.Implications
Rosuvastatin/ezetimibe combination therapy has better efficacy and target achievement rates than rosuvastatin monotherapy in patients with high cardiovascular risk. 相似文献7.
Purpose
Techniques used to identify AmpC β-lactamases in SPICE (Serratia, Pseudomonas, indole-positive Proteus, Citrobacter, and Enterobacter) organisms are not yet optimized for the clinical laboratory and are not routinely used. Clinicians are often left with an uncertainty on the choice of antibiotic when a SPICE organism is isolated. The purpose of this study was to evaluate the outcomes of carbapenem versus noncarbapenem regimens in treating bacteremia or urinary tract infection from a SPICE organism in clinical practice.Methods
This single-center, retrospective, cohort study analyzed data from adult patients who had clinical infection with a SPICE organism isolated from blood or urine cultures. Patients were assigned to a carbapenem- or noncarbapenem-treated group. The primary end point was clinical response, defined as a resolution of signs and symptoms of infection at the end of therapy.Findings
A total of 332 patients were assessed, and 145 patients met the inclusion criteria for the study. There were 20 patients who received a carbapenem, while 125 received a noncarbapenem regimen. The percentage of patients who were bacteremic was 46.2%. Clinical response overall was achieved in 80% of patients on a carbapenem versus 90.3% of patients on a noncarbapenem regimen (P = 0.24). The rate of microbiologic cure was 90% in patients on a carbapenem versus 91.2% in patients on a noncarbapenem regimen (P = 1).Implications
In this study in patients treated for infection with a SPICE organism in clinical practice, the rates of clinical response did not differ significantly between the carbapenem and noncarbapenem groups. Current CLSI breakpoints set for SPICE organisms may still be reliable and may not require additional testing for AmpC β-lactamases. 相似文献8.
Woohyeun Kim Yeonyee E. Yoon Sung-Hee Shin Jang-Whan Bae Bum-Kee Hong Soon Jun Hong Ki Chul Sung Seung Hwan Han Weon Kim Moo-Yong Rhee Sang-Hyun Kim Sang Eun Lee Min Su Hyon Gyo-Seung Hwang Jang Won Son Jang-Young Kim Min Kyu Kim Sang Wook Kim Chang Gyu Park 《Clinical therapeutics》2018,40(6):993-1013
Purpose
The aim of this study was to evaluate the safety and efficacy of combination treatment of rosuvastatin with ezetimibe in patients with primary hypercholesterolemia.Methods
This multicenter, randomized, double-blind study comprised a main study and an extension study. In the main study, the efficacy and safety of a combination of rosuvastatin (5, 10, and 20 mg) with ezetimibe (10 mg) were compared with those of rosuvastatin (5, 10, and 20 mg) alone. The subjects who achieved the National Cholesterol Education Program Adult Treatment Panel III LDL-C goal in the main study and agreed to a further study were enrolled for the extension study. In the extension study, ezetimibe 10 mg was also administered to subjects who had received rosuvastatin (5, 10, and 20 mg) alone in the main study, and the same treatment was continued for subjects who had received a combination of rosuvastatin with ezetimibe in the main study.Findings
At the end of the main study (week 8), LDL-C levels were significantly lower in subjects receiving combination therapy than in those receiving rosuvastatin monotherapy. Other lipid profiles also significantly improved in the combination therapy group. These improvements continued in the extension study. The combination therapy of rosuvastatin and ezetimibe was generally well tolerated. At the end of the main study, more subjects achieved the National Cholesterol Education Program Adult Treatment Panel III LDL-C goal in the combination therapy group than in the monotherapy group. The increased dosage of rosuvastatin was also well tolerated in the combination treatment.Implications
Combination therapy of ezetimibe 10 mg with varying doses of rosuvastatin that are commonly used in the clinical field improved the lipid profile and allowed more subjects to reach the LDL-C goal in primary hypercholesterolemia compared with rosuvastatin monotherapy. In addition, the efficacy of the combination therapy was maintained for the extended period. Additional beneficial changes were also achieved with combination therapy even in patients who responded well to rosuvastatin monotherapy. ClinicalTrials.gov identifier: NCT03288038. 相似文献9.
Purpose
We performed a meta-analysis to investigate the legacy effect of >5 years of intensive blood glucose lowering on cardiovascular outcomes in patients with type 2 diabetes and very high risk or secondary prevention of cardiovascular disease (CVD).Methods
We mainly searched PubMed, Embase, and the Cochrane Library for relevant randomized controlled trials. Patients in the included studies had intensive glucose lowering for >5 years and posttrial follow-up for at least 5 years. Primary end points were all-cause mortality and cardiovascular death. Secondary end points were major macrovascular events, myocardial infarction, and stroke. We used risk ratios (RRs) with 95% CIs as summary statistics.Findings
We included 3 trials that involved 13,684 patients, of whom 6805 received intensive glucose-lowering treatment and 6879 received standard treatment. The mean total follow-up duration was 10.3 years, which included 5.4 years of in-trial intervention and 5.5 years of posttrial follow-up. Intensive glucose control treatment did not significantly reduce all-cause mortality (RR = 0.98; 95% CI, 0.87–1.10) or cardiovascular death (RR = 0.97; 95% CI, 0.87–1.09). No significant risk reduction was found for stroke (RR = 1.02; 95% CI, 0.92–1.14), myocardial infarction (RR = 0.91; 95% CI, 0.75–1.09), or major macrovascular events (RR = 0.99; 95% CI, 0.93–1.06).Implications
A legacy effect of >5-year intensive blood glucose control on cardiovascular outcomes in patients with type 2 diabetes and very high risk or secondary prevention of CVD was not detected, although this effect might be applicable in patients with diabetes and primary prevention of CVD. Further investigation of the legacy effect in different CVD risk populations should therefore be performed. 相似文献10.
Background
Critically reviewing the design, endpoints, and results of clinical trials can be challenging to health care professionals. This paper will review the basic methods of presenting clinical outcomes in randomized trials and will focus on the number needed to treat (NNT) concept. NNT will then be applied to the case of bone-targeted therapies denosumab and zoledronic acid, which are used for the prevention of skeletal-related events (SREs) in a variety of disease sites.Methods
A Medline search was performed to identify randomized trials comparing denosumab to zoledronic acid for the prevention of SREs in patients with advanced breast, prostate, and other cancer sites. The data were extracted, and point estimates for the primary and secondary trial endpoints were converted into the NNT parameter.Results
NNT represents the number of patients that need to be treated with a new intervention in order to avoid one additional patient developing the event and is a powerful approach that can be used to make sense of numerical results from clinical trials. In patients with advanced breast, prostate, and other cancer sites, 18, 22, and 21 patients, respectively, would need to be treated with denosumab for at least 24?months to avoid one patient developing an SRE.Conclusions
The NNT approach is a simple and effective method to express the findings of randomized trials in a clinically meaningful way. In this analysis, the incremental benefits of denosumab would be realized when a minimum of 18 to 22 patients are treated for a prolonged duration. Clinicians would have to weigh the costs and benefits between denosumab and zoledronic acid when bone-targeted therapy is indicated. 相似文献11.
Yujuan Jiao Lei Cui Weihe Zhang Yeqiong Zhang Wei Wang Linwei Zhang Wenxiong Tang Jinsong Jiao 《Clinical therapeutics》2018,40(4):603-612
Purpose
The purposes of this article were to evaluate the short-term outcome of plasma exchange (PLEX) for neuromyelitis optica spectrum disorders (NMOSDs) in Chinese patients and to identify the factors predictive of a favorable response to therapy.Methods
We retrospectively analyzed data from 29 Chinese patients with NMOSD. All patients received 2 to 7 sessions of PLEX every other day. Expanded Disability Status Scale (EDSS) scores were estimated at baseline, at relapse, and before and at follow-up after PLEX. Patients were assigned to 1 of 2 groups according to treatment responses of marked to moderate improvement and mild to no improvement.Findings
Twenty-four of 29 patients (82.8%) showed functional improvement at 1 month after PLEX, 9 of whom experienced moderate to marked improvement. Early PLEX initiation and a lower baseline EDSS score were independent prognostic factors (both, P < 0.05). In addition, relapse symptoms of nonoptic neuritis and acute transverse myelitis plus circumventricular organs, seronegativity for aquaporin-4 antibodies, shorter initial therapy–PLEX interval, and no prior optic neuritis attacks were predictive factors significantly associated with a favorable response to treatment (all, P < 0.05). The delay time pre-PLEX was inversely correlated with reduction in EDSS score. The percentage reductions in EDSS score in groups receiving PLEX on days ≤15 and days 16 to 30 were significantly greater than those in the groups treated on days 31 to 60 and days 61 to 90 (all, P < 0.05). Most PLEX sessions were generally well tolerated.Implications
PLEX is an effective therapy for NMOSD in the Chinese population, and early PLEX initiation was associated with a favorable response. We recommend an optimum PLEX time of 30 days from the time of disease onset. Further long-term prospective, multicenter studies that include a larger sample of patients with NMOSD treated with PLEX are necessary. 相似文献12.
Rahul P. Patel Jilson Jacob Mohammed Sedeeq Long Chiau Ming Troy Wanandy Syed Tabish R. Zaidi Gregory M. Peterson 《Clinical therapeutics》2018,40(4):664-667
Purpose
The aim was to investigate the stability of cefazolin in elastomeric infusion devices.Methods
Elastomeric devices (Infusor LV) that contain cefazolin (3 g/240 mL and 6 g/240 mL) were prepared and stored at 4°C for 72 hours and then at 35°C for 12 hours, followed by 25°C for 12 hours. An aliquot was withdrawn at predefined time points and analyzed for the concentration of cefazolin. Samples were also assessed for changes in pH, solution color, and particle content.Findings
Cefazolin retained acceptable chemical and physical stability over the studied storage period and conditions.Implications
These findings will allow the administration of cefazolin by the Infusor LV elastomeric device in the outpatient and remote settings. 相似文献13.
Stacy M. Harnish Amy D. Rodriguez Deena Schwen Blackett Christopher Gregory Lauren Seeds Jeffrey H. Boatright Bruce Crosson 《Clinical therapeutics》2018,40(1):35-48.e6
Purpose
This study investigated whether participation in aerobic exercise enhances the effects of aphasia therapy, and the degree to which basal serum brain-derived neurotropic factor (BDNF) concentrations fluctuate after the beginning of aerobic exercise or stretching activities in individuals with poststroke aphasia.Methods
The study used a single-subject, multiple-baseline design. Seven individuals with chronic poststroke aphasia participated in 2 Blocks of aphasia therapy: aphasia therapy alone (Block 1), followed by aphasia therapy with the addition of aerobic activity via bicycle ergometer (n = 5) or stretching (n = 2) (Block 2). Serum BDNF concentrations from blood draws were analyzed in 4 participants who exercised and in 1 participant who stretched.Findings
Three of the five exercise participants demonstrated larger Tau-U effects when aphasia therapy was paired with aerobic exercise, whereas 1 of the 2 stretching participants demonstrated a larger effect size when aphasia therapy was paired with stretching. Group-level comparisons revealed a greater overall increase in effect size in the aerobic exercise group, as indicated by differences in Tau-U weighted means. BDNF data showed that all 4 exercise participants demonstrated a decrease in BDNF concentrations during the first 6 weeks of exercise and an increase in BDNF levels near or at baseline during the last 6 weeks of exercise. The stretching participant did not show the same pattern.Implications
Additional research is needed to understand the mechanism of effect and to identify the factors that mediate response to exercise interventions, specifically the optimal dose of exercise and timing of language intervention with exercise. ClinicalTrials.gov identifier: NCT01113879. 相似文献14.
Stefano Raffaele Giannubilo Angela Pasculli Chiara Ballatori Alessandra Biagini Andrea Ciavattini 《Clinical therapeutics》2018,40(4):587-592
Purpose
This was a prospective observational cohort study that aimed to determine whether fetal sex influences the maternal and fetal outcomes of gestational diabetes mellitus (GDM).Methods
In this study, 327 European primiparous women were consecutively recruited after diagnosis of GDM. AUC on the oral glucose tolerance test (OGTT), need for insulin therapy, maternal and obstetrical outcomes, and fetal fat mass (by measuring the thickness of the anterior abdominal subcutaneous tissue) were recorded and compared between the two subgroups of female and male fetuses.Findings
Despite the absence of differences in multiple comparisons of the OGTT, the AUC–OGTT was significantly higher in women carrying a male fetus (22.6 [3.2] mmol/L vs 19.7 [2.8] mmol/L). The abdominal fat thickness appeared to increase with gestational age, with higher growth in male fetuses than in female fetuses. The overall risk of need for insulin therapy was significantly higher in women carrying a male fetus (odds ratio = 1.837). At delivery, birthweight was higher in males than in females only if adjusted for gestational age, similarly for placental weight, otherwise there were no significant differences between the groups in total length of gestation, rates of cesarean delivery, and Apgar scores.Implications
Overall, our data propose an association between fetal sex and GDM outcomes, suggesting the hypothesis that in maternal–fetal interactions, the fetus can affect maternal glucose metabolism. 相似文献15.
Martin O. Weickert Gregory Kaltsas Dieter Hörsch Pablo Lapuerta Marianne Pavel Juan W. Valle Martyn E. Caplin Emily Bergsland Pamela L. Kunz Lowell B. Anthony Enrique Grande Kjell Öberg Staffan Welin Catherine Lombard-Bohas John K. Ramage Ashwin Kittur Qi M. Yang Matthew H. Kulke 《Clinical therapeutics》2018,40(6):952-962.e2
Purpose
In the placebo-controlled Phase III TELESTAR (Telotristat Etiprate for Somatostatin Analogue Not Adequately Controlled Carcinoid Syndrome) trial, the oral tryptophan hydroxylase inhibitor telotristat ethyl significantly reduced bowel movement (BM) frequency during a 12-week, double-blind treatment period in 135 patients with metastatic neuroendocrine tumors with carcinoid syndrome and ≥4 BMs per day. Patients (mean [SD] age, 63.5 [8.9] years; mean [SD] body mass index, 24.9 [4.9] kg/m2) received placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg 3 times per day (TID) in addition to somatostatin analogue therapy. Weight loss is associated with uncontrolled carcinoid syndrome and may be associated with reduced survival.Methods
Assessment of the occurrence of weight change ≥3% at week 12 was prespecified in the statistical analysis plan.Findings
In 120 patients with weight data available, weight gain ≥3% was observed in 2 of 39 patients (5.1%) taking placebo TID, 7 of 41 (17.1%) taking telotristat ethyl 250 mg TID, and 13 of 40 (32.5%) taking telotristat ethyl 500 mg TID (P = 0.0017) at week 12. Weight loss ≥3% was observed in 5 of 39 patients (12.8%) taking placebo TID, 4 of 41 (9.8%) taking telotristat ethyl 250 mg TID, and 6 of 40 (15.0%) taking telotristat ethyl 500 mg TID (P = 0.77). Biochemical and metabolic parameters of serum albumin and cholesterol significantly increased (P = 0.02 and P = 0.001, respectively) in patients gaining weight and decreased in patients who lost weight, suggesting an improvement in overall nutritional status.Implications
Up to 32.5% of patients treated with telotristat ethyl experienced significant, dose-dependent weight gain, associated with reduced diarrhea severity and improved biochemical and metabolic parameters. Improved nutritional status could be an additional aspect of telotristat ethyl efficacy among patients with functioning metastatic neuroendocrine tumors. ClinicalTrials.gov identifier: NCT01677910. 相似文献16.
Eric M. Maiese Claire Ainsworth Jean-Gabriel Le Moine Outi Ahdesmäki Judith Bell Emma Hawe 《Clinical therapeutics》2018,40(3):480-494.e23
Purpose
New therapies, including daratumumab plus lenalidomide plus dexamethasone (DRd) and daratumumab plus bortezomib plus dexamethasone (DVd), have recently been approved in the United States for patients with multiple myeloma (MM) who have received at least 1 prior line of therapy. However, few treatments have been compared in head-to-head clinical trials to determine the most efficacious therapy. In an update of the POLLUX (Phase 3 Study Comparing DRd Versus Rd in Subjects with Relapsed or Refractory Multiple Myeloma [RRMM]) trial, median progression-free survival (PFS) for DRd was not reached; the hazard ratio compared with Rd was 0.41. In an update of the CASTOR (Phase 3 Study Comparing DVd Versus Vd in Subjects with RRMM) trial, median PFS for DVd was 16.7 months, compared with 7.1 months for Vd with a PFS hazard ratio of 0.31. A systematic literature review and network meta-analysis (NMA) was performed to estimate the relative efficacy of treatments for previously treated patients with MM.Methods
A systematic search of MEDLINE, EMBASE, BioSciences Information Service, and the Cochrane Library databases was conducted from initiation to September 2016. Abstracts published by international congresses (2014–2016) and bibliographies of pertinent systematic reviews and meta-analyses were also searched. Eligible studies consisted of randomized controlled trials (RCTs) or long-term follow-up studies with >1 treatment arm assessing the efficacy or safety of MM therapies. An NMA was conducted by using Bayesian fixed effect mixed-treatment comparisons. Outcomes considered were hazard ratios for PFS and odds ratios for overall response rate (ORR).Findings
In total, 108 articles reporting 27 RCTs were included in the NMA. Data formed 2 evidence networks: RCTs with DRd and RCTs with DVd. Primary analysis of PFS found that DRd and DVd had a higher probability of being the best treatments (probability, 0.997 and 0.999, respectively) and had the lowest risk of progression or death than other treatments approved by the US Food and Drug Administration for the treatment of MM. Results from sensitivity analyses using time to progression as a proxy for missing PFS data were consistent. DRd and DVd also showed improved ORR compared with other treatments. Subgroup analyses of PFS in patients treated with only 1 prior therapy were like the results of the primary analyses.Implications
This NMA provides comparative efficacy for MM treatments not studied in head-to-head RCTs. The NMA suggests that, compared with other approved MM treatments in the United States, DRd and DVd have a higher probability of providing the longest PFS in patients who have received at least 1 prior therapy and in patients who have received only 1 prior therapy. 相似文献17.
Purpose
Intranasal vaccines are being developed for protection against many different infectious agents. The currently available intranasal live attenuated influenza vaccine (LAIV) is only approved for administration by medical personnel. We conducted a pilot study to investigate the feasibility of training parents to give LAIV to their own children.Methods
Subjects were recruited from several sources: a university-based outpatient clinic, university employee e-mail announcement, and direct referrals from study subjects. After confirming eligibility to receive LAIV, consented parents were trained by viewing a video with the study staff. LAIV was provided in a cooler with instructions to vaccinate within 24 hours. Telephone follow-up was conducted to confirm proper administration and to assess parental attitudes about home administration. At season’s end, immunization registry and hospital records were reviewed to confirm no additional doses were given.Findings
Twenty-seven families with 41 children were enrolled. All participants successfully administered LAIV to their children, and all preferred or strongly preferred home administration to an office visit for getting vaccinated. Two families stated that without this option they would not have otherwise vaccinated their children. Adverse events were minor. All patients had their state vaccine registries accurately updated and none received duplicate doses. Upon review, no reimbursement was received for vaccination.Implications
Home administration of intranasal LAIV was successful and well received. This option could be used in the future for LAIV or other intranasal vaccines as a way to increase vaccination rates and convenience for parents. ClinicalTrials.gov identifier: NCT01938170. 相似文献18.
Olga Růžičková Zdenko Killinger Petr Kasalický Lisa Hamilton Roman Tyl Soňa Tomková Lama Kalouche-Khalil 《Advances in therapy》2018,35(10):1713-1728
Introduction
Osteoporosis is characterized by low bone mineral density (BMD) and an increased risk of fracture. In randomized controlled trials, denosumab has been shown to significantly reduce the fracture risk in women with osteoporosis. However, little is known about the real-world management of women who are prescribed denosumab.Methods
This multicenter, prospective, observational real-world study in the Czech Republic and Slovakia evaluated the baseline characteristics and clinical management of women with postmenopausal osteoporosis prescribed denosumab for 24 months.Results
A total of 600 women were included (300 in each country). In the Czech Republic and Slovakia, respectively, mean age at enrollment was 69.0 and 64.3 years, 67.7% and 30.0% of patients had a previous osteoporotic fracture, and 85.0% and 48.7% had previously received osteoporosis medication. In both countries, ‘low BMD T score’ and ‘a history of osteoporotic fracture’ were the main reasons for prescribing denosumab. Most patients received all four post-baseline denosumab injections (Czech Republic, 82.0%; Slovakia, 81.0%), and more than 98% of patients in both countries received all injections at the prescribing center. At 24 months, most patients experienced an increase in BMD T score for the lumbar spine, total hip, or femoral neck (Czech Republic, 69.7–91.7%; Slovakia, 67.1–92.9%). Adverse drug reactions were consistent with the known safety profile of denosumab.Conclusion
Baseline characteristics of patients receiving denosumab in the Czech Republic and Slovakia reflect the reimbursement criteria for this agent in each country. The findings of our study in patients who are at high risk for fracture are consistent with the growing body of evidence demonstrating the effectiveness of denosumab in real-world clinical practice.Trial Registration
ClinicalTrials.gov identifier, NCT01652690.Funding
Amgen Inc.19.
Purpose
The ability of sophisticated sensors and medical devices to monitor critical biomarkers has the potential to greatly advance precision medicine initiatives. A stakeholder event was organized to develop working models for the evolution of the field.Methods
A workshop devoted to the subject matter was held at the Tufts Clinical and Translational Science Institute involving clinicians, device developers, regulators, engineers, and scientists.Findings
Several areas for collaborative development were identified and interested teams offered resources for development of research programs.Implications
The diversity of relevant stakeholders presents a major opportunity and challenge in translational research. It is evident that the CTSI national network can take a leadership role in the rapidly advancing and potentially transformative field of digital biomarkers. 相似文献20.