Efficacy and tolerability of once-monthly oral ibandronate (150 mg) and once-weekly oral alendronate (70 mg): Additional results from the monthly oral therapy with ibandronate for osteoporosis intervention (MOTION) study

Background: The MOTION (Monthly Oral Therapy with Ibandronate for Osteoporosis Intervention) study reported that once-monthly ibandronate was noninferior to once-weekly alendronate in terms of increasing bone mineral density (BMD) at the lumbar spine and total hip over 12 months. On analysis of secondary and exploratory end points in MOTION, which included trochanter and femoral neck BMD, monthly ibandronate was found to be noninferior to weekly alendronate. The coprimary, secondary, and exploratory BMD end points from MOTION have been previously reported.Objective: This report presents additional results from the MOTION study, including response rates in terms of lumbar spine and total hip BMD gains above baseline; findings from a comparison of serum concentrations of bone turnover markers; and tolerability analysis, including adverse events that led to withdrawal and gastrointestinal (GI) adverse events.Methods: MOTION was a 12-month (with 15-day follow-up), randomized, multinational, multicenter, double-blind, double-dummy, parallel-group, nonin-feriority study in postmenopausal women aged 55 to <85 years with osteoporosis. Patients were randomly assigned to receive 150-mg-monthly oral ibandronate and weekly alendronate-matched placebo, or 70-mg-weekly oral alendronate and monthly ibandronate-matched placebo, for 12 months. At baseline, day 7 of treatment, 3 and 6 months, 6 months + 7 days, and 12 months, serum concentrations of markers of bone resorption (C-telopeptide of the a chain of type 1 collagen [sCTX]) and bone formation (serum N-terminal propeptides of type 1 collagen) were measured in a subset of the total trial population. At baseline and month 12, BMD was measured using dual-energy x-ray absorptiometry. Exploratory analyses of patients whose spine, total hip, and trochanter BMD at 12 months were above baseline (responders) were also performed.Results: A total of 1760 women were enrolled (ibandronate, 887 patients; alendronate, 873). The median changes in the trough concentrations of sCTX were ?75.5% with monthly ibandronate and ?81.2% with weekly alendronate. The percentage of patients with mean lumbar spine and total hip BMD gains above baseline (responders) were 90% and 87%, respectively, for ibandronate and 92% and 90%, respectively, for alendronate. GI adverse events were reported in ≤30% of patients per group during this 1-year study.Conclusion: The data from these postmenopausal women with osteoporosis suggest that once-monthly 150-mg ibandronate therapy provided clinically comparable efficacy in terms of BMD response, reductions in bone turnover, and GI tolerability similar to that of weekly 70-mg alendronate.     

阿法骨化醇联合阿仑膦酸钠治疗老年骨质疏松症的效果及对患者骨代谢的影响

目的 分析阿法骨化醇联合阿仑膦酸钠治疗老年骨质疏松症(OP)的效果及对患者骨代谢的影响.方法 选取我院2018年11月至2020年5月收治的118例老年OP患者,将其随机分为对照组(59例,阿法骨化醇)和试验组(59例,阿法骨化醇联合阿仑膦酸钠).比较两组治疗效果.结果 治疗后,试验组S-Ca、S-P、BMD、TGF-...     

Effects of self-efficacy, social support and knowledge on adherence to PEFR self-monitoring among adults with asthma: a prospective repeated measures study

BACKGROUND: Long-term adherence to self-monitoring of peak expiratory flow rate (PEFR) is essential for early detection of declining lung function in individuals with asthma. Psychosocial and cognitive factors can influence adherence to PEFR self-monitoring behaviors. OBJECTIVES: The specific aims of this prospective, repeated measures study were to: (1) determine the effects of asthma self-efficacy, perceived satisfaction with social support and asthma knowledge on adherence to PEFR self-monitoring behavior; and (2) examine whether adherence to PEFR self-monitoring mediates the effects of psychosocial/cognitive factors on lung function and asthma symptoms in adults with asthma. DESIGN: Sixty-eight participants completed standardized questionnaires three times at baseline, 1 month, and 3 months and kept the records of PEFR self-monitoring behaviors twice a day. Data were analyzed using multiple linear regressions. Adherence rates to PEFR self-monitoring were 93.5% and 74.9% at 1 and 3 month, representing those who remained in the study (n=39). Other participants withdrew from the study. FINDINGS: Both at 1 and 3 month, psychosocial/cognitive factors as a whole did not account for a significant variance in adherence to PEFR self-monitoring. Univariate analyses, however, indicated that baseline asthma self-efficacy and asthma knowledge at 1 month were significant independent predictors for adherence to PEFR self-monitoring at 3 month. CONCLUSION: Adherence to PEFR self-monitoring did not mediate the effects of asthma self-efficacy, perceived satisfaction with social support, and asthma knowledge on lung function and asthma symptoms. Lung function was low, but participants reported low asthma symptoms, both of which remained stable over time. Because of a small sample size and high attrition, the findings of the study need to be interpreted with caution. Given the importance of long-term adherence to self-management in asthma and other chronic illnesses, factors influencing adherence need to be further investigated to set a basis for future interventions.     

Meeting notes from the 2nd International AIDS Society Conference on HIV Pathogenesis and Treatment. Trizivir vs. efavirenz: results from ACTG 5095

An oral presentation reviewed data from a discontinued study comparing triple-NRTI therapy with 2 efavirenz-containing regimens.     

Bisphosphonate‐associated osteonecrosis of the jaw. Knowledge and attitudes of dentists and dental students: a preliminary study

Objective The objective was to determine the knowledge of dentists and dental students of bisphosphates and osteonecrosis of the jaw (ONJ) in the Autonomous Community of Murcia, Spain. Material and method A structured questionnaire was elaborated on knowledge, attitude and practice regarding aspects of the aetiology, diagnosis and prevention of bisphosphonate‐associated ONJ. The questionnaire was administered to two groups: group I with 60 dental students and group II, 60 dentists with well‐established professional activity. Results As regards the subjects’ knowledge of bisphosphonate‐associated osteonecrosis, 30 (50%) students and 41 (68.36%) dentists (P = 0.0041) had up to date knowledge. Most correctly identified risk factors involved. Only eight (13.33%) students and 20 (33.33%) dentists (P = 0.010) knew how to treat osteonecrosis once established. Conclusions Training strategies need to be established as regards bisphosphonate‐associated ONJ.     

Trauma scissors vs. the rescue hook, exposing a simulated patient: a pilot study

The objective of this study was to compare the exposure times using trauma scissors vs. the rescue hook on a simulated patient. This was a prospectively randomized, parallel group comparison study with two arms. The control group used trauma scissors (15 cycles), and the intervention group used rescue hooks (15 cycles). The uniform and footwear were standardized for each cycle. Ten participants were trained on each instrument. For each cycle, four participants were randomly chosen, and the use of either instrument was randomized. Each participant was then queried about their preferences for either instrument and why. The rescue hook's mean time of exposure was 24 s with a SD of 7 s and a 95% confidence interval (CI) of 20-28 s. The trauma scissors' mean exposure time was 42 s with a SD of 5 s and a 95% CI of 39-45 s. The mean difference was 18 s, with a 95% CI of 13-23 s. On average, the rescue hook was 43% faster. Nine of 10 participants preferred the rescue hook, stating that it was faster, easier, smaller, and more durable. The rescue hook was found to be faster than trauma scissors when exposing a simulated patient, and it was the instrument preferred by the majority of participants.     

Utility of lumbar puncture in the afebrile vs. febrile elderly patient with altered mental status: a pilot study

We conducted a pilot study to compare the diagnostic utility of a lumbar puncture (LP) in febrile vs. afebrile elderly patients with altered mental status (AMS). Our null hypothesis was that there is no utility of performing an LP on the afebrile elderly patient with AMS. A retrospective study was conducted at an urban, university tertiary care referral center. The study population included all elderly patients (age 65 years and older) who had cerebrospinal fluid (CSF) samples sent to the laboratory over 1 year. A structured chart review was performed. Exclusion criteria were normal mental status, recent neurosurgical procedure or presence of a ventricular shunt, and missing medical records. An LP was considered diagnostically useful if it yielded a diagnosis. There were 185 CSF samples from elderly patients recorded over 1 year. Sixty samples were excluded for the following reasons: normal mental status (36), recent neurosurgical procedure (2), presence of ventricular shunt (11), missing medical record (4), repeat LP on same admission (7). Of the 125 patients who met the study criteria, 84 patients were afebrile and 41 patients were febrile. Of the 84 afebrile patients with AMS, 15 patients (18%; 95% confidence interval [CI] 10-26%) had an abnormal LP. Ten (12%) had some form of meningitis and five (6%) had unclear diagnoses. Of the 41 febrile patients with AMS, 10 patients (24%; 95% CI 11-38%) had an abnormal LP. Three (7%) had some form of meningitis or encephalitis. Comparing the elderly patient group without fever with the elderly patient group with fever, there was no statistical difference in the incidence of abnormal LPs or diagnostically useful LPs. Based on the results of this pilot study, we were unable to reject the null hypothesis that there is no utility of performing LP on afebrile elderly patients with altered mental status. We would advocate not relying solely on the presence or absence of fever to determine management in the elderly.     

A comparison of the effect of alendronate and risedronate on bone mineral density in postmenopausal women with osteoporosis: 24-month results from FACTS-International

Objectives: To compare alendronate 70 mg once weekly (OW) with risedronate 35 mg OW with respect to change in bone mineral density (BMD), biochemical markers and upper gastrointestinal (UGI) tolerability over 24 months. Methods: This was a 12‐month extension to the Fosamax^® Actonel^® Comparison Trial international study (FACTS). Postmenopausal women with osteoporosis randomly assigned to either alendronate 70 mg OW or risedronate 35 mg OW for the 12‐month base study continued taking the same double‐blind study medication. Efficacy measurements were BMD at the hip trochanter, lumbar spine, total hip, and femoral neck and levels of four bone turnover markers at 24 months. The primary hypothesis was that alendronate would produce a greater mean per cent increase from baseline in hip trochanter BMD at 24 months. Results: Trochanter BMD increased significantly from baseline to month 24 in both groups, with a significantly larger increase with alendronate: adjusted mean treatment difference of 1.50% (95% confidence interval: 0.74%, 2.26%; p < 0.001). Similar results were seen at all BMD sites. Significant geometric mean per cent decreases (p < 0.001) from baseline were seen for all four bone turnover markers in both groups, with significantly larger decreases (p < 0.001) with alendronate: adjusted mean treatment differences ranged from 8.9% to 25.3%. No significant differences were seen in incidence of UGI or other adverse events. Conclusions: Alendronate 70 mg OW yielded significantly greater BMD gains and larger decreases in bone turnover marker levels than risedronate 35 mg OW over 24 months, with no difference in UGI tolerability.     

Efficacy and safety of secondary prophylactic vs. on-demand sucrose-formulated recombinant factor VIII treatment in adults with severe hemophilia A: results from a 13-month crossover study

Summary. Background: Hemarthroses in severe hemophilia precipitate physical, psychosocial and financial difficulties. Objective: To compare the effects of secondary prophylaxis with on‐demand sucrose‐formulated recombinant factor VIII (rFVIII‐FS) therapy in severe hemophilia A. Patients and methods: This open‐label study included patients aged 30–45 years with factor VIII (FVIII) coagulant activity < 1 IU dL^?1 who were using on‐demand FVIII treatment. Patients were treated with rFVIII‐FS on demand for 6 months, followed by 7 months prophylaxis (20–40 IU kg^?1, three times per week, with the first month considered a run‐in). The primary endpoint was the number of hemarthroses. Results: Twenty patients were enrolled (n = 19 completed); the mean age was 36.4 years, and 16 had target joints. The median (25–75%) number of joint bleeds decreased significantly with prophylaxis [0 (0–3)] vs. on‐demand [15 (11–26); P < 0.001] therapy. The number of all bleeds was 0 (0–3) vs. 20.5 (14–37; P < 0.001), respectively. Median (range) total Gilbert scores improved after prophylaxis [18 (3–39)] compared with on‐demand [25 (4–46)] therapy, predominantly reflecting the improved bleeding score. Median time from last prophylactic infusion to bleed was 2 days; 82.5% of bleeds occurred 2–3 days after the last infusion. Median 48‐h and 72‐h FVIII trough levels measured during months 10 and 13 were consistently > 6 and > 4 IU dL^?1, respectively. Treatment was well tolerated, and no inhibitor formation was observed. Conclusion: Secondary prophylaxis with rFVIII‐FS significantly reduced the frequency of hemarthroses compared with on‐demand therapy in adult patients with severe hemophilia A.     

Effect of early intervention with almotriptan vs placebo on migraine-associated functional disability: results from the AEGIS Trial

OBJECTIVE: To investigate the effect of early acute migraine intervention with almotriptan vs placebo on functional disability and health-related quality of life (HRQoL) indicators. DESIGN/METHODS: In this multicenter, double-blind, parallel-group trial, adults with international classification of headache disorders-defined migraine, with or without aura, were randomized 1:1 to treat 3 consecutive headaches with either almotriptan 12.5 mg or placebo. Patients were instructed to take their study medication at the first sign of migraine headache pain of any intensity, within 1 hour of onset. Patients recorded level of functional disability (normal, disturbed, bed rest required, emergency room [ER]/hospitalization required) at baseline (pretreatment), 0.5, 1, 2, 4, and 24 hours posttreatment and at time of pain-free. Patients completed the Migraine Disability Assessment Scale (MIDAS) at randomization and completed the Migraine Quality-of-Life Questionnaire (MQoL) at 24 hours after each attack. RESULTS: Results are presented for 315 patients (160 almotriptan, 155 placebo) in the evaluable for efficacy population. At 2 hours posttreatment of Attack 1, 54.4%, 32.5%, 13.1%, and 0%, respectively, of almotriptan-treated patients reported normal function, disturbed function, bed rest required, and ER/hospitalization required compared with 38.1%, 45.2%, 16.1%, and 0.6%, respectively, of placebo-treated patients. The differences in level of functional disability between the 2 treatment groups were statistically significant at 2 hours (P = .007; Cochran-Mantel-Haenszel, stratified by center) and at 4 hours (P < .001). Resolution of pain was associated with a normal level of function; at 2 hours posttreatment, 91.7% of patients in the total population who achieved pain-free reported normal function compared with 44.8%, 8.0%, and 0% of patients with mild, moderate, and severe pain, respectively. The absence compared with the presence of photophobia, phonophobia, and nausea at 2 hours also was associated with less disability (P < .0001 for each symptom). Treatment with almotriptan compared with placebo resulted in consistently better 24-hour MQoL scores with significant results for all 3 migraine headache attacks in the social function and feelings/concern domains. A logistic regression model determined that pretreatment functional level (P = .0117), pretreatment pain intensity (P = .0089), and pretreatment MIDAS score (P = .0152) were significant covariates of the proportion of patients who achieved normal function at 2 hours posttreatment. CONCLUSIONS: Early treatment with almotriptan within 1 hour of migraine pain onset significantly reduced levels of functional disability at 2 and 4 hours posttreatment compared with placebo. Consistency in improvement of HRQoL indicators was observed across 3 headaches treated.     

Treatment of in-stent restenosis with sirolimus-eluting-stents: results from the prospective German Cypher stent registry

Aims  Drug-eluting stents have been reported to effectively reduce in-stent restenosis (ISR). However, the effectiveness and safety have yet been investigated only in small trials or case series. The aim of this prospective large scale registry was to show that treatment of ISR with sirolimus eluting stents (SES) is safe, effective and feasible in daily routine. Methods and results  The German Cypher registry prospectively enrolled 6,555 patients undergoing implantation with SES for various indications, including 1,533 patients treated for ISR. Follow-up data (median 6.6 months) of this cohort was available for 1,531 patients (99.8%). Of these patients 75.8% were male. Of these patients 36.5% (n = 552) presented with acute coronary syndromes. In total, 1,932 SES were used with successful implantation in 98.9%. MI during hospitalization was observed in 0.7% (n = 11) while in-hospital mortality was only 0.1% (n = 2). MACE-rate at follow-up was 13.8% (n = 211) including a mortality of 1.3% (n = 20) and MI in 1.9% (n = 29). Total revascularization procedures including CABG (1.7%) were necessary in 12.3% (n = 186). Target vessel revascularization (TVR) rate was 9.3% (n = 139) and thus similar to patients with de novo lesions (8.1%, P = 0.69). Ten patients (0.65%) suffered from subacute stent thrombosis Vs. 0.24% observed in patients with de novo lesions (P = 0.03). Conclusion  This large registry confirms that treatment of ISR with sirolimus-eluting-stents is effective and save with good clinical results at index procedure and follow-up. TVR was not different from de novo lesions.     

Treatment satisfaction with zolmitriptan nasal spray for migraine in a real life setting: results from phase two of the REALIZE study

In phase one of the REALIZE study, zolmitriptan nasal spray demonstrated a significant headache response from 10 min post–dose and total symptom relief from 30 min post–dose. The objective of phase two was to investigate patients' dosing patterns, satisfaction and preference following openlabel treatment with the nasal spray. Up to 3 attacks were treated. The ITT population consisted of 851 patients. The median time from onset of symptoms to treatment was 1 h 15 min (primary endpoint). Most patients reported being satisfied or very satisfied with zolmitriptan nasal spray (75.7%). Furthermore, the majority of patients would be willing to use zolmitriptan nasal spray in the future (59.8%) and preferred zolmitriptan nasal spray over previous therapies (57.8%). Zolmitriptan nasal spray was well tolerated. Most patients were satisfied with zolmitriptan nasal spray, were willing to continue using it and preferred it to previous therapies.     

Individualized vs. group exercise in improving quality of life and physical activity in patients with cardiac disease and low exercise capacity: results from the DOPPELHERZ trial

Purpose: Important goals of cardiac rehabilitation maintenance programs (CMP) are to increase leisure time physical activity (LTPA) and improve health-related quality of life (HRQoL). Elderly patients with cardiac disease and low exercise capacity are simultaneously the most severely affected and have the most to gain from exercise-based rehabilitation. Individualized combined exercise (ICE) may be an effective modality to achieve these goals. We compared six months of ICE to CMP in their effects on LTPA and HRQoL.

Methods: Sixty patients (70?±?9 years, 39% female) with cardiac disease and low exercise capacity (<6 MET) were randomly allocated to six months of once-weekly ICE or CMP. The patients in ICE performed moderate endurance and resistance exercise on machines, based on intensities from individual peak exercise testing. Patients in CMP performed weekly sessions of calisthenics, flexibility, coordination and relaxation activities. LTPA and HRQoL were assessed with accelerometry and questionnaires at baseline and six months.

Results: Sixty patients completed the trial. ICE increased vigorous PA (ICE: Δ?+?12 MET-min/d, CMP: Δ –5 MET-min/d, p?=?.02) and steps per day (ICE:?+1586 steps/d, CMP: –838 steps/d, p?p?Conclusions: ICE resulted in significant improvements in physical activity levels and health related quality of life in moderate to high-risk patients compared to CMP.

• Implications for rehabilitation

• Relatively low volumes and intensities of exercise may lead to substantial improvements in both physical activity levels and health-related quality of life

• Exercise modes in cardiac rehabilitation maintenance programs should not be limited to calisthenics and large group-based exercise

• Supplemental resistance exercise may improve health-related quality of life and increase physical activity levels in patients with low exercise capacity

• Moderate to high-risk elderly patients also benefit from individualized endurance-resistance exercise

     

Risk of venous thrombosis in patients with major illnesses: results from the MEGA study

Summary. Background: The risk of venous thrombosis associated with major illnesses is not well known, and neither is the risk associated with the combined effect of immobilization and thrombophilia. The aim of this study was to assess the effect on the development of venous thrombosis of several major illnesses in combination with immobilization, body mass index, and thrombophilia, to identify high‐risk groups that may provide a basis for personalized prevention.Methods: This study included 4311 consecutive patients with a first episode of venous thrombosis, and 5768 controls from a case–control study (MEGA study). We calculated odds ratios (ORs) for venous thrombosis for patients with a self‐reported history of major illnesses.Results: Venous thrombosis risk was increased for all investigated major illnesses: liver disease, OR 1.7 (95% confidence interval [CI] 1.0–2.9); kidney disease, OR 3.7 (95% CI 2.3–5.9); rheumatoid arthritis, OR 1.5 (95% CI 1.2–1.9); multiple sclerosis, OR 2.4 (95% CI 1.3–4.3); heart failure, OR 1.7 (95% CI 1.2–2.3); hemorrhagic stroke, OR 4.9 (95% CI 2.4–9.9); arterial thrombosis, OR 1.5 (95% CI 1.2–1.8); and the presence of any of the above major illnesses, OR 1.7 (95% CI 1.5–1.9). Combinations of major illnesses with immobilization and increased factor VIII (OR 79.9; 95% CI 33.2–192.2), increased FIX (OR 35.3; 95% CI 14.2–87.8), increased von Willebrand factor (OR 88.0; 95% CI 33.9–228.3), FV Leiden (OR 84.2; 95% CI 19.5–363.6), and blood group non‐O (OR 53.1; 95% CI 30.9–91.4) were associated with increased venous thrombosis risks.Conclusions: All of the major illnesses reported here were associated with an increased risk of venous thrombosis. These risks were most pronounced at the time of immobilization or in the presence of thrombophilia.     

Teaching evidence-based complementary and alternative medicine: 5. Interpreting the results of a study on therapy and applying them to a patient

Practicing evidence-based complementary and alternative medicine (CAM) requires that practitioners develop an ability to understand and appropriately apply the results of published studies addressing questions related to their clinical practice. This paper describes a process by which CAM practitioners can interpret the results of studies evaluating therapeutic interventions and then determine if they can apply these results to their patients. We describe a process for interpreting the results of a study on therapy that involves determining the estimate of the magnitude of the therapy's effect and determining the precision of this estimate. We then describe a process for determining whether the results of a study on therapy can be applied to a given patient that involves determining the extent to which patients in the study differ from the patient being treated and determining if the study addressed all outcomes of interest.