Correction to: Abaloparatide effect on forearm bone mineral density and wrist fracture risk in postmenopausal women with osteoporosis.

The original version of this article, published on 21 March 2019, unfortunately contains some typos in Figs. 2, 3, 4, and Supplemental Fig. 1. The corrected figures are given below.

Correction to: Abaloparatide effect on forearm bone mineral density and wrist fracture risk in postmenopausal women with osteoporosis.

The original version of this article, published on 21 March 2019, unfortunately contained a mistake.

Abaloparatide effect on forearm bone mineral density and wrist fracture risk in postmenopausal women with osteoporosis.

PURPOSE: Wrist fractures are common, contribute significantly to morbidity in women with postmenopausal osteoporosis, and occur predominantly at the ultradistal radius, a site rich in trabecular bone. This exploratory analysis of the phase 3 ACTIVE study evaluated effects of abaloparatide versus placebo and teriparatide on forearm bone mineral density (BMD) and risk of wrist fracture. METHODS: Forearm BMD was measured by dual energy X-ray absorptiometry in a subset of 982 women from ACTIVE, evenly distributed across the three treatment groups. Wrist fractures were ascertained in the total cohort (N = 2463). RESULTS: After 18 months, ultradistal radius BMD changes from baseline were 2.25 percentage points greater for abaloparatide compared with placebo (95% confidence interval (CI) 1.38, 3.12, p < 0.001) and 1.54 percentage points greater for abaloparatide compared with teriparatide (95% CI 0.64, 2.45, p < 0.001). At 18 months, 1/3 radius BMD losses (versus baseline) were similar for abaloparatide compared with placebo (-0.42; 95% CI -1.03, 0.20; p = 0.19) but losses with teriparatide exceeded those of placebo (-1.66%; 95% CI -2.27, -1.06; p < 0.001). The decline with abaloparatide was less than that seen with teriparatide (group difference 1.22%; 95% CI 0.57, 1.87; p < 0.001). The radius BMD findings, at both ultradistal and 1/3 sites, are consistent with the numerically lower incidence of wrist fractures observed in women treated with abaloparatide compared with teriparatide (HR = 0.43; 95% CI 0.18, 1.03; p = 0.052) and placebo (HR = 0.49, 95% CI 0.20, 1.19, p = 0.11). CONCLUSIONS: Compared with teriparatide, abaloparatide increased BMD at the ultradistal radius (primarily trabecular bone) and decreased BMD to a lesser extent at the 1/3 radius (primarily cortical bone), likely contributing to the numerically lower wrist fracture incidence observed with abaloparatide.

Bone mineral density response rates are greater in patients treated with abaloparatide compared with those treated with placebo or teriparatide: Results from the ACTIVE phase 3 trial.

BACKGROUND: Abaloparatide is a 34-amino acid peptide that selectively binds to the RG conformation of the parathyroid hormone receptor type 1. It was developed for the treatment of women with postmenopausal osteoporosis at high risk of fracture. In ACTIVE, an 18-month phase 3 study (NCT01343004), abaloparatide increased bone mineral density (BMD), decreased the risk of vertebral and nonvertebral fractures compared with placebo, and decreased the risk of major osteoporotic fractures compared with placebo and teriparatide. Here, we report a prospective, exploratory BMD responder analysis from ACTIVE. METHODS: Proportions of patients experiencing BMD gains from baseline of >0%, >3%, and >6% at the total hip, femoral neck, and lumbar spine at 6, 12, and 18 months of treatment were compared among the placebo, abaloparatide, and teriparatide groups in ACTIVE. Responders were defined prospectively as patients experiencing BMD gains at all 3 anatomic sites. RESULTS: At months 6, 12, and 18, there were significantly more >3% BMD responders in the abaloparatide group compared with placebo and teriparatide: month 6, 19.1% vs 0.9% for placebo and 6.5% for teriparatide; month 12, 33.2% vs 1.5% and 19.8%; month 18, 44.5% vs 1.9% and 32.0% (P < 0.001 for all comparisons of abaloparatide to placebo and to teriparatide). Findings were similar for the >0% and >6% responder thresholds. CONCLUSIONS: In postmenopausal women with osteoporosis, a significantly greater proportion of patients treated with abaloparatide experienced increases in BMD than did those treated with placebo or teriparatide.

Physical activity and motivational predictors of changes in health behavior and health among DM2 and CAD patients.

This study tested a physical activity intervention and the self-determination theory (SDT) process model of health-behavior change and health among 108 adult patients with both diabetes mellitus type 2 (DM2) and coronary artery disease (CAD). Patients were randomly assigned to an organized physical activity intervention group (led by instructors) or a non-physical activity control group. At baseline and after 12 months, we measured the following: needs satisfaction, autonomous and controlled motivation for physical activity, perceived competence for physical activity and blood sugar testing, physical activity and blood sugar testing, body weight, glucose control (HbA1c), and self-perceptions of general health and vitality. The intervention produced, as hypothesized, significant changes in all study variables in favor of the experimental group (Cohen's d effect sizes: 0.23-0.72), except the non-significant result for controlled motivation and body weight. The data supported the SDT process model, in which the effect of the intervention significantly predicted indirect changes in behavior and health through motivation variables. Considering the moderate to large effects on increases in motivation, behavior, and health, promoting organized physical activity programs that are perceived as need-supportive may have important health implications for patients with DM2 and CAD.

Molecular targeting of drug delivery systems to ovarian cancer by BH3 and LHRH peptides.

Novel targeted proapoptotic anticancer drug delivery systems were developed and evaluated. Poly(ethyleneglycol) (PEG) conjugates were used as carriers. Camptothecin (CPT) was used as an anticancer agent-apoptosis inductor. Two types of molecular targets were investigated: (1) an extracellular membrane receptor specific to ovarian cancer and (2) intracellular controlling mechanisms of apoptosis. Synthetic peptides similar to luteinizing hormone-releasing hormone (LHRH) and BCL-2 homology 3 (BH3) peptide were used as a targeting moiety and a suppressor of cellular antiapoptotic defense, respectively. Three different conjugates (CPT-PEG, CPT-PEG-BH3 and CPT-PEG-LHRH) were synthesized and examined in A2780 human ovarian cancer cells. Cytotoxicity, expression of genes encoding BCL-2, BCL-XL, SMAC, APAF-1 proteins and caspases 3 and 9, the activity of caspases 3 and 9 and apoptosis induction were studied. Taken together the results indicate much higher cytotoxicity and apoptosis-inducing activity of PEG-CPT conjugates when compared to free CPT. Moreover, the effects of targeted CPT-PEG-BH3 and CPT-PEG-LHRH conjugates were more pronounced than the non-targeted PEG-CPT conjugate. The results confirmed the feasibility of this new two-tier molecular targeting strategy for enhancing the efficacy of cancer chemotherapy.

Detection of red reflex asymmetry by pediatric residents using the Brückner reflex versus the MTI photoscreener.

OBJECTIVE: To compare the ability of pediatric residents to differentiate an asymmetric from a symmetric red reflex in patients with anisometropia and microstrabismus using the Brückner reflex and the Medical Technology Innovations (MTI) photoscreener. METHODS: A prospective, masked, case-control study was performed. Twelve pediatric residents evaluated 10 study patients and 6 control subjects in a masked manner in 2 separate sessions, using the Brückner reflex or the MTI photoscreener, evaluating for asymmetric (abnormal) or symmetric (normal) red reflexes between the 2 eyes. Each study patient had asymmetric red reflexes and the amblyogenic risk factor of anisometropia or microstrabismus. Each control subject had symmetric red reflexes. RESULTS: The pediatric residents had a mean correct score of 82% (69%-100%) using the MTI photoscreener versus a mean correct score of 65% (44%-81%) using the Brückner reflex (McNemar test: alpha < 0.01). The sensitivity of the MTI photoscreener evaluation was 89% in comparison to 61% for the Brückner reflex. The specificities for the MTI photoscreener versus the Brückner reflex were similar at 69% and 71%, respectively. CONCLUSIONS: Pediatric residents were better at detecting asymmetric red reflexes in patients with anisometropia and microstrabismus when evaluating MTI photoscreener photographs than when evaluating the red reflexes by the Brückner reflex. The MTI photoscreener may be a more sensitive method than the Brückner reflex to screen for the common amblyogenic risk factors of anisometropia and microstrabismus by easier detection of red reflex asymmetry.

Activating patients for smoking cessation through physician autonomy support.

OBJECTIVE: Test whether physicians' counseling patients for smoking cessation with an autonomy supportive rather than controlling style would increase patients' active involvement in the counseling session and increase maintained abstinence. DESIGN: Randomized trial of 27 community-based physicians using two interview styles, with observer ratings of patient active involvement and assessments of patient smoking status at 6 months, 12 months, and 30 months. PATIENTS: Adult smokers: 336 recruited; 249 for final analyses. INTERVENTION: Physicians used an autonomy- supportive or controlling interpersonal style, randomly assigned within physician, to briefly counsel patients about smoking cessation, using the National Cancer Institute's 4-A's model. MEASUREMENT: Patient active involvement was rated from audio tapes of the interviews. Continuous abstinence came from self-reports at 6 months, 12 months, and 30 months, CO validated at 6 months or 12 months and at 30 months. RESULTS: Physician style did not have a significant direct effect on smoking cessation but did significantly increase patient active involvement in the interview. Active involvement, in turn, increased smoking cessation. Structural equation modeling confirmed a theoretical model in which the intervention positively predicted patient active involvement after controlling for patient reports of wanting to stop smoking, and active involvement significantly predicted continuous abstinence after controlling for previous quit attempts. CONCLUSIONS: Although physicians' autonomy- supportive style while counseling smokers to quit did not have a direct effect on smoking cessation, it increased patients' active involvement in the counseling session which in turn increased continuous abstinence over 30 months. Further research should clarify the direct effects of physician interpersonal style on health outcomes.

Milolides, new briarane diterpenoids from the western Pacific octocoral Briareum stechei.

Eleven new briarane-type diterpene lactones, designated milolides (1--8, 10--12), together with four known diterpene lactones (9, 13--15), were isolated from the Micronesian octocoral Briareum stechei collected at Yap, Federated States of Micronesia. One aspect of the stereochemistry of one of the known compounds, solenolide C (9), is revised. Structures of the new compounds were determined from spectral data.

The effect of nisin on the keeping quality of reduced heat-treated milks.

Milk was subjected to a combination process involving reduced heat treatment (RHT) of 117 degrees C for 2 s and nisin (75 and 150 IU ml(-1)). The microbial activity and other quality aspects were compared with a RHT control (without nisin) and with a ultrahigh temperature (UHT) milk processed at 142 degrees C for 2 s. Nisin was found to inhibit microbial growth for products stored without refrigeration, and RHT-nisin samples stored at 30 degrees C showed very low spoilage rates during 150 days, although not low enough to satisfy requirements for commercial sterility. RHT-nisin samples could be distinguished from and were preferred to the UHT control. Significant browning occurred during storage at 30 degrees C and above but was less in the RHT-nisin milk samples compared with the UHT milk. In RHT-nisin milk samples stored at 20 and 10 degrees C, no microbial activity could be detected in most samples after storage for 1 year. The effectiveness of this combination of RHT, nisin, and low storage temperatures against gram-positive spore-forming bacteria suggests potential for use of nisin in extended shelf life products.

Incidence of brimonidine allergy in patients previously allergic to apraclonidine.

PURPOSE: This study was performed to determine the incidence of allergic reaction to brimonidine in patients who have previously demonstrated an allergic reaction to apraclonidine. METHODS: A retrospective chart review was performed to identify patients who had demonstrated an allergic reaction to apraclonidine of sufficient severity to result in drug discontinuation. Within this group, those patients subsequently treated with brimonidine were isolated and analyzed, and the incidence of allergy to brimonidine was determined. RESULTS: Forty-five patients were identified with a significant allergic reaction to apraclonidine that resulted in drug discontinuation. Of these patients, 22 subsequently received brimonidine. Follow-up on all patients was obtained for at least 15 months. All but two of the 22 patients were taking additional topical glaucoma medications, ranging from one to three additional agents with an average of 1.8+/-0.8 medications. Seventeen patients incurred no allergic reaction to brimonidine. Only five patients (22.7%) previously allergic to apraclonidine developed an allergic reaction to brimonidine. Three of these patients demonstrated only a follicular conjunctival reaction, one had conjunctival hyperemia, and one patient developed a periocular dermatitis. The allergic reactions developed at 8.2+/-1.2 months after initiation of brimonidine therapy. CONCLUSIONS: In this study, the risk of developing an allergic reaction to brimonidine in patients known to be allergic to apraclonidine is 22.7%. This lack of a strong cross-reactive allergic response possibly suggests different allergic mechanisms for these two medications. Therefore, brimonidine therapy in patients previously identified as being allergic to apraclonidine is safe and does not result in a cross-reactive response in the great majority of patients (or in nearly four of five patients).

Eye height scaling of absolute size in immersive and nonimmersive displays.

Eye-height (EH) scaling of absolute height was investigated in three experiments. In Experiment 1, standing observers viewed cubes in an immersive virtual environment. Observers' center of projection was placed at actual EH and at 0.7 times actual EH. Observers' size judgments revealed that the EH manipulation was 76.8% effective. In Experiment 2, seated observers viewed the same cubes on an interactive desktop display; however, no effect of EH was found in response to the simulated EH manipulation. Experiment 3 tested standing observers in the immersive environment with the field of view reduced to match that of the desktop. Comparable to Experiment 1, the effect of EH was 77%. These results suggest that EH scaling is not generally used when people view an interactive desktop display because the altitude of the center of projection is indeterminate. EH scaling is spontaneously evoked, however, in immersive environments.

Why do physicians vary so widely in their referral rates?

OBJECTIVE: To determine which physician practice and psychological factors contribute to observed variation in primary care physicians' referral rates. DESIGN: Cross-sectional questionnaire-based survey and analysis of claims database. SETTING: A large managed care organization in the Rochester, NY, metropolitan area. PARTICIPANTS: Internists and family physicians. MEASUREMENTS AND MAIN RESULTS: Patient referral status (referred or not) was derived from the 1995 claims database of the managed care organization. The claims data were also used to generate a predicted risk of referral based on patient age, gender, and case mix. A physician survey completed by a sample of 182 of the physicians (66% of those eligible) included items on their practice and validated psychological scales on anxiety from uncertainty, risk aversiveness, fear of malpractice, satisfaction with practice, autonomous and controlled motivation for referrals and test ordering, and psycho-social beliefs. The relation between the risk of referral and the physician practice and psychological factors was examined using logistic regression. After adjustment for predicted risk of referral (case mix), patients were more likely to be referred if their physician was female, had more years in practice, was an internist, and used a narrower range of diagnoses (a higher Herfindahl index, also derived from the claims data). Of the psychological factors, only greater psychosocial orientation and malpractice fear was associated with greater likelihood of referral. When the physician practice factors were excluded from the analysis, risk aversion was positively associated with referral likelihood. CONCLUSIONS: Most of the explainable variation in referral likelihood was accounted for by patient and physician practice factors like case mix, physician gender, years in practice, specialty, and the Herfindahl index. Relatively little variation was explained by any of the examined physician psychological factors.

T-cell lymphoproliferative disorder of vitreous associated with mycosis fungoides.

59-year-old man with a history of mycosis fungoides developed loss of visual acuity and visual field in the left eye. Epiretinal lesions were present in the right eye and multifocal choroidal lesions, optic disc edema, and vitritis were present in the left eye. A diagnostic vitrectomy was performed and cytologic examination of the vitreous confirmed the diagnosis of T-cell lymphoproliferative disorder. Systemic and intrathecal chemotherapy resulted in marked improvement in ocular signs and symptoms. At last follow-up, the patient was found to have improved visual acuity in the left eye; however, significant worsening of his systemic condition developed and he died shortly thereafter.

The nutrient-toxin dosage continuum in human evolution and modern health.

Recent findings support the long-recognized principle that nutritive and toxic effects of an ingested material depend not only on its nature but very much on its quantity. The well known observation that essential nutrients can be toxic at high dosages suggests that the same reversal of effect may be true of many substances that could be beneficial but not essential at low dosages (the phenomenon of hormesis). This has been demonstrated for many well known toxins. We suggest a mathematical model that describes these dosage effects as an expected result of the evolution of human metabolic and dietary adaptations for maximizing benefits and minimizing costs of the ingestion or other intake of any substance. Evolved mechanisms for achieving benefits may be unrelated to those for reducing costs. These evolutionary considerations suggest important consequences demonstrable by experimental or epidemiological studies. They also suggest ways in which our evolved dietary adaptations may be currently maladaptive, and individual development of taste preferences poorly calibrated by early experience in modern environments. The apparent reality of hormesis raises the possibility of counterproductive effects of current dosage recommendations and limits for nutrients and pollutants. We propose that some conceptual and factual problems are urgently in need of resolution. Fundamental to evolutionary biology is the tendency for organisms to become increasingly adapted to those environments to which they are most commonly exposed (Parsons 1990).

Presenting the facts about smoking to adolescents: effects of an autonomy-supportive style.

OBJECTIVES: To test the self-determination model of health-related behavior by examining whether the degree to which adolescents experience an appeal to not smoke as autonomy supportive would affect their autonomous motivation for not smoking and, in turn, their behavior of either refraining from smoking or smoking less, and to validate the measures of perceived autonomy support and autonomous motivation for not smoking. DESIGN: Two studies of physicians presenting information about not smoking using 2 message styles, 1 of which was designed to be more autonomy supportive. The preliminary study involved nonrandomized assignment to message style and only immediate assessment of perceptions, motivation, and behavior, while the primary study involved randomized assignment and 4-month longitudinal assessments. SETTING AND PARTICIPANTS: Nearly 400 ninth- through 12th-grade students at 2 suburban high schools in upstate New York. MAIN OUTCOME MEASURES: Adolescents' perceptions of the presentations' autonomy supportiveness of the presenters, as well as adolescents' autonomous motivation for not smoking and their self-reports of smoking. The primary study also assessed change in students' autonomous motivation and change in their self-reported smoking during 4 months. RESULTS: In both studies, the measures were reliable and valid. Students perceived significantly (P = .04 and P<.001, respectively) greater autonomy support in the "It's Your Choice" presentation, after controlling for whether the students were smokers. Perceived autonomy supportiveness of the presentation was positively correlated with autonomous reasons for not smoking in the preliminary study and with increases in autonomous motivation for not smoking in the primary study. Change in autonomous reasons for not smoking significantly (P<.001) predicted reduction in smoking during 4 months. CONCLUSION: When adolescents perceived messages about not smoking as autonomy supportive, they had more autonomous motivation for not smoking, and that, in turn, predicted a decrease in their self-reports of smoking.

Effective use of nisin to control lactic acid bacterial spoilage in vacuum-packed bologna-type sausage.

Lactic acid bacteria (LAB) commonly cause spoilage in minimal heat-treated vacuum-packed cured delicatessen meats. Predominant species are Lactobacillus sake and L. curvatus. LAB strains isolated from spoiled products of this type (liver sausage, ham and bologna sausage) were found to be sensitive to low nisin concentrations (maximum of 1.25 microg g(-1)). Addition of 25 microg g(-1) nisin (as Nisaplin) inhibited the growth of LAB spoilage organisms inoculated into vacuum-packed pasteurized bologna-type sausages stored at 8 degrees C. Control sausages became spoiled (>10(8) LAB CFU g(-1)) by day 7, whereas sausages containing nisin remained unspoiled for >50 days. The effect of three types of phosphates (used as emulsifiers) on nisin activity in the sausages was compared. LAB growth rate was fastest in samples containing orthophosphate, and slowest in sausages containing diphosphate. The shelf life was also greatly extended in the latter. Fat content also affected nisin activity. Nisin activity (as indicated by LAB inhibition) was greatest in samples containing 15% > 25% > 37% (wt/wt) fat. In a sausage formulation containing 37% fat and incorporating diphosphate as emulsifier, levels of nisin as low as 2.5 microg g(-1) showed antibacterial effects. A nisin level of 6.25 microg g(-1) totally inhibited LAB growth for over 4 weeks and 25 microg g(-1) for 5 weeks. Spoilage control was achieved in the same sausage formulation but with 25% (wt/wt) fat; 12.5 microg g(-1) nisin prevented LAB growth for 5 weeks.

The importance of self-determination theory for medical education.

While some theories of human motivation focus exclusively on levels of motivation, self-determination theory argues that different types of motivators, even when the resulting motivation is high, will lead to very different outcomes. This theory differentiates between two primary kinds of motivation, controlled and autonomous. Controlled motivation depends either on explicit or implicit rewards or punishment or on people's internalized beliefs about what is expected of them. Learning in controlled situations, in which students act under pressure and anxiety, is likely to be rote, short-lived, and poorly integrated into students' long-term values and skills. In contrast, autonomous motivation, as its name implies, is personally endorsed and reflects what people find interesting and important. While controlled motivation involves compliance with pressures, autonomous motivation involves behaving with a sense of volition, agency, and choice. Autonomously motivated learning leads to better educational outcomes. There is evidence that medical students who learn in autonomy-supportive environments act in more autonomy-supportive ways in their interactions with patients. Because the reliable implementation of practice guidelines and physicians' use of an autonomy-supportive style have been associated with more positive health outcomes (particularly in the behavior-related areas of smoking cessation, weight loss, etc.), more autonomy-supportive medical education may result in more effective health care delivery.