BackgroundCurrent treatment of vulvovaginal candidiasis (VVC) is largely limited to azole therapy. Ibrexafungerp is a first-in-class triterpenoid antifungal with broad-spectrum anti-Candida fungicidal activity. The objective of this study was to evaluate the efficacy and safety of ibrexafungerp compared with placebo in patients with acute VVC.MethodsPatients were randomly assigned 2:1 to receive ibrexafungerp (300 mg twice for 1 day) or placebo. The primary endpoint was the percentage of patients with a clinical cure (complete resolution of vulvovaginal signs and symptoms [VSS] = 0) at test-of-cure (day 11 ± 3). Secondary endpoints included the percentage of patients with mycological eradication, overall success (clinical cure and mycological eradication), clinical improvement (VSS ≤ 1) at test-of-cure, and symptom resolution at follow-up (day 25 ± 4).ResultsPatients receiving ibrexafungerp had significantly higher rates of clinical cure (50.5% [95/188] vs 28.6% [28/98]; P = .001), mycological eradication (49.5% [93/188] vs 19.4% [19/98]; P < .001), and overall success (36.0% [64/178] vs 12.6% [12/95]; P < .001) compared with placebo. Symptom resolution was sustained and further increased with ibrexafungerp compared with placebo (59.6% [112/188] vs 44.9% [44/98]; P = .009) at follow-up. Post hoc analysis showed similar rates of clinical cure and clinical improvement at test-of-cure for Black patients (54.8% [40/73] and 63.4% [47/73], respectively) and patients with a body mass index >35 (54.5% [24/44] and 68.2% [30/44], respectively) compared with overall rates. Ibrexafungerp was well tolerated. Adverse events were primarily gastrointestinal and mild in severity.ConclusionsIbrexafungerp provides a promising safe and efficacious oral treatment that mechanistically differs from current azole treatment options for acute VVC.

This study aims to evaluate patient perceptions of subcutaneous denosumab or oral alendronate in postmenopausal women with or at risk for osteoporosis and how these perceptions influence adherence. Postmenopausal women with low bone mass were randomized to denosumab 60 mg every 6 months for 1 year (treatment period 1 [TP1]) followed by alendronate 70 mg once weekly for 1 year (treatment period 2 [TP2]), or vice versa. Beliefs about Medicines Questionnaire data were collected at baseline and at 6, 12, 18, and 24 months; a necessity-concerns differential (NCD) was calculated for each time point. Logistic regression analyses were performed to evaluate the influences of baseline characteristics on nonadherence. Participants included 250 women (alendronate/denosumab, n = 124; denosumab/alendronate, n = 126). During TP1, the NCD at month 6 was higher with denosumab than with alendronate (P = 0.0076). In TP2, the NCD was higher for women switched to denosumab than for women switched to alendronate at 6 months (P = 0.0126) and 12 months (P = 0.4605). Denosumab was preferred to alendronate regardless of treatment sequence (P < 0.0001). Covariate analysis revealed that higher TP2 baseline necessity scores were associated with lower odds of nonadherence (P = 0.0055), whereas higher concerns about medication scores were associated with higher odds of nonadherence (P = 0.0247). Higher NCD scores were also associated with lower odds of nonadherence (P = 0.0015). Participants preferred denosumab to alendronate while on treatment and had more positive perceptions of denosumab than alendronate. These perceptions were associated with better adherence.

To compare the efficacy and safety of denosumab to ibandronate in postmenopausal women with low bone mineral density (BMD) previously treated with a bisphosphonate. In a randomized, open-label study, postmenopausal women received 60 mg denosumab subcutaneously every 6 months (n=417) or 150 mg ibandronate orally every month (n=416) for 12 months. End points included percentage change from baseline in total hip, femoral neck, and lumbar spine BMD at month 12 and percentage change from baseline in serum C-telopeptide at months 1 and 6 in a substudy. At month 12, significantly greater BMD gains from baseline were observed with denosumab compared with ibandronate at the total hip (2.3% compared with 1.1%), femoral neck (1.7% compared with 0.7%), and lumbar spine (4.1% compared with 2.0%; treatment difference P<.001 at all sites). At month 1, median change in serum C-telopeptide from baseline was -81.1% with denosumab and -35.0% with ibandronate (P<.001); the treatment difference remained significant at month 6 (P<.001). Adverse events occurred in 245 (59.6%) denosumab-treated women and 230 (56.1%) ibandronate-treated women (P=.635). The incidence of serious adverse events was 9.5% for denosumab-treated women and 5.4% for ibandronate-treated women (P=.046). No clustering of events in any organ system accounted for the preponderance of these reports. The incidence rates of serious adverse events involving infection and malignancy were similar between treatment groups. In postmenopausal women previously treated with a bisphosphonate and low BMD, denosumab treatment resulted in greater BMD increases than ibandronate at all measured sites. No new safety risks with denosumab treatment were identified.

The aim of this study was to report the effects of denosumab on radius cortical and trabecular bone density, mass, and strength, and wrist fracture incidence in the FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months) study. In the FREEDOM study, postmenopausal women with osteoporosis (N = 7,808) received placebo or 60 mg of denosumab every 6 months for 36 months. Radius bone mineral density (BMD), bone mineral content, and strength (polar moment of inertia) were evaluated in two prespecified substudies using dual-energy x-ray absorptiometry (placebo, n = 209; denosumab, n = 232) or quantitative CT (placebo, n = 48; denosumab, n = 62). Prespecified analysis assessed wrist fracture incidence in all FREEDOM participants (placebo, N = 3,906; denosumab, N = 3,902), and post hoc subgroup analyses evaluated those with higher fracture risk (baseline femoral neck T-score ≤-2.5; placebo, N = 1,406; denosumab, N = 1,384). Denosumab significantly increased areal BMD (assessed by dual-energy x-ray absorptiometry) and volumetric BMD, bone mineral content, and polar moment of inertia (assessed by quantitative CT), compared with placebo, in radius cortical and trabecular bone at all time points evaluated (all P < 0.05). Wrist fracture incidence was 2.9% for placebo and 2.5% for denosumab (relative risk reduction, 16%; P = 0.21) on month 36. Participants with a femoral neck T-score of -2.5 or lower were at increased risk for wrist fracture, and denosumab significantly reduced wrist fracture incidence compared with placebo (placebo, 4.0%; denosumab, 2.4%; relative risk reduction, 40%; absolute risk reduction, 1.6%; P = 0.03). Denosumab significantly improves radius bone density, mass, and strength compared with placebo. In higher-risk women, denosumab significantly reduces wrist fracture risk.

Denosumab is an approved therapy for postmenopausal women with osteoporosis at high or increased risk for fracture. In the FREEDOM study, denosumab reduced fracture risk and increased bone mineral density (BMD). We report the spine and hip dual-energy X-ray absorptiometry (DXA) BMD responses from the overall study of 7808 women and from a substudy of 441 participants in which more extensive spine and hip assessments as well as additional skeletal sites were evaluated. Significant BMD improvements were observed as early as 1mo at the lumbar spine, total hip, and trochanter (all p<0.005 vs placebo and baseline). BMD increased progressively at the lumbar spine, total hip, femoral neck, trochanter, 1/3 radius, and total body from baseline to months 12, 24, and 36 (all p<0.005 vs placebo and baseline). BMD gains above the least significant change of more than 3% at 36 months were observed in 90% of denosumab-treated subjects at the lumbar spine and 74% at the total hip, and gains more than 6% occurred in 77% and 38%, respectively. In conclusion, denosumab treatment resulted in significant, early, and continued BMD increases at both trabecular and cortical sites throughout the skeleton over 36mo with important gains observed in most subjects.

We investigated the association between religiosity, spirituality, and anxiety in pregnant women, taking into account potential confounders. From September 2005 through March 2006, pregnant women in three obstetrics practices in the American South were included in a cross-sectional study. The anxiety subscale of the Hospital Anxiety and Depression Scale (HADS) was used to measure anxiety. Of the 344 participating women, 23 screened positive for moderate to severe anxiety (HADS [anxiety] score greater than 10). Overall religiosity or spirituality (odds ratio [OR], 0.53; p=0.006) and social support (OR, 0.42; p<0.0001) were significantly associated with significantly lower odds of a positive anxiety screen. Among the specific measures of religiosity or spirituality, self-rated religiosity, self-rated spirituality, and participation in nonorganizational religious activities were significantly associated with lower odds of moderate to severe anxiety symptoms. Religiosity and spirituality are associated with reduced anxiety in pregnant women. Additional study is needed to evaluate whether the association is causal.

Depression during pregnancy has potential repercussions for both women and infants. Religious and spiritual characteristics may be associated with fewer depressive symptoms. This study examines the association between religiosity/spirituality and depressive symptoms in pregnant women. Pregnant women in three southern obstetrics practices were included in a cross sectional study evaluating religiosity, spirituality, and depressive symptoms. Symptoms of depression were measured using the Edinburgh Postnatal Depression Scale (EPDS). The depression outcome was measured in two ways: the EPDS score as a continuous outcome, and a score at or above the recommended EPDS cutoff (> 14). A wide array of potential confounders was addressed. Special attention was given to the interplay between religiosity/spirituality, social support, and depressive symptoms. The mean EPDS score was 9.8 out of a maximum possible score of 30. Twenty-eight women (8.1%) scored above the recommended EPDS cutoff score. Overall religiosity/spirituality was significantly associated with fewer depressive symptoms when controlling for significant covariates, but there was a significant interaction such that the association became weaker as social support increased. Social support did not appear to be an important mediator (intermediate step) in the pathway between religiosity/spirituality and depressive symptoms. Religiosity and spirituality may help protect from depressive symptoms when social support is lacking. Longitudinal research is needed to assess the directionality of the observed relationships.

Despite the availability of drugs that lower the risk of bone fracture in osteoporotic patients, few patients comply fully with current treatments. The investigators evaluated denosumab-previously known as AMG 162-a fully human monoclonal antibody (immunoglobulin G 2 ) that binds strongly and specifically to RANKL or receptor activator of nuclear factor-KB ligand. RANKL is a protein expressed by osteoblastic stromal cells and is the major mediator of osteoclast differentiation, activation, and survival. RANKL underlies osteoclast-mediated bone resorption. Denosumab acts by blocking the interaction of RANKL with RANK and mimics the effects of osteoprotegerin. This randomized, placebo-controlled study examined the effects of subcutaneously administered denosumab over 12 months in 412 postmenopausal women aged up to 80 years with low bone mineral density (BMD) defined as a T score of -1.8 to -4.0 at the lumbar spine or -1.8 to -3.5 at the proximal femur. Participants were assigned to receive denosumab either every 3 months in a dose of 6, 14, or 30 mg or every 6 months in a dose of 14, 60, 100, or 120 mg; alendronate orally in a dose of 70 mg once a week (on an open-label basis); or placebo. The primary end point was the percentage change in BMD at the lumbar spine after 12 months. A total of 369 women, 90% of the original sample, completed 12 months of treatment. BMD at the lumbar spine increased from 3.0% to 6.7% at 12 months in women given denosumab compared with a decrease of 0.8% in placebo recipients (P <.001). Total hip BMD increased by a mean of 1.9% to 3.6% with denosumab treatment and fell 0.6% in placebo patients (P <.001). BMD also increased in the distal radius in women given denosumab. Alendronate increased BMD compared with placebo at 12 months. Serum levels of C-telopeptide, a marker of bone turnover, decreased in women given denosumab compared with placebo patients. Alendronate also lowered markers of bone turnover. A small reduction in the albumin-adjusted serum calcium level was noted in the denosumab group, and concentrations of intact parathyroid hormone increased. Side effects were similar in all groups except for dyspepsia, which was significantly more frequent in women given alendronate. Denosumab deserves further study as a possible treatment for osteoporosis in postmenopausal women.

Receptor activator of nuclear factor-kappaB ligand (RANKL) is essential for osteoclast differentiation, activation, and survival. The fully human monoclonal antibody denosumab (formerly known as AMG 162) binds RANKL with high affinity and specificity and inhibits RANKL action. The efficacy and safety of subcutaneously administered denosumab were evaluated over a period of 12 months in 412 postmenopausal women with low bone mineral density (T score of -1.8 to -4.0 at the lumbar spine or -1.8 to -3.5 at the proximal femur). Subjects were randomly assigned to receive denosumab either every three months (at a dose of 6, 14, or 30 mg) or every six months (at a dose of 14, 60, 100, or 210 mg), open-label oral alendronate once weekly (at a dose of 70 mg), or placebo. The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months. Changes in bone turnover were assessed by measurement of serum and urine telopeptides and bone-specific alkaline phosphatase. Denosumab treatment for 12 months resulted in an increase in bone mineral density at the lumbar spine of 3.0 to 6.7 percent (as compared with an increase of 4.6 percent with alendronate and a loss of 0.8 percent with placebo), at the total hip of 1.9 to 3.6 percent (as compared with an increase of 2.1 percent with alendronate and a loss of 0.6 percent with placebo), and at the distal third of the radius of 0.4 to 1.3 percent (as compared with decreases of 0.5 percent with alendronate and 2.0 percent with placebo). Near-maximal reductions in mean levels of serum C-telopeptide from baseline were evident three days after the administration of denosumab. The duration of the suppression of bone turnover appeared to be dose-dependent. In postmenopausal women with low bone mass, denosumab increased bone mineral density and decreased bone resorption. These preliminary data suggest that denosumab might be an effective treatment for osteoporosis. (ClinicalTrials.gov number, NCT00043186.).