Teriparatide, currently only available in brand form in the United States, is a costly drug approved for the treatment of postmenopausal osteoporotic women who are at high risk of fracture. Because market exclusivity for brand teriparatide expired in August 2019 in the US, we sought to understand the potential health economic impact of the availability of generic or biosimilar (generic/biosimilar) teriparatide. We examined the cost-effectiveness of daily teriparatide for 2 years followed by weekly alendronate for 10 years (ie, sequential teriparatide/alendronate) compared with alendronate alone for 10 years in community-dwelling white osteoporotic women with prior vertebral fracture at ages 65, 70, 75, and 80. Using an updated version of previously validated Markov microsimulation models, we obtained incremental cost-effectiveness ratios (ICERs) (dollars [$] per quality-adjusted life year [QALY]) with a willingness-to-pay (WTP) of $150,000 per QALY from a societal perspective with a lifelong time horizon. In the base case, we estimated the annual cost of teriparatide to be $20,161, based on the assumption of 10% brand usage (at a cost of $27,618) and 90% generic/biosimilar usage (priced 30% lower than brand). The ICERs of sequential teriparatide/alendronate compared with alendronate alone were greater than $280,000 per QALY at all ages examined. In deterministic sensitivity analyses, results were sensitive to teriparatide's cost, with the cost of a generic/biosimilar product needing to be 65% to 85% lower than brand for sequential teriparatide/alendronate to be cost-effective. In probabilistic sensitivity analyses, under the assumption that the annual cost of teriparatide was $20,161, the probabilities of sequential teriparatide/alendronate being cost-effective were less than 4% at a WTP of $150,000 per QALY. In conclusion, among community-dwelling older osteoporotic women with prior vertebral fracture in the US, even with the potential availability of generic/biosimilar teriparatide, sequential teriparatide/alendronate would not be cost-effective unless the cost of generic/biosimilar teriparatide were heavily discounted with respect to the current brand cost. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Among hypothetical cohorts of older osteoporotic women without prior fragility fracture in Japan, we evaluated the cost-effectiveness of two treatment strategies using a simulation model. Annual intravenous zoledronic acid for 3 years was cost-saving compared with biannual subcutaneous denosumab for 3 years followed by weekly oral alendronate for 3 years.

Purpose

Osteoporosis constitutes a major medical and health economic burden to society worldwide. Injectable treatments for osteoporosis require less frequent administration than oral treatments and therefore have higher persistence and adherence with treatment, which could explain better efficacy for fracture prevention. Although annual intravenous zoledronic acid and biannual subcutaneous denosumab are available, it remains unclear which treatment strategy represents a better value from a health economic perspective. Accordingly, we examined the cost-effectiveness of zoledronic acid for 3 years compared with sequential denosumab/alendronate (i.e., denosumab for 3 years followed by oral weekly alendronate for 3 years, making the total treatment duration 6 years) among hypothetical cohorts of community-dwelling osteoporotic women without prior fragility fracture in Japan at ages 65, 70, 75, or 80 years.

Methods

Using a previously validated and updated Markov microsimulation model, we obtained incremental cost-effectiveness ratios (Japanese yen [¥] (or US dollars [$]) per quality-adjusted life-year [QALY]) from the public healthcare and long-term care payer's perspective over a lifetime horizon with a willingness-to-pay of ¥5 million (or $47,500) per QALY.

Results

In the base case, zoledronic acid was cost-saving (i.e., more effective and less expensive) compared with sequential denosumab/alendronate. In deterministic sensitivity analyses, results were sensitive to changes in the efficacy of zoledronic acid or the cumulative persistence rate with zoledronic acid or denosumab. In probabilistic sensitivity analyses, the probabilities of zoledronic acid being cost-effective were 98-100%.

Conclusions

Among older osteoporotic women without prior fragility fracture in Japan, zoledronic acid was cost-saving compared with sequential denosumab/alendronate.

Using a Markov microsimulation model among hypothetical cohorts of community-dwelling older osteoporotic Japanese women with prior vertebral fracture over a lifetime horizon, we found that daily subcutaneous teriparatide for 2 years followed by weekly oral alendronate for 8 years was not cost-effective compared with alendronate monotherapy for 10 years.

Purpose

Teriparatide has proven efficacy in reducing osteoporotic fractures, but with substantial cost. We examined the cost-effectiveness of sequential teriparatide/alendronate (i.e., daily subcutaneous teriparatide for 2 years followed by weekly oral alendronate for 8 years) compared with alendronate monotherapy for 10 years among community-dwelling older osteoporotic women with prior clinical or morphometric vertebral fracture in Japan.

Methods

Using a previously validated and updated Markov microsimulation model, we obtained incremental cost-effectiveness ratios (Japanese yen [¥] (or US dollars [$]) per quality-adjusted life year [QALY]) from the perspective of a single payer responsible for both public healthcare and long-term care. We assumed a lifetime horizon with a willingness-to-pay of ¥5million (or $47,500) per QALY in the base case. We modeled the cost of biosimilar teriparatide, which has been available since November 2019 in Japan, assuming the efficacy was the same as that of the brand version.

Results

In the base case, sequential teriparatide/alendronate was not cost-effective compared with alendronate monotherapy. In deterministic sensitivity analyses, sequential teriparatide/alendronate would become cost-effective with 85%, 50%, and 15% price discounts to teriparatide at ages 70, 75, and 80, respectively, compared to the current biosimilar cost. Otherwise, results were especially sensitive to changes that affected efficacy of teriparatide or alendronate. In probabilistic sensitivity analyses, the probabilities of sequential teriparatide/alendronate being cost-effective were 0%, 1%, and 37% at ages 70, 75, and 80, respectively.

Conclusions

Among high-risk osteoporotic women in Japan, sequential teriparatide/alendronate was not cost-effective compared with alendronate monotherapy, even with the availability of biosimilar teriparatide.

Polymodal thermo- and mechanosensitive two-pore domain potassium (K_2P) channels of the TREK subfamily generate 'leak' currents that regulate neuronal excitability, respond to lipids, temperature and mechanical stretch, and influence pain, temperature perception and anaesthetic responses. These dimeric voltage-gated ion channel (VGIC) superfamily members have a unique topology comprising two pore-forming regions per subunit. In contrast to other potassium channels, K_2P channels use a selectivity filter 'C-type' gate as the principal gating site. Despite recent advances, poor pharmacological profiles of K_2P channels limit mechanistic and biological studies. Here we describe a class of small-molecule TREK activators that directly stimulate the C-type gate by acting as molecular wedges that restrict interdomain interface movement behind the selectivity filter. Structures of K_2P2.1 (also known as TREK-1) alone and with two selective K_2P2.1 (TREK-1) and K_2P10.1 (TREK-2) activators-an N-aryl-sulfonamide, ML335, and a thiophene-carboxamide, ML402-define a cryptic binding pocket unlike other ion channel small-molecule binding sites and, together with functional studies, identify a cation-π interaction that controls selectivity. Together, our data reveal a druggable K_2P site that stabilizes the C-type gate 'leak mode' and provide direct evidence for K_2P selectivity filter gating.

Strepotocuccus suis (S. suis) infection is known to be caused by the exposure to contaminated animals, specifically pigs and wild boars. This pathogen can cause bacterial meningitis, and one report indicated that it is the most common pathogen causing bacterial meningitis in Vietnam (Mai et al., 2008). A 67-year-old man was diagnosed with S. suis bacteremia and meningitis. In general, identification of this pathogen using standard biochemical methods takes time. We successfully diagnosed S. suis bacteremia in this patient, however, using the relatively new technology called Matrix-Assisted Laser Desorption/Ionization Time-of-Flight mass spectrometry (MALDI-TOF MS). Knowledge of the characteristics of S. suis and this newer technology led to the definitive diagnosis and prompt management of this patient. Herein, we highlight the use of a new technology in the context of sound microbiological knowledge in caring for patients.

Our objective was to examine the associations of lifetime parity and accumulated length of lactation with bone strength in women prior to the menopause transition and fracture risk during and after the transition. Participants were 2239 pre- or early peri-menopausal women from the Study of Women's Health Across the Nation (SWAN), ages 42-53 years at baseline, who had no childbirths after age 42. Bone mineral density (BMD) was measured in the femoral neck and the lumbar spine at the baseline SWAN visit using dual-energy x-ray absorptiometry, and the composite indices of femoral neck strength relative to load (in three failure modes: compression, bending, and impact) were calculated from femoral neck BMD, femoral neck size, and body size. Data on fractures after age 42 were collected for a median follow-up of 15.7 years (interquartile range, 11.4-18.5 years). In multiple linear regressions adjusted for covariates, lifetime parity was associated positively with femoral neck strength relative to load (0.024 standard deviation (SD) increment in impact strength index per childbirth, p=0.049), but accumulated length of lactation was associated negatively with lumbar spine BMD (0.018 SD decrement per every additional 6 months of lactation, p=0.040). In Cox proportional hazards regressions adjusted for covariates, neither parity nor lactation was associated with fracture hazard after age 42. In conclusion, parity and lactation have little impact on peak bone strength prior to menopause, and do not affect fracture risk after age 42 over 16-year follow-up.

Objectives

To determine whether a program that improves the quality of care for falls reduces the number of episodes of care for serious fall-related injuries.

Design

Nonrandomized controlled trial.

Setting

Four community-based primary care practices.

Participants

Individuals aged 75 and older who screened positive for fall risk.

Intervention

A multicomponent quality improvement program (Assessing Care of Vulnerable Elders Practice Redesign for Improved Medical Care for Elders) involving face-to-face clinician education about falls and decision support to prompt primary care providers to implement appropriate care, including referral to appropriate community resources, in response to individuals screening positive for fall risk.

Measurements

Episodes of care for selected fall-related injuries, based on healthcare claims.

Results

Of 1,791 individuals with data available for analysis, 1,187 were in the intervention group, and 604 were in the control group. Mean age was 83, and more than two-thirds of the sample were women. After adjusting for potential confounders, there were no statistically significant differences between intervention and control groups in episodes of care for fall-related injuries during the 12-month (incidence rate ratio (IRR) 1.27, 95% confidence interval (CI) = 0.93-1.73) or 24-month (IRR 1.18, 95% CI = 0.93-1.49) period after initiation of the intervention.

Conclusion

Despite improving the care of falls, this quality improvement initiative did not result in a change in the number of episodes of care for serious fall-related injuries. Future work in community-based settings should test higher-intensity interventions to reduce fall-related injuries.