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Objectives: The aim of these Clinical Practice Guidelines is to provide evidence-based recommendations to assist healthcare providers in the screening, diagnosis and management of patients with postmenopausal osteoporosis (OP)., Methods: A list of key clinical questions on the assessment, diagnosis and treatment of OP was formulated. A literature search using the PubMed, Medline, Cochrane Databases of Systematic Reviews, and OVID electronic databases identified all relevant articles on OP based on the key clinical questions, from 2014 onwards, to update from the 2015 edition. The articles were graded using the SIGN50 format. For each statement, studies with the highest level of evidence were used to frame the recommendation., Results: This article summarizes the diagnostic and treatment pathways for postmenopausal OP. Risk stratification of patients with OP encompasses clinical risk factors, bone mineral density measurements and FRAX risk estimates. Non-pharmacological measures including adequate calcium and vitamin D, regular exercise and falls prevention are recommended. Pharmacological measures depend on patients' fracture risk status. Very high-risk individuals are recommended for treatment with an anabolic agent, if available, followed by an anti-resorptive agent. Alternatively, parenteral anti-resorptive agents can be used. High-risk individuals should be treated with anti-resorptive agents. In low-risk individuals, menopausal hormone replacement or selective estrogen receptor modulators can be used, if indicated. Patients should be assessed regularly to monitor treatment response and treatment adjusted, as appropriate., Conclusions: The pathways for the management of postmenopausal OP in Malaysia have been updated. Incorporation of fracture risk stratification can guide appropriate treatment., Competing Interests: The authors declare no competing interests., (© 2023 The Korean Society of Osteoporosis. Publishing services by Elsevier B.V.)

Serial galactomannan (GM) monitoring can aid the diagnosis of invasive aspergillosis (IA) and optimise treatment decisions. However, widespread adoption of mould-active prophylaxis has reduced the incidence of IA and challenged its use. We evaluated the cost-effectiveness of prophylaxis-biomarker strategies. A Markov model simulating high-risk patients undergoing routine GM surveillance with mould-active versus non-mould-active prophylaxis was constructed. The incremental cost for each additional quality-adjusted life-year (QALY) gained over a lifetime horizon was calculated. In 40- and 60-year-old patients receiving mould-active prophylaxis coupled with routine GM surveillance, the total cost accrued was the lowest at SGD 11,227 (USD 8255) and SGD 9234 (USD 6790), respectively, along with higher QALYs gained (5.3272 and 1.1693). This strategy, being less costly and more effective, dominated mould-active prophylaxis with no GM monitoring or GM surveillance during non-mould-active prophylaxis. The prescription of empiric antifungal treatment was influential in the cost-effectiveness. When the GM test sensitivity was reduced from 80% to 30%, as might be anticipated with the use of mould-active prophylactic agents, the conclusion remained unchanged. The likelihood of GM surveillance with concurrent mould-active prophylaxis being cost-effective was 77%. Routine GM surveillance remained cost-effective during mould-active prophylaxis despite lower IA breakthroughs. Cost-saving from reduced empirical antifungal treatment was an important contributing factor.

Background: The study evaluated the cost-effectiveness of hydrotherapy versus land-based therapy in patients with musculoskeletal disorders (MSDs) in Singapore., Methods: A decision-analytic model was constructed to compare the cost-effectiveness of hydrotherapy to land-based therapy over 3 months from societal perspective. Target population comprised patients with low back pain (LBP), osteoarthritis (OA), rheumatoid arthritis (RA), total hip replacement (THR) and total knee replacement (TKR). Subgroup analyses were carried out to determine the cost-effectiveness of hydrotherapy in individual MSDs. Relative treatment effects were obtained through a systematic review of published data., Results: Compared to land-based therapy, hydrotherapy was associated with an incremental cost-effectiveness ratio (ICER) of SGD 27 471 per quality-adjusted life-year (QALY) gained, which was below the willingness-to-pay threshold of SGD 70 000 per QALY (one gross domestic product per capita in Singapore in 2015). For the respective MSDs, hydrotherapy were dominant (more effective and less costly) in THR and TKR, cost-effective for LBP and RA, and not cost-effective for OA. Treatment adherence and cost of hydrotherapy were key drivers to the ICER values., Conclusions: Hydrotherapy was a cost-effective rehabilitation compared to land-based therapy for a population with MSDs in Singapore. However, the benefit of hydrotherapy was not observed in patients with OA., (© The Author(s) 2018. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Most mainstream automatic speech recognition (ASR) systems consider all feature frames equally important. However, acoustic landmark theory is based on a contradictory idea that some frames are more important than others. Acoustic landmark theory exploits quantal nonlinearities in the articulatory-acoustic and acoustic-perceptual relations to define landmark times at which the speech spectrum abruptly changes or reaches an extremum; frames overlapping landmarks have been demonstrated to be sufficient for speech perception. In this work, experiments are conducted on the TIMIT corpus, with both Gaussian mixture model (GMM) and deep neural network (DNN)-based ASR systems, and it is found that frames containing landmarks are more informative for ASR than others. It is discovered that altering the level of emphasis on landmarks by re-weighting acoustic likelihood tends to reduce the phone error rate (PER). Furthermore, by leveraging the landmark as a heuristic, one of the hybrid DNN frame dropping strategies maintained a PER within 0.44% of optimal when scoring less than half (45.8% to be precise) of the frames. This hybrid strategy outperforms other non-heuristic-based methods and demonstrate the potential of landmarks for reducing computation.

Osteoarthritis prevalence is expected to increase markedly in the Asia-Pacific region due to rapid population aging. Identifying effective and safe therapeutic options to manage osteoarthritic pain is viewed as a priority. The Asia-Pacific Experts on Topical Analgesics Advisory Board developed consensus statements for use of topical NSAIDs in musculoskeletal pain. Evidence supporting these statements in osteoarthritic pain was reviewed. Best available evidence indicates that topical NSAIDs have a moderate effect on relief of osteoarthritic pain, comparable to that of oral NSAIDs but with a better risk-to-benefit ratio. International clinical practice guidelines recommend topical NSAIDs on par with or ahead of oral NSAIDs for pain management in patients with knee and hand osteoarthritis, and as the first-line choice in persons aged ≥75 years.

Objective: Following an osteoporotic fracture, pharmacological treatment is recommended to increase bone mineral density and prevent future fractures. However, the rate of starting treatment after an osteoporotic hip fracture remains low. The objective of this study was to survey the treatment rate following a low-trauma hip fracture at a tertiary private hospital in Malaysia over a period of 5 years., Methods: The computerised hospital discharge records were searched using the terms "hip," "femur," "femoral," "trochanteric," "fracture," or "total hip replacement" for all patients over the age of 50, admitted between 2010 and 2014. The medical charts were obtained and manually searched for demographic data and treatment information. Hip operations done for non-low-trauma-related fracture and arthritis were excluded., Results: Three hundred seventy patients over the age of 50 years were admitted with a hip fracture, of which 258 (69.7%) were low trauma, presumed osteoporotic, hip fractures. The median age was 79.0 years (interquartile range [IQR], 12.0). Following a hip fracture, 36.8% (95 of 258) of the patients received treatment, but out of these, 24.2% (23 of 95) were on calcium/vitamin D only. The median duration of treatment was 1 month (IQR, 2.5). In 2010, 56.7% of the patients received treatment, significantly more than subsequent years 2011-2014, where approximately only 30% received treatment., Conclusions: Following a low-trauma hip fracture, approximately 72% of patients were not started on active antiosteoporosis therapy. Of those who were, the median duration of treatment was 1 month. This represents a missed opportunity for the prevention of future fractures.

Objectives: To evaluate the characteristics of a novel human cell line, F2N78, including growth performance, physicochemical properties, and biological activity via direct comparison with CHO cells., Results: The culture performance and physicochemical properties of antibodies produced from F2N78 and CHO cells were compared. For charge variants, antibodies produced from F2N78 cells contained a greater acidic charge variants than CHO cells. Regarding main glycoforms, degree of galactosylation was 52% in CT-A produced from F2N78 cells compared to CHO cells (37%). For sialic acid forms, α-2,6-linked sialic acid and N-acetylneuraminic acid (NANA) residues were observed in antibodies produced from F2N78 cells. In contrast, only α-2,3 linked sialic acid forms were detected in antibodies produced from CHO cells, and NANA and N-glycolylneuraminic acid were detected. Hybrid structure and bisecting structure were only observed in F2N78 cells., Conclusions: F2N78 cells stably produced antibodies with human specific N-glycan. The novel expression system based on human cells may facilitate the development of an alternative host cell for production of recombinant proteins.

Background: In the management of Asian patients with acute coronary syndrome (ACS), the comparative cost-effectiveness of ticagrelor and prasugrel, referenced to generic clopidogrel, is unknown., Objective: To assess the cost-effectiveness of ticagrelor and prasugrel as compared with generic clopidogrel in patients with ACS in Singapore., Methods: A Markov model simulating a typical cohort of 62-year-old patients with ACS was constructed from a patient's perspective over a lifetime horizon. Treatment effects and adverse events, including nonfatal myocardial infarction, major bleeding related to non-coronary artery bypass grafting, dyspnea, or death, were estimated from pivotal trials comparing clopidogrel with ticagrelor and prasugrel, respectively. Costs were estimated from a tertiary hospital with more than 1500 admissions for ACS per year., Results: The incremental cost-effectiveness ratio (ICER) per life-year gained for ticagrelor was about three times more favorable than for prasugrel (Singapore dollar [SGD] 13,276 vs. SGD 38,809). The ICER per quality-adjusted life-year (QALY) for prasugrel and ticagrelor, however, was comparable at SGD 18,921 and SGD 18,647, respectively. Deterministic sensitivity analysis revealed that the ICER per QALY gained for prasugrel and ticagrelor was most sensitive to the hazard ratio of all-cause mortality and utility for dyspnea, respectively. Probabilistic sensitivity analysis demonstrated that compared with clopidogrel, the probabilities of prasugrel and ticagrelor being cost-effective are 87.1% and 88.3% based on the willingness-to-pay value of SGD 65,000 (one time the gross domestic product per capita in Singapore)., Conclusions: Ticagrelor is more cost-effective than prasugrel in reducing all-cause mortality in patients with ACS. The cost-effectiveness of ticagrelor and prasugrel become similar, however, when accounting for the impact of dyspnea on QALY., (Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Background: For treatment of patients diagnosed with schizophrenia, comparative long-term effectiveness of antipsychotic drugs to reduce relapses when minimising adverse effects is of clinical interest, hence prompting this review., Aims: To evaluate the comparative long-term effectiveness of antipsychotic drugs., Method: We systematically searched electronic databases for reports of randomised controlled trials (RCTs) of antipsychotic monotherapy aimed at reducing relapse risks in schizophrenia. We conducted network meta-analysis of 18 antipsychotics and placebo., Results: Studies of 10 177 patients in 56 reports were included; treatment duration averaged 48 weeks (range 4-156). Olanzapine was significantly more effective than chlorpromazine (odds ratio (OR) 0.35, 95% CI 0.14-0.88) or haloperidol (OR=0.50, 95% CI 0.30-0.82); and fluphenazine decanoate was more effective than chlorpromazine (OR=0.31, 95% CI 0.11-0.88) in relapse reduction. Fluphenazine decanoate, haloperidol, haloperidol decanoate and trifluoperazine produced more extrapyramidal adverse effects than olanzapine or quetiapine; and olanzapine was associated with more weight gain than other agents., Conclusions: Except for apparent superiority of olanzapine and fluphenazine decanoate over chlorpromazine, most agents showed intermediate efficacy for relapse prevention and differences among them were minor. Typical antipsychotics yielded adverse neurological effects, and olanzapine was associated with weight gain. The findings may contribute to evidence-based treatment selection for patients with chronic psychotic disorders., Declaration of Interest: R.J.B. received grants from the Bruce J. Anderson Foundation and the McLean Private Donors Psychopharmacology Research Fund., Copyright and Usage: © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

Invasive fungal infections (IFIs) are associated with high mortality rates and large economic burdens. Triazole prophylaxis is used for at-risk patients with hematological malignancies or stem cell transplants. We evaluated both the efficacy and the cost-effectiveness of triazole prophylaxis. A network meta-analysis (NMA) of randomized controlled trials (RCTs) evaluating fluconazole, itraconazole capsule and solution, posaconazole, and voriconazole was conducted. The outcomes of interest included the incidences of IFIs and deaths. This was coupled with a cost-effectiveness analysis from patient perspective over a lifetime horizon. Probabilities of transitions between health states were derived from the NMA. Resource use and costs were obtained from the Singapore health care institution. Data on 5,505 participants in 21 RCTs were included. Other than itraconazole capsule, all triazole antifungals were effective in reducing IFIs. Posaconazole was better than fluconazole (odds ratio [OR], 0.35 [95% confidence interval [CI], 0.16 to 0.73]) and itraconazole capsule (OR, 0.25 [95% CI, 0.06 to 0.97]), but not voriconazole (OR, 1.31 [95% CI, 0.43 to 4.01]), in preventing IFIs. Posaconazole significantly reduced all-cause deaths, compared to placebo, fluconazole, and itraconazole solution (OR, 0.49 to 0.54 [95% CI, 0.28 to 0.88]). The incremental cost-effectiveness ratio for itraconazole solution was lower than that for posaconazole (Singapore dollars [SGD] 12,546 versus SGD 26,817 per IFI avoided and SGD 5,844 versus SGD 12,423 per LY saved) for transplant patients. For leukemia patients, itraconazole solution was the dominant strategy. Voriconazole was dominated by posaconazole. All triazole antifungals except itraconazole capsule were effective in preventing IFIs. Posaconazole was more efficacious in reducing IFIs and all-cause deaths than were fluconazole and itraconazole. Both itraconazole solution and posaconazole were cost-effective in the Singapore health care setting., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Seeds of two selected clones of Artemisia annua L., TC1 and TC2, were germinated in a greenhouse. Four-week-old seedlings from both clones were grown in the Thù Đúc province of Ho Chi Minh City on 2(nd) January 2009 and Đà Lat on 20(th) January 2009. During this study period in Thù Đúc province, which is situated 4-5 m above sea level, was experiencing a tropical, dry season with temperatures ranging from 26.2°C-32.8°C. Đà Lat, situated at 1500-2000 m above sea level, was having temperate, dry season with lower temperatures, ranging from 10.5°C-18.0°C. The high temperatures and low elevation in Thù Đúc Province led to slow vegetative growth for all of the plants from the two different clones and the artemisinin contents were significantly reduced. The temperate environment of Đà Lat supported robustly growing plants, with plant heights and branch lengths 4-5 times taller and longer that those planted at Thù Đúc Province. The artemisinin contents of A. annua planted at Đà Lat were 3-4 times greater than those cultivated at Thù Đúc Province. Hence, this study indicated that the variations observed in plant growth and artemisinin contents were due to temperature effects because the two selected clones were genetically homogenous. The cold weather of Đà Lat was suitable for planting of A. annua as opposed to the tropical weather of Thù Đúc Province.

Between May 7 and June 7, 1986, 27 residents of a rural county in Maryland developed legionellosis, and two died. Legionella pneumophila serogroup 1 was cultured from the sputum of two patients and identified in lung tissue of a third patient by direct fluorescent antibody staining. An additional 11 patients had four-fold rises in antibody titer to L. pneumophila, and 13 had single titers greater than or equal to 1:256. To determine risk factors for disease, we performed a case-control study. Twelve of 16 case-patients reported visiting store A in the two weeks before onset of illness compared with four of 28 control-patients. A serologic survey of employees showed that employees of store A were 3.63 times more likely than control employees to have titers of antibody to L. pneumophila greater than or equal to 1:256 (95% confidence intervals 0.8, 16.7). Cultures of soil specimens, samples of water from the hot water system of store A and from stagnant ponds near store A collected five weeks after the end of the outbreak were negative for Legionella species. Store A was adjacent to a site of excavation and construction during May 1986, when the community was experiencing an extended drought. This investigation suggests that exposure to excavation and construction activity may be a risk factor for legionellosis.

Ten cases of typhoid fever occurred between 24 August and 1 September 1986 in the vicinity of Silver Spring, Md. Shrimp salad served in a fast-food restaurant was implicated as the source of infection. Stool cultures were obtained from 104 employees, and serum Vi antibodies were assayed in 97 of the employees. Salmonella typhi was isolated from stool cultures of an 18-year-old asymptomatic female employee, who was a food handler. A high level of Vi antibodies (79.0 micrograms/ml), measured by radioimmunoassay, was found in her serum. She had emigrated from an endemic area at the age of 14 years and had visited that endemic area 2 years previously. The causal relation between the carrier and the 10 cases of typhoid fever was confirmed by a common bacteriophage type, denoted "degraded Vi resembling O," in the S. typhi isolates. This phage type is rare in the western hemisphere but common in the endemic area from which the carrier had emigrated. The high level of Vi antibody in the asymptomatic carrier, in contrast to the lower levels in the convalescent- and postimmunization-phase sera, facilitated the identification of the source infection in this outbreak. This radioimmunoassay offers a rapid and standardized method for identifying carriers of S. typhi.