Adherence to dosing schedule of denosumab therapy for osteoporosis during COVID-19 lockdown: an electronic medical record and pharmacy claims database study from Asia.

COVID-19 lockdowns have impacted management of chronic diseases such as osteoporosis. Adherence to the 6-monthly dosing schedule of denosumab, the parenteral anti-osteoporosis medication most often used in Singapore, was significantly reduced during the lockdown period compared to that during pre-COVID-19 times. Patients managed by endocrinologists were more likely to be adherent. PURPOSE: No study thus far has quantified actual adherence rates to anti-osteoporosis therapy with denosumab during COVID-19 or explored factors associated with it. We aimed to estimate the adherence rates to denosumab in Singaporean men and women during COVID-19 lockdown and to compare it with those during the pre-COVID-19 period. METHOD: We conducted this retrospective, electronic medical records, and pharmacy claims database study at Singapore General Hospital, the largest hospital in the country. Patients initiated on subcutaneous denosumab between August 2019 and December 2019 and were thus scheduled to receive the second dose during the COVID-19 first-wave period from February 2020 to June 2020 (lockdown group) were analyzed, as were patients initiated anytime on denosumab between September 2011 and December 2018 (pre-COVID-19 group). Data extracted from the hospital's electronic prescription platform and patients' pharmacy purchase records were matched. Adherence was defined as being punctual (with an allowable delay of up to 4 weeks) with the second dose scheduled 6 months from the 1st dose. A sensitivity analysis with an allowable delay up to 8 weeks was also performed. We compared the adherence rates between the two periods and explored factors associated with adherence. RESULTS: A total of 768 and 1458 patients respectively during the lockdown and pre-COVID-19 periods were analyzed. The mean adherence rate during lockdown was 63.9%. The odds of being adherent during lockdown were higher if patients were managed by endocrinologists as opposed to those by other specialists [OR 2.516 (95% CI: 1.836-3.448); p < 0.001]. Adherence rates during the pre-COVID-19 period was 75.4%. Overall, the odds of being adherent to denosumab was significantly lower during lockdown than that during the pre-COVID-19 period [OR 0.525 (95% CI 0.430-0.640); p < 0.001], and odds of being adherent were higher if patients were managed by endocrinologists than if they were managed by other specialists (OR 1.765 (95% CI: 1.444-2.158; p < 0.001). CONCLUSION: Adherence to denosumab was significantly lower during COVID-19 lockdown than the pre-COVID-19 period. The odds of being adherent were higher in patients managed by endocrinologists. Whether healthcare providers from certain specialties spend more time counselling and educating patients about the importance of adherence to osteoporosis medications needs to be explored further.

Cost-effectiveness of two technology-assisted manual medication picking systems versus traditional manual picking in a hospital outpatient pharmacy.

OBJECTIVE: To evaluate the cost-effectiveness of two technology assisted manual medication picking systems vs traditional manual picking. METHODS: This was a retrospective observational study comparing three outpatient pharmacies of a tertiary referral hospital in Singapore, where a light-emitting diode (LED-guided) manual picking system, an LED-guided manual picking plus lockable drawer (LED-LD) system, and traditional manual picking were implemented, respectively. The primary outcome measure was the incidence of medication near-misses over the observation period. The incremental cost-effectiveness ratio (ICER) per near-miss avoided was also determined. Data on medications picked and near-misses reported between September 2017 and June 2018 were retrieved from electronic databases. The incidence of medication near-misses from the LED-guided and LED-LD systems, relative to traditional picking, was compared using logistic regression. We compared annual operating costs between manual medication picking systems, and reported ICERs per near-miss avoided, to evaluate the cost-effectiveness of each picking system. RESULTS: A total of 358 144, 397 343 and 254 162 medications were picked by traditional manual picking, LED-guided and LED-LD systems, respectively. The corresponding near-miss rates were 8.32, 4.08 and 0.69 per 10 000 medications picked, respectively. Medication near-miss rates were significantly lower for the LED-guided (OR 0.49, 95% CI 0.40 to 0.59, p<0.001) and LED-LD systems (OR 0.08, 95% CI 0.05 to 0.13, p<0.001) compared with traditional picking. The annual operating costs of traditional picking, LED-guided and LED-LD systems were S$60 912, S$129 832 and S$152 894, respectively. The LED-guided and LED-LD systems yielded ICERs of S$189 and S$140 per near-miss avoided, respectively, compared with traditional manual picking. CONCLUSION: The LED-LD system is more cost-effective than both the LED-guided and manual medication picking systems in reducing medication picking near-misses.

Assessment of aPTT-based clot waveform analysis for the detection of haemostatic changes in different types of infections.

Infections cause varying degrees of haemostatic dysfunction which can be detected by clot waveform analysis (CWA), a global haemostatic marker. CWA has been shown to predict poor outcomes in severe infections with disseminated intravascular coagulopathy. The effect of less severe bacterial and viral infections on CWA has not been established. We hypothesized that different infections influence CWA distinctively. Patients admitted with bacterial infections, dengue and upper respiratory tract viral infections were recruited if they had an activated partial thromboplastin time (aPTT) measured on admission. APTT-based CWA was performed on Sysmex CS2100i automated analyser using Dade Actin FSL reagent. CWA parameters [(maximum velocity (min1), maximum acceleration (min2) and maximum deceleration (max2)] were compared against control patients. Infected patients (n = 101) had longer aPTT than controls (n = 112) (34.37 ± 7.72 s vs 27.80 ± 1.59 s, p < 0.001), with the mean (± SD) aPTT longest in dengue infection (n = 36) (37.99 ± 7.93 s), followed by bacterial infection (n = 52) (33.96 ± 7.33 s) and respiratory viral infection (n = 13) (29.98 ± 3.92 s). Compared to controls (min1; min2; max2) (5.53 ± 1.16%/s; 0.89 ± 0.19%/s2; 0.74 ± 0.16%/s2), bacterial infection has higher CWA results (6.92 ± 1.60%/s; 1.04 ± 0.28%/s2; 0.82 ± 0.24%/s2, all p < 0.05); dengue infection has significantly lower CWA values (3.93 ± 1.32%/s; 0.57 ± 0.17%/s2; 0.43 ± 0.14%/s2, all p < 0.001) whilst respiratory virus infection has similar results (6.19 ± 1.32%/s; 0.95 ± 0.21%/s2; 0.73 ± 0.18%/s2, all p > 0.05). CWA parameters demonstrated positive correlation with C-reactive protein levels (min1: r = 0.54, min2: r = 0.44, max2: r = 0.34; all p < 0.01). Different infections affect CWA distinctively. CWA could provide information on the haemostatic milieu triggered by infection and further studies are needed to better define its application in this area.

The direct and indirect costs of axial spondyloarthritis (axSpA) in Singapore.

OBJECTIVE: To estimate the economic annual direct and indirect costs of axial spondyloarthritis (axSpA) in Singapore, and to identify factors associated with these costs. METHODS: A retrospective, cross-sectional, Institutional Review Board-approved study was conducted. A questionnaire was administered to the patients between 2013 and 2016 from the Singapore General Hospital (SGH) spondyloarthritis registry. Direct medical costs and indirect costs were estimated using the SGH database and the human capital approach respectively. Multivariate analyses using generalized linear model with gamma distribution and a log-linked function was conducted to identify factors associated with these total, direct and indirect costs. All costs were adjusted to 2017 using the Singapore Consumer Price Index and converted to 2017 US dollars (USD) by purchasing power parity. RESULTS: A total of 135 consecutive patients were included in the study, with a mean age of 40.4 ± 13.2 years. The overall annual total economic cost to society was around USD 74 790 820, with annual direct cost being the main component of total cost (90.8%). Annual direct cost was around USD 67 931 457, while annual indirect cost was around USD 6 855 951. Presence of extra-spinal symptoms (ever) was associated with an increase in total and direct costs. Higher education level and Patient Global Assessment were associated with an increase in indirect costs. Lack of employment was associated with a decrease in indirect costs. CONCLUSION: The disease burden of axSpA in Singapore is not trivial given that the disease is relatively common. This highlights the need for measures to accommodate patients with axSpA economically in Singapore.

Elevated activated partial thromboplastin time-based clot waveform analysis markers have strong positive association with acute venous thromboembolism.

INTRODUCTION: A hypercoagulable state is a predisposition for venous thromboembolism (VTE). The activated partial thromboplastin time (aPTT)-based clot waveform analysis (CWA) is a global haemostatic measure but its role in assessment of hypercoagulability and thrombotic disorders is uncertain. We aimed to study the changes of CWA parameters in acute VTE. We hypothesized that patients with acute VTE would demonstrate higher CWA values than control patients without VTE and having elevated CWA parameters is associated with acute VTE. MATERIALS AND METHODS: Clot waveform analysis data from patients (N = 45) with objectively proven acute VTE who had an aPTT performed prior to initiation of anticoagulation were compared with controls (N = 111). The CWA parameters measured were min1, min2, max2 and delta change. RESULTS: While the mean aPTT between VTE patients and controls did not differ (P = 0.830), the mean CWA parameters were significantly higher among VTE patients than controls (min1, P < 0.001; min2, P = 0.001; max2, P = 0.002; delta change, P < 0.001). There were significantly more cases within the VTE group exhibiting CWA values above their reference intervals than the control group (all P < 0.001), with the odds ratios for VTE of 8.0, 5.2, 4.8 and 18.6 for min1, min2, max2 and delta change, respectively (all P < 0.001). CONCLUSIONS: Patients with acute VTE had elevated aPTT-based CWA parameters than controls. Higher CWA parameters were significantly associated with acute VTE.

Prevalence of and factors associated with primary medication non-adherence in chronic disease: A systematic review and meta-analysis.

BACKGROUND: Primary medication non-adherence (PMN), defined as failure to obtain newly prescribed medications, results in adverse clinical and economic outcomes. We aimed to (a) assess the prevalence of PMN in six common chronic diseases: asthma and/ or chronic obstructive pulmonary disease, depression, diabetes mellitus, hyperlipidaemia, hypertension and osteoporosis; (b) identify and categorise factors associated with PMN; (c) explore characteristics that contributed to heterogeneity between studies. METHODS: We performed a systematic search in MEDLINE, Embase, Cochrane Library, CINAHL and PsycINFO. Studies published in English between January 2008 and August 2018 assessing PMN in subjects aged ≥18 years were included. We used the Cochrane risk of bias tool, Newcastle-Ottawa Scale and National Heart, Lung and Blood Institute Quality Assessment Tool to assess the quality of randomised controlled trials, cohort and cross-sectional studies, respectively. Findings were reported using the PRISMA checklist. PMN rates were pooled using a random effects model. We summarised factors associated with PMN descriptively. Subgroup analysis was performed to explore sources of heterogeneity. RESULTS: We screened 3083 articles and included 33 (5 randomised controlled trials, 26 cohort and 2 cross-sectional studies, n = 539 156), of which 31 (n = 519 971) were used in meta-analysis. The pooled PMN rate was 17% (95% CI: 15%-20%). Pooled PMN rates were highest in osteoporosis (25%, 95% CI: 7%-44%) and hyperlipidaemia (25%, 95% CI: 18%-32%) and lowest in diabetes mellitus (10%, 95% CI: 7%-12%). Factors commonly associated with PMN include younger age, number of concurrent medications, practitioner specialty and higher co-payment. Type of chronic disease, age, study setting and PMN definition contributed to heterogeneity between studies (all P < 0.001). CONCLUSION: Primary medication non-adherence is common among patients with chronic diseases and more needs to be done to address this issue in order to improve patient outcomes. Future PMN studies could benefit from greater standardisation to enhance comparability.

Trends in medication utilization, glycemic control and outcomes among type 2 diabetes patients in a tertiary referral center in Singapore from 2007 to 2017.

BACKGROUND: Use of glucose-lowering agents is a cornerstone in combating type 2 diabetes (T2DM). Treatment guidelines have changed significantly over the past decade. We report temporal trends in medication utilization, glycemic control and rate of severe hypoglycemia in T2DM patients at a tertiary referral center in Singapore. METHODS: We analyzed data of 36 924 T2DM patients seen at Singapore General Hospital from 2007 to 2017. Annual age-, sex- and racially-standardized proportions of patients (a) prescribed with each class of glucose-lowering agent, (b) on various glucose-lowering regimens, and (c) had an HbA1c of less than 6%, 6% to less than 7%, 7% to less than 8%, 8% to less than 9%, or 9% or more were estimated using logistic regression. Poisson regression was used to estimate standardized rate of severe hypoglycemia. RESULTS: From 2007 to 2017, use of metformin (45.9% to 59.6%) and insulin (24.4% to 57.9%) increased, while utilization of sulfonylureas (52.0% to 44.9%) decreased (all P < 0.001). Utilization of dipeptidyl peptidase-4 inhibitors (1.2% to 31.2%) and sodium-glucose cotransporter-2 inhibitors (0.5% to 7.4%) increased from 2008 to 2017 and 2012 to 2017, respectively (all P < 0.001). More patients were prescribed a combination of insulin and oral agents (17.3% to 46.0%, P < 0.001). The proportion of patients with HbA1c of 8% or more increased (33.7% to 36.0%, P < 0.001). Rates of severe hypoglycemia (5.0 to 8.4 per 100 patient-years, P < 0.001) also rose. CONCLUSION: Medication utilization patterns have changed significantly over the past 11 years with a shift towards newer agents. Glycemic control has remained stable, and rate of severe hypoglycemia increased. Further analysis is required before causal relationships can be inferred.

Outcomes of pharmacist-provided medication review in collaborative care for adult Singaporeans receiving hemodialysis.

Background Patients receiving hemodialysis are predisposed to drug related problems (DRPs). While collaborative care (CC) models with pharmacist involvement can reduce DRP occurrence, few have examined its impact on clinical and economic outcomes. Objective To determine whether a CC model with pharmacist-provided medication review can reduce unplanned admissions and healthcare utilization in patients receiving hemodialysis, compared to usual care (UC). Setting Outpatient nephrology clinic of a tertiary hospital in Singapore. Method In this retrospective observational study, patients who were taking more than 10 medications or had prior unplanned admissions were included. Patients were identified as being managed under CC (n = 134) if they received comprehensive pharmacist-provided review, or under the UC (n = 190) if they did not. Those perceived to be at greater risk were given priority for receiving CC. All outcomes analyses were adjusted for covariates. Main outcome measure The primary outcome was incidence of unplanned admissions within 6 months post index visit. Secondary outcomes included length of stay (LOS), mortality and healthcare utilization cost. Results CC reduced unplanned admissions by 27% (IRR 0.73, 95% CI 0.54-0.99, p = 0.047) and shortened mean LOS by 1.3 days [6.7 (2.6) vs. 8.0 (3.2), p < 0.001] compared to UC. There were no significant differences in mortality (p = 0.189) or mean healthcare utilization cost (p = 0.165) between groups. Pharmacists identified 515 DRPs with 429 (83.3%) resolved after review. Conclusion The CC model with pharmacist-provided medication review reduced unplanned admissions and LOS in patients receiving hemodialysis. Further studies are warranted to confirm reductions in mortality and healthcare utilization.

Evaluation of a care transition program with pharmacist-provided home-based medication review for elderly Singaporeans at high risk of readmissions.

OBJECTIVE: This study aimed to determine whether pharmacist-provided home-based medication review (HBMR) can reduce readmissions in the elderly. DESIGN: Retrospective cohort study. SETTING: Patient's home. PARTICIPANTS: Records of patients referred to a care transition program from March 2011 through March 2015 were reviewed. Patients aged 60 years and older taking more than 5 medications and had at least 2 unplanned admissions within 3 months preceding the first home visit were included. INTERVENTION: Pharmacist-provided HBMR. MAIN OUTCOME MEASURES: Primary outcome was readmission rate over 6 months after the first home visit. Secondary outcomes included emergency department (ED) visits, outpatient visits and mortality. Drug-related problems (DRPs) were reported for the HBMR group. Multivariate incidence rate ratios (IRR) and hazard ratio (HR) were calculated with adjustments for covariates. RESULTS: The study included 499 patients (97 HBMR, 402 no HBMR). Pharmacist-provided HBMR reduced readmissions by 26% (IRR = 0.74, 95% CI: 0.59-0.92, P = 0.007), reduced ED visits by 20% (IRR = 0.80, 95% CI: 0.66-0.98, P = 0.030) and increased outpatient visits by 16% (IRR = 1.16, 95% CI: 0.95-1.41, P = 0.150). There were 8 and 44 deaths in the HBMR and no HBMR groups respectively (HR = 0.73, 95% CI: 0.29-1.81, P = 0.492). Pharmacists identified 464 DRPs, with 169 (36.4%) resolved within 1 month after the home visit. CONCLUSIONS: The study suggests that pharmacist-provided HBMR is effective in reducing readmissions and ED visits in the elderly. More studies in the Asian population are needed to determine its long term benefits and patient's acceptability.

Effectiveness of a multidisciplinary home-based medication review program in reducing healthcare utilization among older adult Singaporeans.

AIM: The study aimed to: (i) evaluate the effectiveness of a multidisciplinary home-based medication review (HBMR) program in reducing hospital admissions and emergency department (ED) visits, cost of hospital admissions and length of stay (LOS); and (ii) determine the prevalence of drug-related problems (DRP) in elderly Singaporeans. METHODS: A retrospective observational study was carried out at an academic medical center in Singapore. Patients referred between 1 March 2011 and 31 December 2012 were included. Frequency of hospital admissions and ED visits, cost of hospital admissions, and LOS 6 months before and after HBMR, number of DRP, their categories, and their outcomes (i.e. resolved/ unresolved) were recorded. RESULTS: The analysis included 107 patients with a mean (SD) age of 75.6 years (7.6 years). HBMR resulted in a 41% reduction in risk for hospital admissions (Incidence rate ratio 0.59, 95% CI 0.47-0.73, P < 0.001). The same magnitude of reduction was observed for ED visits. The mean (SD) cost of hospital admissions reduced from $16 957.77 ($16 118.35) before HBMR to $7488.76 ($12 773.40) after (P < 0.001). Among 62 patients with hospital admissions before and after HBMR, the mean (SD) LOS decreased from 26.5 days (22.4 days) to 17.6 days (17.8 days; P = 0.010). The team identified 525 DRP from 1353 medications reviewed. Of these, 34 (6.7%) and 174 (34.1%) were resolved with and without physician involvement, respectively. The most common DRP identified were failure to receive drug (n = 163, 31.0%) and untreated indication (n = 140, 26.7%). CONCLUSIONS: The multidisciplinary HBMR program was associated with reduced ED visits, hospital admissions, LOS and costs in older adult Singaporeans with multiple DRP. Geriatr Gerontol Int 2017; 17: 302-307.