Search

Brown adipose tissue (BAT) is responsible for non-shivering thermogenesis and is an attractive therapeutic target for combating obesity and related diseases. Human BAT activity has been evaluated by 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18FDG-PET/CT) under acute cold exposure, but the method has some serious limitations, including radiation exposure. Infrared thermography (IRT) may be a simple and less-invasive alternative to evaluate BAT activity. In the present study, to establish an optimal condition for IRT, using a thermal imaging camera, skin temperature was measured in the supraclavicular region close to BAT depots (Tscv) and the control chest region (Tc) in 24 young healthy volunteers. Their BAT activity was assessed as the maximal standardized uptake value (SUVmax) by 18FDG-PET/CT. Under a warm condition at 24–27°C, no significant correlation was found between the IRT parameters (Tscv, Tc,, and the difference between Tscv and Tc,, Δtemp) and SUVmax, but 30–120 min after cold exposure at 19°C, Tscv and Δtemp were significantly correlated with SUVmax (r = 0.40–0.48 and r = 0.68–0.76). Δtemp after cold exposure was not affected by mean body temperature, body fatness, and skin blood flow. A lower correlation (r = 0.43) of Δtemp with SUVmax was also obtained when the participant’s hands were immersed in water at 18°C for 5 min. Receiver operating characteristic analysis revealed that Δtemp after 30–60 min cold exposure can be used as an index for BAT evaluation with 74% sensitivity, 92% specificity, and 79% diagnostic accuracy. Thus, IRT may be useful as a simple and less-invasive method for evaluating BAT, particularly for large-scale screening and longitudinal repeat studies. [ABSTRACT FROM AUTHOR]

Structural and individual level factors in prisons create challenges towards detection and management of HIV/tuberculosis. WHO and India’s HIV/tuberculosis control programs recommend intensified case finding in prisons. Low HIV and tuberculosis detection rates suggest poor implementation of existing surveillance strategies within the prison healthcare system in Mizoram’s capital city of Aizawl. We explored the operational feasibility of implementing the intensified case finding strategy in Aizawl central prison. We implemented the intensified screening through entry screening of new inmates, mass screening of resident inmates and exit screening at release. We set up digital chest radiography, sputum smear microscopy and HIV testing facilities within the prison and referral to external facility for Cartridge Based Nucleic Acid Amplification Test (CBNAAT). We screened 738 inmates (Male: 626; Female: 112). Of 53% inmates having presumptive tuberculosis symptoms, 37% underwent sputum microscopy. We detected 14 new tuberculosis cases; overall tuberculosis positivity 1.9%. We tested 65% of 657 inmates for HIV, of which 41 new cases were detected; overall HIV positivity 16.5%. Three male inmates had HIV-tuberculosis co-infection. It is feasible to implement intensified case detection for tuberculosis/HIV in the prison with inter-departmental coordination, albeit with certain challenges. [ABSTRACT FROM AUTHOR]

In Cambodia, the human immunodeficiency virus (HIV) is predominantly transmitted between spouses and casual partners, with men having higher mortality and morbidity from HIV infection than women due to lesser access to healthcare services and antiretroviral therapy. This study aimed to identify the rate of HIV testing and barriers to HIV testing among the general male population in Cambodia. We analyzed secondary data of men who underwent HIV testing at Voluntary Confidential Counseling and Testing (VCCT) sites in 2006–2017 and of male participants in the Cambodia Demographic and Health Survey (CDHS) in 2005, 2010, and 2014. The number of men who underwent HIV testing at the VCCT sites increased during 2006–2010 and decreased during 2012–2015. CDHS data showed that the lifetime prevalence of HIV testing among men aged 15–49 years gradually increased from 14.7% in 2005 to 36.4% in 2014. Multivariate analysis revealed nine factors associated with a higher lifetime prevalence of HIV testing including: seven sociodemographic factors, namely CDHS year (2010 and 2014), age groups (20–35 and 36–49 years), urban residence, higher education, higher wealth index, having occupations other than agriculture, ever-married status (married and widowed/divorced); and two factors of HIV risk behavior, namely two or more lifetime sexual partners and condom use during the last sexual intercourse. To our knowledge, this is the first study that assessed factors associated with the lifetime prevalence of HIV testing among the general male population in Cambodia. The factors were mostly sociodemographic factors, and no factors were related to condom use, or the diagnosis or symptoms of sexually transmitted infections (STIs). These results suggest that reproductive health education at primary schools and strengthening of healthcare provider-initiated testing and counseling for patients with STIs are highly needed in Cambodia. [ABSTRACT FROM AUTHOR]

Objective: To investigate the cost differences between magnetic resonance-guided focussed ultrasound (MRgFUS) and unilateral deep brain stimulation (DBS) for the treatment of medication-refractory essential tremor (ET) in Japan using a cost-minimisation model. Methods: A cost-minimisation model estimated total costs for MRgFUS and unilateral DBS by summing the pre-procedure, procedure, and post-procedure costs over a 12-month time horizon, using data from published sources and expert clinical opinion. The model base case considered medical costs from fee-for-service tariffs. Scenario analyses investigated the use of Diagnosis Procedure Combination tariffs, a diagnosis-related group-based fixed-payment system, and the addition of healthcare professional labour costs healthcare professionals using tariffs from the Japanese Health Insurance Federation for Surgery. One-way sensitivity analyses altered costs associated with tremor recurrence after MRgFUS, the extraction rate following unilateral DBS, the length of hospitalisation for unilateral DBS and the procedure duration for MRgFUS. The impact of uncertainty in model parameters on the model results was further explored using probabilistic sensitivity analysis. Results: Compared to unilateral DBS, MRgFUS was cost saving in the base case and Diagnosis Procedure Combination cost scenario, with total savings of JPY400,380 and JPY414,691, respectively. The majority of savings were accrued at the procedural stage. Including labour costs further increased the cost differences between MRgFUS and unilateral DBS. Cost savings were maintained in each sensitivity analysis and the probabilistic sensitivity analysis, demonstrating that the model results are highly robust. Conclusions: In the Japanese healthcare setting, MRgFUS could be a cost saving option versus unilateral DBS for treating medication-refractory ET. The model results may even be conservative, as the cost of multiple follow-ups for unilateral DBS and treatment costs for adverse events associated with each procedure were not included. This model is also consistent with the results of other economic analyses of MRgFUS versus DBS in various settings worldwide. [ABSTRACT FROM AUTHOR]

Long working hours and a lack of sleep have been suggested to negatively affect the safety of workers. Here, we examined the association between long working hours/sleep-related problems and near-misses/injuries in industrial settings using a nationally representative sample of workers in Japan. Based on the composition ratio of workers by industry, sex, and age in Japan, data from a web-based cross-sectional survey for 18,682 participant full-time workers (7,098 female and 11,584 male; mean age, 43.7 [standard deviation 11.1] years) were analyzed. Nearly 30% and 5% of participants reported any types of near-misses during the past six months and injuries during the past year, respectively. For all types of near-misses and some types of injuries, a significant difference in frequency distribution was observed by industry. After adjustment for demographic, job-, and life-related variables, participants who worked long hours (i.e., more than 51 hours per week) were more likely to report job-related near-misses/injuries than those who worked 35–40 hours per week. The presence of sleep-related problems was also significantly related to near-misses and injuries. However, while sleep-related problems were significantly associated with near-misses/injuries in all industries, the association between long working hours and near-misses/injuries differed by industry. Odds ratios for near-misses/injuries were strongly significant in the “transport/postal services” industry for those who worked more than 51 hours per week compared to those who worked 35–40 hours per week. Comprehensive protective measures for workers, including (1) reducing total hours of service/job-related fatigue, (2) maintaining sufficient sleep hours/good sleep, and (3) increasing awareness about the impact of overwork/long working hours and sleep-related problems on workers’ safety among employers, workers, clients/customers, and the general public might be effective for preventing near-misses and injuries in industrial settings among workers, especially those who work long hours in the “transport/postal services” industry. [ABSTRACT FROM AUTHOR]

Background: Cultural, environmental and logistical factors promote a sedentary lifestyle within Qatar, particularly for females. Sedentary behaviour is acutely associated with poor cognitive function and fatigue, and chronically may be implicated with cognitive decline (i.e. Alzheimer’s disease). Purpose: To examine the effects of breaking up sitting with short-duration frequent walking bouts on cognitive function and fatigue in Qatari females. Method: Eleven sedentary (sitting ≥7 h/day) females completed three visits; the first being familiarisation. In a cross-over randomised manner, experimental visits two and three were identical, except participants either remained seated for 5-h (SIT) or interrupted their sitting every 30-min with a 3-min moderate-intensity walk (WALK) on a motorised treadmill. The Computerised Mental Performance Assessment System (COMPASS) assessed cognition at baseline (-15-min), and then at 2.5-h and 5-h into the experimental conditions. Specific COMPASS tasks employed were; serial-3 subtractions (2-min), serial-7 subtractions (2-min), simple reaction time (RT; 50 stimuli), rapid visual information processing [RVIP (5-min)], choice reaction time (CRT; 50 stimuli), and Stroop (60 stimuli); and a visual analogue scale for fatigue (VAS-F) was completed at the same time intervals. Results: There was a significant condition effect for CRT (f = 26.7, p = 0.007). On average CRT was 101 s (95% CI = -47 to -156 s) quicker in WALK compared to SIT. There was a significant time effect for CRT (f = 15.5, p = 0.01). On average CRT was 134 s slower at 5-h compared to baseline (p = 0.006; 95% CI = -64 to -203 s), and 114 s slower at 5-h compared to 2.5-h (p = 0.01; 95% CI = -44 to -183 s). There was a significant interaction effect for RT in the Stroop incongruent task (f = 10.0, p = 0.03). On average RT was 210 s quicker at 2.5-h in WALK compared to SIT (p = 0.01; 95% CI = -76 to -346 s). Conclusion: Breaking up prolonged sitting with moderate-intensity walking offers an ecologically valid intervention to enhance some aspects of cognitive function, whilst not affecting fatigue in sedentary Qatari females. Whilst these findings are promising, the long-term effects of breaking up sitting on cognitive function requires testing before population level recommendations can be made. [ABSTRACT FROM AUTHOR]

Background: Developing countries still struggle with late detection and mortality from pertussis. A review of clinical case definitions is necessary for early disease detection. This paper aimed to study possible clinical characteristics for earlier pertussis detection in a sporadic setting. Methods: We conducted a retrospective review of medical and laboratory records in a general paediatric ward of a district hospital in a developing country. Inclusion criteria were all children hospitalised with nasopharyngeal swab taken for Bordetella pertussis. We compared sensitivity and specificity of World Health Organization diagnostic criteria with other clinical characteristics. Polymerase chain reaction Bordetella pertussis was the gold standard used. Results: Out of 207 eligible admissions, the study retrieved 128 complete records. Approximately half of the children were less than 3 months old. The World Health Organization diagnostic criteria had a low sensitivity (15%), but high specificity (92%). In comparison, combinations that included paroxysmal cough, ill contact and facial congestion had higher sensitivity. Increasing cough duration improved specificity while compromising sensitivity. Conclusion: Several clinical characteristics such as paroxysmal cough, facial congestion and a history of ill contact have potential for early clinical detection. Conventional emphasis on cough duration may hamper early detection. [ABSTRACT FROM AUTHOR]

Defining occupational latent tuberculosis infection (LTBI) risk among healthcare workers is needed to support implementation of prevention guidelines. Prospective cohort study of 200 medical residents and nursing students in India was conducted May 2016—December 2017. Tuberculin skin test (TST) and QuantiFERON TB Gold Test-in-tube (QFT-GIT) were performed at study entry and 12 months. Primary outcome was incident LTBI (≥10mm TST induration and/or ≥0.35IU/mL QFT-GIT) at 12 months; secondary outcomes included baseline LTBI prevalence and risk factors for incident and prevalent LTBI using Poisson regression. Among 200, [90 nursing students and 110 medical residents], LTBI prevalence was 30% (95% CI, 24–37); LTBI incidence was 26.8 (95% CI, 18.6–37.2) cases per 100 person-years and differed by testing method (28.7 [95% CI, 20.6–38.9] vs 17.4 [95% CI, 11.5–25.4] cases per 100 person-years using TST and QFT-GIT, respectively). Medical residents had two-fold greater risk of incident LTBI than nursing students (Relative Risk, 2.16; 95% CI, 1.05–4.42). During study period 6 (3%) HCWs were diagnosed with active TB disease. Overall, median number of self-reported TB exposures was 5 (Interquartile Range, 1–15). Of 60 participants with prevalent and incident LTBI who were offered free isoniazid preventive therapy (IPT), only 2 participants initiated and completed IPT. High risk for LTBI was noted among medical residents compared to nursing students. Self-reported TB exposure is underreported, and uptake of LTBI prevention therapy remains low. New approaches are needed to identify HCWs at highest risk for LTBI. [ABSTRACT FROM AUTHOR]

Pertussis is a human respiratory infection caused by the gram-negative bacterium, Bordetella pertussis. To evaluate the pertussis burden and vaccine efficacy, diagnosis and epidemiological surveillance should be based on accurate and valid diagnostic methods. Recently, the serodiagnostic tests Novagnost Bordetella pertussis IgA and IgM were approved in Japan for pertussis diagnostics. Although the anti-pertussis toxin (PT) IgG assay has been used for pertussis diagnosis worldwide, little is known about the anti-B. pertussis IgA and IgM assays. In this study, serum samples from 460 healthy donors were examined to determine the seroprevalence of anti-B. pertussis IgA and IgM in a Japanese population, and its correlation with donor age. Our data demonstrated that anti-B. pertussis IgA and IgM are positively and negatively correlated with age (r = 0.27, r = -0.37; P < 0.001, respectively). Age-specific analysis revealed high titers of anti-B. pertussis IgA in adults (46–50 years), while anti-B. pertussis IgM titers were high in schoolchildren (6–10, 11–15 years). When applying the arbitrary cut-off values for these ages, 17.6% and 39.5% of healthy donors were interpreted as pertussis-positive or indeterminate with anti-B. pertussis IgA (46–50 years) and IgM (11–15 years) titers, respectively. Overall, our findings indicated that the Novagnost Bordetella pertussis IgA and IgM testing could be greatly affected by subject age, limiting its value for pertussis diagnosis. [ABSTRACT FROM AUTHOR]

Background: Misuse of antibiotics is a well-known driver of antibiotic resistance. Given the decentralized model of the Indian health system and the shortage of allopathic doctors in rural areas, a wide variety of healthcare providers cater to the needs of patients in urban and rural settings. This qualitative study explores the drivers of antibiotic use among formal and informal healthcare providers as well as patients accessing care at primary health centers across Paschim Bardhaman district in West Bengal. Materials and methods: We conducted 28 semi-structured, in-depth interviews with four groups of healthcare providers (allopathic doctors, informal health providers, nurses, and pharmacy shopkeepers) as well as patients accessing care at primary health centers and hospitals across Paschim Bardhaman district. Qualitative data was analyzed using the framework method in an inductive and deductive manner. Results: Our results indicate that patients demand antibiotics from healthcare providers and seek the fastest cure possible, which influences the prescription choices of healthcare providers, particularly informal health providers. Many allopathic doctors provide antibiotics without any clinical indication due to inconsistent follow up, lack of testing facilities, risk of secondary infections, and unhygienic living conditions. Pharmaceutical company representatives actively network with informal health providers and formal healthcare providers alike, and regularly visit providers even in remote areas to market newer antibiotics. Allopathic doctors and informal health providers frequently blame the other party for being responsible for antibiotic resistance, and yet both display interdependence in referring patients to one another. Conclusions: A holistic approach to curbing antibiotic resistance in West Bengal and other parts of India should focus on strengthening the capacity of the existing public health system to deliver on its promises, improving patient education and counseling, and including informal providers and pharmaceutical company representatives in community-level antibiotic stewardship efforts. [ABSTRACT FROM AUTHOR]

Background: Population Services International (PSI) Myanmar’s social franchise network of general practitioners, known as Sun Quality Health Clinics (SQHC), provided tuberculosis (TB) diagnosis and treatment with Direct Observed Treatment Short course (DOTs) across Myanmar since 2004, with a total of 898 clinics across the country. People who sought TB treatment from these SQHC by themselves were regarded as walk-in patients. To augment TB case notification, PSI Myanmar developed two treatment seeking channels: Community Health Services Providers (CHSP) and Interpersonal Communicators (IPC). They actively sought people who were suspected to have TB and referred them to SQH clinics. In this study, we compared the loss to follow-up rates of TB patients across three treatment seeking channels; and investigated risk-factors for loss to follow-up. Methods and findings: A retrospective cohort design was applied using TB client records between 2012 and 2016. Outcome was defined as loss to follow-up in comparison to successful TB treatment (completed or cured). Multivariate Poisson regression was conducted to estimate incidence rate ratio of loss to follow-up. Of the 62,664 TB patients registered at the SQHC, around 10% each were actively screened by the CHSP and the IPC, and 78.9% were walk-in patients. Overall cumulative incidence for loss to follow-up rate was significantly higher in the IPC channel (14.2%, 95% CI 13.4–15.1%) than walk-in patients (8.9%, 95% CI 8.6–9.1%) and the CHSP channel (5.5%, 95% CI 5.0–6.1%) (p<0.001). The median time after which patients were lost to follow-up from treatment was 4.04 months. We found that patients with older age, male sex, patients residing in hilly region, unknown smear status, retreated cases, HIV co-infection, and unknown HIV status were risk-factors for loss to follow-up in the continuation phase of treatment; whereas patients with higher initial body weight, patients who received travel support and patients taking treatment in older providers were less likely to be lost to follow-up. Conclusions: Based on these findings, we recommend that implementation strategies for improving case notification and treatment seeking should carefully consider retention strategies in parallel, and the identified influencing factors for loss to follow-up should be taken account for such consideration. [ABSTRACT FROM AUTHOR]

Background: Assessing the illness perception of patients with tuberculosis (TB) could improve our understanding of their beliefs about disease and help address problems in their health-seeking behavior. Study aim: We assessed illness perception in patients with pulmonary TB in association with patients’ demographic, socioeconomic, and clinical features. Methods: Adult patients who were newly diagnosed with pulmonary TB at three tertiary hospitals in South Korea were included from November 2016 and September 2018. Participants’ illness perception was assessed using the Brief Illness Perception Questionnaire (BIPQ) at the start of anti-TB treatment. Results: In total, 390 patients with pulmonary TB completed this survey. The mean BIPQ score was 31.6 ± 13.2, and that was positively correlated with clinical TB scores. Patients were highly concerned about their illness, but believed in the treatment. Unhealthy eating habits were mentioned as the most prevalent perceived cause. Coughing for more than one month and alarming symptoms were significantly associated with BIPQ scores ≥ 33. Non-adherent patients had significantly higher BIPQ scores. Conclusions: Assessing the illness perceptions of those with severe TB-related symptoms and signs may help to identify TB patients with vulnerable to poor treatment outcomes. [ABSTRACT FROM AUTHOR]

Background: NTZ is approved in Russia for the treatment of highly active relapsing remitting multiple sclerosis and is reimbursed via federal budget program. However, no data about NTZ treatment in Russia and the effect of federal reimbursement have been performed so far. Objective: To characterize the population of patients receiving natalizumab and assess the efficacy and risk-management plan (RMP) implementation of NTZ therapy in routine clinical practice in Russia. Methods: We analyzed data for 334 patients, who received at least one infusion of NTZ. Relapse rate, MRI activity, NEDA-3 status after 2 years were assessed. Anti-JC virus antibodies status and RMP implementation were evaluated. Drop-out rate and reasons for therapy discontinuation were analyzed. Results: Patients switched to natalizumab in Russia are mainly female (63%), with median EDSS score of 3.5 and high disease activity: 93% had at least 1 relapse and 58% had both T1Gd+ and new T2 lesion a year before therapy initiation. Introduction of federal reimbursement allowed patients with less relapses to start therapy with natalizumab. The only predictor of 6-month progression was EDSS score at the baseline of therapy (HR = 2.1375, 95%CI 1.0026–4.5570, p = 0.0492). 82% patients reached NEDA-3 at 24 month of therapy. 25% of patients discontinued NTZ for reasons: tolerability (14.5%), JCV antibody status (61%), and patient’s decision (17%). RMP was implemented in only 36% patients. Conclusion: Natalizumab appeared to have high efficacy in Russian clinical practice. Federal reimbursement allowed less active patients to start natalizumab. More efforts should be done to improve RMP implementation. [ABSTRACT FROM AUTHOR]

To investigate how changes in eGFR can affect medical costs, a regional cohort of national health insurance beneficiaries in Japan was developed from a nationwide database system (Kokuho database, KDB), and non-individualized data were obtained. From 105,661 people, subjects on chronic dialysis and subjects without consecutive medical checkups were excluded. Finally, medical costs in the follow-up year categorized by annual changes in eGFR between baseline and the next year were longitudinally examined in 70,627 people ranging in age from 40 to 74 years. Global mean costs for subjects with a rapid decrease in eGFR (≤-30%/year) were the highest among all ΔeGFR categories. In men, the cost was 1.42 times that for a stable eGFR. A total of 6,268 (19.4%) men and 5,381 (14.0%) women with eGFR <60 ml/min/1.73 m2 were identified in the baseline year. The mean cost was higher with a low eGFR than without a low eGFR, and there were also higher proportions newly initiating dialysis in 2014 (low eGFR with rapid decrease in eGFR vs. with stable eGFR: 9.61% vs. 0.02% in women, P<0.001). Moreover, the costs for low eGFR subjects with a rapid decrease in eGFR were more than twice those of non-low eGFR subjects with a rapid decrease in eGFR and also compared to low eGFR subjects with a stable eGFR. Moreover, initiating chronic dialysis was considered one of the major causes of high medical costs in women with rapid eGFR decline. To the best of our knowledge, this is the first study of renal disease using a cohort developed from the KDB system recently established in Japan. [ABSTRACT FROM AUTHOR]

Background: Multiple Sclerosis (MS) is a chronic neurological disease with heavy economic and social burdens resulting in significant disability. Objective: This study aims to (1) measure the cost of health resources utilization by MS patients and (2) to examine the difference in utilization and its attributed costs amongst patients who may have a different course of MS and expanded disability status scale (EDSS) scores. Methods: A cross-sectional study using Kuwait National MS registry was conducted to estimate the costs of utilization of resources from 2011 to 2015. Results: Between the period 2011–2015, 1344 MS patients were included in the registry. The average annual cost per MS patient has increased from $10,271 in 2011 to $17,296 in 2015. Utilization of disease-modifying therapies (DMTs) was the main driver of costs reaching 89.9% in 2015. Throughout the five-year period, the occurrence of relapses decreased from 21.8% to 12.2% (p <0.0001). During this same period, ambulatory relapse treatment increased by 5.8% while hospitalizations decreased by 2.6%. Patients with a moderate EDSS score (3.5–6) had the highest average cost (p<0.0001) compared to mild and severe EDSS scores. Conclusions: Multiple sclerosis has been a significant economic burden on the Kuwait healthcare system. DMTs are the main driver of cost. [ABSTRACT FROM AUTHOR]

Background: China has a substantial tuberculosis (TB) disease burden and an aging population. Seniors have a higher risk of developing TB disease compared to younger age groups. Active case finding (ACF) could help identify seniors with TB disease. Methods: From March to June 2017, we included ACF during annual physical check-ups for persons aged ≥ 65 years in Bayi, Sichuan Province. Seniors with clinical TB symptoms (i.e., cough lasting ≥ 2 weeks and/or hemoptysis) or one or more risk factors (e.g., previous TB disease, diabetes, and heavy alcohol consumption) were offered chest x-rays. We used acid-Fast Bacilli smear and solid culture laboratory testing for TB confirmation. We calculated the yield (i.e., cases identified among seniors screened) and cost per new each TB case detected. Focus group-interviews were conducted with health care workers and seniors to evaluate project acceptability. Participation rates and acceptability were used to assess feasibility. Results: Of the 2,393 seniors residing in Bayi, 2,049 (85.6%) were enrolled in the pilot project. Of these seniors, 794 (38.7%) presented with at least one TB risk factor and 74 (3.6%) had symptoms consistent with active TB disease. Three seniors (0.2%)–each presenting with at least one risk factor—were diagnosed with active TB. The project yielded 146 TB cases per 100,000 seniors screened; the cost per case detected was $4,897. Most workers supported ACF if additional resources and staff could be provided. Seniors appreciated the convenience of this integrated health service approach. Conclusions: Although the yield was lower than expected, ACF appeared feasible in Bayi. Targeting seniors with at least one known TB risk factor could help detect previously unidentified TB cases. However, similar projects in communities with a higher TB prevalence are needed to further evaluate the yield and required resources prior to implementation on a larger scale. Findings from our pilot project should be combined with data from these future ACF projects to improve TB screening criteria. [ABSTRACT FROM AUTHOR]

Background: The crushed-tablet rivaroxaban concentration has been previously reported to be lower than the non-crushed concentration. However, the rivaroxaban concentration of fine granules has not yet been investigated. The anticoagulation intensity of rivaroxaban with fine granules, tablets, and crushed tablets was compared in acute stroke patients to assess the efficacy of each form. Methods and findings: Hospitalized patients over 75 years old with acute stroke who started taking rivaroxaban from April 2012 to September 2017 were included. Blood samples were drawn just before and 4 hours after taking rivaroxaban on a median of 5 days after treatment initiation for concentration measurements (C0h, C4h) based on an anti-factor Xa chromogenic assay. Of 114 patients (49 female, 83±5 years old), 97 had ischemic strokes, 9 had transient ischemic attacks, and 8 had intracerebral hemorrhages. Rivaroxaban was administered a median of 7 days after onset. Of these, 38 patients were given the 15 mg dose, and 76 were given the 10 mg dose. In the 15 mg dose group, C0h was significantly higher in the fine granule group than in the crushed tablet group, with no significant difference compared to the tablet group [C0h: 27.6±6.8 vs 4.0±4.1 (P = 0.01) vs. 33.3±25.2 ng/ml, (P = 0.51), respectively], as was C4h [223.0±66.6 vs 103.0±79.5 (P = 0.02) vs. 229.5±121.6 ng/ml (P = 0.88)]. In the 10 mg dose group, C0h was significantly higher in the fine granule group than in the crushed tablet group and comparable to that in the tablet group [23.2±7.9 vs 7.5±6.2 (P<0.01) vs 19.0±15.8 ng/ml, (P = 0.35)], as was C4h [150.7±85.4 vs 85.1±46.8 (P<0.01) vs 189.8±92.7 ng/ml (P = 0.18)]. Conclusions: The rivaroxaban concentration with fine granules was consistent with that in the tablet group and higher than that in the crushed tablet group. [ABSTRACT FROM AUTHOR]