Denosumab treatment and infection risks in patients with osteoporosis: propensity score matching analysis of a national-wide population-based cohort study.

Introduction: Denosumab demonstrates efficacy in reducing the incidence of hip, vertebral, and nonvertebral fractures in postmenopausal women with osteoporosis. We present a population-based national cohort study to evaluate the infection risks in patients with osteoporosis after long-term denosumab therapy. Methods: We used the Taiwan National Health Insurance Research Database (NHIRD) to identify patients with osteoporosis. The case cohort comprised patients treated with denosumab. Propensity score (PS) matching was used to select denosumab nonusers for the control cohort. The study period was between August 2011 and December 2017. Our study comprised 30,106 pairs of case and control patients. Results: Patients receiving denosumab therapy had high risks of the following infections: pneumonia and influenza (adjusted hazard ratio [aHR]: 1.33; 95% confidence interval [CI]: 1.27 -1.39), urinary tract infection (aHR: 1.36; 95% CI:1.32 -1.40), tuberculosis (aHR: 1.60; 95% CI: 1.36 -1.87), fungal infection (aHR: 1.67; 95% CI:1.46 -1.90), candidiasis (aHR: 1.68; 95% CI: 1.47 -1.93), herpes zoster infection (aHR: 1.27; 95% CI: 1.19 -1.35), sepsis (aHR: 1.54; 95% CI:1.43 -1.66), and death (aHR: 1.26; 95% CI: 1.20 -1.32). However, the longer the duration of denosumab treatment, the lower the risk patients had of developing infections. Discussion: Denosumab therapy is associated with a higher infection risk at the early periods of treatment. Nevertheless, the risk attenuates significantly after the 2nd year of therapy. Clinicians should closely monitor infection status in patients with osteoporosis during the initial stages of denosumab therapy.

Metabolic Syndrome Prevalence among High School First-Year Students: A Cross-Sectional Study in Taiwan.

Different types of high schools in Taiwan have the same physical education curriculum. In this cross-sectional study, we investigated the difference in the prevalence of metabolic syndrome between senior and vocational high school students. We retrospectively collected health check-up data from 81,076 first-year senior and 68,863 vocational high school students in Taipei City from 2011 to 2014, including their blood pressure, height, weight, waist circumference, fasting blood glucose, total cholesterol, triglyceride, and HDL-c levels. The prevalence of metabolic syndrome was determined using definitions from the Taiwan Pediatric Association (TPA), International Diabetes Federation (IDF), and de Ferranti et al. The prevalence of metabolic syndrome was 1.73% (senior and vocational high school students: 1.22% and 2.33%, respectively) using TPA criteria, 1.02% (0.69% and 1.40%, respectively) using IDF criteria, and 5.11% (3.92% and 6.51%, respectively) using de Ferranti et al. criteria. The most prevalent risk factors overall were increased blood pressure and central obesity. Given the significantly higher prevalence of metabolic syndrome in vocational school students regardless of the criteria, and that metabolic syndrome causes future adult health risks, the physical education curriculum and health education program in vocational schools should be strengthened to decrease the risk and prevalence of metabolic syndrome.

Evaluation of a Rapid Antigen Test for the Diagnosis of SARS-CoV-2 during the COVID-19 Pandemic.

OBJECTIVES: Reverse transcriptase-polymerase chain reaction (RT-PCR), the reference laboratory method of confirmed SARS-CoV-2 diagnosis, though requiring equipment, is time-consuming. There is a crucial demand for rapid techniques such as antigen detection test during the pandemic. This study assessed whether a rapid antigen detection (RAD) test was an effective and essential method for the early diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the COVID-19 pandemic. The probability of public screening at home and the application of RAD during the novel SARS-CoV-2 outbreak were also topics of interest. METHODS: A retrospective analysis based on the systemic screening for COVID-19 was conducted at Taipei City Hospital (TCH) from May 28 to June 06, 2021, the first week of outbreak in Taiwan. The results of the RAD and RT-PCR tests were collected from 5 major branches of the TCH. RESULTS: We collected a total number of 6368 cases. We found that the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy ranged from 60.5% to 78.6% (mean 66.0%), 98.2% to 99.9% (mean 99.0%), 74.4% to 97.8% (mean 82.8%), 94.0% to 98.4% (mean 97.5%), and 93.8% to 98.3% (mean 94.2%), respectively. Although the sensitivity score was not high (up to 95% or higher), the other results were satisfactory, with an accuracy of more than 93% in all branches. Furthermore, it had high specificity, PPV, NPV, and accuracy. CONCLUSION: We concluded that RAD could be a quick and feasible method to identify individuals infected with SARS-CoV-2 from non-contagious individuals during the COVID-19 outbreak. A RAD test was an effective and essential method for the early diagnosis of SARS-CoV-2 during the COVID-19 pandemic.

Systematic Screening for SARS-CoV-2 to Detect Asymptomatic Infections: An Epitome of Taiwan's Outbreak.

BACKGROUND: Increased studies have revealed that asymptomatic carriers substantially impact the epidemic and that asymptomatic transmission is very common. Therefore, the asymptomatic transmission threat to the spread of the pandemic should not be neglected. METHODS: The local outbreak in Taiwan, especially in Taipei City, is unprecedented and paramount and has claimed hundreds of lives, tens of thousands of cases, and enormous economic costs. As care providers and gatekeepers of infectious diseases, Taipei City Hospital has to perform regular polymerase chain reaction (PCR) results of admitted patients and healthcare workers (HCWs) to achieve these goals. RESULTS: In this study, the results revealed a low positive rate of less than 1%, but the asymptomatic proportions could range from 42% to 46%, which bolsters that systematic screening was effective in controlling coronavirus disease-19 (COVID-19) of Novel Coronavirus or Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) and might be an exemplar to other similar scenarios. Universal screening of admitted patients may be important and necessary, especially in asymptomatic patients. CONCLUSIONS: Regular screening for healthcare providers is also important during this pandemic, and it is recommended that admitted patients and healthcare providers undergo systemic PCR testing.

Determinants of latent tuberculosis infection and treatment interruption in long-term care facilities: A retrospective cohort study in Taiwan.

BACKGROUND/PURPOSE: Latent tuberculosis infection (LTBI) treatment is challenging in long-term care facilities (LTCFs) residents due to the occurrence of medical complexities. However, factors associated with treatment interruption have not been extensively studied. This retrospective cohort study aimed to determine LTBI-associated factors and treatment interruption in LTCF residents and employees in Taiwan. METHODS: From May 2017 through September 2020, the residents and employees of 20 LTCFs in Taipei, Taiwan, were screened for LTBI by using QuantiFERON-TB Gold In-Tube test. The LTBI individuals underwent directly observed preventive therapy (DOPT), including regimens of 9-month daily isoniazid (9H) and 3-month weekly isoniazid plus rifapentine (3HP). All the LTBI cases were followed up till treatment completion, death, or treatment interruption. RESULTS: Among 2207 LTCF subjects, 16.8% had LTBI. After controlling for other covariates, residents of public facilities had a significantly higher LTBI prevalence than those of private facilities (adjusted odds ratio [AOR] = 1.43; 95% confidence interval [CI]: 1.08-1.88). Among 264 LTBI cases receiving preventive therapy, 52 (19.7%) had treatment interruption. LTBI cases receiving 3HP were less likely to have treatment interruption than those receiving 9H (AOR = 0.22; 95% CI: 0.07-0.71). CONCLUSIONS: LTCF residents, particular those living in public facilities, had a high LTBI prevalence. 3HP with DOPT is considered the priority regimen for preventive therapy among LTBI cases in LTCFs.

Increased risk of pulmonary and extrapulmonary tuberculosis infection in patients with polycystic kidney disease: a nationwide population-based study with propensity score-matching analysis.

BACKGROUND: Polycystic kidney disease (PKD) is a common renal disorder affecting approximately 1 in 1000 live births. Tuberculosis (TB) is an infectious disease worldwide. This study investigated the risk of TB infection in patients with PKD. METHODS: A nationwide population-based cohort study was performed using Taiwan's National Health Insurance Research Database. We used patients' hospitalization files for the entire analysis during 2000-2012. As per diagnosis, we divided patients into PKD and non-PKD cohorts and the major outcome was TB infection. RESULTS: A total of 13,540 participants with 6770 patients in each cohort were enrolled. The PKD cohort had a higher risk of TB infection than did the non-PKD cohort after adjusting for age, sex, and comorbidities (adjusted hazard ratio (aHR) = 1.91, 95% confidence interval [CI] = 1.51-2.43). When classifying by sites of pulmonary TB (PTB) and extrapulmonary TB (EPTB), the PKD cohort demonstrated a significantly higher risk of EPTB (aHR = 2.44, 95% CI = 1.46-4.08) as well as a risk of PTB (aHR = 1.69, 95% CI = 1.29-2.22). When stratified by the presence or absence of a comorbidity, high TB infection risk was noted in the PKD patients without any comorbidity (HR = 2.69, 95% CI = 1.69-4.30). CONCLUSIONS: Taken together, our findings suggest that PKD is associated with a 1.91-fold increased risk of TB infection. Medical professionls should maintain a high index of suspicion in daily practice for patients with PKD, particularly those with EPTB infection.

Facing the Coronavirus Pandemic: An Integrated Continuing Education Program in Taiwan.

This study aimed to identify knowledge gaps regarding coronavirus disease 2019 (COVID-19) and develop an integrated educational program for healthcare workers. First, we designed and validated ten multiple-choice questions to identify knowledge gaps among healthcare workers. Within one month of the online test and curriculum offering, 5533 staff had completed the test, with a completion rate of 84.97%. There were 2618 healthcare workers who answered the pre-test 100% correctly. Those who did not answer the pre-test 100% correctly took multiple tests after learning through the online teaching materials. Eventually, 5214 staff passed the test (pre-test or post-test with 100% correct answers). The result showed that all staff had a low correct rate for personal protective equipment (PPE) use recommendations. The Infection Control Center conducted training sessions for hospital staff on how to wear protective clothing. Information on the selection and use of PPE for infection prevention was provided, and participants were allowed time to practice and familiarize themselves with the correct way to wear PPE. Moreover, the Department of Education and Research continued updating the online learning materials based on the most important updated peer-reviewed published articles. The attending teaching physicians helped to search, translate, and take notes on articles in the local language (traditional Chinese) for other colleagues to read easily. We expect to increase learning opportunities for healthcare workers, even during uncertain times such as the current coronavirus pandemic through (1) the hospital-wide course announcements, (2) the continuous placement of test questions and learning files on the digital learning platform, (3) the placement of journal highlights in cloud folders, and (4) the use of the digital learning platform on mobile phones accessible outside the hospital.

Olfactory disorder in patients infected with SARS-CoV-2.

Three (60%) of five patients with coronavirus disease 2019 (COVID-19) had olfactory disorder. Two exhibited anosmia at the onset of COVID-19, while one had hyposmia 4 days after the onset of COVID-19. All patients with olfactory disorder were completely recovered with a mean recovery length of 11.3 days.

Effect of ventilation improvement during a tuberculosis outbreak in underventilated university buildings.

The role of ventilation in preventing tuberculosis (TB) transmission has been widely proposed in infection control guidance. However, conclusive evidence is lacking. Modeling suggested the threshold of ventilation rate to reduce effective reproductive ratio (ratio between new secondary infectious cases and source cases) of TB to below 1 is corresponding to a carbon dioxide (CO2 ) level of 1000 parts per million (ppm). Here, we measured the effect of improving ventilation rate on a TB outbreak involving 27 TB cases and 1665 contacts in underventilated university buildings. Ventilation engineering decreased the maximum CO2 levels from 3204 ± 50 ppm to 591-603 ppm. Thereafter, the secondary attack rate of new contacts in university dropped to zero (mean follow-up duration: 5.9 years). Exposure to source TB cases under CO2 >1000 ppm indoor environment was a significant risk factor for contacts to become new infectious TB cases (P < .001). After adjusting for effects of contact investigation and latent TB infection treatment, improving ventilation rate to levels with CO2 <1000 ppm was independently associated with a 97% decrease (95% CI: 50%-99.9%) in the incidence of TB among contacts. These results show that maintaining adequate indoor ventilation could be a highly effective strategy for controlling TB outbreaks.

Sequential risk of depression in children born prematurely: A nationwide population- based analysis.

BACKGROUND: Whether children born prematurely are at a high risk of depression is still unknown. The present study examined the risk of depression in children who were born prematurely, by analyzing a national cohort in Taiwan. METHODS: All premature births between January 1, 2000, and December 31, 2010, by using the Taiwan National Health Insurance Research Database. A total of 21,478 preterm children and 85,903 full-term children were enrolled in this study. Sex, level of urbanization of residential area, and parental occupation were considered. We included participants who received a diagnosis of depression in more than two clinical visits or were hospitalized due to depression. RESULTS: Preterm children had a 2.75-fold higher risk of depression than full-term children (95% confidence interval [CI] = 1.58-4.79, p < 0.001). Sex was not likely to be associated with depression in this study (p = 0.95). The lowest level of urbanization significantly contributed to the risk of depression in preterm children (adjusted hazard ratio = 6.8, 95% CI = 1.63-28.46, p < 0.01). Regarding parental occupation, preterm children whose parents had blue-collar and other occupations had a 3.4- and 6.06-fold higher risk of depression, respectively, compared with other children (blue-collar occupations: 95% CI = 1.04-11.15, p < 0.05; other occupations: 95% CI = 1.71-21.49, p < 0.01). CONCLUSIONS: Preterm children had a 2.7-fold higher risk of depression than children born full-term. Early identification, timely psychiatric care, intervention strategies, and support for their families may reduce the complications of mental illness in preterm children.

Long-Term Outcomes of Systemic Lupus Erythematous Patients after Pregnancy: A Nationwide Population-Based Cohort Study.

BACKGROUND: Data on long-term maternal outcomes in patients with systemic lupus erythematosus (SLE) are lacking. The study aimed to explore the relationships among SLE, pregnancy, outcomes of end-stage renal disease (ESRD), and overall mortality. METHODS: We established a retrospective cohort study consisting of four cohorts: pregnant (case cohort) and nonpregnant SLE patients, as well as pregnant and nonpregnant non-SLE patients. One case cohort and three comparison cohorts were matched by age at first pregnancy and index date of pregnancy by using the Taiwan National Health Insurance Research Dataset. All study subjects were selected based on the index date to the occurrence of ESRD or overall death. Cox proportional hazard regression models and Kaplan-Meier curves were used in the analysis. RESULTS: SLE pregnant patients exhibited significantly increased risk of ESRD after adjusting for other important confounders, including immunosuppressant and parity (HR = 3.19, 95% CI: 1.35-7.52 for pregnant non-SLE; and HR = 2.77, 95% CI: 1.24-6.15 for nonpregnant non-SLE patients). No significant differences in ESRD incidence were observed in pregnant and nonpregnant SLE patients. Pregnant SLE patients exhibited better clinical condition at the baseline and a significantly lower risk of overall mortality than nonpregnant SLE patients. CONCLUSIONS: Our data support current recommendations for SLE patients to avoid pregnancy until disease activity is quiescent. Multicenter recruitment and clinical information can be used to further examine the association of SLE and ESRD (or mortality) after pregnancy.

Molecular diagnosis and clinical presentations of enteroviral infections in Taipei during the 2008 epidemic.

BACKGROUND: In 2008, an epidemic of enterovirus (EV) infection caused hand, foot, and mouth disease (HFMD) and herpangina in children in Taiwan, and some of them died. To establish an early detection and effective management for children with EV71 infection, sensitive molecular diagnostic methods were applied from May to July 2008. METHODS: We used virus isolation, EV71 real-time reverse-transcription polymerase chain reaction (RT-PCR), and viral protein 1 (VP1) RT-PCR followed by direct sequencing to detect EV71 and the other EVs in the infected outpatient or inpatient children. Clinical presentations of children infected with EV71 and other EVs were compared. RESULTS: From May 2008 to July 2008, 255 swabs were tested by both PCR diagnostic methods. Based on the viral isolation results, the sensitivities of EV71 real-time RT-PCR and VP1 RT-PCR followed by direct sequencing were 71% and 86%, respectively. Among the 221 children who were enrolled for clinical analysis, 73% (161 of 221) had herpangina, and 27% (60 of 221) had HFMD. Coxsackievirus A2 (CA2) was the most prevalent among the identifiable viruses (65%, 104 of 160), followed by EV71 (28%, 45 of 160). EV71 was the most commonly detected virus among the HFMD cases (63%, 38 of 60), whereas herpangina was mainly caused by CA2 (61%, 98 of 161). Of the CA2 cases, 94% (98 of 104) had herpangina, and the most common manifestation of EV71 infection was HFMD with or without complications (84%, 38 of 45). Phylogenetic study revealed that the genotype of EV71 cases during this epidemic was of B5 lineage. CONCLUSION: During the 2008 EV epidemic, most of the HFMD was caused by EV71, whereas herpangina was mainly caused by CA2. Real-time RT-PCR for EV71 is a time-saving and sensitive diagnostic tool.

Tourette syndrome in children: an updated review.

Tourette syndrome (TS) is a common neuropsychiatric disorder in children characterized by multiple motor and vocal tics that fluctuate in severity and lasting for at least 1 year. Boys are more commonly affected than girls. Symptoms usually begin with simple motor or vocal tics which then evolve into more complex motor and vocal tics over time. Premonitory sensory urges are common in children over the age of 8 years, and these urges help distinguish tics from symptoms of other movement disorders. Common comorbidities of TS include attention deficit hyperactivity disorder, obsessive-compulsive disorder and learning difficulties. Several genes have been assessed as candidate genes for TS; environmental factors such as stress and streptococcal infections might also contribute to its etiology. The pathophysiology of TS mainly involves dysfunction of basal ganglia-related circuits and hyperactive dopaminergic innervations. A thorough history assessment and neurological examination are important for the correct diagnosis and differentiation from other movement disorders. Treatment for TS should focus on improving the patient's social functioning, minimizing the impairment from cormobid disorders, and controlling tics, if they are severe. Commonly used medications for TS include a2-adrenergic agonists and atypical neuroleptics. Habit reversal therapy is an effective option for TS, and repetitive transcranial magnetic stimulation may be a promising approach for severe cases.

Oral bioavailability, urinary excretion and organ distribution of melamine in Sprague-Dawley rats by high-performance liquid chromatography with tandem mass spectrometry.

High-performance liquid chromatography with tandem mass spectrometry (HPLC/MS/MS) was used to determine melamine oral bioavailability (BA) and urinary excretion. Organ distribution after a 14-day consecutive oral melamine administration (100 mg/kg/day, once a day) was also evaluated. A noncompartmental model was utilized to obtain pharmacokinetic parameters. According to the results, the BA of melamine was estimated to be 98.1%. Approximately 63% of administered melamine was recovered in urine within 96 h after a single oral administration (100 mg/kg). The bladder had the highest melamine concentration of all the organs after a 14-day consecutive oral administration of melamine, and almost no melamine was found in the rat brain. This result indicated that the oral absorption of melamine was almost complete and urinary excretion was the major route for its elimination. Repeated exposure to high-dose melamine may result in only slight accumulation in organs.

Determination of melamine in rat plasma, liver, kidney, spleen, bladder and brain by liquid chromatography-tandem mass spectrometry.

In this study, we describe a method for the analysis of melamine in rat plasma, liver, kidney, spleen, bladder, and brain using trichloroacetic acid precipitation with mixed-mode cation-exchange solid-phase extraction and hydrophilic interaction chromatography coupled to tandem mass spectrometry detection. Method validation was investigated completely, including linearity, precision, accuracy, matrix effect, extraction recovery, and carryover for the determination of melamine. The method exhibited a good linear range covering 20-500 ng/mL, and the overall precision ranged from 1.6 to 16.3%, with the accuracy varying from -7.9 to 15.1%. The mean matrix effects of melamine in rat plasma, liver, kidney, spleen, bladder, and brain ranged from 66.2+/-6.7 to 95.5+/-13.2%, and the mean recoveries for melamine varied from 79.8+/-8.2 to 113.0+/-9.6%. Rat kidney showed the highest level among the organs (192.5% of the plasma melamine level), and the average concentration of melamine in the brain was only 7.5% of the plasma melamine concentration. This work has pointed out that even with the application of two popular preparation procedures (acid precipitation and solid-phase extraction) of melamine, the matrix effect in analyzing biological samples still exists in certain kinds of matrices.