No increased risk of tuberculosis-related immune reconstitution inflammatory syndrome with integrase inhibitor-based antiretroviral therapy in people with HIV with profound immunosuppression.

INTRODUCTION: The issue of whether integrase inhibitors (INSTIs) may confer a higher risk of paradoxical tuberculosis-related immune reconstitution inflammatory syndrome (TB-IRIS) compared with other classes of antiretroviral in people with HIV with a profound level of immunosuppression remains insufficiently explored. We aimed to assess whether such a higher risk exists by examining a cohort of patients with TB-HIV initiating antiretroviral therapy (ART) in Hong Kong. METHODS: This was a retrospective review of 133 patients registered in the TB-HIV Registry of the Department of Health during the period 2014-2021. RESULTS: Sixteen of 70 patients (22.9%; 95% confidence interval [CI] 13.0-32.7) and 14 of 63 patients (22.2%; 95% CI 12.0-32.5) from the INSTI and non-INSTI groups experienced TB-IRIS (p = 0.920). The median intervals between ART initiation and IRIS among patients from the two groups were similar (3 weeks [interquartile range IQR 2.0-7.8] vs. 4 weeks [IQR 2.0-5.1], p = 0.620). The proportion of patients requiring steroid therapy were similar, as were the hospitalization rates. There was no IRIS-related death in either group. The risk of TB-IRIS with INSTI versus non-INSTI was also similar in a stratified analysis in a subgroup of patients with a baseline CD4 count of <50 µL (10/33 [30.3%; 95% CI 14.6-46.0] vs. 10/22 [45.5%; 95% CI 24.7-66.3], p = 0.252) and another subgroup of patients with ART initiated within 4 weeks of anti-TB treatment (10/26 [38.5%; 95% CI 19.8-57.2] vs. 10/23 [43.5%; 95% CI 23.2-63.7], p = 0.721). CONCLUSION: Our cohort study did not offer support for an increased risk of TB-IRIS with INSTIs compared with non-INSTIs, even in severely immunocompromised people with HIV.

Association of smoking cessation with airflow obstruction in workers with silicosis: A cohort study.

BACKGROUND: Studies in general population reported a positive association between tobacco smoking and airflow obstruction (AFO), a hallmark of chronic obstructive pulmonary disease (COPD). However, this attempt was less addressed in silica dust-exposed workers. METHODS: This retrospective cohort study consisted of 4481 silicotic workers attending the Pneumoconiosis Clinic during 1981-2019. The lifelong work history and smoking habits of these workers were extracted from medical records. Spirometry was carried out at the diagnosis of silicosis (n = 4177) and reperformed after an average of 9.4 years of follow-up (n = 2648). AFO was defined as forced expiratory volume in one second (FEV1)/force vital capacity (FVC) less than lower limit of normal (LLN). The association of AFO with smoking status was determined using multivariate logistics regression, and the effect of smoking cessation on the development of AFO was evaluated Cox regression. RESULTS: Smoking was significantly associated with AFO (current smokers: OR = 1.92, 95% CI 1.51-2.44; former smokers: OR = 2.09, 95% CI 1.65-2.66). The risk of AFO significantly increased in the first 3 years of quitting smoking (OR = 1.23, 95% CI 1.02-1.47) but decreased afterwards with increasing years of cessation. Smoking cessation reduced the risk of developing AFO no matter before or after the confirmation of silicosis (pre-silicosis cessation: HR = 0.58, 95% CI 0.46-0.74; post-silicosis cessation: HR = 0.62, 95% CI 0.48-0.79). CONCLUSIONS: Smoking cessation significantly reduced the risk of AFO in the workers with silicosis, although the health benefit was not observed until 3 years of abstinence. These findings highlight the importance of early and long-term smoking cessation among silicotic or silica dust-exposed workers.

Association of ambient PM2.5 concentration with tuberculosis reactivation diseases-an integrated spatio-temporal analysis.

Objectives: While the plausible role of ambient particulate matter (PM)2.5 exposure in tuberculosis (TB) reactivation has been inferred from in vitro experiments, epidemiologic evidence is lacking. We examined the relationship between ambient PM2.5 concentration and pulmonary TB (PTB) in an intermediate TB endemicity city dominated by reactivation diseases. Methods: Spatio-temporal analyses were performed on TB notification data and satellite-based annual mean PM2.5 concentration in Hong Kong. A total of 52,623 PTB cases from 2005-2018 were mapped to over 400 subdistrict units. PTB standardized notification ratio by population subgroups (elderly aged ≥65, middle-aged 50-64, and young adults aged 15-49) was calculated and correlated with ambient PM2.5 concentration. Results: Significant associations were detected between high ambient PM2.5 concentration and increased PTB among the elderly. Such associations were stable to the adjustment for socio-economic factors and other criteria pollutants. Unstable patterns of association between PM2.5 and PTB risk were observed in the middle-aged population and young adults, for which the observed associations were confounded by other criteria pollutants. Conclusion: With elderly PTB almost exclusively attributable to reactivation, our findings suggested that increased TB reactivations have occurred in association with high ambient PM2.5 exposure, lending support to preventive measures that minimize PM2.5-related TB reactivation.

Association of spirometric restriction with mortality in the silicotics: a cohort study.

BACKGROUND: Restrictive spirometry pattern (RSP), defined as reduced forced vital capacity (FVC) in absence of airflow obstruction (AFO), is associated with increased risk of mortality in general population. However, evidence in the patients with silicosis is limited. This study was aimed to investigate the relationship between RSP and the risk of death in a silicotic cohort. METHOD: This retrospective cohort study used data from the Pneumoconiosis Clinic, Hong Kong Department of Health that containing 4315 patients aged 18-80 years and diagnosed with silicosis during 1981-2019, with a follow-up till 31 December 2019. Spirometry was carried out at the diagnostic examination of silicosis. Lung function categories were classified as normal spirometry (FEV1/FVC ≥ 0.7, FVC ≥ 80% predicted), RSP only (FEV1/FVC ≥ 0.7, FVC < 80% predicted), AFO only (FEV1/FVC < 0.7, FVC ≥ 80% predicted), and RSP&AFO mixed (FEV1/FVC < 0.7, FVC < 80% predicted). The hazard ratio (HR) and 95% confidence intervals (95% CI) were computed using a Cox proportional hazards model adjusting for age, body mass index, history of tuberculosis, smoking status, pack-years, and radiographic characteristics of silicotic nodules. RESULTS: Among the 4315 patients enrolled in the study, the prevalence of RSP was 24.1% (n = 1038), including 11.0% (n = 473) with RSP only and 13.1% (n = 565) with mixed RSP and AFO. During the follow-up period, a total of 2399 (55.6%) deaths were observed. Compared with the silicotics with normal spirometry, those with RSP only had significantly increased risk of all-cause mortality (HR = 1.63, 95% CI 1.44-1.85) and respiratory-related mortality (HR = 1.56, 95% CI 1.31-1.85). Notably, a higher risk of mortality was observed in silicotics with mixed ventilatory defects of both RSP and AFO (all-cause mortality: HR = 2.22, 95% CI 1.95-2.52; respiratory-related mortality: HR = 2.59, 95% CI 2.18-3.07) than in those with RSP only. CONCLUSION: RSP is significantly associated with increased risk of all-cause and respiratory-related mortality in the silicotics, and patients with mixed restrictive and obstructive ventilatory defect have higher risk of mortality than those with single RSP or AFO. These findings emphasize the importance of recognizing RSP in the occupational settings, especially for the silicotic patients with mixed ventilatory defect.

Sex differences in the associations of sleep-wake characteristics and rest-activity circadian rhythm with specific obesity types among Hong Kong community-dwelling older adults.

BACKGROUND: Sex differences exist in sleep characteristics, circadian rhythm and body composition but the evidence on their associations with obesity risk remains unclear. We aimed to examine sex differences in the associations of sleep-wake cycle and rest-activity circadian rhythm with specific obesity types among aged Chinese population. METHODS: This report pooled data from 2 population-based surveys conducted during 4/2018-9/2018 and 7/2019-9/2020. All participants wore actigraphy on wrists for 7 days to measure their objective sleep patterns and rest-activity circadian rhythm. We measured participants' anthropometric data, and obtained their body weight, body fat percentage(fat%), visceral fat rating, muscle mass by calibrated bioelectrical impedance analysis device. Hand-grip strength was assessed by Jamar Hydraulic hand dynamometer. Multinomial logistic regression was performed to assess the odds ratio(OR) and 95% confidence intervals(95%CI). RESULTS: We recruited 206 male and 134 female older adults with complete actigraphy data, with obesity prevalence of 36.9% and 31.3%, respectively. Male participants who had delayed sleep-wake cycle(i.e.,sleep-onset-time and wake-up time) was associated with higher risk of obesity(late sleep-onset-time:OR=5.28, 95%CI=2.00-13.94), and the results remained consistent for different types of obesity. Males with late M10(i.e., most active 10-hours) onset had higher adipose outcomes with an adjusted OR of 2.92(fat%:95%CI=1.10-7.71; visceral fat:95%CI=1.12-7.61). Among female participants, those with lower relative amplitude were associated with higher BMI and lower hand-grip strength. CONCLUSIONS: This study revealed that circadian rhythm fragmentation was associated with obesity and muscle loss. Promoting good sleep quality and maintaining robust circadian rhythm and physical activity can prevent poor muscle strength among older adults.

Association of circadian rhythm with mild cognitive impairment among male pneumoconiosis workers in Hong Kong: a cross-sectional study.

Weakened circadian activity rhythms (CARs) were associated with mild cognitive impairment (MCI) in the general population. However, it remains unclear among pneumoconiosis patients. We aimed to address this knowledge gap. This cross-sectional study comprised 186 male pneumoconiosis patients (71.3 ± 7.8 years) and 208 healthy community men. Actigraphy was used to determine CARs parameters (percent rhythm, amplitude, MESOR, and acrophase). Values below the corresponding medians of the CARs parameters represented weakened CARs. The Cantonese version of Mini-Mental State Examination (CMMSE) was used to assess cognitive function, MCI, and the composite outcome of MCI plus cognitive impairment. Compared with the community referents, pneumoconiosis patients had worse cognition and dampened CARs. Compared with the community referents or pneumoconiosis patients with robust circadian rhythm, pneumoconiosis patients with weakened circadian rhythm were consistently associated with increased risk of MCI and the composite outcome. However, significant association was only observed between MESOR and the composite outcome (adjusted OR = 1.99, 95%: 1.04-3.81). A delayed phase of CARs was insignificantly associated with MCI and the composite outcome. Our findings showed that weakened CARs were associated with worse cognitive function among male pneumoconiosis workers. Intervention in improving CARs may mitigate cognitive deterioration in male pneumoconiosis workers.

Independent effect of weather, air pollutants, and seasonal influenza on risk of tuberculosis hospitalization: An analysis of 22-year hospital admission data.

BACKGROUND: While influenza infections and environmental factors have been documented as potential drivers of tuberculosis, no investigations have simultaneously examined their impact on tuberculosis at a population level. This study thereby made use of Hong Kong's surveillance data over 22 years to elucidate the temporal association between environmental influences, influenza infections, and tuberculosis activity. METHODS: Weekly total numbers of hospital admissions due to tuberculosis, meteorological data, and outdoor air pollutant concentrations in Hong Kong during 1998-2019 were obtained. All-type influenza-like illness positive (ILI+) rate and type-specific ILI+ rates were used as proxies for influenza activity. Quasi-Poisson generalized additive models together with distributed lag non-linear models were used to assess the association of interest. RESULTS: A total of 164,116 hospital admissions due to tuberculosis were notified in public settings over a period of 22 years. The cumulative adjusted relative risk (ARR) of hospital admission due to tuberculosis was 1.07 (95% CI, 1.00-1.14) when the mean ambient temperature increased from 15.1 °C (the 5th percentile) to 24.5 °C (median). Short-term exposure to air pollutants was not found to be statistically significantly related to tuberculosis hospitalization. Accounting for the environmental covariates in the analysis, the cumulative ARR of tuberculosis admission was elevated to 1.05 (95% CI, 1.01-1.08) when the rate of ILI+ total increased from zero to 19.9 per 1000 consultations, the 95th percentile. CONCLUSION: Our findings demonstrated that increased influenza activity and higher temperature were related to a higher risk of tuberculosis admissions. Stepping up the promotion of influenza vaccination, especially before the summer season, may lower the risk of tuberculosis infection/reactivation for vulnerable groups (e.g. elderly born before the launch of Bacillus Calmette-Guérin vaccination programme).

Differences in Sleep Patterns and Mental Health Problems During Different Periods of COVID-19 Outbreak Among Community-Dwelling Older Men in Hong Kong.

Objectives: To determine the association of sleep with mental health among Hong Kong community-dwelling older men in the context of the COVID-19 pandemic. Methods: This additional analysis was derived from the community-dwelling men aged >60 recruited during three COVID-19 outbreaks (i.e., pre-outbreak, between the second and third wave, and during the third wave) in Hong Kong from July 2019 to September 2020. Sleep and mental health were measured by Pittsburgh Sleep Quality Index questionnaire and Hospital Anxiety and Depression Scale, respectively. Multivariate logistic regression models were performed for the associations between sleep and mental health after considering the outbreaks' impact. Results: Subjects enrolled between the second and third wave tended to have better sleep but worse mental health. Positive associations between poor sleep and depression (AOR = 3.27, 95% CI: 1.60-7.03) and anxiety (AOR = 2.40, 95% CI: 1.07-5.76) were observed. The period "between second and third wave" was positively associated with depression (AOR = 2.65, 95% CI: 1.22-5.83), showing an additive interaction with poor sleep. Conclusion: The positive association between poor sleep and depression was aggravated by the period "between the second and third wave" among community-dwelling older males in Hong Kong.

Seasonality of tuberculosis in intermediate endemicity setting dominated by reactivation diseases in Hong Kong.

Summer-spring predominance of tuberculosis (TB) has been widely reported. The relative contributions of exogenous recent infection versus endogenous reactivation to such seasonality remains poorly understood. Monthly TB notifications data between 2005 and 2017 in Hong Kong involving 64,386 cases (41% aged ≥ 65; male-to-female ratio 1.74:1) were examined for the timing, amplitude, and predictability of variation of seasonality. The observed seasonal variabilities were correlated with demographics and clinical presentations, using wavelet analysis coupled with dynamic generalised linear regression models. Overall, TB notifications peaked annually in June and July. No significant annual seasonality was demonstrated for children aged ≤ 14 irrespective of gender. The strongest seasonality was detected in the elderly (≥ 65) among males, while seasonal pattern was more prominent in the middle-aged (45-64) and adults (30-44) among females. The stronger TB seasonality among older adults in Hong Kong suggested that the pattern has been contributed largely by reactivation diseases precipitated by defective immunity whereas seasonal variation of recent infection was uncommon.

Changes in physical activity and rest-activity circadian rhythm among Hong Kong community aged population before and during COVID-19.

BACKGROUND: This study aims to determine the changes in physical activity and actigraphy-measured rest-activity circadian rhythm among Hong Kong community aged population before and during the outbreak of COVID-19. METHODS: This is a three repeated measure population-based cross-sectional study. We recruited community older men aged > 60 years in three periods of the COVID-19 outbreak in Hong Kong, i.e., before the COVID-19 outbreak (2 July 2019-8 January 2020), between the 2nd and 3rd waves of COVID-19 (23 June 2020-9 July 2020), and during the 3rd wave of COVID-19 (15 September 2020-29 September 2020). Participants reported detailed information on their physical activity habits using the International Physical Activity Questionnaire and wore actigraphs continuously for 7 days (168 h). The actigraph data were then transferred to four rest-activity circadian rhythm parameters: midline statistic of rhythm (MESOR), amplitude, acrophase and percent rhythm. Multivariate logistic regression was performed to estimate the association of period effect of COVID-19 on physical activity and rest-activity circadian rhythm parameters. RESULTS: Among the 242 community older men, 106 (43.8%) of them were recruited before the COVID-19 outbreak, 66 (27.3%) were recruited between the 2nd and 3rd waves of COVID-19, and 70 (28.9%) were recruited during the late phase of the 3rd wave of COVID-19. Compared with those recruited before COVID-19, participants recruited between the 2nd and 3rd waves of COVID-19 had lower physical activity (adjusted odds ratio (AOR) = 2.03, 95% confidence interval (95%CI) =1.05-3.93), MESOR (AOR = 2.05, 95%CI = 1.01-4.18), and amplitude (AOR = 1.91, 95%CI = 0.95-3.83). There was no difference in physical activity or circadian rhythm parameters between subjects recruited before and during the late phase of the 3rd wave. CONCLUSIONS: This study found that the effect of COVID-19 on physical activity and rest-activity circadian rhythm for the community people may be short-term, indicating strong resilience of the community population. Although maintaining physical activity are encouraged for the older adults to sustain good health, a rebound in their physical activity may be a sign for the next wave of outbreak if insufficient social distancing and population protection are facilitated.

Abrupt Subsidence of Seasonal Influenza after COVID-19 Outbreak, Hong Kong, China.

The onset of the 2019-20 winter influenza season in Hong Kong coincided with the emergence of the coronavirus disease epidemic in neighboring mainland China. After widespread adoption of large-scale social distancing interventions in response to the impending coronavirus disease outbreak, the influenza season ended abruptly with a decrease to a low trough.

Epidemic and pandemic viral infections: impact on tuberculosis and the lung: A consensus by the World Association for Infectious Diseases and Immunological Disorders (WAidid), Global Tuberculosis Network (GTN), and members of the European Society of Clinical Microbiology and Infectious Diseases Study Group for Mycobacterial Infections (ESGMYC).

Major epidemics, including some that qualify as pandemics, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), HIV, influenza A (H1N1)pdm/09 and most recently COVID-19, affect the lung. Tuberculosis (TB) remains the top infectious disease killer, but apart from syndemic TB/HIV little is known regarding the interaction of viral epidemics and pandemics with TB. The aim of this consensus-based document is to describe the effects of viral infections resulting in epidemics and pandemics that affect the lung (MERS, SARS, HIV, influenza A (H1N1)pdm/09 and COVID-19) and their interactions with TB. A search of the scientific literature was performed. A writing committee of international experts including the European Centre for Disease Prevention and Control Public Health Emergency (ECDC PHE) team, the World Association for Infectious Diseases and Immunological Disorders (WAidid), the Global Tuberculosis Network (GTN), and members of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Mycobacterial Infections (ESGMYC) was established. Consensus was achieved after multiple rounds of revisions between the writing committee and a larger expert group. A Delphi process involving the core group of authors (excluding the ECDC PHE team) identified the areas requiring review/consensus, followed by a second round to refine the definitive consensus elements. The epidemiology and immunology of these viral infections and their interactions with TB are discussed with implications for diagnosis, treatment and prevention of airborne infections (infection control, viral containment and workplace safety). This consensus document represents a rapid and comprehensive summary on what is known on the topic.

Antiviral Therapy for Hepatitis B Prevents Liver Injury in Patients With Tuberculosis and Hepatitis B Coinfection.

BACKGROUND: Chronic hepatitis B virus (HBV) infection increases the risk of liver injury in patients who undergo antituberculosis treatment. It is uncertain whether antiviral treatment for HBV at the time of tuberculosis diagnosis would reduce the risk of liver injury. METHODS: We performed a population-level, retrospective, cohort study that involved all patients with tuberculosis-HBV coinfection treated in public hospitals in Hong Kong over a 16-year period. Patients who received antiviral treatment at the time of tuberculosis diagnosis were considered "patients on antiviral therapy." A multivariable Cox proportional hazards model was used to determine the adjusted hazard ratio of hospitalization due to drug-induced liver injury within 1 year in patients on antiviral therapy, adjusting for the propensity score. RESULTS: Of 3698 patients with tuberculosis-HBV coinfection, 488 (13.2%) were patients on antiviral therapy. Of the remaining 3210 patients, 446 (13.9%) started antiviral therapy within 1 year of tuberculosis diagnosis. Adjusting for the propensity score, patients on antiviral therapy had a lower risk of hospitalization due to drug-induced liver injury compared with those not on treatment (adjusted hazard ratio, 0.44; 95% confidence interval .26-.72). Compared with patients who started antiviral therapy within 1 year of tuberculosis diagnosis, patients on antiviral therapy also had a lower risk of hospitalization due to drug-induced liver injury and a lower risk of liver-related mortality. CONCLUSIONS: We show that antiviral treatment for HBV given at the time of tuberculosis diagnosis reduced the risk of liver injury in tuberculosis-HBV coinfected patients.