Delayed diagnosis of tuberculosis: risk factors and effect on mortality among older adults in Hong Kong.

OBJECTIVE: To assess the risk factors and effects of delayed diagnosis on tuberculosis (TB) mortality in Hong Kong. METHODS: All consecutive patients with TB notified in 2010 were tracked through their clinical records for treatment outcome until 2012. All TB cases notified or confirmed after death were identified for a mortality survey on the timing and causes of death. RESULTS: Of 5092 TB cases notified, 1061 (20.9%) died within 2 years of notification; 211 (4.1%) patients died before notification, 683 (13.4%) died within the first year, and 167 (3.3%) died within the second year after notification. Among the 211 cases with TB notified after death, only 30 were certified to have died from TB. However, 52 (24.6%) died from unspecified pneumonia/sepsis possibly related to pulmonary TB. If these cases are counted, the total TB-related deaths increases from 191 to 243. In 82 (33.7%) of these, TB was notified after death. Over 60% of cases in which TB diagnosed after death involved patients aged ≥80 years and a similar proportion had an advance care directive against resuscitation or investigation. Independent factors for TB notified after death included female sex, living in an old age home, drug abuse, malignancy other than lung cancer, sputum TB smear negative, sputum TB culture positive, and chest X-ray not done. CONCLUSIONS: High mortality was observed among patients with TB aged ≥80 years. Increased vigilance is warranted to avoid delayed diagnosis and reduce the transmission risk, especially among elderly patients with co-morbidities living in old age homes.

Diagnostic stewardship programme for urine culture: impact on antimicrobial prescription in a multi-centre cohort.

BACKGROUND: Restricting urine culture to patients with genuine urinary tract infection (UTI) reduces excessive antimicrobial prescription for asymptomatic bacteriuria. AIM: To evaluate the impact of urine culture diagnostic stewardship on antimicrobial consumption. METHODS: This quasi-study involved two general hospitals and 10 community clinics. In the pre-intervention (control) phase (25th November 2018-2nd February 2019), microscopy and culture results of all urine specimens were reported. In the post-intervention (study) phase (25th November 2019-2nd February 2020), urine cultures were processed and reported only if at least one of the following criteria were met: presence of white blood cells or bacteria on microscopy; patient from obstetrics, urology, paediatrics, oncology or renal transplant ward; specimen labelled as 'pregnancy', 'urological procedure', 'renal transplant' or 'neutropenic'; and ureteric, nephrostomy or suprapubic urine. For urine samples that did not fulfil these criteria, the microscopy results and a rejection comment were reported. FINDINGS: In total, 12,282 urine specimens were included in the intervention phase. Of these, 4757 (38.7%) specimens did not fulfil the screening criteria, and the microscopy result and a rejection comment were reported. One hundred and sixty-three (3.4%) of these non-reported urine cultures yielded significant bacterial growth, and the majority were Escherichia coli (N=58, 35.6%). Diagnostic stewardship was independently associated with lower antimicrobial consumption [adjusted odds ratio 0.76, 95% confidence interval (CI) 0.70-0.83, P<0.001] on multi-variable logistic regression across all healthcare settings. Diagnostic stewardship had no effect on patient mortality (adjusted hazard ratio=0.95, 95% CI 0.89-1.01, P=0.08). No patients with unreported urine culture developed bacteraemia from untreated UTI. CONCLUSION: Diagnostic stewardship of urine culture safely reduced excessive antimicrobial prescription for asymptomatic bacteriuria.

Healthcare workers acquired COVID-19 disease from patients? An investigation by phylogenomics.

The increasing number of coronavirus disease 2019 (COVID-19) cases in the community has posed a significant epidemic pressure on healthcare settings. When healthcare workers (HCWs) acquire COVID-19, contact tracing and epidemiological investigation might not be adequate for determining the source of transmission. Here, we report a phylogenetic investigation involving two infected HCWs and nine patients to determine whether patient-to-HCW transmission had occurred in a hospital without a previous COVID-19 outbreak. This is the first study to apply phylogenomics to investigate suspected nosocomial transmission in a region with low prevalence of COVID-19. Our results do not support the occurrence of direct patient-to-HCW transmission.

Early and late tuberculosis risks among close contacts in Hong Kong.

SETTING: Tuberculosis (TB) notification is a statutory requirement in Hong Kong, where contact investigations are performed by the Tuberculosis and Chest Service. OBJECTIVES: 1) To evaluate the risk of active TB in close contacts within 5 years, and 2) to identify risk factors associated with early and late development of active TB disease. DESIGN: The characteristics of consecutive TB cases notified from 18 January to 17 April 2000 were collected together with those of their contacts. Contacts were prospectively followed up through the territory-wide TB notification registry for 5 years for the development of disease. RESULTS: A total of 1537 index cases and 4661 close contacts were analysed. Screening found 31 (0.67%) active TB cases within a 3-month period, and another 58 (1.24%) cases presented subsequently. Index cases with cough or pulmonary cavities and diabetic contacts were independent risk factors of early cases (all P<0.05). Adjusted at risk index characteristics for late TB development included positive sputum smear (2.79, 95%CI 1.31-5.95) and family history of TB (4.26, 95%CI 2.01-9.03). Contact risk factors included diabetes mellitus (3.44, 95%CI 1.04-11.33) and institutionalisation (3.61, 95%CI 1.70-7.65). CONCLUSION: Considerable TB risk remains after initial contact screening. A number of possible risk factors were identified.

Tuberculosis is associated with increased lung cancer mortality.

SETTING: Elderly persons living in the community in Hong Kong. OBJECTIVE: To examine the association between tuberculosis (TB) and lung cancer. DESIGN: Elderly clients enrolled in a health programme from 2000 to 2003 were retrospectively cross-matched with the territory-wide TB notification registry for TB before enrolment. The cohort was followed up prospectively through linkage with the territory-wide death registry for cause of death until 31 December 2011. All subjects with suspected malignancy or recent weight loss (≥5%) at enrolment and deaths within the first 2 years of follow-up were excluded. RESULTS: Of the 61,239 subjects included, 516 had TB before enrolment. After 490,258 person-years of follow-up, respectively 1344, 910 and 2003 deaths were caused by lung cancer, other tobacco-related malignancies and non-tobacco-related malignancies. TB before enrolment was associated with death due to lung cancer (Mantel-Haenszel weighted relative risk 2.61, 95%CI 1.82-3.74, P < 0.001) but not other malignancies after stratification by sex. TB remained an independent predictor of lung cancer death (adjusted hazard ratio 2.01, 95%CI 1.40-2.90; P < 0.001), after adjustment for multiple potential confounders. CONCLUSIONS: TB was independently associated with subsequent mortality due to lung cancer. This finding calls for intensification of tobacco control and better targeting of lung cancer screening in high TB burden areas.

Role of whole-blood interferon-gamma release assay in the diagnosis of smear-negative tuberculosis.

SETTING: Hong Kong Chest Clinics. OBJECTIVES AND METHODS: To conduct a prospective study investigating the role of a whole-blood interferon-gamma release assay, QuantiFERON®-TB Gold In-Tube (QFT-GIT), in the diagnosis of smear-negative tuberculosis (TB). The QFT-GIT result was compared with the final confirmed diagnosis after 12 months. RESULTS: Of 262 smear-negative subjects, 188 had active TB, 167 (88.8%) of whom were QFT-GIT-positive; 74 had inactive/non-TB, 30 (40.5%) of whom were QFT-GIT-negative. The positive (PPV) and negative predictive values for active TB were respectively 79.1% and 58.8%. For this target group with high TB prevalence (71.8%), a positive test increased the chance of active disease by only 7.3%. Despite a positive likelihood ratio (LR) of 1.49, the negative LR was 0.28, making the diagnosis of active TB much less likely after a negative test. Although sensitivity and specificity showed no difference across different age groups, the PPV decreased (P < 0.001) with increasing age, likely reflecting the increased prevalence of competing diagnoses. CONCLUSION: In an area with a high prevalence of latent TB infection, a positive QFT-GIT test does not add much to confirm the diagnosis of smear-negative TB, while a negative test indicates a need for further investigation.

Peak plasma rifampicin level in tuberculosis patients with slow culture conversion.

The clinical utility of therapeutic drug monitoring in tuberculosis has not been adequately evaluated by controlled clinical trials. To examine the relationship between slow culture conversion and peak plasma rifampicin level (Cmax-rfm) in a case-control study, patients with persistence of positive sputum smear despite at least 8 weeks of directly observed treatment with standard pyrazinamide-containing regimens were enrolled prospectively in government chest clinics from 16 December 2005 to 15 November 2006. Patients with multidrug-resistant tuberculosis, human immunodeficiency virus infection, or poor treatment adherence were excluded. Cases referred to patients with persistence of positive culture whereas controls had negative culture despite positive smear. Blood was checked at 2 and 4 hours post-dosing to capture Cmax-rfm. A cohort of 88 patients was identified. After excluding 16 patients, there were 36 controls and 36 cases. None had symptoms of malabsorption. Cmax-rfm was below 6 mg/l among 47% of controls and 44% of cases. Univariate and multiple logistic regression analyses showed no significant association between slow culture conversion and Cmax-rfm after logarithmic transformation. Thus, there is probably no association between Cmax-rfm and slow culture conversion.

Spinal lipoma misinterpreted as a meningomyelocele on antenatal MRI scan in a baby girl.

INTRODUCTION: Antenatal screening for spina bifida with ultrasound and MR imaging is increasingly used. CASE REPORT: A baby girl's antenatal MRI examination showed features originally interpreted as a lumbar meningomyelocele. Repeat MRI examination soon after birth showed features of a spinal lipoma (lipomeningomyelocele). This was excised surgically and complete spinal cord untethering was achieved. CONCLUSION: As antenatal MR scanning is increasingly used, and fetal surgery is becoming more prominent, the correct interpretation of such images is crucial. We present a rare case of a misleading antenatal radiological diagnosis of spina bifida, which would have had severe implications if termination of the pregnancy or intra-uterine surgical repair had been considered.

Predicting prosthetic rehabilitation outcome in lower limb amputee patients with the functional independence measure.

OBJECTIVE: To determine the value of the Functional Independence Measure (FIM) score as a prognostic indicator for prosthetic use in the lower limb amputee patient. DESIGN: Cohort study of 41 patients with lower limb amputations. SETTING: University hospital rehabilitation unit. MAIN OUTCOME MEASURES: FIM motor subscore and Houghton Scale for prosthetic use. RESULTS: FIM score on admission did not correlate with prosthetic use as measured by the Houghton Scale; however, FIM motor subscore at discharge did. CONCLUSION: The admission FIM score is not useful in predicting successful prosthetic rehabilitation in lower extremity amputee patients. Only the motor subscore at discharge correlates with the use of prosthesis.

Flagellar determinants of bacterial sensitivity to chi-phage.

Bacteriophage chi is known to infect motile strains of enteric bacteria by adsorbing randomly along the length of a flagellar filament and then injecting its DNA into the bacterial cell at the filament base. Here, we provide evidence for a "nut and bolt" model for translocation of phage along the filament: the tail fiber of chi fits the grooves formed by helical rows of flagellin monomers, and active flagellar rotation forces the phage to follow the grooves as a nut follows the threads of a bolt.

Phase I clinical trial of allogeneic mixed lymphocyte culture (cytoimplant) delivered by endoscopic ultrasound-guided fine-needle injection in patients with advanced pancreatic carcinoma.

BACKGROUND: To the authors' knowledge, there are no other published clinical studies that have employed either systemic or local biologic response modifiers in the treatment of patients with pancreatic carcinoma. The purpose of this study was to determine the feasibility and safety of allogeneic mixed lymphocyte culture (cytoimplant) delivered by endoscopic ultrasound (EUS)-guided fine-needle injection (FNI) in patients with advanced pancreatic carcinoma. METHODS: Eight patients with unresectable adenocarcinoma of the pancreas were enrolled: 4 patients in Stage II, 3 in Stage III, and 1 in Stage IV. Cytoimplants were delivered locally into the tumor using a novel EUS-guided FNI technique. Escalating doses of 3, 6, or 9 billion cells were implanted into the pancreatic tumor by a single EUS-guided FNI. Toxicity (modified National Cancer Institute criteria) was assessed at Day 1, Week 1, and Months 1 and 3. Clinical endpoints included Karnofsky performance status (KPS), CA 19-9, tumor response (computed tomography and/or EUS), and survival with follow-up examinations and imaging tests on months 3, 6, 9, 12, and 24. RESULTS: There were no bone marrow, hemorrhagic, infectious, renal, cardiac, or pulmonary toxicities. There were 3 transient Grade 3 gastrointestinal toxicities, and 3 patients had transient episodes of hyperbilirubinemia that were reversed by replacement of biliary stents. Seven of 8 patients (86%) experienced low grade fever that responded to acetaminophen, and all fever was resolved within the first 4 weeks. There were no procedure-related complications. There were 2 partial responses and 1 minor response, with a median survival of 13.2 months. CONCLUSIONS: A single injection of cytoimplant immunotherapy by EUS-guided FNI appears to be feasible and is not associated with substantial toxicity.