Risk of tuberculosis in patients with rheumatoid arthritis in Hong Kong--the role of TNF blockers in an area of high tuberculosis burden.

OBJECTIVES: To elucidate the incidence rate and relative risk of tuberculosis (TB) in patients with rheumatoid arthritis (RA) compared to the general population in Hong Kong between 2004 and 2008, and to assess whether this risk is associated with exposure to tumour necrosis factor (TNF) blockers after adjusting for other known risk factors. METHODS: We reviewed all the medical records of RA patients to determine the standardised incidence ratio (SIR) of TB in RA patients. Independent explanatory variables associated with active TB in RA were ascertained using the Cox regression model. RESULTS: A total of 2441 RA patients followed at the 5 centres were recruited. The mean age at the start of follow up was 56±14 years. The median follow-up duration was 6,616 and 185 patient-years for the TNF naive and TNF treated groups, respectively. Compared to age- and sex-matched population controls, the SIR of active TB in RA was significantly increased (SIR for TNF naïve RA: 2.35, 95% CI 1.17-4.67, p=0.013, SIR for TNF treated RA: 34.92, 95% CI 8.89-137.20, p<0.001). Independent explanatory variables associated with an increase risk of active TB included older age at study entry (RR 1.05, p=0.013) a past history of pulmonary TB (RR 5.48, p=0.001), extra-pulmonary TB (RR 16.45, p<0.001), Felty's syndrome (RR 43.84, p=0.005), prednisolone>10mg daily (RR 4.44, p=0.009) and the use of TNF blockers (RR 12.48, p<0.001). CONCLUSIONS: Exposure to TNF blockers remained to be an independent risk factor for TB in RA after adjusting for other known risk factors.

Very long-term outcome of pure lupus membranous nephropathy treated with glucocorticoid and azathioprine.

The aim of this study is to report the long-term outcome of pure membranous lupus nephropathy (MLN) treated with glucocorticoid and azathioprine (AZA). A cohort of patients with SLE who had biopsy-confirmed pure MLN was treated initially with prednisone (0.8-1.0 mg/kg/day) and AZA (targeted to 2 mg/kg/day). Patients were followed for the following outcomes: remission rate at 12 months, renal flares, extra-renal flares and renal function deterioration. The cumulative risks of renal flares and renal function decline were studied by Kaplan-Meier analysis. Thirty-eight patients were studied (31 women; age 35.0 +/- 9.2 years; mean SLE duration 48.5 +/- 59 months; WHO Class Va 45%, Vb 55%). Twenty-two (58%) patients were nephrotic and four (11%) were hypertensive at presentation. All patients were treated with prednisolone (0.85 +/- 0.24 mg/kg/day) and AZA (1.72 +/- 0.43 mg/kg/day). At 12 months, 24 (67%) patients achieved complete response (CR), 8 (22%) had partial response (PR) and 4 (11%) were treatment resistant. After a follow-up of 12 +/- 5.8 years, 19 episodes of renal flares (15 proteinuric and 4 nephritic) occurred in 13 (34%) patients. The cumulative risks of renal flares at 5, 10 and 15 years were 19.4, 32.0 and 36.8%, respectively. Retreatment with an augmented dosage of prednisolone, +/- another immunosuppressive agent, resulted in CR and PR in 15 (79%) and 4 (21%) of these flare episodes, respectively. At last visit, three (8%) patients had doubling of serum creatinine, whereas six (16%) patients had decline of creatinine clearance by >/=30% (none developed end stage renal failure). Seven episodes of thromboembolic complications occurred in five (13%) patients and 11 episodes of infective complications (five major, six minor) were reported in seven (18%) patients. In the absence of co-existing proliferative lesions, MLN runs a relatively benign course with low risk of renal function deterioration. Treatment with high-dose prednisolone and AZA is effective, inexpensive and well-tolerated. Prolonged observation shows that one of three patients develop renal flares, which are often proteinuric and responsive to reinduction therapy.

Survival prediction in patients with chronic obstructive pulmonary disease following a pulmonary rehabilitation programme in Hong Kong.

BACKGROUND AND OBJECTIVE: Pulmonary rehabilitation programme (PRP) is an important component in the management of chronic obstructive pulmonary disease (COPD). However, to date so far there has been limited literature on the survival outcomes of patients with COPD after a PRP in Hong Kong. This study aimed to investigate the outcomes of a pulmonary rehabilitation programme on the survival rates of a retrospective cohort of patients with COPD. METHODS: This was a retrospective study that included subjects who participated in the PRP in a rehabilitation hospital from the year 2003 to 2015. A total of 431 patients with chronic obstructive pulmonary disease were identified from the electronic record system of the hospital. The dataset were split into two age groups for reporting and analysis using the mean age of 72 as the cut-off. Their median survival times were calculated using Kaplan-Meier analysis. Cox-proportional regression model was used to explore factors that predicted better survival. The most significant predictors were used as strata, and their respective effects on survival functions were analysed with Kaplan-Meier analysis again. RESULTS: The overall median survival of the cohort was 4.3 years. The median survival times of the younger patient group (aged <72) and the older patient group (aged ≥72) were 5.3 and 3.6 years, respectively. For the patients, aged <72 years old, Moser's Activities of Daily Living class and the pulmonary rehabilitation programme completion rate were the most significant survival predictors. For the patients aged ≥72 years old, Monitored Functional Task Evaluation score was the most significant survival predictor. CONCLUSION: Moser's Activities of Daily Living class ≥2 and non-completion of PRP for younger group, low exercise capacity with Monitored Functional Task Evaluation score <17 for older group were identified as significant predictors of poor survival. The findings of this study helped identifying those patients with COPD who have the needs to be more intensively treated and closely monitored.

Behçet's syndrome in a family with inflammatory bowel disease.

Although the gastrointestinal and systemic features of Behcet's syndrome and inflammatory bowel disease overlap to a considerable extent, they are generally viewed as two distinct diseases. We evaluated three members of a family who have inflammatory bowel lesions, two of whom met criteria for Behcet's syndrome. The propositus had classic features of both Crohn's ileocolitis and Behcet's syndrome. A daughter, who never met criteria for Behcet's syndrome, had undergone colectomy for ulcerative colitis. A second daughter had classic features of Behcet's syndrome, including recurrent episodes of colitis with distinct aphthous ulcers in the colon. The findings in this family suggest that inflammatory bowel disease and Behcet's syndrome may be closely related and part of a spectrum of disease rather than distinct disease entities.

Penetration of oral doxycycline into the cerebrospinal fluid of patients with latent or neurosyphilis.

Five patients with laboratory evidence of latent or neurosyphilis were treated orally with doxycycline (200 mg) twice a day for 21 days. After the seventh dose, the mean level of doxycycline in serum was 5.8 micrograms/ml, with a mean drug level in cerebrospinal fluid of 1.3 micrograms/ml. The mean penetration into cerebrospinal fluid was 26%. These preliminary findings suggest that doxycycline, administered orally at a dose of 200 mg twice a day, reaches a sufficient concentration in cerebrospinal fluid to be worthy of further evaluation as an alternative regimen to penicillin therapy for latent or neurosyphilis.

Aspirin dosing using 15 grain enteric coated tablets.

A high unit dose (15 grain/975 mg) enteric coated aspirin preparation was studied in normal individuals and patients with arthritis to determine how readily well tolerated, therapeutic (150-300 micrograms/ml) salicylate (SA) levels could be achieved using a twice daily dosing regimen. Of 36 participants enrolled, 33 (92%) achieved this goal (mean SA = 224 micrograms/ml), while in the remaining 3 an initially toxic level fell below the therapeutic range after reducing the dose by one tablet/day. Although the relationship between dose (mg/kg) and steady state SA levels was roughly linear (r = 0.74), in some subjects there was a striking incremental change in the SA level when the dose was adjusted. Over 90% of subjects taking a starting dose between 45-60 mg/kg/day achieved a therapeutic level. Thus, antiinflammatory therapy using 15 grain/975 mg enteric coated aspirin given twice daily appears to be feasible.