Potential clinical and economic outcomes of active beta-D-glucan surveillance with preemptive therapy for invasive candidiasis at intensive care units: a decision model analysis.

Early initiation of antifungal treatment for invasive candidiasis is associated with change in mortality. Beta-D-glucan (BDG) is a fungal cell wall component and a serum diagnostic biomarker of fungal infection. Clinical findings suggested an association between reduced invasive candidiasis incidence in intensive care units (ICUs) and BDG-guided preemptive antifungal therapy. We evaluated the potential cost-effectiveness of active BDG surveillance with preemptive antifungal therapy in patients admitted to adult ICUs from the perspective of Hong Kong healthcare providers. A Markov model was designed to simulate the outcomes of active BDG surveillance with preemptive therapy (surveillance group) and no surveillance (standard care group). Candidiasis-associated outcome measures included mortality rate, quality-adjusted life year (QALY) loss, and direct medical cost. Model inputs were derived from the literature. Sensitivity analyses were conducted to evaluate the robustness of model results. In base-case analysis, the surveillance group was more costly (1387 USD versus 664 USD) (1 USD = 7.8 HKD), with lower candidiasis-associated mortality rate (0.653 versus 1.426 per 100 ICU admissions) and QALY loss (0.116 versus 0.254) than the standard care group. The incremental cost per QALY saved by the surveillance group was 5239 USD/QALY. One-way sensitivity analyses found base-case results to be robust to variations of all model inputs. In probabilistic sensitivity analysis, the surveillance group was cost-effective in 50 % and 100 % of 10,000 Monte Carlo simulations at willingness-to-pay (WTP) thresholds of 7200 USD/QALY and ≥27,800 USD/QALY, respectively. Active BDG surveillance with preemptive therapy appears to be highly cost-effective to reduce the candidiasis-associated mortality rate and save QALYs in the ICU setting.

Close contact investigation of TB in high-burden, low- and middle-income countries.

Tuberculosis (TB) remains a very common disease in most of the low- and middle-income countries. As a result of high disease burden, TB control measures in these countries are usually concentrated on intensifying active disease case-finding and early treatment of infectious TB. On the contrary, in countries with low disease burden, the focus is on contact investigation to identify latently infected individuals and prophylactically treating them to prevent disease reactivation and transmission. These two strategies are deemed important for the effective TB control. Nonetheless, WHO cautions that targeted contact investigation and latent TB infection (LTBI) treatment should only be undertaken by countries that have the operational capacity/ resources and have achieved ≥ 85% treatment success rate of active TB. The screening of LTBI is further challenged by the lack of a "gold standard" test to identify and validate individuals with this condition. Tuberculin skin test (TST) is still the preferred investigation as it is cheap, widely available and validated in many trials. The sensitivity and specificity of the newer test-interferon gamma release assay (IGRA) for LTBI screening has been encouraging in low prevalence countries. However, the evidence supporting such usage remains uncertain in high burden settings. Diagnosis of LTBI should adhere to the strict criteria outlined in the guidelines to avoid misdiagnosing active TB as LTBI. The treatment of the latter involved only one or two anti-TB drugs. It has been demonstrated that in the properly conducted contact screening and LTBI treatment, chances of the emergence of multi-drug-resistant TB is very low.

Antiphospholipid syndrome with pulmonary artery embolism and multiple venous thromboses.

We report a case of a 21-year-old university student with underlying lupus nephritis who presented with recurrent symptoms of fever, haemoptysis, and pleuritic chest pain. CT pulmonary angiogram confirmed pulmonary embolism in the right subsegmental pulmonary arteries. One week later, she developed left renal vein and left common iliac vein thromboses, with new emboli in the left subsegmental pulmonary arteries. We hereforth discuss the diagnostic issues of a patient with systemic lupus erythematosus (SLE) on corticosteroids therapy, and also treatment of the antiphospholipid syndrome.

Diagnostic yield of flexible bronchoscopic procedures in lung cancer patients according to tumour location.

INTRODUCTION: This study aims to determine whether the diagnostic yield of flexible bronchoscopy sampling procedures in patients with lung cancer was dependent on tumour location. METHODS: A retrospective analysis was conducted on the diagnostic yield of bronchial washing (BW), endobronchial biopsy (EBB), bronchial brushing (BB), bronchoalveolar lavage (BAL), blind brushing (B) and transbronchial biopsy (TBB) specimens obtained at fibre-optic bronchoscopy for patients with lung cancer. RESULTS: Of 503 patients who underwent fibre-optic bronchoscopy examination, BW, EBB, BB, BAL, B and TBB were performed on 254, 325, 67, 155, 70 and 54 patients, respectively. For patients with bronchoscopically-visible tumours, BW, EBB and BB yielded diagnostic specimens for lung cancer in 28.3 percent, 77.5 percent and 53.7 percent of patients, respectively. For patients whose tumours were not visible bronchoscopically, BAL, B and TBB yielded diagnostic specimens for lung cancer in 35.5 percent, 22.9 percent and 31.5 percent of patients, respectively. EBB was less likely to be diagnostic in patients with tumours in the middle or lingular lobe bronchi. The diagnostic yields of all the other sampling techniques were not influenced by the location of the bronchoscopically-visible or non-visible tumours. CONCLUSION: The diagnostic yields of bronchoscopic sampling procedures were dependent on tumour visibility during bronchoscopy and location of bronchoscopically-visible tumours.

Tracheobronchial stenting is safe and effective in relieving upper airway obstruction.

Many studies have shown that tracheobronchial stenting is effective in relieving respiratory distress secondary to major airway obstruction due to lung or oesophageal cancer. A retrospective review on the benefits and complications of self-expandable metallic stent (SEMS) insertion through flexible bronchoscopy for the palliative treatment of upper airway obstruction in University Malaya Medical Centre was performed. Ten patients underwent this procedure. Relief of dyspnoea was immediate following stent insertion in all patients. Stent migration occurred in one patient and three patients had restenosis of the central airway. We conclude that tracheobronchial stenting via flexible bronchoscopy is feasible and safe.

Double-cycle high-dose chemotherapy with peripheral blood stem cells and hematopoietic growth factor support in patients with advanced solid tumor. A pilot study by the Hong Kong Biotherapy Group.

BACKGROUND: High-dose chemotherapy with autologous bone marrow transplantation has been useful in some patients with advanced breast, lymphoma, or germ cell tumors. Double-cycle high-dose chemotherapy may be able to deliver an even higher total dose within a given time period. It is important to determine whether peripheral blood stem cells and hematopoietic growth factors can diminish the hematopoietic toxicity of such a treatment. METHODS: From November 1989 to May 1991, 14 patients were enrolled in two cycles of high-dose chemotherapy consisting of cyclophosphamide, 4.5 g/m2; cisplatin, 150 mg/m2; and etoposide, 900 mg/m2 in each cycle. The first five patients received peripheral blood stem cells harvested from 8-10 leukaphereses during steady state. The next nine patients, besides receiving peripheral blood stem cells mobilized by growth factors, also received either granulocyte-macrophage colony-stimulating factor (GM-CSF) at 250 micrograms/m2/day by two subcutaneous (s.c.) injections given 12 hours apart from day 6 until neutrophil recovery or granulocyte colony-stimulating factor (G-CSF) at 200 micrograms/m2 as daily s.c. injections. RESULTS: For the first five patients, there was a median of 14 days from the first day of absolute marrow suppression to neutrophil count exceeding 500/microliters and a median of 15 days for a platelet count exceeding 20,000/microliters. For the next nine patients, with the use of either G-CSF or GM-CSF, there was a median of 8 days for a neutrophil count exceeding 500/microliters and and a median of 11 days for a platelet count exceeding 20,000/microliters. CONCLUSION: With the use of peripheral stem cells and growth factors, high-dose chemotherapy could be given safely every 30 days with acceptable toxicity. A high complete response rate was seen in patients with nasopharyngeal carcinoma and in patients with small cell and non-small cell lung cancer who either had not received previous chemotherapy or who had responded to previous chemotherapy.

Short-duration in vitro interleukin-2-activated mononuclear cells for advanced cancer. A Hong Kong biotherapy pilot study trial.

BACKGROUND: In vitro studies have demonstrated that a brief exposure of peripherally collected mononuclear cells to high-dose human recombinant interleukin-2(rIL-2) will generate a population of pulsed lymphokine-activated killer (LAK) cells. These cells have similar cytotoxicity against natural killer cells and resistant and sensitive target cells as compared with the standard LAK cells incubated for 3-7 days with rIL-2. Therefore, the authors conducted a pilot study to investigate the activity of pulsed LAK cells in patients with advanced cancer. METHODS: Nineteen patients were enrolled in a pilot study, and pulsed LAK cell treatment was administered two times per week for 4 weeks, followed by similar cycles if patients remained free of disease progression and unacceptable toxic effects. RESULTS: Toxic effects consisted mainly of fever, chills, nausea, and dizziness but were self-limiting and mild. Most cycles were administered on an outpatient basis. There were six partial responses (31%), occurring in two of three patients with renal cell carcinoma, two of four with hepatocellular carcinoma, one of seven with non-small cell lung carcinoma, and one of one with ovarian carcinoma. Two minimal responses were seen in one case each of melanoma and carcinoma of colon. Nine other patients had disease stabilization for 16 weeks, and two additional patients had disease progression. Phenotyping of peripheral mononuclear cells showed increases in CD56 and CD25 populations with no in vivo rIL-2 being administered after treatment with pulsed LAK cells. CONCLUSIONS: The relative ease in generating pulsed LAK cells and the associated mild toxic effects enable prolonged stimulation of the effector cells of the patients against sensitive tumor targets, with a response rate comparable to those of high-dose rIL-2 and LAK cell treatment. Therefore, it may be a theoretically ideal adjuvant for patients with renal cell carcinoma, melanoma, and hepatoma and other applicable patients after bone marrow transplantation. The initial high response rate in patients with late-stage renal cell carcinoma and hepatocellular carcinoma indicates the need for additional confirmation.