Integrating CT-based radiomic model with clinical features improves long-term prognostication in high-risk prostate cancer.

Objective: High-risk prostate cancer (PCa) is often treated by prostate-only radiotherapy (PORT) owing to its favourable toxicity profile compared to whole-pelvic radiotherapy. Unfortunately, more than 50% patients still developed disease progression following PORT. Conventional clinical factors may be unable to identify at-risk subgroups in the era of precision medicine. In this study, we aimed to investigate the prognostic value of pre-treatment planning computed tomography (pCT)-based radiomic features and clinical attributes to predict 5-year progression-free survival (PFS) in high-risk PCa patients following PORT. Materials and methods: A total of 176 biopsy-confirmed PCa patients who were treated at the Hong Kong Princess Margaret Hospital were retrospectively screened for eligibility. Clinical data and pCT of one hundred eligible high-risk PCa patients were analysed. Radiomic features were extracted from the gross-tumour-volume (GTV) with and without applying Laplacian-of-Gaussian (LoG) filter. The entire patient cohort was temporally stratified into a training and an independent validation cohort in a ratio of 3:1. Radiomics (R), clinical (C) and radiomic-clinical (RC) combined models were developed by Ridge regression through 5-fold cross-validation with 100 iterations on the training cohort. A model score was calculated for each model based on the included features. Model classification performance on 5-year PFS was evaluated in the independent validation cohort by average area-under-curve (AUC) of receiver-operating-characteristics (ROC) curve and precision-recall curve (PRC). Delong's test was used for model comparison. Results: The RC combined model which contains 6 predictive features (tumour flatness, root-mean-square on fine LoG-filtered image, prostate-specific antigen serum concentration, Gleason score, Roach score and GTV volume) was the best-performing model (AUC = 0.797, 95%CI = 0.768-0.826), which significantly outperformed the R-model (AUC = 0.795, 95%CI = 0.774-0.816) and C-model (AUC = 0.625, 95%CI = 0.585-0.665) in the independent validation cohort. Besides, only the RC model score significantly classified patients in both cohorts into progression and progression-free groups regarding their 5-year PFS (p< 0.05). Conclusion: Combining pCT-based radiomic and clinical attributes provided superior prognostication value regarding 5-year PFS in high-risk PCa patients following PORT. A large multi-centre study will potentially aid clinicians in implementing personalised treatment for this vulnerable subgroup in the future.

Hong Kong Drug Allergy Delabelling Initiative (HK-DADI) consensus statements for penicillin allergy testing by nonallergists.

Introduction: Penicillin allergy testing has been traditionally performed by allergists, but there remains a huge deficit of specialists. A multidisciplinary effort with nonallergists would be invaluable to overcome the magnitude of penicillin allergy labels via the Hong Kong Drug Allergy Delabelling Initiative (HK-DADI). These consensus statements (CSs) offer recommendations and guidance to enable nonallergists to screen for low-risk (LR) patients and perform penicillin allergy testing. Methods: CSs were formulated by the HK-DADI Group using the Delphi method. An agreement was defined as greater than or equal to 80% consensus. Results: A total of 26 CSs reached consensus after multiple rounds of Delphi. CSs were categorized into risk assessment, skin testing, drug provocation testing (DPT), and post-testing management. For risk assessment, the essentials of allergy history and exclusion criteria were detailed. Patients with only LR features can proceed with testing by nonallergists. Skin tests should be performed prior to DPT. Details regarding the timing, preparation, and interpretation of skin tests were elaborated. DPT remains the gold standard to diagnose genuine allergy or tolerance and should be performed when there is a low pretest probability following negative skin testing. Details of DPT preparations, dosing protocols, and interpretation were elaborated. For post-testing management, inaccurate allergy labels should be delabeled following negative DPT with proper patient counseling. Conclusion: CSs support penicillin allergy testing by nonallergists in Hong Kong. LR cases can be managed by nonallergists at Spoke Clinics, with training and support of an allergist-led Hub.

Risk factors for hospital readmission for COPD after implementation of the GOLD guidelines.

BACKGROUND: Few updated studies have investigated risk factors for readmission for chronic obstructive pulmonary disease (COPD) since the implementation of the latest treatment guidelines. OBJECTIVE: To evaluate a series of potential risk factors for readmission in patients with COPD and in a subgroup with very frequent readmissions after implementation of the Global Initiative for Chronic Obstructive Lung Disease guidelines. DESIGN: Two hundred and fifty patients admitted for acute exacerbation of COPD (AECOPD) were recruited over 1 year. The readmission frequency in the ensuing year following hospital discharge was recorded and analysed against potential risk factors collected during the index admission. RESULTS: In the ensuing year, 183 (73.2%) patients were readmitted at least once for AECOPD. Previous non-invasive ventilation for AECOPD (HR 1.56, 95%CI 1.08-2.26), COPD Assessment Test score (HR 1.03, 95%CI 1.00-1.05), 6-minute walk distance (HR 0.98 per 10 m increase, 95%CI 0.97-0.99) and number of admissions for AECOPD in the previous year (HR 1.11, 95%CI 1.06-1.16) were independently associated with time to first readmission. Subgroup analysis showed that anxiety (OR 3.97, 95%CI 1.49-10.57) was strongly associated with very frequent readmissions (⩾4 in 1 year). CONCLUSIONS: AECOPD is associated with high rates of readmission. Anxiety is a potential modifiable factor associated with very frequent readmissions.

Three cases of atypical pneumonia caused by Chlamydophila psittaci.

Psittacosis is a zoonotic disease caused by Chlamydophila psittaci. The most common presentation is atypical pneumonia. Three cases of pneumonia of varying severity due to psittacosis are described. All patients had a history of avian contact. The diagnosis was confirmed by molecular detection of Chlamydophila psittaci in respiratory specimens. The cases showed good recovery with doxycycline treatment. Increased awareness of psittacosis can shorten diagnostic delay and improve patient outcomes.

A pilot trial of non-invasive home ventilation after acidotic respiratory failure in chronic obstructive pulmonary disease.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) who survive an episode of acute hypercapnic respiratory failure (AHRF) after treatment with non-invasive ventilation (NIV) have a high risk of recurrent AHRF. We hypothesised that continuation of NIV at home in these patients would reduce the likelihood of recurrent AHRF. METHODS: A pilot prospective randomised controlled study was designed to compare continuation of active home NIV and continuous positive airway pressure (CPAP) 5 cm H(2)O (controls) in COPD patients who had survived an episode of AHRF treated with acute NIV. Patients with significant obstructive sleep apnoea, non-COPD causes of AHRF, adverse psychosocial circumstances and serious comorbidities were excluded. The primary end-point was recurrent AHRF requiring acute NIV, intubation or resulting in death in the first year. RESULTS: Twenty-three patients were randomised to receive home NIV and 24 received CPAP. There was no significant difference in the baseline characteristics between the two study groups. The proportion of patients developing recurrent AHRF in the NIV and the CPAP groups was 38.5% vs. 60.2% at 1 year (P = 0.039). Four and eight patients, respectively, were withdrawn from the CPAP and NIV groups before the end of the pre-defined study duration. CONCLUSIONS: In selected COPD patients with AHRF treated with acute NIV, continuation with home NIV is associated with a lower risk of recurrent severe COPD exacerbation with AHRF when compared with CPAP.

The effects of diet and orlistat on body weight and lipid profiles in high risk Chinese patients with coronary artery disease, obesity and hypercholesterolemia.

BACKGROUND: Orlistat is a gastrointestinal lipase inhibitor approved for use in obesity. So far, no evidence has been reported on the use of orlistat in obese patients with coronary artery disease (CAD). AIM: To investigate the effect of orlistat on body weight and lipid profiles in obese patients with CAD and hypercholesterolemia. METHODS: Thirty non-diabetic patients with CAD, body mass index (BMI) > or = 25 kg/m(2) and low-density lipoprotein cholesterol (LDL-C) > or = 2.6 and < 4.1 mmol/L were put on diet for 12 weeks. Those still having a BMI > or = 25 kg/m(2) received orlistat 120 mg thrice daily for another 24 weeks. RESULTS: BMI was significantly reduced by 1.7% after 12 weeks of dietary treatment. The 24-week orlistat treatment resulted in further significant reduction in BMI (-2.8%) and LDL-C (-7.0%). CONCLUSION: Diet and orlistat treatment significantly reduced BMI and improved LDL-C in obese patients with CAD and hypercholesterolemia.

Cost analysis of management in acute appendicitis with CT scanning under a hospital global budgeting scheme.

BACKGROUND: CT scanning of the abdomen is a highly accurate diagnostic tool for acute appendicitis. However, it is still relatively expensive in Taiwan, especially in hospitals which have adopted a global budgeting scheme. The purpose of this study was to analyse the cost of the management of this disease with and without CT scanning. METHOD: A retrospective observational study was undertaken from 1 January to 30 June 2005. Patients with a working diagnosis of "acute appendicitis", "acute appendicitis should be ruled out" and "differential diagnosis including acute appendicitis" were enrolled in the study. Patient demographic data, chief complaints, working diagnoses, laboratory data, CT reports, surgical findings and costs in the emergency department (ED) and ward were collected. RESULT: A total of 266 patients were admitted to an ED with symptoms suggesting acute appendicitis. Of these, 207 underwent an emergency appendectomy. An abdominal CT scan was performed in 71% of patients with a diagnosis of "differential diagnosis including acute appendicitis", which was higher than in the other two diagnostic groups (18% and 60%). Patient age, high sensitivity C-reactive protein (hsCRP) concentration, ED stay, ED expenses and hospital stay were lower in the group that did not have a CT scan than in those who did. The net cost per patient with acute appendicitis in the group who underwent CT scanning was New Taiwan dollar (NT$)40,728, which was nearly equal to the net cost per patient in the group without CT scanning (NT$39,192). CONCLUSION: Routine CT scanning in patients with possible appendicitis is not necessary. History taking and physical examination combined with laboratory tests are still useful and cost-effective methods of diagnosing acute appendicitis.

Impact of enhanced infection control procedures on clinical outcome following resuscitation attempts.

The impact of infection control measures (ICMs) on emergency resuscitation during an outbreak is unclear. The purpose of this retrospective observational study was to investigate the outcomes of emergency resuscitation after implementation of ICMs. Data were collected for the period 1 January to 4 July in 2003 from a 1732-bed tertiary care hospital in central Taiwan. Non-trauma patients who required emergency resuscitation were classified into two groups: before (period 1), and after (period 2), the date on which strict ICMs were implemented. The analysis variables included demographic data of patients, place of resuscitation, number of participating resuscitators, response time and duration of resuscitation, fever, pneumonia status and results of resuscitation. The response time was unchanged but the number of patient resuscitations without an emergency intubation, rapid sequence intubation or a 'do not resuscitate' order increased from 88 (24.4%), 23 (6.4%) and 16 (4.4%) in period 1 to 103 (33.0%), 32 (10.3%) and 29 (9.3%) in period 2, respectively. The failure rate of resuscitation was significantly higher in period 2 (odds ratio: 1.59, 95% confidence interval: 1.17-2.16). The number of emergency resuscitations in patients with fever or pneumonia was not significantly different between these two periods. In conclusion, strict ICM implementation appeared to play a role in the increased failure rate in emergency resuscitation. Normal provision of healthcare to patients and adequate protection of healthcare workers during emergency resuscitation will be of paramount importance during the next outbreak of a highly contagious disease.

Complicated parapneumonic effusion and empyema thoracis: microbiology and predictors of adverse outcomes.

OBJECTIVES: To describe the microbiological characteristics of a cohort of patients with complicated parapneumonic effusion and empyema thoracis, and to identify the potential risk factors for adverse outcomes, with particular reference to the choice of empirical antibiotics, intrapleural fibrinolytics, adherence to management guidelines, and input from pulmonologists. DESIGN: Retrospective review. SETTING: Regional hospital, Hong Kong. PATIENTS: All patients with a diagnosis of complicated parapneumonic effusion/empyema thoracis admitted between January 2003 and June 2005. MAIN OUTCOME MEASURES: Microbiological characteristics, mortality, and surgery-free survival. RESULTS. There were 63 patients, with a mean age of 64 (standard deviation, 16) years and a male-to-female ratio of 45:18. The pleural fluid culture positivity rate was 68%; Streptococcus milleri (19%), Bacteroides (14%), Klebsiella pneumoniae (12%), and Peptostreptococcus (7%) were the most common organisms. Thirteen (21%) patients died during their index admission. Use of intrapleural fibrinolytics according to the guideline was associated with survival (P=0.001) while discordant initial antibiotic use was associated with mortality (P=0.002). Discordant initial antibiotic use was also independently associated with reduced surgery-free survival (P<0.001). Subgroup analysis showed that early intrapleural fibrinolytic use (within 4 days of diagnosis) was associated with decreased mortality (P<0.001), increased surgery-free survival (P=0.005), and shorter hospital stay (P=0.039). CONCLUSION: Organisms identified from complicated parapneumonic effusion and empyema thoracis differ from those giving rise to community-acquired pneumonia. In these patients, adherence to guidelines, early concordant antibiotic treatment, intrapleural fibrinolytics, and input from a pulmonologist were associated with improved outcomes.

Duration of RT-PCR positivity in severe acute respiratory syndrome.

Severe acute respiratory syndrome (SARS) is a highly infectious respiratory infection with a high mortality. The duration of infectivity is unknown. The RT-PCR positivity for SARS-associated coronavirus (SARS-CoV) was followed in 45 virologically confirmed SARS patients. Serial RT-PCRs for SARS-CoV were performed in the nasopharyngeal aspirate, stool and urine of 45 SARS patients who survived until discharge. All patients had at least one site that was positive for SARS-CoV on presentation. Time to RT-PCR conversion was studied in all patients. There were 15 males (33.3%) and 30 females (66.7%), with a mean+/- SD age of 40.7+/-14.7 yrs. The median (range) time of RT-PCR conversion was 30 days (2-81). On discharge from the hospital, 18 (40%) remained RT-PCR positive in at least one site. For patients with positive RT-PCR on discharge, the median (range) time to RT-PCR conversion after discharge was 13 days (2-60). A significant proportion of severe acute respiratory syndrome patients remained RT-PCR positive for severe acute respiratory syndrome-associated coronavirus for a substantial duration after discharge. The clinical significance is unknown and this finding merits further study. It is prudent to advise patients to adhere to strict personal hygiene on discharge until RT-PCR becomes negative.

Readmission rates and life threatening events in COPD survivors treated with non-invasive ventilation for acute hypercapnic respiratory failure.

BACKGROUND: Non-invasive ventilation (NIV) has been shown to reduce intubation and in-hospital mortality in patients with chronic obstructive pulmonary disease (COPD) and acute hypercapnic respiratory failure (AHRF). However, little information exists on the outcomes following discharge. A study was undertaken to examine the rates of readmission, recurrent AHRF, and death following discharge and the risk factors associated with them. METHODS: A cohort of COPD patients with AHRF who survived after treatment with NIV in a respiratory high dependency unit was prospectively followed from July 2001 to October 2002. The times to readmission, first recurrent AHRF, and death were recorded and analysed against potential risk factors collected during the index admission. RESULTS: One hundred and ten patients (87 men) of mean (SD) age 73.2 (7.6) years survived AHRF after NIV during the study period. One year after discharge 79.9% had been readmitted, 63.3% had another life threatening event, and 49.1% had died. Survivors spent a median of 12% of the subsequent year in hospital. The number of days in hospital in the previous year (p = 0.016) and a low Katz score (p = 0.018) predicted early readmission; home oxygen use (p = 0.002), APACHE II score (p = 0.006), and a lower body mass index (p = 0.041) predicted early recurrent AHRF or death; the MRC dyspnoea score (p<0.001) predicted early death. CONCLUSIONS: COPD patients with AHRF who survive following treatment with NIV have a high risk of readmission and life threatening events. Further studies are urgently needed to devise strategies to reduce readmission and life threatening events in this group of patients.

Spontaneous pneumomediastinum in patients with severe acute respiratory syndrome.

Spontaneous pneumomediastinum (SP) unrelated to assisted ventilation is a newly recognised complication of severe acute respiratory syndrome (SARS). The objective of the present study was to examine the incidence, risk factors and the outcomes of SP in a cohort of SARS victims from a community outbreak. Data were retrieved from a prospectively collected database of virologically confirmed SARS patients. One hundred and twelve cases were analysable, with 13 patients developing SP (11.6%) at a mean +/- SD of 19.6 +/- 4.6 days from symptom onset. Peak lactate dehydrogenase level was associated with the development of SP. SP was associated with increased intubation and a trend towards death. Drainage was required in five cases. For patients who survived, the SP and/or the associated pneumothoraces took a median of 28 days (interquartile range: 15-45 days) to resolve completely. In conclusion, spontaneous pneumomediastinum appeared to be a frequent complication of severe acute respiratory syndrome. Further research is needed to investigate its pathogenesis.

Prolonged jaundice following percutaneous coronary intervention and ticlopidine therapy.

Ticlopidine, an adenosine diphosphate receptor blocker, is widely used to prevent subacute stent thrombosis after percutaneous coronary intervention. Along with neutropenia and thrombotic thrombocytopenic purpura, cholestatic hepatitis is one of the most serious potential side-effects of ticlopidine therapy. Four patients with prolonged jaundice after ticlopidine therapy, including one fatal case, are presented. Alternative antithrombotic therapy for subsequent percutaneous coronary intervention is also described. Clopidogrel therapy was found to be safe and effective in two patients with a history of ticlopidine-related cholestatic hepatitis.

Early unplanned readmission of patients with newly diagnosed tuberculosis discharged from acute hospital to ambulatory treatment.

OBJECTIVE: The aim of this study was to examine whether patients with newly diagnosed tuberculosis (TB) discharged to ambulatory treatment are at risk of unplanned readmission through the emergency department within 28 days of discharge, and the risk factors associated with such readmission. METHODOLOGY: A cohort of 134 patients admitted to an acute medical department with TB, who were subsequently discharged to ambulatory treatment of TB, were studied by a retrospective record review for unplanned readmission in 28 days. Potential risk factors associated with the readmission were recorded during hospital stay and follow-up visits, including age, sex, length of stay, substance abuse, need of assistance in the activities of daily living (ADL), comorbidities, non-compliance, drug complications and use of non-standard drug regimen. RESULTS: Up to 20.1% of patients were readmitted. Factors independently associated with early unplanned readmission were need of assistance in ADL, drug complications, the need to use a non-standard drug regimen and more than three non-chest comorbidities. CONCLUSIONS: A significant readmission rate was found in these patients and potential risk factors were identified. Ambulatory treatment for TB may not be appropriate for selected patients. Local guidelines for the management of TB patients at high risk of readmission is needed.

Overexpression of Escherichia coli oxidoreductases increases recombinant insulin-like growth factor-I accumulation.

Transient overexpression of either DsbA or DsbC can double the yield of periplasmic insulin-like growth factor (IGF)-I in Escherichia coli to 8.5 g/liter. Strikingly, most of the overexpressed DsbA or DsbC is found in the reduced form, implying that enhanced disulfide isomerization is responsible for the substantial increase in IGF-I yield. All of the accumulated IGF-I has had the signal sequence removed, underscoring the secretion capacity of this organism as well as its utility for efficient production of polypeptide with the correct amino terminus. The overexpressed IGF-I constitutes approximately 30% of the total cell protein. Overproduction of active site mutants of DsbA instead of the wild-type gene do not produce this increase in yield. With wild-type levels of DsbA and DsbC, most of the secreted IGF-I is found in disulfide-linked aggregates, although 10% is soluble and about 5% is correctly folded. Contrary to expectations, overexpression of the disulfide oxidoreductases decreased the soluble fraction. Because the aggregated protein can be efficiently solubilized and refolded, the increased yield is a significant benefit for the production of IGF-I.