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Background and Purpose: The AFFINITY trial (Assessment of Fluoxetine in Stroke Recovery) reported that oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and seizures. After trial medication was ceased at 6 months, survivors were followed to 12 months post-randomization. This preplanned secondary analysis aimed to determine any sustained or delayed effects of fluoxetine at 12 months post-randomization. Methods: AFFINITY was a randomized, parallel-group, double-blind, placebo-controlled trial in adults (n=1280) with a clinical diagnosis of stroke in the previous 2 to 15 days and persisting neurological deficit who were recruited at 43 hospital stroke units in Australia (n=29), New Zealand (4), and Vietnam (10) between 2013 and 2019. Participants were randomized to oral fluoxetine 20 mg once daily (n=642) or matching placebo (n=638) for 6 months and followed until 12 months after randomization. The primary outcome was function, measured by the modified Rankin Scale, at 6 months. Secondary outcomes for these analyses included measures of the modified Rankin Scale, mood, cognition, overall health status, fatigue, health-related quality of life, and safety at 12 months. Results: Adherence to trial medication was for a mean 167 (SD 48) days and similar between randomized groups. At 12 months, the distribution of modified Rankin Scale categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio, 0.93 [95% CI, 0.76–1.14]; P =0.46). Compared with placebo, patients allocated fluoxetine had fewer recurrent ischemic strokes (14 [2.18%] versus 29 [4.55%]; P =0.02), and no longer had significantly more falls (27 [4.21%] versus 15 [2.35%]; P =0.08), bone fractures (23 [3.58%] versus 11 [1.72%]; P =0.05), or seizures (11 [1.71%] versus 8 [1.25%]; P =0.64) at 12 months. Conclusions: Fluoxetine 20 mg daily for 6 months after acute stroke had no delayed or sustained effect on functional outcome, falls, bone fractures, or seizures at 12 months poststroke. The lower rate of recurrent ischemic stroke in the fluoxetine group is most likely a chance finding. Registration: URL: http://www.anzctr.org.au/ ; Unique identifier: ACTRN12611000774921.

Since the outbreak of COVID‐19, there have already been over 26 million people being infected and it is expected that the pandemic will not end in near future. Not only the daily activities and lifestyles of individuals have been affected, the medical practice has also been modified to cope with this emergency catastrophe. In particular, the cancer services have faced an unprecedented challenge. While the services may have been cut by the national authorities or hospitals due to shortage of manpower and resources, the medical need of cancer patients has increased. Cancer patients who are receiving active treatment may develop various kinds of complications especially immunosuppression from chemotherapy, and they and their carers will need additional protection against COVID‐19. Besides, there is also evidence that cancer patients are more prone to deteriorate from COVID‐19 if they contract the viral infection. Therefore, it is crucial to establish guidelines so that healthcare providers can triage their resources to take care of the most needed patients, reduce less important hospitalization and visit, and to avoid potential complications from treatment. The Asia and Oceania Federation of Obstetrics and Gynecology (AOFOG) hereby issued this opinion statement on the management of gynecological cancer patients during the COVID‐19.

Background: Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population.Methods: AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921.Findings: Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [Interpretation: Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke.Funding: National Health and Medical Research Council of Australia.

Candida infections of the central nervous system (CNS) are rare. We report a case of Candida glabrata meningitis successfully treated with combination antifungal therapy followed by step-down therapy with fluconazole. New-onset hypercalcaemia, an uncommon side effect of the prolonged fluconazole treatment, prompted early treatment cessation. A negative cerebrospinal fluid (CSF) β-d-glucan supported the decision of treatment cessation despite incomplete resolution of CSF biochemical parameters. No disease relapse was encountered after 2 years post-treatment.

Background Germline BRCA1/2 mutations account for approximately 15% of invasive ovarian carcinomas. Referral of all women with non-mucinous epithelial tubo-ovarian and peritoneal cancer, especially high-grade serous carcinoma (HGSC) to genetic services for genetic counselling and subsequent BRCA testing, has become standard of care in many countries. Publicly funded BRCA testing was restricted to women ≤70 years old with HGSC in New Zealand for most of our study period. Referral rates of women with HGSC for BRCA mutation testing in New Zealand have not previously been reported. Aims To determine the proportion of eligible patients with tubo-ovarian or peritoneal HGSC referred to Auckland Gynaecologic Oncology Centre who were referred for genetic counselling. To determine the number of patients who underwent BRCA1/2 genetic testing and the rate of germline BRCA mutations. Methods Eligible cases were identified from Auckland Gynaecologic Oncology multidisciplinary meetings database from 1 January 2012 to 31 December 2014. Genetic referrals sent were checked against the genetic services database to ensure that referrals were received. Genetic counselling clinic attendance, uptake and results of genetic testing were also collected. Results One hundred and four eligible patients were identified with 58 patients referred. Referral rates increased from 37.5% in 2012 to 64.3% in 2014. Of the 58 patients referred, 53 attended genetic counselling, and 49 underwent BRCA mutation testing, of whom 10 (20.4%) tested positive for a germline BRCA mutation. Conclusion Overall, 55.8% of eligible patients were referred for genetic testing; however, referral rates increased with time. This BRCA mutation-positive rate is comparable with current international data.

Summary Background Current guidelines recommend echinocandins as first‐line therapy for candidemia. However, several non‐Candida yeast are non‐susceptible to echinocandins (echinocandin non‐susceptible yeast, ENSY), including Cryptococcus, Geotrichum, Malassezia, Pseudozyma, Rhodotorula, Saprochaete, Sporobolomyces and Trichosporon. In laboratories that are not equipped with rapid diagnostic tools, it often takes several days to identify yeast, and this may lead to inappropriate presumptive use of echinocandins in patients with ENSY fungemia. The aim of this study was to determine the distribution of ENSY species during a 1‐year, laboratory surveillance programme in Asia. Methods Non‐duplicate yeast isolated from blood or bone marrow cultures at 25 hospitals in China, Hong Kong, India, Singapore, Taiwan and Thailand were analysed. Isolates were considered to be duplicative if they were obtained within 7 days from the same patient. Results Of 2155 yeast isolates evaluated, 175 (8.1%) were non‐Candida yeast. The majority of non‐Candida yeast were ENSY (146/175, 83.4%). These included Cryptococcus (109 isolates), Trichosporon (23), Rhodotorula (10) and Malassezia (4). The proportion of ENSY isolates (146/2155, 6.7%) differed between tropical (India, Thailand and Singapore; 51/593, 8.6%) and non‐tropical countries/regions (China, Hong Kong and Taiwan; 95/1562, 6.1%, P = 0.038). ENSY was common in outpatient clinics (25.0%) and emergency departments (17.8%) but rare in intensive care units (4.7%) and in haematology‐oncology units (2.9%). Cryptococcus accounted for the majority of the non‐Candida species in emergency departments (21/24, 87.5%) and outpatient clinics (4/5, 80.0%). Conclusions Isolation of non‐Candida yeast from blood cultures was not rare, and the frequency varied among medical units and countries.

Aims and objectives To understand women's perspectives about the trajectory from first bodily changes to diagnosis. Background With endometrial cancer, as with all gynaecological cancers, early diagnosis is key to successful outcomes. However, women do not always seek clinical advice early. Previously, this gap has been referred to as a "delay," blamed on fear or refusal to acknowledge symptoms. Methods A qualitative research project which involved face-to-face interviews with 16 women who had presented with symptoms of endometrial cancer. The paucity of research in the trajectory of women who experience a diagnosis of endometrial cancer required an exploratory overview of the data. Accordingly, an inductive thematic analysis was conducted using the framework of Braun and Clarke (Qualitative Research in Psychology, 3, 2006, 77). Results Women and health professionals both resorted to satisficing, using heuristics to make decisions about the importance of symptoms depending on their severity and duration. Most women initially determined that the bodily changes were within the realms of normal. Time to diagnosis was also affected by the following: women's long-standing assumptions; communication with health professionals; liminality-women oscillating between their self-assessment that these changes were something significant or nothing important; and gaps in health literacy. Conclusions The journey from noticing bodily changes to diagnosis was a nonlinear trajectory. Women worked to make sense of what was happening to them, informed by their sociocultural environment. In particular, confusion about the purpose of cervical screening led a number of participants who had regular smears to assume they were "safe" from cancer worries. Relevance to clinical practice Women and some health professionals may be unfamiliar with symptoms potentially indicative of endometrial cancer. There may be structural and communication barriers for women navigating healthcare systems. It is vital that nurses take time both to listen to women and to provide them with resources to enhance their health literacy.

Background: Adenocarcinoma in situ (AIS) of the cervix is a precursor to cervical adenocarcinoma. When AIS is detected by cervical screening an excision biopsy is mandatory to exclude invasion. Two common procedures are loop electrosurgical excision procedure (LEEP) and ‘cold knife cone biopsy’ (CKC), yet no randomised trials have compared these modalities. We aimed to compare margins status, specimen size and fragmentation after LEEP and CKC. Methods: The EXCISE Trial was an investigator-initiated, multicentre, open-label, parallel-group, phase 2, randomised study. Patients were enrolled at seven hospitals in Australia and New Zealand. We randomly assigned women aged ≥18 to ≤45 years with screen detected AIS to LEEP or CKC by computer generated random numbers. Co-primary endpoints were margin status, specimen size and fragmentation. Analysis was by intention-to-treat. Findings: Between August 2, 2017 and September 6, 2019, 40 patients were randomly assigned 2:1 to LEEP or CKC. All patients were included in the analysis. Margin status was evaluable in 36 cases. The proportion of patients with involved margins did not differ between groups. 25 of 26 LEEP and all 14 CKC biopsies were excised as single specimens (p=1.00). There were no differences in specimen dimensions. Patients in the CKC group had more post-operative complications (64.3% compared to 15.4% for LEEP p=.00). There were no differences in grade three complications (p=.65). Interpretation: LEEP was not associated with a greater likelihood of positive margins, specimen fragmentation or smaller excision compared to CKC when performed according to a standardised protocol. However, the study was not powered to establish non-inferiority of LEEP and a definitive phase 3 trial to compare margin status and rates of treatment failure after LEEP and CKC is warranted. Trial Registration: The study is registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR registration number ACTRN12617000132347). Funding Statement: Australia New Zealand Gynaecological Oncology Group [#FNR2016/03]. Declaration of Interests: PAC and CDHW have received honoraria from Seqirus unrelated to this work. All other authors declare no competing interests. Ethics Approval Statement: Ethical approval for the study was granted by the St John of God Healthcare Human Research Ethics Committee (Reference number #1137) and approvals were obtained at all participating sites.

Background and objective Malignant pleural effusion (MPE) affects >90% of mesothelioma patients. Research on MPE has focused on its physical impact on breathlessness; MPE is rich in growth mediators but its contribution to tumour biology has not been investigated. We aimed to examine the potential effects of MPE in promoting growth, migration and chemo-resistance of mesothelioma. Methods Pleural fluid samples from 151 patients (56 mesothelioma, 60 metastatic pleural cancer and 35 benign) were used. Seven validated human mesothelioma cell lines and three primary cultured mesothelioma lines were employed. Results Pleural fluid from mesothelioma patients (diluted to 30%) consistently stimulated cell proliferation (trypan-blue cell viability assay) in five mesothelioma cell lines tested by (median) 2.23-fold over controls (all P

Background Burkholderia pseudomallei is a gram negative bacteria that causes a spectrum of human diseases in the tropics. Although melioidosis is endemic in Southeast Asia, large clinical case series were rarely reported from metropolitan Singapore. Methods This is a retrospective study of 219 consecutive patients with culture proven infections due to Burkholderia pseudomallei between the years 2001 to 2016 managed in Singapore General Hospital (SGH). We aimed to review local patients’ characteristics and identify clinical factors associated with mortality and recurrent melioidosis. Results Culture proven melioidosis occurred in 219 patients, 83.1% were male with a mean age of 55.7 ± 14.3 years and 63.0% had diabetes mellitus. Most patients (71.7%) present within 4 weeks of symptom onset and the most common symptom was fever. The majority of patients had bacteremia (67.6%) and had infection involving the respiratory system (71.2%), presenting most frequently with multi-lobar pneumonia. Thirty-four (15.5%) deaths occurred during the initial hospitalisation with a median time from presentation to death of 6.0 days (interquartile range: 2.8–16.3). Twelve patients demised before the diagnosis of melioidosis was made. Univariate analysis identified patients with symptom duration of longer than 4 weeks, bacteremia, and disease requiring mechanical ventilation, inotropic support or temporary dialysis as factors that were significantly associated with mortality. Having bacteremia and disease requiring mechanical ventilation remained statistically significant factors in the multivariable analysis. Twenty-one (11.4%) patients developed at least 1 episode of culture proven recurrent infection, with 15 recurring within the first 12 months of their initial infection. Eight patients developed more than 1 episode of culture proven recurrent infection. Patients with multifocal infection were more likely to develop recurrent infection. Conclusion In metropolitan Singapore, melioidosis was associated with mortality in excess of 15%, where more than a third occurred before diagnosis. This study reminds local physicians that melioidosis is still a serious infection affecting local male diabetic patients and an important differential diagnosis in a patient presenting with severe multi-lobar pneumonia and septic shock. Recurrent infections occurred in 11.4% and the weight-based dosing of oral eradication antibiotics may improve the management of this disease locally.

BackgroundRising antibiotic resistance poses a challenge to the management of febrile neutropenia in patients with haematological malignancies receiving chemotherapy.AimWe studied an alternating first-line antibiotic strategy to determine its impact on all-cause mortality and bacteremia rates in patients with febrile neutropenia.MethodsAn alternating first-line antibiotic strategy was established in mid-2013. Data for 2012 (before strategy implementation) and 2014 (post-strategy implementation) were compared. Antibiotic Heterogeneity Index (AHI) for each of the two time-periods was also calculated.FindingsThere were 2012 admissions (26082 patient-days) in 2012 and 1843 admissions (24331 patient-days) in 2014. There was no significant difference in the baseline characteristics of patients in the two groups. The defined daily doses (DDD) of cefepime (CEF) fell while the DDD of piperacillin-tazobactam (PTZ) rose in 2014 compared with 2012. Vancomycin DDD fell in 2014. The AHI was 0.466 in 2012 and 0.582 in 2014. The difference in all-cause mortality was not statistically significant. There was no difference in rates of bacteremia with CEF-resistant, PTZ-resistant and carbapenem-resistant gram-negative organisms in the two groups. Rates of new cases of Methicillin-resistant Staphylococcus aureus (MRSA) were 2.38/1000 and 2.59/1000 patient-days in 2012 and 2014 respectively. Rates of new cases of Vancomycin-resistant Enterococcus (VRE) were 1.84/1000 and 1.81/1000 patient-days in 2012 and 2014 respectively. There was no Carbapenem-resistant Enterobacteriaceae (CRE) bacteremia in 2012 and 1 in 2014.ConclusionAn alternating first-line antibiotic strategy resulted in an increase in antibiotic heterogeneity, without increasing mortality. There was also no significant increase in bacteremia rates.

Purpose To survey the demographics, risk factors, microbiology, and outcomes for infectious keratitis in Asia. Design Prospective, nonrandomized clinical study. Methods Thirteen study centers and 30 sub-centers recruited consecutive subjects over 12-18 months, and performed standardized data collection. A microbiological protocol standardized the processing and reporting of all isolates. Treatment of the infectious keratitis was decided by the managing ophthalmologist. Subjects were observed for up to 6 months. Main outcome measures were final visual acuity and the need for surgery during infection. Results A total of 6626 eyes of 6563 subjects were studied. The majority of subjects were male (n = 3992). Trauma (n = 2279, 34.7%) and contact lens wear (n = 704, 10.7%) were the commonest risk factors. Overall, bacterial keratitis was diagnosed in 2521 eyes (38.0%) and fungal keratitis in 2166 eyes (32.7%). Of the 2831 microorganisms isolated, the most common were Fusarium species (n = 518, 18.3%), Pseudomonas aeruginosa (n = 302, 10.7%), and Aspergillus flavus (n = 236, 8.3%). Cornea transplantation was performed in 628 eyes to manage ongoing infection, but 289 grafts (46%) had failed by the end of the study. Moderate visual impairment (Snellen vision less than 20/60) was documented in 3478 eyes (53.6%). Conclusion Demographic and risk factors for infection vary by country, but infections occur predominantly in male subjects and are frequently related to trauma. Overall, a similar percentage of bacterial and fungal infections were diagnosed in this study. Visual recovery after infectious keratitis is guarded, and corneal transplantation for active infection is associated with a high failure rate.

Introduction Tinea unguium is a common nail infection. We conducted a retrospective ten-year study of the patient demographics and species distribution of dermatophytes causing tinea unguium in a tertiary hospital from Singapore. Methods Results of fungal nail cultures were retrieved from our hospital's microbiology department. Samples from nail scrapings and clippings were inoculated onto agar plates (Sabouraud dextrose agar with chloramphenicol and Mycosel agar). Nail specimens that grew dermatophytes were included in the study. Results Overall, 229 (male: n = 164, 71.6%; female: n = 65, 28.4%) nail specimens grew dermatophytes. Mean patient age was 58 (range 18-93) years. A majority of specimens came from patients aged over 50 years (n = 162, 70.7%) and 60-79 years (n = 100, 43.7%). Ethnically, 160 (69.9%) patients were Chinese, 36 (15.7%) Indian, 18 (7.9%) Malay and 15 (6.6%) of other ethnicities. Among dermatophytes isolated were Trichophyton rubrum (n = 93, 40.6%), Trichophyton mentagrophytes (n = 60, 26.2%), unidentified Trichophyton spp. (n = 57, 24.9%), Trichophyton tonsurans (n = 10, 4.4%), Epidermophyton floccosum (n = 5, 2.2%), Trichophyton verrucosum (n = 2, 0.9%), Trichophyton soudanense (n = 1, 0.4%) and Trichophyton violaceum (n = 1, 0.4%). Conclusion A majority of isolates were from elderly patients. Compared to Singapore's general population, patients of Indian and other ethnicities were over-represented for tinea unguium when compared to Chinese and Malay patients. Trichophyton rubrum was the most common dermatophyte isolated, while Trichophyton verrucosum, Trichophyton violaceum and Trichophyton soudanense were rare causes of tinea unguium.

Purpose Computer-assisted assessment of vessel tortuosity is clinically useful in retinopathy of prematurity (ROP). However, poor image quality is often prohibitive for accurate segmentation by fully automated systems and semi-automated systems are prone to unreliability. In the present work, we describe a method of retinal vessel tortuosity measurement by means of purpose-built image analysis software that does not require high image quality yet is also reliable. Methods Images were obtained from neonates at risk of ROP with Retcam Shuttle®. Individual vessels were assessed with the semi-automated Novel Evidenced Assessment of Tortuosity (NEAT) system by two masked experimenters. Scores were compared to assess reliability. They were also compared against clinical scoring of individual vessels by two ROP screeners to assess relationship with clinical assessment. In a second image cohort, the mean of the most tortuous vessel in each of four quadrants in each eye (NEAT-O) was compared against the documented gold standard clinical grading of plus disease. Results Reliability of the NEAT system for 50 individual vessels using Bland–Altman plots was excellent. NEAT tortuosity scores for 50 individual vessels compared to clinical scoring showed strong correlation (0.706). Correlation between the NEAT-O score for average tortuosity and gold standard for 167 eyes was modest (0.578). Conclusions The NEAT system is intuitive, user-friendly and robust enough to be clinically useful in poor-quality images. It allows for a rapid, valid and reliable assessment of tortuosity of individual vessels and produces a tortuosity score that correlates well with severity of plus disease.

Invasive aspergillosis (IA) remains a major cause of morbidity in immunocompromised hosts. This is due to the inability of the host immunity to respond appropriately to Aspergillus. An established risk factor for IA is neutropenia that is encountered by patients undergoing chemotherapy. Herein, we investigate the role of neutrophils in modulating host response to Aspergillus. We found that neutrophils had the propensity to suppress proinflammatory cytokine production but through different mechanisms for specific cytokines. Cellular contact was requisite for the modulation of interleukin-1 beta production by Aspergillus with the involvement of complement receptor 3. On the other hand, inhibition of tumour necrosis factor-alpha production (TNF-α) was cell contact-independent and mediated by secreted myeloperoxidase. Specifically, the inhibition of TNF-α by myeloperoxidase was through the TLR4 pathway and involved interference with the mRNA transcription of TNF receptor-associated factor 6/interferon regulatory factor 5. Our study illustrates the extended immune modulatory role of neutrophils beyond its primary phagocytic function. The absence of neutrophils and loss of its inhibitory effect on cytokine production explains the hypercytokinemia seen in neutropenic patients when infected with Aspergillus.

Formal, large-scale, multicenter studies of invasive mould infection (IMI) in Asia are rare. This 1-year, retrospective study was designed to assess the incidence and clinical determinants of IMI in centers in five countries (Thailand, Taiwan, Singapore, China, India). Patients treated in a single year (2012) were identified through discharge diagnoses, microbiology, and histopathology logs, and entered based on published definitions of IMI. A total of 155 cases were included (median age 54 years; 47.7% male). Of these, 47.7% had proven disease; the remainder had probable IMI. The most frequent host factors were prolonged steroid use (39.4%) and recent neutropenia (38.7%). Common underlying conditions included diabetes mellitus (DM; 30.9%), acute myeloid leukemia (19.4%), and rheumatologic conditions (11.6%). DM was more common in patients with no recent history of neutropenia or prolonged steroid use (P = .006). The lung was the most frequently involved site (78.7%), demonstrating a range of features on computed tomography (CT). Aspergillus was the most common mould cultured (71.6%), primarily A. fumigatus and A. flavus, although proportions varied in different centers. The most often used antifungal for empiric therapy was conventional amphotericin. Ninety-day mortality was 32.9%. This is the first multicenter Asian study of IMI not limited to specific patient groups or diagnostic methods. It suggests that DM and rheumatologic conditions be considered as risk factors for IMI and demonstrates that IMI should not be ruled out in patients whose chest features on CT do not fit the conventional criteria.

Trichosporon is an ubiquitous yeast that has emerged as an opportunistic pathogen in the immunocompromised host. We describe a case of invasive trichosporonosis in an allogeneic hematopoietic stem cell transplant (allo-HSCT) recipient while on caspofungin antifungal prophylaxis. She developed disseminated trichosporonosis in the pre-engraftment period and was successfully treated with voriconazole. She later developed 2 further episodes of invasive trichosporonosis involving the central nervous system. This case highlights the challenges of managing trichosporonosis in allo-HSCT recipients and suggests the need for lifelong therapy in some patients.

Background Mortality for candidemia ranges from 15% to 35%. Current guidelines recommend inoculating blood into three aerobic and three anaerobic blood culture bottles when candidemia is suspected, without mention of a fungal blood culture bottle. Objective To determine the value of the BACTEC Myco/F Lytic blood culture media in the diagnosis of fungemia. Methods A two-year retrospective cross-sectional study was performed for patients who had fungemia with submitted BACTEC Plus Aerobic/F (Aer), BACTEC Plus Anaerobic/F (Anaer) or Myco/F Lytic (Myco) blood culture bottles. Results The detection rate of fungemia was 77.4% in 93 patients with contemporaneously submitted blood culture bottles when limited to only Aer/Anaer culture results. The detection rate improved significantly with the addition of the Myco culture bottle results (p

Introduction: We present a case of cutaneous penicilliosis in a paediatric patient with acute myeloid leukaemia (AML). Case report: A 2-year-old boy with AML first developed probable pulmonary aspergillosis during induction chemotherapy in an overseas centre in May 2013, and was treated with AmBisome and voriconazole. When he was admitted to our centre with relapsed AML in October 2013, he was given a fifth course of chemotherapy, and treated with AmBisome for probable pulmonary aspergillosis in view of pulmonary nodular opacities on computed tomography. He thereafter developed an erythematous skin lesion with central eschar on his right hand and left calf. Serum and bronchoalveolar lavage galactomannan antigen (GM Ag) indices increased to a value of >10. AmBisome was changed to voriconazole, and caspofungin was added for 10 days. The left calf skin biopsy showed abundant fungal hyphae with septations. A skin culture grew Penicillium citrinum with MICs (μg ml− 1) of: caspofungin 0.016, itraconazole 0.5, amphotericin 1.5 and voriconazole >256.Caspofungin and itraconazole were commenced, and voriconazole was discontinued. The skin lesions and serial GM Ag indices improved. The patient later developed increasing GM Ag indices to a value of >10, which was attributed to Aspergillus flavus left pulmonary mycetoma, which was surgically resected. He eventually succumbed to relapsed AML after a bone-marrow transplant. Conclusion: To the best of our knowledge, this is the first paediatric case of P. citrinum infection. Rising GM Ag indices were attributed to cross-reactivity of Penicillium spp. with GM Ag enzyme immunoassays.

An infective aetiology, including fungal infection, should be considered in the differential diagnosis of immunocompromised patients presenting with skin lesions. Dematiaceous fungi are recognised as pathogens in organ transplant recipients. Herein, we describe a rare case of a chronic necrotising granulomatous skin lesion caused by Pyrenochaeta romeroi in a renal transplant recipient, and review the existing literature on the topic. To the best of our knowledge, this is the first report of such a case in Singapore. Recognition of infections caused by dematiaceous fungi is important because some strains are difficult to identify and require special molecular diagnostic techniques. Treatment involves surgical excision and long-term antifungal therapy. Data on the optimal antifungal regimen in such a diagnosis is limited.

Objective To evaluate the feasibility, complications and preliminary results of laparoscopic pelvic lymphadenectomy and radical vaginal hysterectomy for the treatment of early invasive carcinoma of the cervix. Design A retrospective randomized clinical study. Setting The Gynaecology Oncology Unit at the National Women's Hospital, Auckland, New Zealand. Subjects These were 30 women who had presented to the unit with early stage cervical cancer for whom surgery was thought to be the most appropriate primary treatment. Interventions The first 15 consecutive patients who were diagnosed in 1997 (group A) underwent a standard class 2 abdominal radical hysterectomy and pelvic lymphadenectomy The first 15 consecutive patients who were diagnosed in 1998 (group B) underwent a laparoscopic pelvic lymphadenectomy and a vaginal radical hysterectomy. Main outcome measures These included the clinical factors of operating times, blood loss, complications and hospital stay, and the pathological factors of lymph node yield, surgical margins and residual tumour size. Results The operating time was slightly longer in group B (mean = 3.18 h). There were no complications in either group but blood loss was halved in group B (mean = 353 ml). Hospital stay was also shorter (mean = 6 days) compared with group A (mean = 8 days). Lymph node yield was comparable to that obtained in open surgery (mean = 18.1 nodes) and clear margins were obtained in 14 out of 15 patients. Conclusion Our preliminary results demonstrate the feasibility and safety of laparoscopic pelvic lymphadenectomy and vaginal radical hysterectomy as an alternative to open radical hysterectomy and pelvic lymphadenectomy.

Pleural inflammation underlies the formation of most exudative pleural effusions and the plasma kallikrein-kinin system (KKS) is known to contribute. Mesothelial cells are the predominant cell type in the pleural cavity, but their potential role in plasma KKS activation and BK production has not been studied. Bradykinin concentrations were higher in pleural fluids than the corresponding serum samples in patients with a variety of diseases. Bradykinin concentrations did not correlate with disease diagnosis, but were elevated in exudative effusions. It was demonstrated, using a range of primary and transformed mesothelial and mesothelioma cell lines, that cells assembled high molecular weight kininogen and plasma prekallikrein to liberate bradykinin, a process inhibited by novobiocin, a heat shock protein 90 (HSP90) inhibitor, cysteine, bradykinin and protamine sulphate. Of the common plasma prekallikrein activators, mesothelial cells expressed HSP90, but not prolylcarboxypeptidase or Factor XII. Calcium mobilisation was induced in some mesothelium-derived cell lines by bradykinin. Des-Arg9-bradykinin was inactive, indicating that mesothelial cells are responsive to bradykinin, mediated via the bradykinin receptor subtype 2. In summary, pleural mesothelial cells support the assembly and activation of the plasma KKS by a mechanism dependent on HSP90, and may contribute to KKS-mediated inflammation in pleural disease.

Objective:To assess the role of the multidisciplinary tumor conference in patient management in a tertiary gynecologic oncology service.Methods:Data were analyzed from the records of all patients presented at the gynecologic oncology tumor conferences at Auckland City Hospital from August 1, 2005, to August 1, 2006. Patient information including referral source, cancer site, stage, whether surgery had been performed before the tumor conference and if so where and by whom, and benign versus malignant was extracted from the records. The radiological and pathological findings and diagnosis for each patient both before and after each tumor conference were compared. A discrepancy was defined as a change in tumor site, histological type, grade, or stage that resulted from findings discussed at the conferences. Diagnostic discrepancies that resulted in a change in patient management were classified as major discrepancies. Discrepancies that did not affect patient management were classified as minor discrepancies.Results:A total of 509 cases were discussed during the study period. Forty-six discrepancies (9%) were noted, with 30 major (5.9%) and 16 minor (3.1%) discrepancies. The most common changes to patient management that resulted from the tumor conferences were the addition of chemotherapy and surgery.Conclusions:This study demonstrates that gynecologic oncology tumor conferences alter the diagnosis in a significant number of cases and therefore affect patient management.

ContextFungal keratitis is a potentially blinding condition that is rarely seen with contact lens wear.ObjectiveTo describe a nationwide outbreak of fungal keratitis caused by Fusarium species among contact lens wearers in Singapore.Design, Setting, and PatientsNationwide, hospital-based case series. All cases of fungal keratitis among contact lens wearers in all ophthalmology departments in Singapore were reviewed along with the charts of all contact lens wearers with culture-proven fungal keratitis from March 2005 through May 2006. A standardized telephone interview was conducted to obtain additional clinical information.Main Outcome MeasureDiagnosis of Fusarium keratitis associated with contact lens wear.ResultsDuring the study period, 66 patients (68 affected eyes) were diagnosed with Fusarium keratitis associated with contact lens wear; the estimated annual national incidence is 2.35 cases per 10 000 contact lens wearers (95% confidence interval, 0.62-7.22). Patients ranged in age from 13 to 44 years (mean [SD], 27.1 [8.4] years), of which 32 (48.5%) were men. The vast majority (65 patients; 98.5%) wore soft, disposable contact lenses; 62 patients (93.9%) reported using 1 brand of contact lens cleaning solution (ReNu, Bausch & Lomb, Rochester, NY), including 42 patients (63.6%) who recalled using ReNu with MoistureLoc. Most patients (81.8%) reported poor contact lens hygiene practices, including overnight use of daily wear contact lenses (19.7%), and use of contact lenses past the replacement date (43.9%). The final best-corrected visual acuity ranged from 20/20 to 20/80. Five patients (5 eyes; 7.4%) required emergency therapeutic or tectonic corneal transplantation.ConclusionsA new and evolving epidemic of Fusarium keratitis associated with contact lens wear was found in Singapore. Physicians and eye care practitioners worldwide need to be aware of the likelihood of similar outbreaks emerging among contact lens wearers.

The antimicrobial susceptibility of Burkholderia pseudomallei isolates identified by the bacteriology laboratory at Singapore General Hospital was reviewed. Laboratory data were found to be available since 1987 and showed that ceftazidime, amoxicillin-clavulanate, chloramphenicol and tetracycline had remained effective through the years. Imipenem was added to the list of antimicrobials tested after 1989, and the isolates showed high susceptibility rates. Co-trimoxazole was found to be useful based on Etest results, but the isolates had low susceptibility rates when tested using disk diffusion.

To the Editor: We read with interest the letter by Marriott et al. (1) describing the first case of Candida dubliniensis fungemia in Australia. We report the first two cases of C. dubliniensis infection in Singapore. We have been using the API 20C AUX on all yeast isolates from blood, sterile fluids, and tissue to screen for C. dubliniensis since May 2000. To our knowledge, this infection has not been previously reported from a Southeast Asian country. The first patient was a 49-year-old woman with adult polycystic kidney and liver disease; she had mild chronic renal failure and a past history of nephrotic syndrome. She was admitted to the renal unit on May 9, 2001, for management of ascites. A septic workup showed leukocytosis (34.67 x 109/L) with predominance of neutrophils (95%). Blood culture received on May 31 grew yeast with two slightly different forms, one large and one small. The isolates, investigated separately, were germ-tube positive. The API 20C AUX profile for the larger isolate was 6072114 at 48 hours’ incubation (96.2% certainty for C. dubliniensis) and 6072134 for the smaller isolate (99.8% certainty for C. dubliniensis). The yeasts grew well on potato dextrose agar at 35°C but poorly at 42°C and 45°C. In addition, electrophoretic karyotyping with pulsed-field gel electrophoresis showed that both isolates had identical patterns, with eight chromosome fragments, one of which was 1 Mb. Five control strains—C. dubliniensis (RCPA Microbiology QAP item 2001:2:7A), C. albicans ATCC 90028, and three clinical strains of C. albicans—were also run together with the two strains; the results obtained were consistent with those of Jabra-Rizk et al. (2). The MIC of the isolates to fluconazole by E-test was 0.75 μg/mL, indicating susceptibility. Disseminated intravascular coagulopathy due to sepsis from a possible ruptured liver cyst developed in the patient. Despite broad-spectrum antibiotics and amphotericin B, hemodialysis, and intensive-care support, she died 5 weeks after admission. Except for C. dubliniensis candidemia, Candida species isolated from the urine and endotracheal secretions (speciation not done), and Acinetobacter baumannii (cultured from the endotracheal secretions and femoral catheter tip), no other important microorganisms were isolated. Peritoneal fluid cultures did not yield any microorganisms. Soon after the first case, C. dubliniensis was isolated from a sputum culture and bronchial alveolar lavage cultures from a 50-year-old Chinese woman, who had myelodysplastic syndrome and was hospitalized for pneumonia. She had been previously treated with chemotherapy and had multiple admissions for infection. The same phenotypic and karyotypic methods as the first patient were used to identify the isolate. The API 20C AUX profile was 2152134 at 48 hours (98.5% certainty for C. dubliniensis). The MIC of fluconazole by E-test was also 0.75 μg/mL. Pancytopenia developed, and the patient’s condition deteriorated. She died of pneumonia despite transfusions and treatment with broad-spectrum antibiotics and amphotericin B. Microbiologic investigations for bacteria, tuberculosis, pneumocystis, Legionella, and viruses did not yield positive results except for Corynebacterium species in the bronchial alveolar lavage fluid. Although C. dubliniensis was first associated with oral candidiasis in HIV-infected persons (3), several reports now link the organism to non-HIV patients who were immunosuppressed due to chemotherapy, hematologic malignancy (4), and end-stage liver disease (1). Our two patients were not HIV positive but were immunosuppressed. In vitro susceptibility results showed that our patients should have responded to the usual antifungal treatment. However, they died despite appropriate therapy.

Background Human papillomavirus (HPV) is the necessary cause of cervical cancer. Published data on the epidemiology of HPV in women with invasive cervical cancer (ICC) in New Zealand (NZ) are limited. This cross-sectional study investigated the distribution of high-risk and low-risk HPV types in cervical specimens collected from women throughout NZ who had been diagnosed with ICC between 2004 and 2010. Methods Women aged ≥18 years, with ICC International Federation of Gynecology and Obstetrics stage Ib or greater were identified from the five tertiary public hospitals in NZ regularly treating women with ICC. Women were enrolled in the study only after obtaining informed consent. Stored, formalin fixed, paraffin-embedded cervical specimens were retrieved and histopathologically reviewed to confirm the diagnosis of ICC. Cervical specimens were tested for HPV using polymerase chain reaction-short fragment10; HPV DNA was detected using DNA enzyme immunoassay and typed by reverse hybridization line probe assay. Results 242 women were enrolled and ICC was histologically confirmed in 227 samples. HPV infection was detected in 88.5% (n = 201; 95% CI: 83.7–92.4) of women with ICC; high-risk HPV types were detected in 87.2% of women. The most commonly detected HPV types were HPV-16 (51.1%) and HPV-18 (20.7%), followed by HPV-31 (4.0%), HPV-45 and HPV-52 (3.1% each). Overall, HPV distribution was highest (94.3%) in women aged 30–39 years at diagnosis and a higher distribution of HPV-16 (68.8%) was observed in women younger than 30 years. The overall distribution of HPV types between Maori and non-Maori women were similar. HPV-positive women with ICC stage II or greater were less likely to be infected with HPV-16/18 (P = 0.002) or HPV-18 (P = 0.029) compared with the other high-risk types. Single type infection and multiple infections were detected in 93.5% and 5.5% of women, respectively. Conclusions HPV-16, HPV-18, HPV-31, HPV-45 and HPV-52 were the most commonly detected high-risk HPV types. Findings from the study fill an important data gap on HPV type distribution from NZ which will help facilitate better understanding of the epidemiology of HPV in NZ women. Clinical trial registration NCT01328028.