Research activities in general medicine: a scoping survey by the Internal Medicine Society of Australia and New Zealand.

BACKGROUND: In developing an effective framework for a collaborative research network (RN) that supports members involved in research, the Internal Medicine Society of Australia and New Zealand (IMSANZ) required a better understanding of the current level of research activity and engagement by general physicians, and factors influencing such engagement. AIMS: To explore the current research landscape amongst general physicians in Australia and Aotearoa New Zealand. METHODS: A questionnaire exploring research participation, scope, research enablers and barriers was disseminated to IMSANZ members over a 3-month period. Core functions of IMSANZ-RN, research priorities, potential solutions to perceived barriers and required level of support were also evaluated. RESULTS: A total of 82 members, mostly senior medical staff (74.4%), responded to the survey (11.8% response rate). More than 70% were involved in impactful research across multiple disciplines, encompassing a wide range of research themes and topics. However, there is limited support and resources available to conduct research, with most projects being self-instigated and self-funded. There is overwhelming support to increasing the profile of research in general medicine through the establishment of IMSANZ-RN, whose principal purposes, as identified by respondents, are to foster collaboration, promote research, provide research education and training, and share information among general physicians. Quality improvement studies (56.1%) and clinical trials (41.5%) were also identified as priority research types. CONCLUSIONS: This study has profiled the constraints faced by general physicians in conducting high-quality collaborative research and provides insights into what is needed to support greater research engagement, through development of a discipline-specific clinical RN.

Urine cultures at the onset of febrile neutropenia rarely impact antibiotic management in asymptomatic adult cancer patients.

PURPOSE: There is a paucity of data regarding the utility of routine urine cultures in adults with febrile neutropenia (FN) without urinary symptoms receiving protocolised antibiotics. This is reflected by inconsistent recommendations in international and regional FN guidelines. We addressed this issue by retrospectively reviewing the impact of routine urine cultures on antibiotic management in haematology cancer inpatients at a tertiary hospital. METHODS: All haematology inpatients over a 5-year period (2011-2015) were retrospectively reviewed for episodes of FN (neutrophil count < 0.5 × 109/L and fever > 37.5 °C). For each episode, demographic data, urinary tract symptoms and signs (absence of which was termed 'asymptomatic'), urinalysis and urine culture results, antibiotic therapy and duration, and patient outcomes were collected. A urine culture was considered positive if > 105 colony forming units (CFU)/L were detected. Empiric antibiotic therapy for FN consisted of intravenous piperacillin/tazobactam in stable patients, with the addition of vancomycin and a single dose of gentamicin if systemically compromised. RESULTS: Four hundred and thirty-three episodes of FN were identified in 317 patients. Urine cultures were performed in 362 (84%) episodes. Cultures were positive in 9 of 48 (19%) symptomatic episodes versus 8 of 314 (2.5%) asymptomatic episodes (RR = 7.4, p < 0.0001). A change in antibiotic management due a positive urine culture occurred in only 5 episodes (1.4%): 3 of 48 (6.3%) symptomatic and 2 of 314 (0.6%) asymptomatic episodes respectively (RR = 9.8, p = 0.01). CONCLUSION: Routine urine cultures in FN patients without urinary symptoms who are already receiving protocolised broad spectrum antibiotics rarely impact subsequent antibiotic management.

Development of Acute Decompensated Heart Failure Among Hospital Inpatients: Incidence, Causes and Outcomes.

BACKGROUND: We aimed to investigate the incidence, precipitants, and outcomes of acute decompensated heart failure (ADHF) that develops during the inpatient stay. METHODS: We undertook a case-control study in the medical, oncology, surgical, and orthopaedic wards of a tertiary referral hospital (February-May, 2016). Patients aged ≥18 years who developed ADHF during their inpatient stay were enrolled as cases. One control patient was matched to each case by age, gender, presenting complaint/surgery performed and co-morbidities. Multivariate regression was employed to determine variables associated with ADHF. RESULTS: The incidence of ADHF was 1.0% of patients. Eighty cases were well-matched to 80 controls (p>0.05). ADHF precipitants comprised infection (30%), inappropriate intravenous (IV) fluid and medication management (23.8% and 8.8%, respectively), tachyarrhythmia (12.5%), ischaemic heart disease (8.8%), renal failure (1.3%), and other/unclear causes (15%). Three variables were associated with ADHF: not having English as the preferred language (OR 3.5, 95%CI 1.2-9.8), a history of ischaemic heart disease (OR 3.3, 95%CI 1.2-9.1), and the administration of >2000ml of IV fluid on the day before the ADHF (OR 8.3, 95%CI 1.5-48.0). The day before the ADHF, cases were administered significantly more IV fluids than controls (median 2,757.5 versus 975ml, p=0.001). Medication errors mostly related to failure to restart regular diuretics. Cases had significantly greater length of stay (median 15 versus 6 days, p<0.001) and mortality (12.5% versus 1.3%, p=0.01). CONCLUSIONS: New onset ADHF is common and a substantial proportion of cases are iatrogenic. Cases experience significantly increased length of hospital stay, morbidity, and mortality.

Management of dengue in Australian travellers: a retrospective multicentre analysis.

OBJECTIVES: To describe the epidemiology, clinical and laboratory features and outcomes of dengue in returned Australian travellers, applying the revised WHO dengue classification (2009) to this population. DESIGN, SETTING AND PARTICIPANTS: Retrospective case series analysis of confirmed dengue cases hospitalised at one of four Australian tertiary hospitals, January 2012 - May 2015. MAIN OUTCOME MEASURES: Clinical features, laboratory findings and outcomes of patients with dengue; dengue classification according to 2009 WHO guidelines. RESULTS: 208 hospitalised patients (median age, 32 years; range, 4-76 years) were included in the study. Dengue was most frequently acquired in Indonesia (94 patients, 45%) and Thailand (40, 19%). The most common clinical features were fever (98% of patients) and headache (76%). 84 patients (40%) met the WHO criteria for dengue with warning signs, and one the criteria for severe dengue; the most common warning signs were mucosal bleeding (44 patients, 21%) and abdominal pain (43, 21%). Leukopenia (176 patients, 85%), thrombocytopenia (133, 64%), and elevated liver enzyme levels (154, 76%) were the most common laboratory findings. 46 patients (22%) had serological evidence of previous exposure to dengue virus. WHO guidelines were documented as a management benchmark in ten cases (5%); 46 patients (22%) received non-steroidal anti-inflammatory drugs (NSAIDs). CONCLUSIONS: A significant proportion of returning Australian travellers hospitalised for dengue have unrecognised warning signs of severe disease. Many received NSAIDs, which can increase the risk of haemorrhage in dengue. As travel to Asia from Australia continues to increase, it is vital for averting serious outcomes that clinicians can recognise and manage dengue.

Commencement of cardioselective beta-blockers during hospitalisation for acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: In patients with chronic obstructive pulmonary disease (COPD) and co-morbid cardiovascular disease, emerging evidence suggests a benefit in commencing cardioselective beta-blockers. AIM: Our objective was to determine the safety of beta-blocker commencement during hospitalisation for acute exacerbation of COPD. METHODS: A retrospective cohort study of 1071 patients hospitalised for acute exacerbation of COPD was conducted across two tertiary hospitals over a 12-month period. We identified 36 patients in whom beta-blocker therapy was commenced during admission. The primary outcome of the study was to assess cardiovascular and respiratory adverse events related to the commencement of beta-blocker therapy. RESULTS: The most common indications for beta-blockers were atrial fibrillation (53%) and acute coronary syndrome (36%). Metoprolol was the most commonly prescribed beta-blocker (75%). No patients suffered clinically significant declines of respiratory function following the commencement of a beta-blocker, including worsening respiratory symptoms, oxygen, bronchodilator or ventilation requirements. These results were demonstrable in patients with reversible airways disease and advanced COPD. Only one patient (2.8%) experienced symptomatic hypotension after 48 h of therapy. CONCLUSION: The commencement of cardioselective beta-blockers during acute exacerbations of COPD appears to be well-tolerated.

Old but not forgotten: Antibiotic allergies in General Medicine (the AGM Study).

OBJECTIVES: To determine the nature, prevalence and description accuracy of recorded antibiotic allergy labels (AALs) in a cohort of general medical inpatients, and to assess the feasibility of an oral antibiotic re-challenge study. DESIGN: Multicentre cross-sectional study. SETTING AND PARTICIPANTS: All patients admitted to the general medical units of Austin Health and Alfred Health, 18 May - 5 June 2015. MAIN OUTCOME MEASURES: Baseline demographics, medical and allergy history, infection diagnoses and antibiotic prescribing data for general medical inpatients were collected. A questionnaire was administered to clarify AAL history, followed by correlation of responses with electronic and admissions record descriptions. A hypothetical oral re-challenge in a supervised setting was offered to patients with low risk allergy phenotypes (non-immediate reaction, non-severe cutaneous adverse reaction, or unknown reaction more than 10 years ago). RESULTS: Of the 453 inpatients, 107 (24%) had an AAL (median age, 82 years; interquartile range, 74-87 years); 160 individual AALs were recorded, and there was a mismatch in AAL description between recording platforms in 25% of cases. Most patients with an AAL were women (64%; P < 0.001), and more presented with concurrent immunosuppression than those without an AAL (23% v 8%; P < 0.001). ß-Lactam penicillins were employed less frequently in patients with an AAL (16% v 35%; P = 0.02), while ceftriaxone (32% v 20%; P = 0.02) and fluoroquinolones (6% v 2%; P = 0.04) were used more often. Fifty-four per cent of patients with AALs were willing to undergo oral re-challenge, of whom 48% had a low risk allergy phenotype. CONCLUSIONS: AAL prevalence in general medical inpatients was 24%, and was associated with excessive use of broad spectrum antibiotics. Allergies in a large proportion of patients with AALs were incorrectly documented, and were non-immune-mediated and potentially amenable to oral re-challenge. A direct oral re-challenge study in carefully selected patients with low risk allergy phenotypes appears feasible.

Impact of a heart failure nurse practitioner service on rehospitalizations, emergency presentations, and survival in patients hospitalized with acute heart failure.

AIMS: Heart failure nurse practitioners (HF NPs) are an emerging component of the heart failure (HF) specialist workforce but their impact in an inpatient setting is untested. The aim of this paper is to explore the impact of an inpatient HF NP service on 12-month all-cause rehospitalizations, emergency department (ED) presentations, and mortality in patients hospitalized with HF compared with usual hospital care. METHODS AND RESULTS: Retrospective, two-group comparative design involving patients (n = 408) admitted via ED with acute HF to a metropolitan quaternary hospital between January 2013 and August 2017. Doubly robust estimation with augmented inverse probability weighting (DR-AIPW) was used to account for the non-random allocation of patients to usual hospital care or the HF NP service in addition to usual in-hospital care. Among 408 patients (186 usual care and 222 HF NP service) admitted with acute HF, the mean age was 76.5 [standard deviation (SD) 12.0] years and 56.4% (n = 230) were male. After IPW adjustment, patients seen by the HF NP service had a lower risk of 12-month rehospitalization (61.3 vs. 78.3% usual care; difference -16.9%, 95% CI: -26.4%, -6.6%) and ED presentations (12.6 vs. 22.0%; difference -9.4%, 95% CI: -17.3%, -1.4%) with no difference in 6- or 12-month mortality. The HF NP service improved referrals to a home visiting programme that was available to HF patients (64.4 vs. 45.4%; difference 19%, 95% CI: 8.8%, 28.8%). CONCLUSION: Additional support by an inpatient HF NP service has the potential to significantly reduce rehospitalizations and ED presentations over 12 months. Further evidence from a multicentre randomized control trial is warranted.

Ophthalmic manifestations of Cryptococcus gattii species complex: a case series and review of the literature.

AIM: To report 4 cases of Cryptococcus gattii (C. gattii) species complex infection with diverse ophthalmic manifestations, and to review the literature to examine pathobiology of disease, classical ophthalmic presentations and outcomes, and treatment modalities for this emerging pathogen. METHODS: Cases of C. gattii meningoencephalitis with ophthalmic manifestations were identified via chart review at two institutions in Australia and one institution in the mid-west region of the United States and are reported as a case series. Additionally, a MEDLINE literature review was conducted to identify all reported cases of C. gattii with ophthalmic manifestations from 1990-2020. Cases were reviewed and tabulated, together with our series of patients, in this report. RESULTS: Four cases of C. gattii with ophthalmic manifestations are presented; three from Australia and one from the USA. A literature review identified a total of 331 cases of C. gattii with visual sequelae. The majority of cases occurred in immunocompetent individuals. Blurred vision and diplopia were the most common presenting symptoms, with papilloedema the most common sign, reported in 10%-50% of cases. Visual loss was reported in 10%-53% of cases, as compared to rates of visual loss of 1%-9% in C. neoformans infection. Elevated intracranial pressure, cerebrospinal fluid (CSF) fungal burden, and abnormal neurological exam at presentation correlated with poor visual outcomes. The mainstays of treatment are anti-fungal agents and aggressive management of intracranial hypertension with serial lumbar punctures. CSF diversion procedures should be considered for refractory cases. Acetazolamide and mannitol are associated with high complication rates, and adjuvant corticosteroids have demonstrated higher mortality rates; these treatments should be avoided. CONCLUSION: Permanent visual loss represents a devastating yet potentially preventable sequelae of C. gattii infection. Intracranial hypertension needs to be recognised early and aggressively managed. Referral to an ophthalmologist/neuro-ophthalmologist in all cases of cryptococcal infection independent of visual symptoms at time of diagnosis is recommended.

Effect of a Multiorgan Focused Clinical Ultrasonography on Length of Stay in Patients Admitted With a Cardiopulmonary Diagnosis: A Randomized Clinical Trial.

Importance: There are accumulating data about the utility of diagnostic multiorgan focused clinical ultrasonography (FCU) in the assessment of patients admitted with cardiopulmonary symptoms. Objective: To determine whether adding multiorgan FCU to the initial clinical evaluation of patients admitted with cardiopulmonary symptoms reduces hospital length of stay, hospital readmissions, and in-hospital costs. Design, Setting, and Participants: This is a prospective, parallel-group, superiority, randomized clinical trial with a 1:1 allocation ratio. The study was conducted at The Royal Melbourne Hospital, a tertiary public hospital located in Melbourne, Victoria, Australia. Adults aged 18 years or older admitted to the internal medicine ward with a cardiopulmonary diagnosis were enrolled between September 2018 and December 2019 and were followed up until hospital discharge. Data analysis was performed from August 2020 to January 2021. Interventions: The intervention involved an internal medicine physician-performed heart, lung, and 2-point vein compression FCU in addition to standard clinical evaluation. Main Outcomes and Measures: The primary outcome was the difference in the mean length of hospital stay, defined as the number of hours from admission to the internal medicine ward to hospital discharge. A difference of 24 hours was defined as clinically important. Secondary outcomes included hospital readmissions at 30 days and hospital care costs. Results: A total of 250 participants were enrolled and 2 were excluded, leaving 248 participants (mean [SD] age, 80.1 [11.0] years; 121 women [48.7%]) in the final analysis. There were 124 patients in the intervention group and 124 patients in the control group. The most common initial diagnoses were acute decompensated heart failure (113 patients [45.5%]), pneumonia (45 patients [18.1%]), and exacerbated chronic pulmonary disease (32 patients [12.9%]). The length of hospital stay was 113.4 hours (95% CI, 91.7-135.1 hours) in the FCU group and 125.3 hours (95% CI, 101.7-148.8 hours) in the control group (P = .53). The 30-day readmission rate was not different between groups (FCU vs control, 20 of 124 patients [16.1%] vs 15 of 124 patients [12.0%]), nor were total in-hospital costs (FCU vs control, A$7831.1 [95% CI, A$5586.1-A$10 076.1] vs A$7895.7 [95% CI, A$6385.9-A$9.405.5]). Conclusions and Relevance: In this randomized clinical trial, adult patients admitted to an internal medicine ward with a cardiopulmonary diagnosis, who underwent multiorgan FCU of the heart, lungs, and lower extremities veins during their initial clinical assessment, did not have a shorter hospital length of stay by more than 24 hours, compared with patients who received standard care. Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12618001442291.

Impact of general social distancing measures on incidence of influenza in Australia.

General social distancing measures enacted for control of the #SARSCoV2 pandemic have achieved a profound reduction in incidence of #influenza in Australia https://bit.ly/3hXjOkl.

Measuring antimicrobial prescribing quality in outpatient parenteral antimicrobial therapy (OPAT) services: development and evaluation of a dedicated national antimicrobial prescribing survey.

BACKGROUND: Antimicrobial stewardship programmes are important in driving safety and quality of antimicrobial prescribing. The National Antimicrobial Prescribing Survey (NAPS) is a point-prevalence audit of inpatient antimicrobial prescribing in Australian hospitals. OBJECTIVES: To design and adapt the NAPS tool for use in the outpatient parenteral antimicrobial therapy (OPAT) and hospital-in-the-home (HITH) setting. METHODS: An inter-disciplinary working group with expertise in OPAT and HITH services was established to adapt the NAPS template for use in the OPAT setting-called HITH-NAPS. This was initially trialled in 5 HITH services, subsequently adapted following participant feedback, then offered nationally to 50 services in 2017. RESULTS: There were 1154 prescriptions for 715 patients audited via the HITH-NAPS. The most common antimicrobials prescribed were cefazolin (22%), flucloxacillin (12%), piperacillin/tazobactam (10%) and ceftriaxone (10%). The most common infections treated were cellulitis (30%) and respiratory tract infections (14%). Eighty-seven percent of prescriptions were assessed as appropriate, 11% inappropriate and 2% not assessable. Prolonged durations of antimicrobials and unnecessarily broad-spectrum antibiotics were used in 9% of prescriptions. CONCLUSIONS: The HITH-NAPS pilot project revealed that auditing of this type is feasible in HITH. It showed that antibiotic use in these HITH services was generally appropriate, but there are some areas for improvement. A national OPAT/HITH-NAPS can facilitate benchmarking between services, identify potentially inappropriate prescribing and help guide quality improvement.

Donor mannose-binding lectin deficiency increases the likelihood of clinically significant infection after liver transplantation.

BACKGROUND: Mannose-binding lectin (MBL) is an important mediator of innate immunity and is synthesized primarily by the liver. Low MBL levels are common, are due primarily to polymorphisms in the gene encoding MBL (MBL2), and are associated with an increased risk of infection, particularly when immunity is compromised. We report a large, retrospective study that examined the association between MBL status and clinically significant infection following orthotopic liver transplantation. METHODS: One hundred two donor-recipient orthotopic liver transplantation pairs were studied. Five polymorphisms in the promoter and coding regions of MBL2 were examined. MBL levels were measured, using the mannan-binding and C4-deposition assays, in serum samples obtained before and after transplantation. Associations between MBL status, as assessed by serum MBL levels and MBL2 genotype, and time to first clinically significant infection (CSI) after transplantation were examined in survival analysis with consideration of competing risks. RESULTS: The median duration of follow-up after orthotopic liver transplantation was 4 years. Thirty-six percent of recipients developed CSI after transplantation. The presence of MBL2 coding mutations in the donor was significantly associated with CSI in the recipient; the cumulative incidence function of infection was 55% in recipients of deficient livers, compared with 32% for recipients of wild-type livers (P = .002). Infection was not associated with recipient MBL2 genotype. Low MBL levels after orthotopic liver transplantation levels (mannan-binding <1 microg/mL or C4 deposition <0.2 C4 U/microL) were also associated with CSI (cumulative incidence function, 52% vs. 20%, P = .003; and cumulative incidence function, 54% vs. 24%, P = .007, respectively). In multivariate analysis, mutation in the MBL2 coding region of the donor (hazard ratio, 2.8; P = .005) and the use of cytomegalovirus prophylaxis (hazard ratio, 2.6; P = .005) were independently associated with CSI. CONCLUSIONS: Recipients of MBL-deficient livers have almost a 3-fold greater likelihood of developing CSI and may benefit from MBL replacement.

Outcomes following resection of non-small cell lung cancer in octogenarians.

BACKGROUND: The treatment of choice for early stage non-small cell lung cancer (NSCLC) is surgical resection. Little is known about the short- and long-term outcomes among very elderly patients. We sought to determine predictors of short- and long-term survival among octogenarians undergoing curative-intent resection for NSCLC in Victoria, Australia. METHODS: We retrospectively reviewed data from all patients aged ≥80 years who underwent curative-intent resection for NSCLC over 12 years (January 2005-December 2016) across five tertiary centres. We examined effect of age, stage of disease, extent of surgery and lung function on short- and long-term survival. RESULTS: Two hundred patients aged ≥80 years underwent curative-intent resections. Mortality at 30 and 120 days was 2.9% and 5.9%, respectively. Increased early mortality was observed among those ≥83 years, at 30 days (6.8% versus 0.8%, P = 0.044) and 120 days (12.2% versus 2.3%, P = 0.0096). Early mortality was highest among patients ≥83 years requiring lobectomy, compared to sub-lobar resection at 120 days (17% versus 3.8%, P = 0.019). Long-term survival was predicted by age and stage of disease. Among patients with Stage I disease aged <83 years, lobectomy was associated with superior 5-year survival, compared to sub-lobar resection (83% versus 61%, P = 0.02). CONCLUSION: In carefully selected elderly patients undergoing curative-intent resection of early stage NSCLC, both short- and long-term outcomes appear consistent with younger historical cohorts. Early mortality was associated with lobectomy in those with advanced age. Older patients undergoing lobectomy appeared to be at highest risk for early mortality, while younger patients with Stage I disease undergoing at least lobectomy appear to have the best long-term survival.

An unusual presentation of carcinomatous meningitis.

A 67-year old previously well male presented with a 1 week history of confusion on a background of 3 weeks of headache. Past history included two superficial melanomas excised 5 years ago. Treatment for meningoencephalitis was commenced based on lumbar puncture (LP) and non-contrast brain magnetic resonance imaging (MRI) results. Lack of a clinical response to antibiotics resulted in a second LP and contrast brain MRI which demonstrated hydrocephalus and leptomeningeal disease. Ongoing deterioration led to a whole-body computed tomographic and spinal MRI that showed widespread metastatic disease and extensive leptomeningeal involvement of the spinal cord. The diagnosis of metastatic melanoma with carcinomatous meningitis was made based on cytological analysis of cerebrospinal fluid. He died 2 weeks later in a palliative care facility. This case illustrates that the diagnosis of carcinomatous meningitis can be difficult to make as the heterogeneous nature of its presentation often delays the diagnosis.