"What do I think about implementing lung cancer screening? It all depends on how." Acceptability and feasibility of lung cancer screening in Australia: The view of key stakeholders about health system factors.

BACKGROUND: Lung cancer is the number one cause of cancer death worldwide. Although international trials demonstrate that targeted screening using low dose computed tomography (LDCT) significantly reduces lung cancer mortality, implementation of screening in the high-risk population presents complex health system challenges that need to be thoroughly understood to support policy change. AIM: To elicit health care providers' and policymakers' views about the acceptability and feasibility of lung cancer screening (LCS) and barriers and enablers to implementation in the Australian setting. METHODS: We conducted 24 focus groups and three interviews (22 focus groups and all interviews online) in 2021 with 84 health professionals, researchers, and current cancer screening program managers and policy makers across all Australian states and territories. Focus groups included a structured presentation about lung cancer and screening and lasted approximately one hour each. A qualitative approach to analysis was used to map topics to the Consolidated Framework for Implementation Research. RESULTS: Nearly all participants considered LCS to be acceptable and feasible but identified a wide range of implementation challenges. Topics (five specific to health systems and five cross-cutting with participant factors) identified were mapped to CFIR constructs, of which 'readiness for implementation', 'planning' and 'executing' were most salient. Health system factor topics included delivery of the LCS program, cost, workforce considerations, quality assurance and complexity of health systems. Participants strongly advocated for streamlined referral processes. Practical strategies to address equity and access, such as using mobile screening vans, were emphasised. CONCLUSIONS: Key stakeholders readily identified the complex challenges associated with the acceptability and feasibility of LCS in Australia. The barriers and facilitators across health system and cross-cutting topics were clearly elicited. These findings are highly relevant to the scoping of a national LCS program by the Australian Government and a subsequent recommendation for implementation.

Predictive factors of upstaging DCIS to invasive carcinoma in BCT vs mastectomy.

BACKGROUND: Upstaging from DCIS to invasive ductal carcinoma varies widely from 0 to 59%. We aim to identify risk factors associated with upstaging in all DCIS patients and based on specific surgical intervention. METHODS: Patients with a pre-operative diagnosis of DCIS undergoing BCT or mastectomy were reviewed. Multivariable analysis was performed to identify risk factors for upstaging. RESULTS: In total, 623 patients had a preoperative diagnosis of DCIS. Upstaging occurred in 74 patients (12%) overall. There was no difference in upstaging rates between mastectomy and BCT (11% v 14% p = 0.27). Sentinel lymph node biopsy was positive in 4/212 patients (1%). Multivariable analysis revealed suspicion of microinvasion (OR 5.7 95%CI2.2-14.9), surgeon suspicion of invasive disease (OR 2.7, 95% CI 1.2-6.4) and larger size/multicentric/extensive tumor (OR 1.9 95% CI 1.1-3.4) increase risk of upstaging. CONCLUSIONS: Suspicion of microinvasion, surgeon suspicion, and tumor size can be used to help guide the use of sentinel lymph node biopsy. For patients without these high risk characteristics, it is hard to justify the use of concurrent SLN biopsy for patients who undergo BCT.

Implementation research to assess a health workers performance-based management system in Nepal.

AIM: To test and refine a performance-based management system to improve health worker performance in Nepal. METHODS: A mixed-methods implementation research in three districts. The study assessed health workers' job satisfaction at the start and end of the study. Qualitative techniques were used to document processes, and routine health service data were analysed to measure outcomes. RESULTS: Job satisfaction significantly increased in six of nine key areas, and the proportion of staff absenteeism significantly declined in the study districts. It demonstrated an increase in immunisation coverage, the proportion of women who had a first antenatal check-up also having a fourth check-up and the proportion of childbirth in a health facility. The greatest perceived strengths of the system were its robust approach to performance planning and evaluation, supportive supervision, outcome-based job descriptions and a transparent reward system. A functional health facility environment, leadership and community engagement support successful implementation. CONCLUSION: The performance-based management system has the potential to increase health workers' job satisfaction, and it offers a tool to link facility-wide human resource management. A collaborative approach, ownership and commitment of the health system are critical to success. Considering the Nepal context, a management system that demonstrates a positive improvement has potential for improved health care delivery.

Identification and Characterization of Salmonella enterica Serotype Newport Isolates with Decreased Susceptibility to Ciprofloxacin in the United States.

Nontyphoidal Salmonella (NTS) causes an estimated 1.2 million illnesses, 23,000 hospitalizations, and 450 deaths each year in the United States. Decreased susceptibility to ciprofloxacin (DSC) has historically been associated with chromosomal mutations of the quinolone resistance determining region (QRDR), but plasmid-mediated quinolone resistance (PMQR) genes are increasing. To investigate DSC among Salmonella enterica serotype Newport strains, we examined 40 isolates from 1996 to 2016 with DSC. Thirty isolates (71%) contained the PMQR gene qnrB and eight isolates (19%) contained a QRDR.

Safety and efficacy of bariatric surgery in patients with advanced fibrosis.

BACKGROUND: Bariatric surgery is performed safely in non-alcoholic fatty liver disease (NAFLD) patients with minimal fibrosis (stage 1-2). However, the safety and potential benefits of bariatric surgery for NAFLD with advanced fibrosis (stage 3-4) remain unclear. This study was designed to compare the safety and efficacy of bariatric surgery in patients with biopsy proven advanced fibrosis to those with minimal fibrosis. METHODS: All patients who underwent bariatric surgery between 2005 and 2014 and had evidence of NAFLD with fibrosis score 3-4 (advanced fibrosis) based on the staging system defined by Kleiner et al. on intraoperative liver biopsy were included and compared with patients who had fibrosis score 1-2 (minimal fibrosis). The groups were compared for length of hospital stay after bariatric surgery and incidence of postoperative complications over a follow-up period of 1 year. An improvement in hepatic function tests before and 1 year after surgery was used as a parameter to evaluate for NAFLD improvement. RESULTS: Ninety-nine patients with F3-4 (group 1) and 198 patients with F1-2 (group 2) were included. Mean age (51.9 vs 50.1 years) and body mass index (46.4 vs 46.5 kg m-2) were similar in the two groups. Median serum aspartate aminotransferase (43 vs 30 U l-1; normal 10-40 U l-1) and alanine aminotransferase (40.5 vs 34 U l-1; normal 10-50 U l-1) were significantly higher in group 1 and improved 1 year after surgery. Median length of hospital stay after surgery was higher in group 1 than that in group 2 (4 days vs 3 days; P-value=0.002). The proportion of patients developing postoperative complications over 1 year was similar in both groups (36.4% vs 32.8%; P-value=0.54). CONCLUSIONS: Advanced fibrosis does not increase the risk of developing postoperative complications in medically optimized patients undergoing bariatric surgery. Improvement in serum transaminase levels suggests a reduction in hepatic necroinflammatory activity following bariatric surgery.

Higher visceral to subcutaneous fat ratio is associated with small intestinal bacterial overgrowth.

BACKGROUND AND AIMS: There is a lack of studies evaluating the association between small intestinal bacterial overgrowth (SIBO) and abdominal fat. The aim of this study was to evaluate whether visceral fat area (VFA), subcutaneous fat area (SFA) or visceral to subcutaneous fat ratio (VFA/SFA ratio) were associated with SIBO. METHODS AND RESULTS: In this case-control study, 152 eligible patients submitted to glucose hydrogen/methane breath test who also had computed tomography (CT) of the abdomen performed were included. Clinical and demographic information was obtained. VFA and SFA were measured using Image J software at lumbar 3 level on CT cross-sectional image of the 152 patients included in this study, 68 patients (44.7%) tested positive for SIBO. In the univariate analysis, the presence of SIBO was associated with older age (65.2 ± 1.5 vs. 59.3 ± 1.5, p = 0.007); type 2 diabetes mellitus (33.8% vs. 17.9%; p = 0.019); hypertension (63.2% vs. 39.3%; p = 0.003); metabolic syndrome (85.3% vs. 64.3%; p = 0.003); and higher VFA/SFA ratio (1.0 ± 0.1 vs. 0.7 ± 0.1; p < 0.001). In multivariate analysis, metabolic syndrome (odds ratio [OR]: 2.5; 95% confidence interval [CI]: 1.1-5.7; p = 0.035) and higher VFA/SFA ratio (OR: 3.3; 95% CI: 1.6-7.2; p = 0.002) remained independently associated with SIBO. CONCLUSION: The presence of SIBO was found to be associated with high VFA/SFA ratio measured from cross-sectional CT image.

Association between high visceral fat area and postoperative complications in patients with Crohn's disease following primary surgery.

AIM: The aim of this study was to determine the association between visceral fat area (VFA) on CT and postoperative complications after primary surgery in patients with Crohn's disease (CD). METHOD: Inclusion criteria were patients with a confirmed diagnosis of CD who had preoperative abdominal CT scan. The areas of total fat, subcutaneous fat and visceral fat were measured using an established image-analysis method at the lumbar 3 (L3) level on CT cross-sectional images. Visceral obesity was defined as a visceral fat area (VFA) of ≥ 130 cm(2) . Clinical variables, intra-operative outcomes and postoperative courses within 30 days were analysed. RESULTS: A total of 164 patients met the inclusion criteria. Sixty-three (38.4%) patients had postoperative complications. The mean age of the patients with complications (the study group) was 40.4 ± 15.4 years and of those without complications (the control group) was 35.8 ± 12.9 years (P = 0.049). There were no differences in disease location and behaviour between patients with or without complications (P > 0.05). In multivariable analysis, VFA [odds ratio (OR) = 2.69; 95% confidence interval (CI): 1.09-6.62; P = 0.032] and corticosteroid use (OR = 2.86; 95% CI: 1.32-6.21; P = 0.008) were found to be associated with postoperative complications. Patients with visceral obesity had a significantly longer operative time (P = 0.012), more blood loss (P = 0.019), longer bowel resection length (P = 0.003), postoperative ileus (P = 0.039) and a greater number of complications overall (P < 0.001). CONCLUSION: High VFA was found to be associated with an increased risk for 30-day postoperative complications in patients with CD undergoing primary surgery.

A systematic review of the public's knowledge and beliefs about antibiotic resistance.

OBJECTIVES: The objective of this study was to systematically review quantitative and qualitative studies on the public's knowledge and beliefs about antibiotic resistance. METHODS: We searched four databases to July 2014, with no language or study design restrictions. Two reviewers independently extracted data. We calculated the median (IQR) of the proportion of participants who agreed with each statement and synthesized qualitative data by identifying emergent themes. RESULTS: Of 3537 articles screened, 54 studies (41 quantitative, 3 mixed methods and 10 qualitative) were included (55 225 participants). Most studied adults (50; 93% studies) and were conducted in Europe (23; 43%), Asia (14; 26%) or North America (12; 22%). Some participants [median 70% (IQR 50%-84%); n = 8 studies] had heard of antibiotic resistance, but most [median 88% (IQR 86%-89%); n = 2 studies] believed it referred to changes in the human body. Many believed excessive antibiotic use [median 70% (IQR 59%-77%); n = 11 studies] and not completing antibiotic courses [median 62% (IQR 47%-77%); n = 8 studies] caused resistance. Most participants nominated reducing antibiotic use [median 74% (IQR 72%-85%); n = 4 studies] and discussing antibiotic resistance with their clinician (84%, n = 1 study) as strategies to reduce resistance. Qualitative data supported these findings and additionally identified that: participants believed they were at low risk from antibiotic resistance participants; largely attributed its development to the actions of others; and strategies to minimize resistance should be primarily aimed at clinicians. CONCLUSIONS: The public have an incomplete understanding of antibiotic resistance and misperceptions about it and its causes and do not believe they contribute to its development. These data can be used to inform interventions to change the public's beliefs about how they can contribute to tackling this global issue.

Not in my backyard: a systematic review of clinicians' knowledge and beliefs about antibiotic resistance.

OBJECTIVES: To systematically review clinicians' knowledge and beliefs about the importance and causes of antibiotic resistance, and strategies to reduce resistance. METHODS: Four databases were searched (until July 2014), without restrictions on language, setting or study design. Fixed responses (from surveys) were grouped into categories. The proportion of participants who agreed with each category was expressed as median, percentage and IQR. Qualitative data were coded into emergent themes. Quantitative categories and qualitative themes were grouped into four overarching categories that emerged from the data. RESULTS: There were 57 included studies (38 quantitative, 14 qualitative, 5 mixed methods) of 11593 clinicians. Most clinicians (69%, IQR 63%-72%, n=5 studies) had heard of antibiotic resistance and 98% (IQR 93%-99%, n=5 studies) believed it was serious. The proportion who believed it was a problem for their practice (67%, IQR 65%-74%, n=13 studies) was smaller than the proportion who believed it was a problem globally (89%, IQR 85%-97%, n=5 studies) or nationally (92%, IQR 88%-95%, n=21 studies). Most believed excessive antibiotic use (97%, IQR 91%-98%, n=12 studies) and patient non-adherence (90%, IQR 82%-92%, n=7 studies) caused resistance. Most knew of strategies to reduce resistance (e.g. clinician education, 90%, IQR 85%-96%, n=7 studies). Qualitative findings support these data: they attributed responsibility for antibiotic resistance to patients, other countries and healthcare settings; resistance was considered a low priority and a distant consequence of antibiotic prescribing. CONCLUSIONS: Clinicians believe antibiotic resistance is a serious problem, but think it is caused by others. This needs to be accommodated in interventions to reduce antibiotic resistance.

EGFR expression is associated with decreased benefit from trastuzumab in the NCCTG N9831 (Alliance) trial.

BACKGROUND: Epidermal growth factor receptor (EGFR) has been hypothesised to modulate the effectiveness of anti-HER2 therapy. We used a standardised, quantitative immunofluorescence assay and a novel EGFR antibody to evaluate the correlation between EGFR expression and clinical outcome in the North Central Cancer Treatment Group (NCCTG) N9831 trial. METHODS: Tissue microarrays were constructed that allowed analysis of 1365 patients randomly assigned to receive chemotherapy alone (Arm A), sequential trastuzumab after chemotherapy (Arm B) and chemotherapy with concurrent trastuzumab (Arm C). Measurement of EGFR was performed using the EGFR antibody, D38B1, on the fluorescence-based AQUA platform. The result was validated using an independent retrospective metastatic breast cancer cohort (n=130). RESULTS: Epidermal growth factor receptor assessed as a continuous (logarithmic transformed) variable shows an association with disease-free survival in Arm C (P=0.009) but not in Arm A or B. High EGFR expression was associated with worse outcome (Hazard ratio (HR)=2.15; 95% CI 1.28-3.60, P=0.004). Validation in a Greek metastatic breast cancer cohort showed an HR associated with high EGFR expression of 1.92 (P=0.0073). CONCLUSIONS: High expression of EGFR appears to be associated with decreased benefit from adjuvant concurrent trastuzumab. Since other treatment options exist for HER2-driven tumours, further validation of these data may select patients for alternative or additive therapy.

Early management of the severely injured major trauma patient.

The major trauma team relies on an efficient, communicative team to ensure patients receive the best quality care. This requires a comprehensive handover, rapid systematic review, and early management of life- and limb-threatening injuries. These multiple injured patients often present with complex conditions in a dynamic situation. The importance of team work, communication, senior decision-making, and documentation cannot be underestimated.

The impact of a managed clinical network on referral patterns of sarcoma patients in Grampian.

In 2004, the Scottish Sarcoma Managed Clinical Network (SSMCN) was established with the aim of optimising the management of patients diagnosed with sarcoma in Scotland. Clinical, radiological, oncological and pathological details of all bone and soft tissue sarcomas presenting in Scotland are registered and cases discussed in a weekly multi-centre, tele-link multidisciplinary team (MDT) forum. Sarcoma surgery and pathology assessment is undertaken in three specialist centres, Aberdeen, Edinburgh and Glasgow with oncological services provided within these units as well as in Dundee and Inverness. The aim of this study was to establish any difference in referral patterns, time to specialist review, preoperative magnetic resonance imaging scanning and whether complete margins were achieved on formal resection before and after establishment of the Scottish Sarcoma Network. A database was established of all patients presenting with sarcomas of the trunk or extremity in Grampian between 1991 and 2009. Notes for 158 patients were available for review. Seventy-nine (50%) patients presented prior to the establishment of the Scottish Sarcoma Network. Cohort analysis reveals that the establishment of the SSMCN has had a positive impact on the management of sarcoma. The number of patients undergoing formal resection by the specialist surgical team has significantly increased while the waiting time from referral to assessment by the sarcoma service has decreased.

An open-label, long-term evaluation of the safety, efficacy and tolerability of avanafil in male patients with mild to severe erectile dysfunction.

AIM: Determine the long-term efficacy, safety and tolerability of avanafil, a highly specific, rapidly absorbed phosphodiesterase type 5 inhibitor in male patients with mild to severe erectile dysfunction (ED), with or without diabetes. METHODS: This was a 52-week, open-label extension of two 12-week, randomised, placebo-controlled, phase 3 trials. Patients were assigned to avanafil 100 mg, but could request 200 mg (for increased efficacy; '100/200-mg' group) or 50 mg (for improved tolerability). Primary end points included percentage of sexual attempts ending in successful vaginal penetration [Sexual Encounter Profile 2 (SEP2)] and intercourse (SEP3) and erectile function domain score per the International Index of Erectile Function (IIEF-EF). RESULTS: Some 712 patients enrolled; 686 were included in the intent to treat population and contributed to the data. All primary end points showed sustained improvement. SEP2 and SEP3 success rates improved from 44% to 83% and from 13% to 68% (100-mg group) and from 43% to 79% and from 11% to 66% (100/200-mg group), respectively. Mean IIEF-EF domain scores improved from 13.6 to 22.2 (100-mg group) and from 11.9 to 22.7 (100/200-mg group). Avanafil was effective in some patients ≤ 15 min and > 6 h postdose. Sixty-five per cent (112/172) of 'nonresponders' to avanafil 100 mg responded to the 200-mg dose. The most common (≥ 2%) treatment-emergent adverse events were headache, flushing, nasopharyngitis and nasal congestion; < 3% of patients discontinued therapy because of adverse events. CONCLUSIONS: The long-term tolerability and improvement in sexual function, coupled with rapid onset, suggest that avanafil is well suited for the on-demand treatment of ED.

The evaluation of North Carolina's state-sponsored youth tobacco prevention media campaign.

In 2003, the state of North Carolina (NC) implemented a multi-component initiative focused on teenage tobacco use prevention and cessation. One component of this initiative is Tobacco.Reality.Unfiltered. (TRU), a tobacco prevention media campaign, aimed at NC youth aged 11-17 years. This research evaluates the first 5 years of the TRU media campaign, from 2004 to 2009, using telephone surveys of NC youth. Overall, TRU campaign awareness was moderate among youth in its first year, with awareness significantly increasing over time. The majority of youth who saw the advertisements reported that they were convincing, attention grabbing and gave good reasons not to smoke. In 2009, logistic regression models revealed awareness of the TRU advertisements was associated with decreased odds of current smoking and experimenting with cigarettes for at-risk NC youth. Results from this research may help other states to define, evaluate and modify their own media campaigns, especially within financially or politically constraining environments.

The changing landscape of axillary surgery: which breast cancer patients may still benefit from complete axillary lymph node dissection?

BACKGROUND AND OBJECTIVES: Many breast cancer patients undergoing completion axillary lymph node dissection (CALND) for sentinel lymph node (SLN) metastases have no further disease. Predicting patients at high risk of non-sentinel lymph node (NSLN) metastasis may help guide effective utilization of CALND. METHODS: SLN+ breast cancer patients undergoing frozen section (FS) analysis at a single institution (2004-2010) were studied retrospectively. Factors associated with NSLN metastases were identified. RESULTS: Two-hundred forty SLN+ patients were identified. The incidence of NSLN metastases was 45% in FS(+) patients undergoing CALND, compared to 10% of FS(-) patients following CALND (P < 0.001). Multivariate analysis revealed that FS positivity, tumor size, and the presence of angiolymphatic invasion were significant factors associated with NSLN metastases (all P < 0.05). Further analysis of FS(+) patients revealed that tumor size, ER(-) status, and lymph node metastasis size were also associated with risk of NSLN metastases. An algorithm for the management of the axilla in SLN+ breast cancer patients was devised, based on clinic-pathologic predictors of NSLN metastases. CONCLUSION: A SLN+ biopsy by FS predicts the presence of NSLN metastases and, in combination with other factors, may justify immediate CALND. CALND may, however, be avoided in selected low-risk SLN+ patients.