Risk of COVID-19 death for people with a pre-existing cancer diagnosis prior to COVID-19-vaccination: A systematic review and meta-analysis.

While previous reviews found a positive association between pre-existing cancer diagnosis and COVID-19-related death, most early studies did not distinguish long-term cancer survivors from those recently diagnosed/treated, nor adjust for important confounders including age. We aimed to consolidate higher-quality evidence on risk of COVID-19-related death for people with recent/active cancer (compared to people without) in the pre-COVID-19-vaccination period. We searched the WHO COVID-19 Global Research Database (20 December 2021), and Medline and Embase (10 May 2023). We included studies adjusting for age and sex, and providing details of cancer status. Risk-of-bias assessment was based on the Newcastle-Ottawa Scale. Pooled adjusted odds or risk ratios (aORs, aRRs) or hazard ratios (aHRs) and 95% confidence intervals (95% CIs) were calculated using generic inverse-variance random-effects models. Random-effects meta-regressions were used to assess associations between effect estimates and time since cancer diagnosis/treatment. Of 23 773 unique title/abstract records, 39 studies were eligible for inclusion (2 low, 17 moderate, 20 high risk of bias). Risk of COVID-19-related death was higher for people with active or recently diagnosed/treated cancer (general population: aOR = 1.48, 95% CI: 1.36-1.61, I2 = 0; people with COVID-19: aOR = 1.58, 95% CI: 1.41-1.77, I2 = 0.58; inpatients with COVID-19: aOR = 1.66, 95% CI: 1.34-2.06, I2 = 0.98). Risks were more elevated for lung (general population: aOR = 3.4, 95% CI: 2.4-4.7) and hematological cancers (general population: aOR = 2.13, 95% CI: 1.68-2.68, I2 = 0.43), and for metastatic cancers. Meta-regression suggested risk of COVID-19-related death decreased with time since diagnosis/treatment, for example, for any/solid cancers, fitted aOR = 1.55 (95% CI: 1.37-1.75) at 1 year and aOR = 0.98 (95% CI: 0.80-1.20) at 5 years post-cancer diagnosis/treatment. In conclusion, before COVID-19-vaccination, risk of COVID-19-related death was higher for people with recent cancer, with risk depending on cancer type and time since diagnosis/treatment.

Cutaneous melanoma, prostate-specific antigen testing and the subsequent risk of prostate cancer diagnosis: a prospective analysis of the 45 and Up Study.

BACKGROUND: The association between cutaneous melanoma and subsequent risk of prostate cancer (PC) was examined in a large population-based cohort study. METHODS: Male participants in the Sax Institute's 45 and Up Study (Australia) were recruited between 2006 and 2009. Questionnaire data and linked administrative health data from the Centre for Health Record Linkage and Services Australia identified melanomas diagnosed between 1/1/1994 and 12 months before Study recruitment (i.e., between 2005 and 2008), incident PCs, primary healthcare utilisation and prostate-specific antigen (PSA) tests. Men were excluded from the current analyses if they had a recorded PC or other cancer diagnosis other than melanoma and non-melanoma skin cancer prior to recruitment. Multivariable Cox regression was used to estimate hazard ratios (HRs) adjusting for PSA-testing frequency before PC diagnosis. RESULTS: Of 96,548 eligible men, 1899 were diagnosed with melanoma during the melanoma diagnosis period and 3677 incident PC diagnosed during follow-up (latest date 31/12/2013). Men with melanoma diagnosis had increased risk of a subsequent PC diagnoses (vs. no melanoma; fully adjusted HR = 1.32; 95% CI: 1.09-1.60). There was weak evidence of higher risks of a subsequent PC diagnosis for men diagnosed with more than one melanoma compared to men diagnosed with only one melanoma (p = 0.077), and if first melanoma diagnosis was 10 to 15 years before Study recruitment (fully adjusted HR = 2.05; 95% CI [1.35, 3.12]). CONCLUSION: Melanoma diagnosis was associated with increased risk of subsequent PC diagnosis, after adjusting for PSA testing and primary healthcare utilisation. While our ability to adjust for PC screening reduced risk of detection bias, we acknowledge that residual confounding from increased medical surveillance after melanoma diagnoses cannot be entirely ruled out.

Colon and rectal cancer treatment patterns and their associations with clinical, sociodemographic and lifestyle characteristics: analysis of the Australian 45 and Up Study cohort.

BACKGROUND: Colorectal cancer is the third most diagnosed cancer globally and the second leading cause of cancer death. We examined colon and rectal cancer treatment patterns in Australia. METHODS: From cancer registry records, we identified 1,236 and 542 people with incident colon and rectal cancer, respectively, diagnosed during 2006-2013 in the 45 and Up Study cohort (267,357 participants). Cancer treatment and deaths were determined via linkage to routinely collected data, including hospital and medical services records. For colon cancer, we examined treatment categories of "surgery only", "surgery plus chemotherapy", "other treatment" (i.e. other combinations of surgery/chemotherapy/radiotherapy), "no record of cancer-related treatment, died"; and, for rectal cancer, "surgery only", "surgery plus chemotherapy and/or radiotherapy", "other treatment", and "no record of cancer-related treatment, died". We analysed survival, time to first treatment, and characteristics associated with treatment receipt using competing risks regression. RESULTS: 86.4% and 86.5% of people with colon and rectal cancer, respectively, had a record of receiving any treatment ≤2 years post-diagnosis. Of those treated, 93.2% and 90.8% started treatment ≤2 months post-diagnosis, respectively. Characteristics significantly associated with treatment receipt were similar for colon and rectal cancer, with strongest associations for spread of disease and age at diagnosis (p<0.003). For colon cancer, the rate of "no record of cancer-related treatment, died" was higher for people with distant spread of disease (versus localised, subdistribution hazard ratio (SHR)=13.6, 95% confidence interval (CI):5.5-33.9), age ≥75 years (versus age 45-74, SHR=3.6, 95%CI:1.8-7.1), and visiting an emergency department ≤1 month pre-diagnosis (SHR=2.9, 95%CI:1.6-5.2). For rectal cancer, the rate of "surgery plus chemotherapy and/or radiotherapy" was higher for people with regional spread of disease (versus localised, SHR=5.2, 95%CI:3.6-7.7) and lower for people with poorer physical functioning (SHR=0.5, 95%CI:0.3-0.8) or no private health insurance (SHR=0.7, 95%CI:0.5-0.9). CONCLUSION: Before the COVID-19 pandemic, most people with colon or rectal cancer received treatment ≤2 months post-diagnosis, however, treatment patterns varied by spread of disease and age. This work can be used to inform future healthcare requirements, to estimate the impact of cancer control interventions to improve prevention and early diagnosis, and serve as a benchmark to assess treatment delays/disruptions during the pandemic. Future work should examine associations with clinical factors (e.g. performance status at diagnosis) and interdependencies between characteristics such as age, comorbidities, and emergency department visits.

Platinum-based chemotherapy for early triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer associated with shorter survival and a higher likelihood of the cancer returning. In early TNBC, platinum-based chemotherapy has been shown to improve pathological complete response (pCR); however, its effect on long-term survival outcomes has not been fully elucidated and recommendations to include platinum chemotherapy are not consistent in international guidelines. OBJECTIVES: To evaluate the benefits and harms of platinum-based chemotherapy as adjuvant and neoadjuvant treatment in people with early triple-negative breast cancer. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 4 April 2022. SELECTION CRITERIA: We included randomised controlled trials examining neoadjuvant or adjuvant platinum chemotherapy for early TNBC. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were disease-free survival (DFS) and overall survival (OS). Our secondary outcomes were pCR, treatment adherence, grade III or IV toxicity related to chemotherapy, and quality of life. Prespecified subgroups included BRCA mutation status, homologous recombination deficiency (HRD) status, frequency of chemotherapy, type of platinum agent used, and the presence or absence of anthracycline chemotherapy. We assessed risk of bias using Cochrane's RoB 1 tool and certainty of evidence using the GRADE approach. MAIN RESULTS: From 3972 records, we included 20 published studies involving 21 treatment comparisons, and 25 ongoing studies. For most domains, risk of bias was low across studies. There were 16 neoadjuvant chemotherapy studies (one of which combined neoadjuvant and adjuvant therapy) and four adjuvant chemotherapy trials. Most studies used carboplatin (17 studies) followed by cisplatin (two), and lobaplatin (one). Eight studies had an anthracycline-free intervention arm, five of which had a carboplatin-taxane intervention compared to an anthracycline-taxane control. All studies reporting DFS and OS used carboplatin. Inclusion of platinum chemotherapy improved DFS in neoadjuvant and adjuvant settings (neoadjuvant: hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.53 to 0.75; 7 studies, 8 treatment comparisons, 1966 participants; high-certainty evidence; adjuvant: HR 0.69, 95% CI 0.54 to 0.88; 4 studies, 1256 participants; high-certainty evidence). Platinum chemotherapy in the regimen improved OS (neoadjuvant: HR 0.69, 95% CI 0.55 to 0.86; 7 studies, 8 treatment comparisons, 1973 participants; high-certainty evidence; adjuvant: 0.70, 95% CI 0.50 to 0.96; 4 studies, 1256 participants; high-certainty evidence). Median follow-up for survival outcomes ranged from 36 to 97.6 months. Our analysis confirmed platinum chemotherapy increased pCR rates (risk ratio (RR) 1.44, 95% CI 1.31 to 1.59; 15 studies, 16 treatment comparisons, 3083 participants; high-certainty evidence). Subgroup analyses showed no evidence of differences in DFS according to BRCA mutation status, HRD status, lymph node status, or whether the intervention arm contained anthracycline chemotherapy or not. Platinum chemotherapy was associated with reduced dose intensity, with participants more likely to require chemotherapy delays (RR 2.23, 95% CI 1.70 to 2.94; 4 studies, 5 treatment comparisons, 1053 participants; moderate-certainty evidence), dose reductions (RR 1.77, 95% CI 1.56 to 2.02; 7 studies, 8 treatment comparisons, 2055 participants; moderate-certainty evidence) and early cessation of treatment (RR 1.20, 95% CI 1.04 to 1.38; 16 studies, 17 treatment comparisons, 4178 participants; moderate-certainty evidence). Increased haematological toxicity occurred in the platinum group who were more likely to experience grade III/IV neutropenia (RR 1.53, 95% CI 1.43 to 1.63; 19 studies, 20 treatment comparisons, 4849 participants; moderate-certainty evidence), anaemia (RR 8.20, 95% CI 5.66 to 11.89; 18 studies, 19 treatment comparisons, 4757 participants; moderate-certainty evidence) and thrombocytopenia (RR 7.59, 95% CI 5.10 to 11.29; 18 studies, 19 treatment comparisons, 4731 participants; moderate-certainty evidence). There was no evidence of a difference between chemotherapy groups in febrile neutropenia (RR 1.16, 95% CI 0.89 to 1.49; 11 studies, 3771 participants; moderate-certainty evidence). Renal impairment was very rare (0.4%, 2 events in 463 participants; note 3 studies reported 0 events in both arms; 4 studies; high-certainty evidence). Treatment-related death was very rare (0.2%, 7 events in 3176 participants and similar across treatment groups; RR 0.58, 95% 0.14 to 2.33; 10 studies, 11 treatment comparisons; note 8 studies reported treatment-related deaths but recorded 0 events in both groups. Thus, the RR and CIs were calculated from 3 studies rather than 11; 3176 participants; high-certainty evidence). Five studies collected quality of life data but did not report them. AUTHORS' CONCLUSIONS: Platinum-based chemotherapy using carboplatin in the adjuvant or neoadjuvant setting improves long-term outcomes of DFS and OS in early TNBC, with no evidence of differences by subgroup. This was at the cost of more frequent chemotherapy delays and dose reductions, and greater haematological toxicity, though serious adverse events including neuropathy, febrile neutropenia or treatment-related death were not increased. These findings support the use of platinum-based chemotherapy for people with early TNBC. The optimal dose and regimen are not defined by this analysis, but there is a suggestion that similar relative benefits result from the addition of carboplatin to either anthracycline-free regimens or those containing anthracycline agents.

Family history, obesity, urological factors and diabetic medications and their associations with risk of prostate cancer diagnosis in a large prospective study.

BACKGROUND: Prostate cancer (PC) aetiology is unclear. PC risk was examined in relation to several factors in a large population-based prospective study. METHODS: Male participants were from Sax Institute's 45 and Up Study (Australia) recruited between 2006 and 2009. Questionnaire and linked administrative health data from the Centre for Health Record Linkage and Services Australia were used to identify incident PC, healthcare utilisations, Prostate Specific Antigen (PSA) testing reimbursements and dispensing of metformin and benign prostatic hyperplasia (BPH) prescriptions. Multivariable Cox and Joint Cox regression analyses were used to examine associations by cancer spread, adjusting for various confounders. RESULTS: Of 107,706 eligible men, 4257 developed incident PC up to end 2013. Risk of PC diagnosis increased with: PC family history (versus no family history of cancer; HRadjusted = 1.36; 95% CI:1.21-1.52); father and brother(s) diagnosed with PC (versus cancer-free family history; HRadjusted = 2.20; 95% CI:1.61-2.99); severe lower-urinary-tract symptoms (versus mild; HRadjusted = 1.77; 95% CI:1.53-2.04) and vasectomy (versus none; HRadjusted = 1.08; 95% CI:1.00-1.16). PC risk decreased with dispensed prescriptions (versus none) for BPH (HRadjusted = 0.76; 95% CI:0.69-0.85) and metformin (HRadjusted = 0.57; 95% CI:0.48-0.68). Advanced PC risk increased with vasectomy (HRadjusted = 1.28; 95% CI:1.06-1.55) and being obese (versus normal weight; HRadjusted = 1.31; 95% CI:1.01-1.69). CONCLUSION: Vasectomy and obesity are associated with an increased risk of advanced PC. The reduced risk of localised and advanced PC associated with BPH, and diabetes prescriptions warrants investigation.

Evaluating laser photobiomodulation for chemotherapy-induced peripheral neuropathy: a randomised phase II trial.

PURPOSE: This study aims to evaluate the efficacy and safety of laser photobiomodulation (PBM) for treatment of established chemotherapy-induced peripheral neuropathy (CIPN) in cancer survivors. METHODS: We conducted a randomised phase II, non-comparative, sham-controlled, single-blinded clinical trial in 44 cancer survivors reporting CIPN symptoms at least 3 months following completion of neurotoxic chemotherapy. Participants were randomised 2:1 to either PBM laser or sham control delivered twice weekly for 12 sessions. Assessments were conducted at baseline, the end of intervention (6 weeks), and 6 weeks post intervention (12 weeks). Participants completed neuropathy, quality of life and function questionnaires, and a clinical neurological assessment. The primary outcome was proportion of participants with CIPN response, defined as either symptom resolution or reduction of minimally clinically important difference. RESULTS: In the laser and control groups, CIPN response rates were - 48% and 53% at 6 weeks and 45% and 33% at 12 weeks, respectively. The null hypothesis that the true response rate is 5% in the laser arm was rejected at both 6 and 12 weeks (p < 0.001 for both). Compared to baseline, patient-reported CIPN improved in both laser and control groups after the intervention. At 12 weeks, improvement was sustained in the laser group and approaching baseline in the control group. Clinical signs, quality of life, and function remained stable in both groups. Low-grade "side-effects" were observed in both arms. CONCLUSION: PBM may offer clinically meaningful symptom benefit in cancer survivors with established CIPN with improvement potentially continuing beyond completion of the intervention. A larger study is warranted to evaluate this further.

Systematic review of long-term chemotherapy-induced peripheral neuropathy (CIPN) following adjuvant oxaliplatin for colorectal cancer.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is the most common dose-limiting side effect of oxaliplatin. It often persists and can adversely affect quality of life of colorectal cancer (CRC) survivors. This systematic review explored the proportions of patients with persistent CIPN and the reporting methods used. METHODS: MEDLINE, EMBASE, Web of Science and CINAHL were searched up to March 2021 for publications reporting CIPN outcomes following adjuvant oxaliplatin-containing chemotherapy at prespecified timepoints in participants with CRC. Secondary outcomes assessed the tools used to measure CIPN. Two authors reviewed full text publications for eligibility, data extraction and appraisal. Meta-analysis was performed where Common Terminology Criteria for Adverse Events (any grade) was reported at the most frequent timepoints. RESULTS: From 7895 citations identified, 27 studies met the eligibility criteria: six were randomised control trials, and 21 were non-randomised studies. Pooled prevalence of CIPN at 6, 12, 24 and 36 months after chemotherapy were 58%, 45%, 32% and 24% respectively. The average prevalence of CIPN decreased by 26% per year after chemotherapy (pooled RR = 0.74; 95% CI 0.72-0.75). Across all studies, ten separate tools were used as the primary measure of CIPN. Quality appraisal identified open-label design and inadequate reporting of participants lost to follow-up as the main methodological limitations. CONCLUSION: Our summary of reported rates of persistent CIPN indicates substantial long-term toxicity affecting CRC survivors, and will help clinicians estimate CIPN risk and its change over time. The heterogeneity of CIPN measures identified in the review highlights the need for a standardised CIPN assessment.

Tobacco purchasing motivations and behaviours in alcohol-licensed venues: A cross sectional survey of Australian young adults.

ISSUE ADDRESSED: The widespread retail availability of tobacco contributes to increased tobacco consumption and undermines quit attempts. Given the ready availability of tobacco in alcohol-licensed venues which young adults frequent, tobacco sales in these venues are likely to influence the purchase and consumption of tobacco by young adults. This study aimed to investigate Australian young adults' tobacco purchasing motivations and behaviours in alcohol-licensed venues. METHODS: A cross-sectional survey was conducted with a sample of 18- to 30-year-old Australians (n = 307) who had purchased tobacco at an alcohol-licensed venue within the previous 6 months. Purchaser characteristics, levels of alcohol consumption and whether the purchase was planned were assessed, along with anticipated responses to tobacco sales ceasing at the venue. RESULTS: The majority of participants (57%) reported their recent cigarette purchase at an alcohol-licensed venue as unplanned. Area of residence was the only characteristic associated with an unplanned purchase, with those living in urban areas significantly less likely to have made an unplanned purchase than regional participants (OR = 0.51, 95% CI [0.29, 0.89]). During the occasion when the tobacco purchase was made, the majority of participants (51%) had consumed five or more standard alcoholic drinks. If tobacco sales ceased at the venue, 22% indicated they would stay and not smoke. CONCLUSIONS: Unplanned tobacco purchases appear to be influenced by the alcohol-licensed settings, rather than socio-demographic factors associated with the individual. SO WHAT?: Policies that restrict the sale of tobacco in alcohol-licensed venues are likely to reduce tobacco consumption among young adults and support smokers to quit.

Cancer incidence and cancer death in relation to tobacco smoking in a population-based Australian cohort study.

Tobacco smoke is a known carcinogen, but the magnitude of smoking-related cancer risk depends on country-specific, generational smoking patterns. We quantified cancer risk in relation to smoking in a population-based cohort, the 45 and Up Study (2006-2009) in New South Wales, Australia. Cox proportional hazards regressions estimated adjusted hazard ratios (HR) by self-reported smoking history at baseline (2006-2009) for incident, primary cancers via linkage to cancer registry data to 2013 and cancer death data to 2015. Among 229 028 participants aged ≥45 years, 18 475 cancers and 5382 cancer deaths occurred. Current-smokers had increased risks of all cancers combined (HR = 1.42, 95% confidence interval [CI], 1.34-1.51), cancers of the lung (HR = 17.66, 95%CI, 14.65-21.29), larynx (HR = 11.29, 95%CI, 5.49-23.20), head-and-neck (HR = 2.53, 95%CI, 1.87-3.41), oesophagus (HR = 3.84, 95%CI, 2.33-6.35), liver (HR = 4.07, 95%CI, 2.55-6.51), bladder (HR = 3.08, 95%CI, 2.00-4.73), pancreas (HR = 2.68, 95%CI, 1.93-3.71), colorectum (HR = 1.31, 95%CI, 1.09-1.57) and unknown primary site (HR = 3.26, 95%CI, 2.19-4.84) versus never-smokers. Hazards increased with increasing smoking intensity; compared to never-smokers, lung cancer HR = 9.22 (95%CI, 5.14-16.55) for 1-5 cigarettes/day and 38.61 (95%CI, 25.65-58.13) for >35 cigarettes/day. Lung cancer risk was lower with quitting at any age but remained higher than never-smokers for quitters aged >25y. By age 80y, an estimated 48.3% of current-smokers (41.1% never-smokers) will develop cancer, and 14% will develop lung cancer, including 7.7% currently smoking 1-5 cigarettes/day and 26.4% for >35 cigarettes/day (1.0% never-smokers). Cancer risk for Australian smokers is significant, even for 'light' smokers. These contemporary estimates underpin the need for continued investment in strategies to prevent smoking uptake and facilitate cessation, which remain key to reducing cancer morbidity and mortality worldwide.

Alcohol consumption, drinking patterns and cancer incidence in an Australian cohort of 226,162 participants aged 45 years and over.

BACKGROUND: Although overall alcohol consumption is known to increase the risk of a number of cancers internationally, evidence for Australia and evidence regarding the pattern of drinking and cancer risk is limited. METHODS: Adjusted hazard ratios (HR) and 95% confidence intervals (CI) for cancer risk in relation to overall alcohol consumption (drinks/week) and pattern of drinking were calculated using Cox proportional hazard regressions for 226,162 participants aged ≥45 years (2006-2009) in the 45 and Up Study, an Australian prospective cohort study. Incident primary cancer cases were ascertained by linkage to the New South Wales Cancer Registry to 2013 by the Centre for Health Record Linkage. RESULTS: Over a median of 5.4 years, 17,332 cancers were diagnosed. Increasing levels of alcohol intake were associated with increased risk of cancers of the upper aerodigestive tract (1.19; 1.10-1.29), mouth and pharynx (1.18; 1.08-1.29), oesophagus (1.22; 1.04-1.43), colorectum (1.09; 1.04-1.15), colon (1.13; 1.06-1.20), liver (1.22; 1.04-1.44) and breast (1.11; 1.02-1.21). Breast cancer risk was marginally associated with drinking pattern, with higher risk when intake was concentrated on 1-3 days/week compared to the same amount spread over 4-7 days (Pinteraction = 0.049). CONCLUSIONS: Alcohol consumption confers a significant risk of cancer, and drinking pattern may be independently related to breast cancer risk.

Has Human Papillomavirus (HPV) Vaccination Prevented Adverse Pregnancy Outcomes? Population-Level Analysis After 8 Years of a National HPV Vaccination Program in Australia.

BACKGROUND: Human papillomavirus (HPV) infection, and its sequelae of precancerous cervical lesions and their subsequent treatment, have been linked with an increased risk of adverse pregnancy outcomes. Publicly funded HPV vaccination of female adolescents began in Australia in 2007 with initial catch-up to age 26 years. METHODS: Using data from the National Perinatal Data Collection we compared rates of preterm births and small-for-gestational-age infants born in Australia 2000-2015. We used generalized linear models, assuming a Poisson distribution and log link function, with single-year categories of infant birth year, maternal age, and age-specific HPV vaccination coverage as independent variables. RESULTS: In maternal cohorts with 60%-80% HPV vaccination coverage as achieved in Australia, there was a relative rate reduction of 3.2% (95% confidence interval, 1.1%-5.3%) in preterm births and 9.8% (8.2% to 11.4%) in small-for-gestational-age infants, after adjustment for infant's birth year and maternal age. CONCLUSION: This analysis provides provisional population-level evidence of a reduction in adverse pregnancy outcomes in cohorts of women offered HPV vaccination. Confounding by smoking or other variables and/or ecological analysis limitations, however, cannot be excluded. These findings indicate potential broader benefits of HPV vaccination than have been documented to date.

Who sells tobacco, who stops? A comparison across different tobacco retailing schemes.

BACKGROUND: Licensing of tobacco retailers has been proposed as a mechanism to encourage retailers to stop selling tobacco. However, previous studies of tobacco licensing and/or of retailers who have stopped selling have been restricted to one legislative environment. This study examines patterns of tobacco retailing across three legislative environments with three different licensing schemes (an annual fee-based licence, a zero-cost, one-off notification scheme and no notification/licensing scheme). METHOD: A telephone survey was conducted of 2928 potential tobacco retailers who could personally choose whether or not to sell tobacco (rather than the decision being made at a head office). RESULTS: Unexpectedly, the annual licence fee to sell tobacco was not significantly associated with a lower rate of selling tobacco or a higher rate of stopping. After allowing for other factors, probability of selling, stopping selling and reported importance of tobacco sales varied across outlet types (p<0.001 for all three outcomes), and according to the remoteness of the retailer (p<0.001, p trend=0.041 and p=0.025 respectively). CONCLUSION: A fee of $A286 was not associated with a lower rate of selling, or a higher rate of stopping. The effect of licensing on retailer numbers will presumably be greater for higher licence fees, but will also depend on the perceived importance of tobacco sales to the retailer. In turn, importance of tobacco sales appears to depend on market factors, including proximity to major urban centres and low-cost competitors. A higher licence fee is likely to have a larger effect on discouraging retailers from selling.

'Friends with benefits': how tobacco companies influence sales through the provision of incentives and benefits to retailers.

BACKGROUND: In countries banning advertising and display of tobacco at point-of-sale, little is known about tobacco companies' continuing promotion of products through incentives and benefits to retailers. METHOD: A telephone survey of 4527 randomly selected Australian retailers was conducted in August 2018, and identified 800 current tobacco retailers (response rate: 72.4%) who were asked a series of questions about benefits offered to them by tobacco companies and what retailers agreed to in return. RESULTS: 41.1% of retailers reported being provided with a tobacco cabinet and 38.3% reported having a price list supplied by a tobacco company. One-third (33.3%) reported being offered at least one benefit from a tobacco company for doing something in return. Price discounts were the most frequently reported benefit (19.0%), followed by rebates (8.4%) and gifts (3.0%). Retailers also reported offers of prizes and incentives for increasing sales or demonstrating product knowledge. In return, retailers reported giving companies benefits such as prominence on the price list and/or in the tobacco cabinet and/or influence over the product range and stock levels. CONCLUSION: Tobacco companies are continuing to market tobacco and influence sales through provision of incentives and benefits to retailers. Laws that ban the supply of benefits to consumers should be extended to also prohibit the provision of benefits to tobacco retailers.

Understanding why some Australian retailers have stopped selling tobacco, some might and some are unlikely.

BACKGROUND: Widespread availability of tobacco has been shown to contribute to ongoing smoking and make quitting harder. This study investigates why some retailers in three Australian states decided to stop selling tobacco, others might stop selling and why others continue to sell in a declining market. METHODS: A telephone survey of 4527 randomly selected retailers was conducted in August 2018 (response rate=72.4%). This study examines responses to open-ended questions in the survey probing retailers' attitudes and beliefs regarding selling (or not selling) tobacco. RESULTS: 27.3% of the sample sold tobacco, and 13.3% had formerly sold. Outlets that had stopped selling most frequently mentioned minimal profit and/or sales as the reason for stopping selling (27.7% across all states). This was also the most frequent reason why retailers said they might stop selling. Uniquely in Western Australia (the only state in the study with a fee-based licensing scheme), 12.5% of former tobacco retailers named tobacco licensing as the reason for stopping sales-the second most frequent reason in Western Australia. Of current sellers who were unlikely to stop, the potential to lose sales was the most frequently named reason (31.0% across all states). CONCLUSION: Retailers report being driven by the profitability of tobacco when deciding whether or not to stop selling, although only a small percentage discussed losing incremental sales if they stopped selling. An annual licence fee contributed to some retailers stopping selling, showing that a fee-based tobacco license can contribute to a decline in retail availability of tobacco.

Platinum-containing regimens for triple-negative metastatic breast cancer.

BACKGROUND: In a previous Cochrane Review, we found that for women with metastatic breast cancer unselected for triple-negative disease, there is little or no survival benefit and excess toxicity from platinum-based regimens. In subgroup analyses, however, we found preliminary low-quality evidence of a survival benefit from platinum-based regimens for women with metastatic triple-negative breast cancer (mTNBC). This review updates the evidence from the mTNBC subgroup analyses in the previous Cochrane Review. OBJECTIVES: To assess the effects of platinum-containing chemotherapy regimens with regimens not containing platinum in the management of women with mTNBC. SEARCH METHODS: We obtained relevant studies published prior to 2015 and their extracted results from the mTNBC subgroup analysis in the previous Cochrane Review. We searched the Cochrane Breast Cancer Group's Specialised Register, CENTRAL, MEDLINE, Embase, the World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials.gov between 2015 and 27 September 2019. We identified further potentially relevant studies from previous trial reports, systematic reviews, and meta-analyses. SELECTION CRITERIA: Randomised trials comparing platinum-containing chemotherapy regimens with regimens not containing platinum in women with mTNBC. Individual trials could compare one or more platinum-based regimens to one or more non-platinum regimens; hence there could be more 'treatment-comparisons' (i.e. platinum regimen versus non-platinum regimen comparison) than trials. Trial participants may have been purposely selected for mTNBC or inadvertently selected as a subgroup. DATA COLLECTION AND ANALYSIS: At least two independent reviewers assessed studies for eligibility and quality, and extracted all relevant data from each study. We derived hazard ratios (HRs) for time-to-event outcomes, where possible, and used fixed-effect models for meta-analyses. We analysed objective tumour response rates (OTRRs) and toxicities as binary (dichotomous) outcomes with risk ratios (RRs) used as measures of effects. We extracted quality of life data, if available. We used GRADE to rate the quality of evidence for time-to-event and tumour response outcomes. MAIN RESULTS: This review includes 13 treatment-comparisons involving 1349 women from 10 studies. Twelve of the 13 treatment-comparisons were included in one or more meta-analyses. Of the 13 treatment-comparisons, six and eight had published or provided time-to-event data on overall survival (OS) or progression-free survival/time to progression (PFS/TTP), respectively, that could be included in meta-analyses. Ten treatment-comparisons published or provided OTRR data that could be included in meta-analyses. Eight of the 13 treatment-comparisons were from studies that selected participants on the basis of mTNBC status, while the other five treatment-comparisons were from studies that reported mTNBC results as part of subgroup analyses. Analysis of six treatment-comparisons indicated that platinum-containing regimens may have provided a small survival benefit to mTNBC patients (HR 0.85, 95% CI 0.73 to 1.00; 958 women; moderate-quality evidence) with no evidence of heterogeneity (P = 0.41; I2 = 1%). Data from eight treatment-comparisons showed that platinum regimens may improve PFS/TTP (HR 0.77, 95% CI 0.68 to 0.88; 1077 women; very low-quality evidence). There was marked evidence of heterogeneity (P < 0.0001; I2 = 80%). There was also low-quality evidence of better tumour response for platinum recipients (RR 1.40, 95% CI 1.22 to 1.59; 1205 women) with some evidence of heterogeneity (P = 0.01; I2 = 58%). The observed heterogeneity for the PFS/TTP and OTRR outcomes may reflect between-study differences and general difficulties in assessing tumour response, as well as the varying potencies of the comparators. Compared with women receiving non-platinum regimens: rates of grade 3 and 4 nausea/vomiting were higher for platinum recipients (RR 4.77, 95% CI 1.93 to 11.81; 655 women; low-quality evidence) and rates of grade 3 and 4 anaemia were higher for platinum recipients (RR 3.80, 95% CI 2.25 to 6.42; 843 women; low-quality evidence). In general, however, relatively few intervention-comparisons could be included in meta-analyses for adverse events. None of the studies reported quality of life. AUTHORS' CONCLUSIONS: For women with mTNBC, there was moderate-quality evidence of a small survival benefit from platinum-based regimens compared to non-platinum regimens. This finding is consistent with findings of a PFS/TTP benefit and improved tumour response from platinum-based regimens. These potential benefits, however, should be weighed against previously identified excess toxicities from platinum-based regimens, particularly regimens containing cisplatin. Further randomised trials of platinum-based regimens among women with mTNBC are required.

Body weight management in overweight and obese breast cancer survivors.

BACKGROUND: Studies suggest that overweight and obese breast cancer survivors are at increased risk of cancer recurrence and have higher all-cause mortality. Obesity has an impact on breast cancer survivor's quality of life (QOL) and increases the risk of longer-term morbidities such as type 2 diabetes mellitus and cardiovascular disease. Many cancer guidelines recommend survivors maintain a healthy weight but there is a lack of evidence regarding which weight loss method to recommend. OBJECTIVES: To assess the effects of different body weight loss approaches in breast cancer survivors who are overweight or obese (body mass index (BMI) ≥ 25 kg/m2). SEARCH METHODS: We carried out a search in the Cochrane Breast Cancer Group's (CBCG's) Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 6), MEDLINE (2012 to June 2019), Embase (2015 to June 2019), the World Health Organisation International Clinical Trials Registry Platform (WHO ICTRP) and Clinicaltrials.gov on 17 June 2019. We also searched Mainland Chinese academic literature databases (CNKI), VIP, Wan Fang Data and SinoMed on 25 June 2019. We screened references in relevant manuscripts. SELECTION CRITERIA: We included randomised controlled trials (RCTs), quasi-RCTs and randomised cross-over trials evaluating body weight management for overweight and obese breast cancer survivors (BMI ≥ 25 kg/m2). The aim of the intervention had to be weight loss. DATA COLLECTION AND ANALYSIS: Two review authors independently performed data extraction and assessed risk of bias for the included studies, and applied the quality of the evidence using the GRADE approach. Dichotomous outcomes were analysed as proportions using the risk ratio (RR) as the measure of effect. Continuous data were analysed as means with the measure of effect being expressed as the mean differences (MDs) between treatment groups in change from baseline values with 95% confidence intervals (CIs), when all studies reported exactly the same outcomes on the same scale. If similar outcomes were reported on different scales the standardised mean difference (SMD) was used as the measure of effect. Quality of life data and relevant biomarkers were extracted where available. MAIN RESULTS: We included a total of 20 studies (containing 23 intervention-comparisons) and analysed 2028 randomised women. Participants in the experimental groups received weight loss interventions using the core element of dietary changes, either in isolation or in combination with other core elements such as 'diet and exercise', 'diet and psychosocial support' or 'diet, exercise and psychosocial support'. Participants in the controls groups either received usual care, written materials or placebo, or wait-list controls. The duration of interventions ranged from 0.5 months to 24 months. The duration of follow-up ranged from three months to 36 months. There were no time-to-event data available for overall survival, breast cancer recurrence and disease-free survival. There was a relatively small amount of data available for breast cancer recurrence (281 participants from 4 intervention-comparisons with 14 recurrence events; RR 1.95, 95% CI 0.68 to 5.60; low-quality evidence) and the analysis was likely underpowered. Overall, we found low-quality evidence that weight loss interventions for overweight and obese breast cancer survivors resulted in a reduction in body weight (MD: -2.25 kg, 95% CI: -3.19 to -1.3 kg; 21 intervention-comparisons; 1751 women), body mass index (BMI) (MD: -1.08 kg/m2, 95% CI: -1.61 to -0.56 kg/m2; 17 intervention-comparisons; 1353 women), and waist circumference (MD:-1.73 cm, 95% CI: -3.17 to -0.29 cm; 13 intervention-comparisons; 1193 women), and improved overall quality of life (SMD: 0.74; 95% CI: 0.20 to 1.29; 10 intervention-comparisons; 867 women). No increase was seen in adverse events for women in the intervention groups compared to controls (RR 0.94, 95% CI: 0.76 to 1.17; 4 intervention-comparisons; 394 women; high-quality evidence). Subgroup analyses revealed that decreases in body weight, BMI and waist circumference were present in women regardless of their ethnicity and menopausal status. Multimodal weight loss interventions (which referred to 'diet, exercise and psychosocial support') appeared to result in greater reductions in body weight (MD: -2.88 kg, 95% CI: -3.98 to -1.77 kg; 13 intervention-comparisons; 1526 participants), BMI (MD: -1.44 kg/m2, 95% CI: -2.16 to -0.72 kg/m2; 11 studies; 1187 participants) and waist circumference (MD:-1.66 cm, 95% CI: -3.49 to -0.16 cm; 8 intervention-comparisons; 1021 participants) compared to dietary change alone, however the evidence was low quality. AUTHORS' CONCLUSIONS: Weight loss interventions, particularly multimodal interventions (incorporating diet, exercise and psychosocial support), in overweight or obese breast cancer survivors appear to result in decreases in body weight, BMI and waist circumference and improvement in overall quality of life. There was no increase in adverse events. There is a lack of data to determine the impact of weight loss interventions on survival or breast cancer recurrence. This review is based on studies with marked heterogeneity regarding weight loss interventions. Due to the methods used in included studies, there was a high risk of bias regarding blinding of participants and assessors. Further research is required to determine the optimal weight loss intervention and assess the impact of weight loss on survival outcomes. Long-term follow-up in weight loss intervention studies is required to determine if weight changes are sustained beyond the intervention periods.

Tobacco smoking and risk of 36 cardiovascular disease subtypes: fatal and non-fatal outcomes in a large prospective Australian study.

BACKGROUND: Tobacco smoking is a leading cause of cardiovascular disease (CVD) morbidity and mortality. Evidence on the relation of smoking to different subtypes of CVD, across fatal and non-fatal outcomes, is limited. METHODS: A prospective study of 188,167 CVD- and cancer-free individuals aged ≥ 45 years from the Australian general population joining the 45 and Up Study from 2006 to 2009, with linked questionnaire, hospitalisation and death data up to the end of 2015. Hazard ratios (HRs) for hospitalisation with or mortality from CVD among current and past versus never smokers were estimated, including according to intensity and recency of smoking, using Cox regression, adjusting for age, sex, urban/rural residence, alcohol consumption, income and education. Population-attributable fractions were estimated. RESULTS: During a mean 7.2 years follow-up (1.35 million person-years), 27,511 (crude rate 20.4/1000 person-years) incident fatal and non-fatal major CVD events occurred, including 4548 (3.2) acute myocardial infarction (AMI), 3991 (2.8) cerebrovascular disease, 3874 (2.7) heart failure and 2311 (1.6) peripheral arterial disease (PAD) events. At baseline, 8% of participants were current and 34% were past smokers. Of the 36 most common specific CVD subtypes, event rates for 29 were increased significantly in current smokers. Adjusted HRs in current versus never smokers were as follows: 1.63 (95%CI 1.56-1.71) for any major CVD, 2.45 (2.22-2.70) for AMI, 2.16 (1.93-2.42) for cerebrovascular disease, 2.23 (1.96-2.53) for heart failure, 5.06 (4.47-5.74) for PAD, 1.50 (1.24-1.80) for paroxysmal tachycardia, 1.31 (1.20-1.44) for atrial fibrillation/flutter, 1.41 (1.17-1.70) for pulmonary embolism, 2.79 (2.04-3.80) for AMI mortality, 2.26 (1.65-3.10) for cerebrovascular disease mortality and 2.75 (2.37-3.19) for total CVD mortality. CVD risks were elevated at almost all levels of current smoking intensity examined and increased with smoking intensity, with HRs for total CVD mortality in current versus never smokers of 1.92 (1.11-3.32) and 4.90 (3.79-6.34) for 4-6 and ≥ 25 cigarettes/day, respectively. Risks diminished with quitting, with excess risks largely avoided by quitting before age 45. Over one third of CVD deaths and one quarter of acute coronary syndrome hospitalisations in Australia aged < 65 can be attributed to smoking. CONCLUSIONS: Current smoking increases the risk of virtually all CVD subtypes, at least doubling the risk of many, including AMI, cerebrovascular disease and heart failure. Paroxysmal tachycardia is a newly identified smoking-related risk. Where comparisons are possible, smoking-associated relative risks for fatal and non-fatal outcomes are similar. Quitting reduces the risk substantially. In an established smoking epidemic, with declining and low current smoking prevalence, smoking accounts for a substantial proportion of premature CVD events.

A Prospective Study of Health Conditions Related to Alcohol Consumption Cessation Among 97,852 Drinkers Aged 45 and Over in Australia.

BACKGROUND: Evidence suggests that people who develop serious health conditions are likely to cease drinking alcohol (sometimes known as "sick-quitters"). We quantified the likelihood of quitting drinking in relation to the onset of a variety of health conditions. METHODS: Odds ratios (ORs) and 95% confidence intervals (CIs) of ceasing alcohol consumption after diagnosis of 28 health conditions and 4 general indicators of health were derived from logistic regression among 97,852 drinkers aged ≥ 45 years between baseline (2006 to 2009) and median 5.3 years of follow-up in the New South Wales 45 and Up Study. Incident health conditions at follow-up were self-reported. RESULTS: At follow-up, 9.6% (n = 9,438) of drinkers had ceased drinking. Drinking cessation was significantly associated with 24 of 32 health conditions examined: 15.4% of participants with newly diagnosed diabetes quit drinking (OR for quitting vs. continuing 1.77, 95% CI: 1.60 to 1.96), 16.4% with Parkinson's disease (1.71, 1.35 to 2.17), 17.8% with poor memory (1.68, 1.43 to 1.97), 19.2% with hip fracture (1.64, 1.30 to 2.06), 14.7% with stroke (1.45, 1.27 to 1.66), 12.5% with depression (1.40, 1.26 to 1.55), 15.0% with breast cancer (1.38, 1.18 to 1.61), 12.3% with heart disease (1.34, 1.25 to 1.44), and 13.3% with osteoarthritis (1.22, 1.12 to 1.33). Strong associations with quitting were observed in those with a decline in self-rated overall health (2.93, 2.53 to 3.40) and quality of life (2.68, 2.24 to 3.21). Some health conditions not significantly associated with quitting were prostate cancer, melanoma, nonmelanoma skin cancer, hay fever, and hearing loss. Findings were generally consistent for men and women, by age group and by smoking status. CONCLUSIONS: Diagnosis with a variety of health conditions appears to prompt drinking cessation in older adults.

Observed retail price of Australia's market-leading cigarette brand before and up to 3 years after the implementation of plain packaging.

OBJECTIVE: Despite claims by tobacco companies that plain packaging would lead to lower cigarette prices, recommended and observed real cigarette prices in Australia rose in the 9-11 months after plain packaging was introduced. However, little is known about trends in prices longer term. In this report, we assess whether inflation (Consumer Price Index; CPI) and tax adjusted ('CPI-tax-adjusted') prices of the market-leading Australian cigarette brand changed in the 3-year period after plain packaging, and whether price changes were associated with retailer characteristics. METHOD: Cigarette prices were ascertained from a panel of tobacco retailers at three time points: (1) in November 2012 (n=857) (before full implementation of plain packaging, compulsory in retail outlets from December 2012), (2) between October 2014 and February 2015 (n=789) and (3) between November 2015 and March 2016 (n=579). Generalised estimating equations were used to estimate percentage change in mean CPI/tax-adjusted cigarette prices over time. RESULTS: CPI/tax-adjusted adjusted mean stick prices rose by 13.7% (95% CI 13.0 to 16.0) and 15.2% (95% CI 14.3 to 16.0) at 2.1 and 3.1 years after plain packaging was introduced, respectively. Increases in mean CPI/tax-adjusted stick prices varied by outlet type (p<0.001), socioeconomic status (p=0.013) and remoteness of retailer's area (p=0.028) and whether twin packs were sold (p=0.009). CONCLUSIONS: Contrary to tobacco company predictions of a fall in prices, the price of the market-leading Australian cigarette brand increased significantly in the 3 years after plain packaging was introduced, and these increases were above the combined effects of inflation and increases in excise/customs duty.

Risk of childhood mortality associated with death of a mother in low-and-middle-income countries: a systematic review and meta-analysis.

BACKGROUND: Death of a mother at an early age of the child may result in an increased risk of childhood mortality, especially in low-and-middle-income countries. This study aims to synthesize estimates of the association between a mother's death and the risk of childhood mortality at different age ranges from birth to 18 years in these settings. METHODS: Various MEDLINE databases, EMBASE, and Global Health databases were searched for population-based cohort and case-control studies published from 1980 to 2017. Studies were included if they reported the risk of childhood mortality for children whose mother had died relative to those whose mothers were alive. Random-effects meta-analyses were used to pool effect estimates, stratified by various exposures (child's age when mother died, time since mother's death) and outcomes (child's age at risk of child death). RESULTS: A total of 62 stratified risk estimates were extracted from 12 original studies. Childhood mortality was associated with child's age at time of death of a mother and time since a mother's death. For children whose mother died when they were ≤ 42 days, the relative risk (RR) of dying within the first 1-6 months of the child's life was 35.5(95%CI:9.7-130.5, p [het] = 0.05) compared to children whose mother did not die; by 6-12 months this risk dropped to 2.8(95%CI:0.7-10.7). For children whose mother died when they were ≤ 1 year, the subsequent RR of dying in that year was 15.9(95%CI:2.2-116.1,p [het] = 0.02), compared to children whose mother lived. For children whose mother died when they were ≤ 5 years of age, the RR of dying before aged 12 was 4.1(95%CI:3.0-5.7),p [het] = 0.83. Mortality was also elevated in specific analysis  among children whose mother died when child was older than 42 days. Overall, for children whose mother died < 6 and 6+ months ago, RRs of dying before reaching adulthood (≤18 years) were 4.7(95%CI:2.6-8.7,p [het] = 0.2) and 2.1(95%CI:1.3-3.4,p [het] = 0.7), respectively, compared to children whose mother lived. CONCLUSIONS: There is evidence of an association between the death of a mother and childhood mortality in lower resource settings. These findings emphasize the critical importance of women in family outcomes and the importance of health care for women during the intrapartum and postpartum periods and throughout their child rearing years.