Tubulointerstitial nephropathy is the predominant finding in men in a review of more than 3000 renal biopsies over a 10-year period from Sri Lanka.

BACKGROUND: Chronic kidney disease (CKD) is a significant clinical challenge in Sri Lanka. The present study presents histopathological diagnoses from native renal biopsies in Kandy District, 2011-2020. METHODS: Reports of 5,014 renal biopsies principally performed at Kandy Teaching Hospital over 2011-2020 were reviewed. After exclusions for post-kidney transplant biopsies (1,572) and those without evident pathology (347), 3,095 biopsies were included. The predominant histopathological entities were grouped and categorised according to diagnosis and stratified by age and sex. RESULTS: The main histopathological entities (all biopsies) were tubulointerstitial nephropathy (TIN) 25% (n = 760), glomerulonephritis (GN) 15% (467), lupus nephropathy 14% (429), focal segmental glomerular sclerosis (FSGS) 10% (297), and IgA nephropathy (IgAN) 8% (242). For adult women ≥ 15 years, the main histopathological entities were lupus nephropathy 24% (325), TIN 17% (228), and GN 16% (217). For adult men ≥ 15 years, the main histopathological entities were TIN 34% (449), GN 14% (180), and IgAN 10% (125). The proportion of TIN in the present study was higher than international studies of a similar size. CONCLUSION: This is the largest study of renal biopsies reported from Sri Lanka to date. TIN was the most common diagnosis in adults ≥ 15 years at 25%. Notable sex differences showed TIN was the most common histopathology in men (34%) but not in women (17%). No previously published similar study of this size has found TIN as the predominant diagnosis amongst renal biopsies in men. Further research is required into the possible causes of these observations in Sri Lanka. CLINICAL TRIAL NUMBER: Not applicable.

Estimated incidence of disruptions to event-free survival from non-metastatic cancers in New South Wales, Australia - a population-wide epidemiological study of linked cancer registry and treatment data.

Introduction: Population cancer registries record primary cancer incidence, mortality and survival for whole populations, but not more timely outcomes such as cancer recurrence, secondary cancers or other complications that disrupt event-free survival. Nonetheless, indirect evidence may be inferred from treatment data to provide indicators of recurrence and like events, which can facilitate earlier assessment of care outcomes. The present study aims to infer such evidence by applying algorithms to linked cancer registry and treatment data obtained from hospitals and universal health insurance claims applicable to the New South Wales (NSW) population of Australia. Materials and methods: Primary invasive cancers from the NSW Cancer Registry (NSWCR), diagnosed in 2001-2018 with localized or regionalized summary stage, were linked to treatment data for five common Australian cancers: breast, colon/rectum, lung, prostate, and skin (melanomas). Clinicians specializing in each cancer type provided guidance on expected treatment pathways and departures to indicate remission and subsequent recurrence or other disruptive events. A sample survey of patients and clinicians served to test initial population-wide results. Following consequent refinement of the algorithms, estimates of recurrence and like events were generated. Their plausibility was assessed by their correspondence with expected outcomes by tumor type and summary stage at diagnosis and by their associations with cancer survival. Results: Kaplan-Meier product limit estimates indicated that 5-year cumulative probabilities of recurrence and other disruptive events were lower, and median times to these events longer, for those staged as localized rather than regionalized. For localized and regionalized cancers respectively, these were: breast - 7% (866 days) and 34% (570 days); colon/rectum - 15% (732 days) and 25% (641 days); lung - 46% (552 days) and 66% (404 days); melanoma - 11% (893 days) and 38% (611 days); and prostate - 14% (742 days) and 39% (478 days). Cases with markers for these events had poorer longer-term survival. Conclusions: These population-wide estimates of recurrence and like events are approximations only. Absent more direct measures, they nonetheless may inform service planning by indicating population or treatment sub-groups at increased risk of recurrence and like events sooner than waiting for deaths to occur.

Improving the timeliness of birth registration in Fiji through a financial incentive.

Background: Fiji is a Pacific Island nation with the predominant ethnic groups indigenous Fijians (iTaukei) (62 %) and Fijians of Indian descent (31 %). This study reports on the effect of a Parental Assistance Payment Program (PAPP) tied to on-time birth registration, available in Fiji from August 2018 to July 2020. Methods: Unit record birth registration data (n = 117,829) for children born during 2016-22 were used to calculate mean birth-to-registration intervals and the likelihood of on-time birth registration (within 365 days) before the PAPP (January 2016-July 2018) compared to during the PAPP (August 2018-July 2020), by population disaggregations (sex, ethnicity, age, marital status). Results: During the PAPP, mean birth-to-registration intervals declined sharply by 81 %, from 665 days (95 %CI: 658-671) to 124 days (121-127). The largest declines were among i-Taukei children (803 to 139 days, 83 %) compared to non-iTaukei (283 to 76 days, 73 %); mothers aged 10-19 years (880 to 134 days, 85 %) compared to ≥20 years (653 to 123 days, 81 %); and single mothers (983 to 145 days, 85 %) compared to married mothers (570 to 115 days, 80 %). On-time birth registration increased from 57 % to 93 %, and the adjusted hazard ratio showed children born during the PAPP were 2.3 times more likely (95 %CI: 2.2-2.4) to have their birth registered on-time compared to children born before the PAPP. When the PAPP was discontinued in August 2020, the birth-to-registration interval increased sharply in all population groups. Conclusions: During the two-year period the PAPP was available, it was highly effective at improving the timeliness of birth registration, particularly among iTaukei children, young mothers, and single mothers. After the PAPP was discontinued, the timeliness of birth registration deteriorated sharply. Longer post-PAPP follow-up time (≠5 years) is required to determine whether the timeliness of birth registration has deteriorated to levels similar to those during the pre-PAPP period.

Adult mortality from non-communicable diseases in Fiji's major ethnic groups 2013-17.

Background: Sustainable Development Goal 3.4.1 (SDG3.4.1) targets a one-third reduction in non-communicable disease (NCD) mortality in ages 30-69-years by 2030 (relative to 2015). Directing interventions to achieve this aim requires reliable estimates of underlying cause of death (UCoD). This may be problematic when both cardiovascular diseases (CVD) and diabetes are present due to a lack of consistency in certification of such deaths. We estimate empirically 2013-17 NCD mortality in Fiji, by sex and ethnicity, from CVD, diabetes, cancer, and chronic lower respiratory diseases (CRD), and aggregated as NCD4. Methods: UCoD was determined from Medical Certificates of Cause-of-Death (MCCD) from the Fiji Ministry of Health after pre-processing of mortality data where diabetes and/or hypertension were present in order to generate internationally comparable UCoD. If no potentially fatal complications from diabetes or hypertension accompanied these causes in Part I (direct cause) of the MCCD, these conditions were re-assigned to Part II (contributory cause). The probability of a 30-year-old dying before reaching age 70-years (PoD30-70), by cause, was calculated. Findings: The PoD30-70 from NCD4 over 2013-17 differed by sex and ethnicity: in women, it was 36% (95%CI 35-37%) in i-Taukei and 27% (26-28%) in Fijians of Indian descent (FID); in men, it was 41% (40-42%) in both i-Taukei and FID.PoD30-70 from CVD, diabetes, cancer and CRD in women was: 18%, 10%, 13% and 1·0% in i-Taukei; 13%, 10%, 5·6% and 1·1% in FID; in men was: 28%, 8.4%, 7·6% and 2·2% in i-Taukei; 31%, 8.3%, 3.5% and 3·1% in FID. Interpretation: To achieve SDG3.4.1 goals in Fiji by 2030, effective population wide and ethnic-specific interventions targeting multiple NCDs are required to reduce PoD30-70 from NCD4: from 36% to 24% in i-Taukei, and 27% to 18% in FID women; and from 41% to 27% in i-Taukei and FID men. Funding: Not applicable.

Effects of inappropriate cause-of-death certification on mortality from cardiovascular disease and diabetes mellitus in Tonga.

BACKGROUND: Cardiovascular disease (CVD) and diabetes mellitus are major health issues in Tonga and other Pacific countries, although mortality levels and trends are unclear. We assess the impacts of cause-of-death certification on coding of CVD and diabetes as underlying causes of death (UCoD). METHODS: Tongan records containing cause-of-death data (2001-2018), including medical certificates of cause-of-death (MCCD), had UCoD assigned according to International Classification of Diseases 10th revision (ICD-10) coding rules. Deaths without recorded cause were included to ascertain total mortality. Diabetes and hypertension causes were reallocated from Part 1 of the MCCD (direct cause) to Part 2 (contributory cause) if potentially fatal complications were not recorded, and an alternative UCoD was assigned. Proportional mortality by cause based on the alternative UCoD were applied to total deaths then mortality rates calculated by age and sex using census/intercensal population estimates. CVD and diabetes mortality rates for unaltered and alternative UCoD were compared using Poisson regression. RESULTS: Over 2001-18, in ages 35-59 years, alternative CVD mortality was higher than unaltered CVD mortality in men (p = 0.043) and women (p = 0.15); for 2010-18, alternative versus unaltered measures in men were 3.3/103 (95%CI: 3.0-3.7/103) versus 2.9/103 (95%CI: 2.6-3.2/103), and in women were 1.1/103 (95%CI: 0.9-1.3/103) versus 0.9/103 (95%CI: 0.8-1.1/103). Conversely, alternative diabetes mortality rates were significantly lower than the unaltered rates over 2001-18 in men (p < 0.0001) and women (p = 0.013); for 2010-18, these measures in men were 1.3/103 (95%CI: 1.1-1.5/103) versus 1.9/103 (95%CI: 1.6-2.2/103), and in women were 1.4/103 (95%CI: 1.2-1.7/103) versus 1.7/103 (95%CI: 1.5-2.0/103). Diabetes mortality rates increased significantly over 2001-18 in men (unaltered: p < 0.0001; alternative: p = 0.0007) and increased overall in women (unaltered: p = 0.0015; alternative: p = 0.014). CONCLUSIONS: Diabetes reporting in Part 1 of the MCCD, without potentially fatal diabetes complications, has led to over-estimation of diabetes, and under-estimation of CVD, as UCoD in Tonga. This indicates the importance of controlling various modifiable risks for atherosclerotic CVD (including stroke) including hypertension, tobacco use, and saturated fat intake, besides obesity and diabetes. Accurate certification of diabetes as a direct cause of death (Part 1) or contributory factor (Part 2) is needed to ensure that valid UCoD are assigned. Examination of multiple cause-of-death data can improve understanding of the underlying causes of premature mortality to better inform health planning.

Groin Surveillance by Serial Ultrasonography Rather Than Sentinel Node Biopsy or Inguinofemoral Lymphadenectomy for Patients with Vulvar Cancer: A Pilot Study.

A pilot study was conducted to determine whether 3-monthly groin ultrasonography could eliminate groin dissection after a negative bilateral groin ultrasound in three groups of patients: (i) Those with a unifocal stage 1B squamous cell carcinoma of up to 20 mm in diameter. (ii) Those with an ipsilateral squamous cell carcinoma of any size which extended to within 1 cm either side of the midline. These patients underwent ipsilateral inguinofemoral lymphadenectomy and ultrasonic surveillance of the contralateral groin. (iii) Patients with multifocal invasive lesions with the largest individual focus 20 mm or less in diameter. Three additional patients were added because they either refused groin dissection or were considered unfit for surgery. All ultrasonically positive nodes were confirmed histologically. Thirty-two patients were entered, and no patients were lost to follow-up. Forty-three groins were followed. With a median follow-up of 37 months, three positive nodes (9.4%) were detected. One patient died of her recurrence (3.1%), and 39 groins (90.7%) were preserved. The overall sensitivity of ultrasonic surveillance was 100% (95% CI: 44-100%), with a specificity of 97% (95% CI: 83-99%) and a negative predictive value of 100% (95% CI: 88-100%). This pilot justifies a larger study on serial ultrasonography in lieu of groin dissection in selected patients with vulvar cancer.

Maternal Mortality in a Rural District of Pakistan and Contributing Factors.

INTRODUCTION: Pakistan is among the ten countries that account for 60% of global maternal mortality. Lack of accurate data on maternal mortality and a complex interrelation of access and quality of healthcare services, healthcare delivery system, and socio-economic and demographic factors contribute significantly to inadequate progress in reducing maternal mortality. MATERIAL AND METHODS: A population-based prospective cohort study was conducted in a rural district of Pakistan using data obtained from an enhanced surveillance system. A total of 7572 pregnancies and their outcomes were recorded by 273 Lady Health Workers and 73 Community Health Workers over 2016-2017. Logistic regression was used to calculate the unadjusted and adjusted odds ratios (OR) for maternal mortality for each risk factor. Population Attributable Fraction (PAF) was derived from the ORs and risk factor prevalence. RESULTS: The study recorded 18 maternal deaths. The maternal mortality rate was estimated at 238/100,000 pregnancies (95% CI 141-376), and the maternal mortality ratio was 247/100,000 live births (95% CI 147-391). Half of the maternal deaths (9) were from obstetric hemorrhage, and 28% (5) from puerperal sepsis. Postpartum hemorrhage was associated with a 17-fold higher risk of maternal mortality (PAF = 40%) and puerperal sepsis with a 12-fold higher mortality risk (PAF = 29%) compared to women without these conditions. Women delivered by unskilled birth attendants had a three-fold (PAF = 21%), and women having prolonged labour had a fourfold risk of maternal mortality compared to those with these conditions. Women with leg swelling (47%) and pre-eclampsia (26%) are at seven times the risk of maternal mortality compared to those without these conditions. Mortality in women delivered by unskilled birth attendants was three times higher than with skilled attendants. CONCLUSION: The study, among a few large-scale prospective cohort studies conducted at the community level in a rural district of Pakistan, provides a better understanding of the risk factors determining maternal mortality in Pakistan. Poverty emerged as a significant risk factor for maternal mortality in the study area and contributes to the underutilization of health facilities and skilled birth attendants. Incorporating poverty reduction strategies across all sectors, including health, is urgently required to address higher maternal mortality in Pakistan. A paradigm shift is required in Maternal and Child health related programs and interventions to include poverty estimation and measuring mortality through linking mortality surveillance with the Civil Registration and Vital Statistics system. Accelerated efforts to expand the coverage and completeness of mortality data with risk factors to address inequalities in access and utilization of health services.

Antibiotic exposure within six months before systemic therapy was associated with lower cancer survival.

OBJECTIVES: The objective of the study was to quantify associations between cancer survival and antibiotic exposure before systemic anticancer therapy. STUDY DESIGN AND SETTING: This population-based cohort study compares cause-specific survival according to antibiotic exposure before non-immune checkpoint inhibitor (ICI) systemic therapy in patients diagnosed with single primary cancers in New South Wales between 2013 and 2016. Proportional hazards regression was used to control for confounding, with no antibiotic exposure in the six months before non-ICI systemic therapy serving as the comparator. RESULTS: After adjusting for tumour spread, cancer site, age, sex and comorbidity, people having antibiotic exposure within 180 days before non-ICI systemic therapy had poorer cancer survival (hazard ratios ranging from 1.21 [95% confidence interval: 1.06-1.39] to 1.58 [1.34-1.87]) for shorter periods since antibiotic exposure (P < .0001). Similarly, poorer survival trends applied for localized and metastatic cancer. Of six prevalent cancers studied, lung and breast primaries showed the strongest associations of lower survival with prior antibiotic exposure. CONCLUSION: Antibiotic exposure within 180 days before non-ICI systemic cancer treatment is associated with poorer survival. If confirmed in other studies, it provides another reason for vigilant antibiotic stewardship.

Medial Inguino-Femoral Lymphadenectomy for Vulvar Cancer: An Approach to Decrease Lymphedema without Compromising Survival.

BACKGROUND: Lower limb lymphedema is a long-term complication of inguino-femoral lymphadenectomy and is related to the number of lymph nodes removed. Our hypothesis was that lymph nodes lateral to the femoral artery could be left in situ if the medial nodes were negative, thereby decreasing this risk. METHODS: We included patients with vulvar cancer of any histological type, even if the cancer extended medially to involve the urethra, anus, or vagina. We excluded patients whose tumor extended (i) laterally onto the thigh, (ii) posteriorly onto the buttocks, or (iii) anteriorly onto the mons pubis. After resection, the inguinal nodes were divided into a medial and a lateral group, based on the lateral border of the femoral artery. RESULTS: Between December 2010 and July 2018, 76 patients underwent some form of groin node dissection, and data were obtained from 112 groins. Approximately one-third of nodes were located lateral to the femoral artery. Positive groin nodes were found in 29 patients (38.2%). All patients with positive nodes had positive nodes medial to the femoral artery. Five patients (6.6%) had positive lateral inguinal nodes. The probability of having a positive lateral node given a negative medial node was estimated to be 0.00002. CONCLUSION: Provided the medial nodes are negative, medial inguino-femoral lymphadenectomy may suffice and should reduce lower limb lymphedema without compromising survival.

Trends in mortality and life expectancy in Fiji over 20 years.

BACKGROUND: Fiji, a Pacific Island nation of 884,887 (2017 census), has experienced a prolonged epidemiological transition. This study examines trends in mortality and life expectancy (LE) in Fiji by sex and ethnicity over 1996-2017, with comparisons to published estimates. METHODS: Trends in infant mortality rates (IMR), under-5 mortality (U5M), adult mortality (probability of dying), LE (at birth) and directly age-standardised death rates (DASRs) by sex and ethnicity, are calculated (with 95% confidence limits) using unit death records from the Fiji Ministry of Health and Medical Services. The LE gap between populations, or within populations over time, is examined using decomposition by age. Period trends are assessed for statistical significance using linear regression. RESULTS: Over 1996-98 to 2014-17: IMR and U5M for i-Taukei and Fijians of Indian descent declined; U5M decline for i-Taukei (24.6 to 20.1/1000 live births) was significant (p = 0.016). Mortality (15-59 years) for i-Taukei males was unchanged at 27% but declined for Indians 33 to 30% (p = 0.101). Mortality for i-Taukei females increased 22 to 24% (p = 0.011) but declined for Indians 20 to 18% (p = 0.240). DASRs 1996-2017 were lower for i-Taukei (9.3 to 8.2/1000 population) than Indian males (10.6 to 9.8/1000). DASRs declined for i-Taukei (both sexes, p < 0.05), and for Indians (both sexes, p > 0.05). Over 22 years, LE at birth increased by 1 year or less (p = 0.030 in male i-Taukei). In 2014-17, LE (years) for males was: i-Taukei 64.9, Indians 63.5; and females: i-Taukei 67.0 and Indians 68.2. Mortality changes in most 5-year age groups increased or decreased the LE gap less than 10 weeks over 22 years. Compared to international agency reports, 2014-17 empirical LE estimates (males 64.7, females 67.8) were lower, as was IMR. CONCLUSIONS: Based on empirical data, LE in Fiji has minimally improved over 1996-2017, and is lower than some international agencies report. Adult mortality was higher in Indian than i-Taukei men, and higher in i-Taukei than Indian women. Exclusion of stillbirths resulted in IMRs lower than previously reported. Differing mortality trends in subgroups highlight the need to collect census and health data by ethnicity and sex, to monitor health outcomes and inform resource allocation.

Mortality in Tonga over three triennia, 2010-2018.

BACKGROUND: Tonga is a South Pacific Island country with a population of 100,651 (2016 Census). This study examines Tongan infant mortality rates (IMR), under-five mortality rates (U5MR), adult mortality and life expectancy (LE) at birth from 2010 to 2018 using a recent collation of empirical mortality data over the past decade for comparison with other previously published mortality estimates. METHODS: Routinely collected mortality data for 2010-2018 from the Ministry of Health, national (Vaiola) hospital, community nursing reports, and the Civil Registry, were consolidated by deterministic and probabilistic linkage of individual death records. Completeness of empirical mortality reporting was assessed by capture-recapture analysis. The reconciled data were aggregated into triennia to reduce stochastic variation, and used to estimate IMR and U5MR (per 1000 live births), adult mortality (15-59, 15-34, 35-59, and 15-64 years), and LE at birth, employing the hypothetical cohort method (with statistical testing). Mortality trends and differences were assessed by Poisson regression. Mortality findings were compared with published national and international agency estimates. RESULTS: Over the three triennia in 2010-2018, levels varied minimally for IMR (12-14) and U5MR (15-19) per 1000 births (both ns, p > 0.05), and also for male LE at birth of 64-65 years, and female LE at birth 69-70 years. Cumulated risks of adult mortality were significantly higher in men than women; period mortality increases in 15-59-year women from 18 to 21% were significant (p < 0.05). Estimated completeness of the reconciled data was > 95%. International agencies reported generally comparable estimates of IMR and U5MR, with varying uncertainty intervals; but they reported significantly lower adult mortality and higher LE than the empirical estimates from this study. CONCLUSIONS: Life expectancy in Tonga over 2010-2018 has remained relatively low and static, with low IMR and U5MR, indicating the substantial impact from premature adult mortality. This analysis of empirical data (> 95% complete) indicates lower LE and higher premature adult mortality than previously reported by international agencies using indirect and modelled methods. Continued integration of mortality recording and data systems in Tonga is important for improving the completeness and accuracy of mortality estimation for local health monitoring and planning.

Evaluation of Combined Artificial Intelligence and Radiologist Assessment to Interpret Screening Mammograms.

Importance: Mammography screening currently relies on subjective human interpretation. Artificial intelligence (AI) advances could be used to increase mammography screening accuracy by reducing missed cancers and false positives. Objective: To evaluate whether AI can overcome human mammography interpretation limitations with a rigorous, unbiased evaluation of machine learning algorithms. Design, Setting, and Participants: In this diagnostic accuracy study conducted between September 2016 and November 2017, an international, crowdsourced challenge was hosted to foster AI algorithm development focused on interpreting screening mammography. More than 1100 participants comprising 126 teams from 44 countries participated. Analysis began November 18, 2016. Main Outcomes and Measurements: Algorithms used images alone (challenge 1) or combined images, previous examinations (if available), and clinical and demographic risk factor data (challenge 2) and output a score that translated to cancer yes/no within 12 months. Algorithm accuracy for breast cancer detection was evaluated using area under the curve and algorithm specificity compared with radiologists' specificity with radiologists' sensitivity set at 85.9% (United States) and 83.9% (Sweden). An ensemble method aggregating top-performing AI algorithms and radiologists' recall assessment was developed and evaluated. Results: Overall, 144 231 screening mammograms from 85 580 US women (952 cancer positive ≤12 months from screening) were used for algorithm training and validation. A second independent validation cohort included 166 578 examinations from 68 008 Swedish women (780 cancer positive). The top-performing algorithm achieved an area under the curve of 0.858 (United States) and 0.903 (Sweden) and 66.2% (United States) and 81.2% (Sweden) specificity at the radiologists' sensitivity, lower than community-practice radiologists' specificity of 90.5% (United States) and 98.5% (Sweden). Combining top-performing algorithms and US radiologist assessments resulted in a higher area under the curve of 0.942 and achieved a significantly improved specificity (92.0%) at the same sensitivity. Conclusions and Relevance: While no single AI algorithm outperformed radiologists, an ensemble of AI algorithms combined with radiologist assessment in a single-reader screening environment improved overall accuracy. This study underscores the potential of using machine learning methods for enhancing mammography screening interpretation.

Imaging prior to radiotherapy impacts in-vitro survival.

BACKGROUND AND PURPOSE: Cone Beam Computed Tomography (CBCT) is routinely used in radiotherapy to identify the position of the target volume. The aim of this study was to determine whether the CBCT dose, when followed by the treatment, influences the therapeutic outcomes as determined by in-vitro clonogenic cell survival in a radiobiological experiment. MATERIALS AND METHODS: Human cell lines, four cancer and one normal, were exposed to a 6 MV photon beam, produced by a linear accelerator. For half of each sample, a prior imaging dose was delivered using the on-board CBCT. A sample size of n = 103 was used to achieve statistical power. RESULTS: The experimental group of cell lines exposed to CBCT imaging prior to treatment exhibited a reduction in mean cancer cell survival of ~17 times (p = 0.02) greater than predicted from the average dose response and equivalent to more than 5% of the therapeutic dose, compared to 11 times greater than predicted for normal cells (n.s.). CONCLUSION: The greater than predicted reduction in survival resulting from the additional CBCT dose is consistent with radiation-induced bystander effects.

The burden of cancer on primary and secondary health care services before and after cancer diagnosis in New South Wales, Australia.

BACKGROUND: Primary and secondary healthcare service usage is assessed in the year before and following a cancer diagnosis, in cancer cases versus matched non-cancer controls in New South Wales (NSW), Australia over 2006-2012, for all invasive cancers collectively and for selected common sites: breast, prostate, colorectal and lung, and melanoma. METHODS: The 45 and Up cohort (n ≈267,000) was linked to NSW Cancer Register (NSWCR), Emergency Department Data Collection (EDDC) and Medical Benefits Schedule (MBS) data using probabilistic record linkage. First-ever malignant cancers diagnosed after enrolment in the 45 and Up study comprised the study cases. Where possible, five controls were randomly selected per case from the 45 and Up cohort, matched by sex and year of birth. Controls comprised those with no cancer recorded on the NSWCR. For each month in the year preceding and following the cancer diagnosis, general practitioner, specialist and specified hospital ED service use was compared between cases and controls using proportions, means, and odds ratios derived from conditional logistic regression. RESULTS: Compared to controls, cases of all cancers combined had a significantly higher likelihood of GP and specialist consultation in the year leading up to diagnosis. This was most pronounced in the 3-4 months leading up diagnosis for all cancers, similarly for lung cancer (GPs and specialists) and melanoma (GPs), and colorectal cancer (specialists). Likelihood of a GP consultation remained significantly higher in cases than controls in the 12 months following diagnosis. During most of the year preceding cancer diagnosis, the likelihood of specified ED presentations was also significantly higher in cases than controls for all cancers, and most pronounced in the 2-3 months before diagnosis. Excepting melanoma, the likelihood of specified ED presentations remained significantly elevated for most of the year following diagnosis for all cancers combined and for the selected cancers. CONCLUSIONS: People with cancer experience a higher use of primary and secondary healthcare services in the year preceding and following diagnosis, with GPs continuing to play a significant role post diagnosis. The higher likelihood of pre-diagnosis GP consultations among cancer cases requires further investigation, including whether signals might be derived to alert GPs to possibilities for earlier cancer detection.

Changes in proportional mortality from diabetes and circulatory disease in Mauritius and Fiji: possible effects of coding and certification.

BACKGROUND: Many developing countries are experiencing the epidemiological transition, with the majority of deaths attributed to cardiovascular disease, cancer, Type 2 diabetes (T2DM) and others. In some countries, large proportional mortality attributed to diabetes is evident in official mortality statistics, with Mauritius and Fiji rated as the highest in the world. METHODS: This study investigates trends in recorded diabetes and cardiovascular disease mortality in Mauritius and Fiji under coding from the International Classification of Diseases (ICD) versions 9 and 10, using mortality data reported from these countries to the World Health Organization (WHO). RESULTS: In Mauritius over 1981-2004, T2DM proportional mortality varied between 4% and 7% in males (M) and 5% and 9% in females (F). In 2005 there was a sudden increase to M 20% and F 25%, which continued to M 25% and F 30% by 2012. Over 1981-2004 the proportion of circulatory disease mortality rose from 44% to 49% in males, and from 46% to 57% in females. In 2005, circulatory disease mortality proportions fell precipitously to 34% in males and 37% in females, and declined to 31% and 34% by 2013. ICD-10 coding was introduced in 2005. In Fiji, sharp rises in proportional T2DM mortality from 3% in both sexes in 2001 to M 15% and F 20% in 2002 were followed by more gradual trend increases to M 20% and F 26% by 2012-13. Circulatory disease proportions fell steeply from M 57% and F 53% in 2001 to M 44% and M 38% by 2004, with subsequent less steep declines to M 39% and F 30% by 2012. ICD-10 coding was introduced in 2001. CONCLUSIONS: Large, abrupt changes in diabetes and circulatory disease proportional mortality in Fiji and Mauritius coincided with the local introduction of ICD-10 coding in different years. There is also evidence for diabetes-related misclassification of underlying cause of death in Australia and the USA. These artefacts can undermine accurate monitoring of cause of death for evaluation of effectiveness of prevention and control, especially of circulatory disease mortality which is demonstrably reversible in populations.

Differences in cancer incidence by age at diagnosis between Aboriginal and non-Aboriginal people for cancer types included in Australian national screening programs.

BACKGROUND: This study examined age distributions and age-specific incidence of screened cancers by Aboriginal status in New South Wales (NSW) to consider the appropriateness of screening target age ranges. METHODS: The NSW Cancer Registry identified invasive (female) breast, cervical and bowel cancers in people diagnosed in 2001-2014. RESULTS: Aboriginal people were younger at diagnosis with higher proportions of breast and bowel cancers diagnosed before the screening target age range (<50 years) compared with non-Aboriginal people (30.6% vs. 22.8%, and 17.3% vs. 7.3%, respectively). Age-specific incidence rate ratios (IRRs) were lower/similar for breast and bowel cancers in younger and higher in older Aboriginal than non-Aboriginal people. All age-specific cervical cancer IRRs were higher for Aboriginal compared with non-Aboriginal people. CONCLUSION: Although higher proportions of breast and colorectal cancers were diagnosed before screening commencement age in Aboriginal people, this does not necessarily indicate a need for earlier screening commencement. Other aspects needing consideration include benefits, harms and cost-effectiveness.

Absence of sustained breast cancer incidence inflation in a national mammography screening programme.

OBJECTIVE: To investigate the impact of population mammography screening on breast cancer incidence trends in New Zealand. METHODS: Trends in age-specific rates of invasive breast cancer incidence (1994-2014) were assessed in relation to screening in women aged 50-64 from 1999 and 45-69 following the programme age extension in mid-2004. RESULTS: Breast cancer incidence increased significantly by 18% in women aged 50-64 compared with 1994-98 (p<0.0001), coinciding with the 1999 introduction of mammography screening, and remained elevated for four years, before declining to pre-screening levels. Increases over 1994-99 incidence occurred in the 45-49 (21%) and 65-69 (19%) age groups following the 2004 age extension (p<0.0001). Following establishment of screening (2006-10), elevated incidence in the screening target age groups was compensated for by lower incidence in the post-screening ⩾70 age groups than in 1994-98. Incidence in women aged ⩾45 was not significantly higher (+5%) after 2006 than in 1994-98. The cumulated risk of breast cancer in women aged 45-84 for 1994-98 was 10.7% compared with 10.8% in 2006-10. CONCLUSIONS: Increases in breast cancer incidence following introduction of mammography screening in women aged 50-64 did not persist. Incidence inflation also occurred after introduction of screening for age groups 45-49 and 65-69. The cumulated incidence for women aged 45-84 over 2006-10 after screening was well established, compared with 1994-98 prior to screening, shows no increase in diagnosis. Over-diagnosis is not inevitable in population mammography screening programmes.

Breast cancer mortality and screening mammography in New Zealand: Incidence-based and aggregate analyses.

OBJECTIVE: To investigate trends in breast cancer mortality in New Zealand women, to corroborate or negate a causal association with service screening mammography. METHOD: Cumulated mortality rates from breast cancer deaths individually linked to incident cases diagnosed before and after screening commencement were compared, in women aged 50-64 (from 2001) and aged 45-49 and 65-69 (from 2006). Trends and differences in aggregate invasive breast cancer mortality (1975-2013) were assessed in relation to introduction of mammography screening targeting women aged 50-64 and 45-69. Joinpoint analysis was also undertaken. RESULTS: The reduction in incidence-based cumulated breast cancer mortality before and after the introduction of screening was -15% (p = 0.006) for women aged 45-69, and 17% (p = 0.005) for those aged 50-64. Aggregate mortality declined by -34% (2005-13 compared with 1992-98) in the age group 50-64, and by -28% among women aged 45-49 and -25% among women aged 65-74. For women aged 50-64 the 2-joinpoint model shows a 1990 turning point, from prior rising mortality to a mean -1.8% decline per annum, coinciding with improvements in primary treatment of breast cancer; and a steepening of the decline (-3.0% p.a.) from the late 1990s, coinciding with the introduction of service mammography screening. CONCLUSION: Breast cancer mortality declines occurring since the advent of screening mammography in New Zealand are consistent with other incidence-based and aggregate studies of screening mammography in populations, individual-based cohort studies, and randomized controlled trials.

Continued increases in blood pressure over two decades in Samoa (1991-2013); around one-third of the increase explained by rising obesity levels.

BACKGROUND: To analyse trends over the period 1991-2013 in systolic blood pressure (SBP), diastolic blood pressure (DBP) and the prevalence of hypertension in adults aged 25-64 years in Samoa; and to assess the contribution of rising obesity levels to period trends. METHODS: Unit record data from seven population-based surveys (n = 10,881) conducted between 1991 and 2013 were included for analysis. Surveys were adjusted to the nearest previous census to improve national representativeness. Hypertension was defined as SBP ≥140 mmHg and/or DBP ≥90 mmHg and/or on medication for hypertension. Obesity was measured by body mass index (BMI). Poisson, linear and meta-regression were used to assess period trends. RESULTS: Over 1991-2013 mean SBP and DBP (mmHg), and the prevalence of hypertension (%) increased in both sexes. Increases in hypertension were: from 18.3 to 33.9% (p < 0.001) in men (mean BP from 122/74 to 132/78); and from 14.3 to 26.4% (p < 0.001) in women (mean BP from 118/73 to 126/78). The estimate of the age-adjusted mean SBP and DBP over 1991-2013, and the relative risk for hypertension in 2013 compared to 1991, were attenuated after adjusting for BMI: by 22% (men) and 32% (women) for mean SBP; 37% (men) and 32% (women) for mean DBP; and 19% in both sexes for hypertension. CONCLUSIONS: Significant increases have occurred in SBP/DBP and hypertension prevalence in both sexes in Samoa during 1991-2013, which would contribute significantly to premature mortality from cardiovascular disease. Obesity accounts for around one-third of the rising trend in blood pressure in the Samoan population. Strengthening of population control of hypertension through reduction in obesity and salt intake, and case detection and treatment through primary care, is required to reduce premature mortality from cardiovascular disease in Samoa.

Confluence of suicide and drug overdose epidemics in young Australian males: common causality?

BACKGROUND: Young adult (aged 20-34) males experience higher mortality than females, and in age groups immediately younger and older, and with considerable variation in death rates over time. Trends in mortality and the cause structure of deaths among young adult Australian males over 1979-2011 are investigated, with a focus on suicide and drug overdose. METHODS: Mortality data by age for the period 1979 to 2011 and Australian population figures were obtained from the Australian Bureau of Statistics (ABS). Cause of death was investigated using relevant International Classification of Diseases (ICD) codes, and mortality by cause was examined graphically over time according to various ICD aggregations. Mortality trends were contextualised in relation to labour market changes occurring in Australia from the 1980s to early 2000s. RESULTS: Although motor vehicle accident (MVA) mortality declined by half between 1980 and 1998 in males, this did not translate into a reduction in total young male mortality because of simultaneous increases in suicide, and drug-related deaths classified as either poisoning (external cause) or drug dependence (mental disorders). When both suicide and drug-related deaths declined concurrently after 1998, total 20-34 year male mortality declined by almost half (46%) over 1998-2011. Declines in external cause mortality accounted for 63% of the total mortality decline in 20-34 year males over 1998-2011. The close temporal coincidence (statistically significant) of increases and declines in suicide and drug-related deaths over a decade suggests related causality. CONCLUSIONS: The coincidence of young male suicide and drug overdose mortality epidemics over the study period (excess deaths: 5000) suggest related causality such as exposure to common factors, including the labour market liberalisation and de-regulation of the 1990s, and deserves further investigation.