Interval cancers in a national colorectal screening programme based on faecal immunochemical testing: Implications for faecal haemoglobin concentration threshold and sex inequality.

OBJECTIVE: To compare interval cancer proportions (ICP) in the faecal immunochemical test (FIT)-based Scottish Bowel Screening Programme (SBoSP) with the former guaiac faecal occult blood test (gFOBT)-based SBoSP and investigate associations between interval cancer (IC) and faecal haemoglobin concentration (f-Hb) threshold, sex, age, deprivation, site, and stage. METHODS: The ICP data from first year of the FIT-based SBoSP and the penultimate year of the gFOBT-based SBoSP were compared in a prospective cohort design. RESULTS: With FIT, 801 colorectal cancers (CRCs) were screen detected (SDC), 802 were in non-participants, 548 were ICs, 39 were colonoscopy missed and 72 were diagnosed after incomplete screening; with gFOBT: 540, 904, 556, 45, and 13, respectively. FIT had a significantly higher proportion of SDC compared to IC than gFOBT. For FIT and gFOBT, ICP was significantly higher in women than men. As f-Hb threshold increased, ICP increased and, for any f-Hb threshold for men, a lower threshold was required for comparable ICP in women. In Scotland, the current threshold of ≥80 µg Hb/g faeces would have to be lowered to ≥40 µg Hb/g faeces for women to achieve sex equality for ICP. In the FIT-based SBoSP, there were four times as many stage I SDC than IC. This was reversed in advanced stages, with twice as many stage IV CRC diagnosed as IC versus SDC. CONCLUSIONS: Reducing the numbers of IC requires lowering the f-Hb threshold. Using different f-Hb thresholds for women and men could eliminate the sex disparity, but with additional colonoscopy.

India's Opportunity to Address Human Resource Challenges in Healthcare.

India's health indicators have improved in recent times but continue to lag behind those of its peer nations. The country with a population of 1.3 billion, has an estimated active health workers density of doctors and nurses/midwives of 5.0 and 6.0 respectively, for 10,000 persons, which is much lower than the WHO threshold of 44.5 doctors, nurses, and midwives per 10,000 population. The issue is compounded by the skewed inter-state, urban-rural, and public-private sector divide. Calls to urgently augment the skilled health workforce reinforce the central role human resources have in healthcare, which has evolved into a complex multifactorial issue. The paucity of skilled personnel must be addressed if India is to accelerate its progress toward achieving universal health coverage and its sustainable development goals (SDGs). The recent increase in the federal health budget offers an unprecedented opportunity to do this. This article utilizes the ready materials, extract and analyze data, distill findings (READ) approach to adding to the authors' experiential learning to analyze the health system in India. The growing divide between the public and the burgeoning private health sector systems, with the latter's booming medical tourism industry and medical schools, are analyzed along with the newly minted National Medical Council, to recommend policies that would help India achieve its SDGs.

Cost-effectiveness analysis of superabsorbent wound dressings in patients with moderate-to-highly exuding leg ulcers in Germany.

The study aims to estimate the cost-effectiveness of superabsorbent wound dressings compared to the standard-of-care (SoC) dressings mix for treatment of patients with moderate-to-highly exuding leg ulcers in the German healthcare settings. A model-based cost-effectiveness analysis was conducted from the German statutory health insurance perspective, following German specific and international recommendations of good research practice. An individual-level (microsimulation) state-transition model has been used with a cycle length of 1 week and time horizon of 6 months. Several comprehensive systematic reviews were conducted to inform all model inputs, including clinical parameters, efficacy, quality of life, resources utilisation, and cost inputs. In addition, primary data from two clinical trials were used. Based on this cost-effectiveness analysis, using superabsorbent wound dressings instead of the SoC dressings of patients with moderate-to-highly exuding leg ulcers in Germany can lead to an improved healing rate of 2.57% (benefit ratio 1.08), improved health-related quality of life of 0.152 quality-adjusted life weeks, and total direct cost savings of €771 per patient in 6 months. Robustness of results was confirmed in sensitivity and scenario analyses.

Transition to quantitative faecal immunochemical testing from guaiac faecal occult blood testing in a fully rolled-out population-based national bowel screening programme.

OBJECTIVE: Faecal immunochemical tests (FIT) are replacing guaiac faecal occult blood tests (FOBT) in colorectal cancer (CRC) screening. Data from the first year of FIT screening were compared with those from FOBT screening and assumptions based on a pilot evaluation of FIT. DESIGN: Data on uptake, positivity, positive predictive value (PPV) for CRC and higher-risk adenoma from participants in the first year of the FIT-based Scottish Bowel Screening Programme (n=919 665), with a threshold of 80 µg Hb/g faeces, were compared with those from the penultimate year of the FOBT-based programme (n=862 165) and those from the FIT evaluation (n=66 225). RESULTS: Overall, uptake of FIT was 63.9% compared with 56.4% for FOBT. Positivity was 3.1% and 2.2% with FIT and FOBT; increases were seen in both sexes, and across age range and deprivation. More CRC and adenomas were detected by FIT, but the PPV for CRC was less (5.2% with FIT and 6.4% with FOBT). However, for higher-risk adenoma, PPV was greater with FIT (24.3% with FIT and 19.3% with FOBT). In the previous FIT evaluation, uptake was 58.5% with FIT compared with 54.0% with FOBT; positivity was 2.5% with FIT and 2.0% with FOBT. CONCLUSION: Transition to FIT from FOBT produced higher uptake and positivity with lower PPV for CRC and higher PPV for adenoma. The FIT pilot evaluation underestimated uptake and positivity. Introducing FIT at the same threshold as the evaluation caused a 67.2% increase in colonoscopy demand instead of a predicted 10%.

Variation in changes in the incidence of colorectal cancer by age and association with screening uptake: an observational study.

OBJECTIVES: In developed countries, the incidence of colorectal cancer (CRC) has declined in the over 50 years age group but increased in younger people. We studied CRC incidence by age and the influence of screening uptake. DESIGN: Age-standardised and sex-standardised incidences for CRC from 1997 to 2017 were obtained from the Scottish Cancer Registry (SCR). In addition, linkage between the Scottish Bowel Screening Database and the SCR allowed investigation of any association between screening participation and CRC incidence. SETTING: Scotland and the Scottish Bowel Screening Programme, in which guaiac faecal occult blood test screening was piloted from March 2000 and fully rolled by December 2009. PARTICIPANTS: From the introduction of screening in 2000 through to 2017, 2 395 172 were invited to participate, of whom 1 487 999 participated at least once. MAIN OUTCOME MEASURES: Incidence of CRC. RESULTS: In the screening age range (50-74 years), CRC incidence peaked at 156.5 cases per 100 000 in 2010 after full roll-out of screening across Scotland but fell to 123.9 per 100 000 in 2017. However, under 50 years, there was a rise from 5.3 cases per 100 000 in 2000 to 6.8 per 100 000 in 2017. When CRC incidence was examined in those who had been offered screening, incidence fell in the participant group more than in the non-participant group after roll-out of screening was complete. Analysis of cumulative incidence demonstrated that CRC incidence in the participant group remained consistently below that of the non-participant from around 7 years of follow-up. CONCLUSIONS: The incidence of CRC in Scotland has declined in the over 50 years age group but increased in younger people. It is likely that population screening has contributed to the reduction in CRC incidence in the over 50 years age group.

Sodium uptake in cell construction and subsequent in operando electrode behaviour of Prussian blue analogues, Fe[Fe(CN)6](1-x)·yH2O and FeCo(CN)6.

The development of electrodes for ambient temperature sodium-ion batteries requires the study of new materials and the understanding of how crystal structure influences properties. In this study, we investigate where sodium locates in two Prussian blue analogues, Fe[Fe(CN)6]1-x·yH2O and FeCo(CN)6. The evolution of the sodium site occupancies, lattice and volume is shown during charge-discharge using in situ synchrotron X-ray powder diffraction data. Sodium insertion is found to occur in these electrodes during cell construction and therefore Fe[Fe(CN)6]1-x·yH2O and FeCo(CN)6 can be used as positive electrodes. NazFeFe(CN)6 electrodes feature higher reversible capacities relative to NazFeCo(CN)6 electrodes which can be associated with a combination of structural factors, for example, a major sodium-containing phase, ∼Na0.5FeFe(CN)6 with sodium locating either at the x = y = z = 0.25 or x = y = 0.25 and z = 0.227(11) sites and an electrochemically inactive sodium-free Fe[Fe(CN)6]1-x·yH2O phase. This study demonstrates that key questions about electrode performance and attributes in sodium-ion batteries can be addressed using time-resolved in situ synchrotron X-ray diffraction studies.

Thymidine phosphorylase expression is associated with response to capecitabine plus irinotecan in patients with metastatic colorectal cancer.

PURPOSE: To evaluate the clinical activity and toxicity of capecitabine plus irinotecan as first-line therapy for patients with metastatic colorectal cancer (mCRC), and to describe the association of expression of thymidine phosphorylase (TP), thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD) with antitumor activity. PATIENTS AND METHODS: Patients with previously untreated mCRC received irinotecan days 1 and 8 intravenously, and capecitabine days 2 to 15 orally in 21-day cycles. Doses were irinotecan 125 mg/m2 and capecitabine 1,000 mg/m2 bid (n = 15; cohort 1), or irinotecan 100 mg/m2 and capecitabine 900 mg/m2 bid (n = 52; cohort 2). Tissues from primary and metastatic sites were assessed for TP, TS, and DPD gene and protein expression. RESULTS: An unacceptable level of GI toxicity in the first 15 patients led to a protocol modification in starting doses. The response rate was 45% (30 of 67 patients). Overall survival was associated with TP expression assessed by immunohistochemistry in both primary tumors (P = .045) and metastases (P = .001). Objective tumor response was associated with TP expression in primary tumors (odds ratio, 4.77; 95% CI, 1.25 to 18.18), with a similar trend in metastases (odds ratio, 8.67; 95% CI, 0.95 to 79.1). TP gene expression in primary tumors was also associated with response. CONCLUSION: These data indicate that capecitabine plus irinotecan is an active regimen against mCRC. The biomarker analysis (including metastatic tissue) was feasible in a multicenter setting, and provides preliminary evidence that TP expression may be a predictive marker for response.