Variation in chemotherapy prescribing rates and mortality in early breast cancer over two decades: a national data linkage study.

BACKGROUND: Regional variation in clinical practice may identify differences in care, reveal inequity in access, and explain inequality in outcomes. The study aim was to measure geographical variation in Scotland for adjuvant chemotherapy use and mortality in early-stage breast cancer. PATIENTS AND METHODS: In this retrospective cohort study using population cancer registry-based data linkage, patients with surgically treated early breast cancer between 2001 and 2018 were identified from the Scottish Cancer Registry. Geographical regions considered were based on NHS Scotland organisational structure including 14 territorial Health Boards as well as three regional Cancer Networks. Regional variation in the proportion receiving chemotherapy, breast cancer mortality and all-cause mortality was investigated. Inter-regional comparisons of chemotherapy use were adjusted for differences in case mix using logistic regression. Comparison of breast cancer-specific mortality and all-cause mortality used regression with a parametric survival model. Time trends were assessed using moving average plots. RESULTS: Chemotherapy use ranged from 35% to 46% of patients across Health Boards without adjustment. Variation reduced between 2001 and 2018. Following adjustment for clinical case mix, variation between cancer networks was within 3 percentage points, but up to 10 percentage points from the national average in some Health Boards. Differences in breast cancer mortality and all-cause mortality between cancer networks were modest, with hazard ratios of between 0.933 (95% confidence interval 0.893-0.975) and 1.041 (1.002-1.082) compared with the national average. Survival improved over the time period studied. CONCLUSION: With adequate case mix adjustment, variation in adjuvant chemotherapy use for early breast cancer in Scotland is small, with a trend towards greater convergence in practice and improved mortality outcomes in more recent cohorts. This suggests very limited regional inequity in access and convergence of clinical practice towards risk-stratified treatment recommendations. Outliers require assessment to understand the reasons for variance.

Risk of missing colorectal cancer with a COVID-adapted diagnostic pathway using quantitative faecal immunochemical testing.

BACKGROUND: COVID-19 has brought an unprecedented challenge to healthcare services. The authors' COVID-adapted pathway for suspected bowel cancer combines two quantitative faecal immunochemical tests (qFITs) with a standard CT scan with oral preparation (CT mini-prep). The aim of this study was to estimate the degree of risk mitigation and residual risk of undiagnosed colorectal cancer. METHOD: Decision-tree models were developed using a combination of data from the COVID-adapted pathway (April-May 2020), a local audit of qFIT for symptomatic patients performed since 2018, relevant data (prevalence of colorectal cancer and sensitivity and specificity of diagnostic tools) obtained from literature and a local cancer data set, and expert opinion for any missing data. The considered diagnostic scenarios included: single qFIT; two qFITs; single qFIT and CT mini-prep; two qFITs and CT mini-prep (enriched pathway). These were compared to the standard diagnostic pathway (colonoscopy or CT virtual colonoscopy (CTVC)). RESULTS: The COVID-adapted pathway included 422 patients, whereas the audit of qFIT included more than 5000 patients. The risk of missing a colorectal cancer, if present, was estimated as high as 20.2 per cent with use of a single qFIT as a triage test. Using both a second qFIT and a CT mini-prep as add-on tests reduced the risk of missed cancer to 6.49 per cent. The trade-off was an increased rate of colonoscopy or CTVC, from 287 for a single qFIT to 418 for the double qFIT and CT mini-prep combination, per 1000 patients. CONCLUSION: Triage using qFIT alone could lead to a high rate of missed cancers. This may be reduced using CT mini-prep as an add-on test for triage to colonoscopy or CTVC.

Metabolomics uncovers dietary omega-3 fatty acid-derived metabolites implicated in anti-nociceptive responses after experimental spinal cord injury.

Chronic neuropathic pain is a frequent comorbidity following spinal cord injury (SCI) and often fails to respond to conventional pain management strategies. Preventive administration of docosahexaenoic acid (DHA) or the consumption of a diet rich in omega-3 polyunsaturated fatty acids (O3PUFAs) confers potent prophylaxis against SCI and improves functional recovery. The present study examines whether this novel dietary strategy provides significant antinociceptive benefits in rats experiencing SCI-induced pain. Rats were fed control chow or chow enriched with O3PUFAs for 8weeks before being subjected to sham or cord contusion surgeries, continuing the same diets after surgery for another 8 more weeks. The paw sensitivity to noxious heat was quantified for at least 8weeks post-SCI using the Hargreaves test. We found that SCI rats consuming the preventive O3PUFA-enriched diet exhibited a significant reduction in thermal hyperalgesia compared to those consuming the normal diet. Functional neurometabolomic profiling revealed a distinctive deregulation in the metabolism of endocannabinoids (eCB) and related N-acyl ethanolamines (NAEs) at 8weeks post-SCI. We found that O3PUFAs consumption led to a robust accumulation of novel NAE precursors, including the glycerophospho-containing docosahexaenoyl ethanolamine (DHEA), docosapentaenoyl ethanolamine (DPEA), and eicosapentaenoyl ethanolamine (EPEA). The tissue levels of these metabolites were significantly correlated with the antihyperalgesic phenotype. In addition, rats consuming the O3PUFA-rich diet showed reduced sprouting of nociceptive fibers containing CGRP and dorsal horn neuron p38 mitogen-activated protein kinase (MAPK) expression, well-established biomarkers of pain. The spinal cord levels of inositols were positively correlated with thermal hyperalgesia, supporting their role as biomarkers of chronic neuropathic pain. Notably, the O3PUFA-rich dietary intervention reduced the levels of these metabolites. Collectively, these results demonstrate the prophylactic value of dietary O3PUFA against SCI-mediated chronic pain.

GSTM1 null and NAT2 slow acetylation genotypes, smoking intensity and bladder cancer risk: results from the New England bladder cancer study and NAT2 meta-analysis.

Associations between bladder cancer risk and NAT2 and GSTM1 polymorphisms have emerged as some of the most consistent findings in the genetic epidemiology of common metabolic polymorphisms and cancer, but their interaction with tobacco use, intensity and duration remain unclear. In a New England population-based case-control study of urothelial carcinoma, we collected mouthwash samples from 1088 of 1171 cases (92.9%) and 1282 of 1418 controls (91.2%) for genotype analysis of GSTM1, GSTT1 and NAT2 polymorphisms. Odds ratios and 95% confidence intervals of bladder cancer among New England Bladder Cancer Study subjects with one or two inactive GSTM1 alleles (i.e. the 'null' genotype) were 1.26 (0.85-1.88) and 1.54 (1.05-2.25), respectively (P-trend = 0.008), compared with those with two active copies. GSTT1 inactive alleles were not associated with risk. NAT2 slow acetylation status was not associated with risk among never (1.04; 0.71-1.51), former (0.95; 0.75-1.20) or current smokers (1.33; 0.91-1.95); however, a relationship emerged when smoking intensity was evaluated. Among slow acetylators who ever smoked at least 40 cigarettes/day, risk was elevated among ever (1.82; 1.14-2.91, P-interaction = 0.07) and current heavy smokers (3.16; 1.22-8.19, P-interaction = 0.03) compared with rapid acetylators in each category; but was not observed at lower intensities. In contrast, the effect of GSTM1-null genotype was not greater among smokers, regardless of intensity. Meta-analysis of the NAT2 associations with bladder cancer showed a highly significant relationship. Findings from this large USA population-based study provided evidence that the NAT2 slow acetylation genotype interacts with tobacco smoking as a function of exposure intensity.

Prolactin serum levels and breast cancer: relationships with risk factors and tumour characteristics among pre- and postmenopausal women in a population-based case-control study from Poland.

BACKGROUND: Previous prospective studies have found an association between prolactin (PRL) levels and increased risk of breast cancer. Using data from a population-based breast cancer case-control study conducted in two cities in Poland (2000-2003), we examined the association of PRL levels with breast cancer risk factors among controls and with tumour characteristics among the cases. METHODS: We analysed PRL serum levels among 773 controls without breast cancer matched on age and residence to 776 invasive breast cancer cases with available pretreatment serum. Tumours were centrally reviewed and prepared as tissue microarrays for immunohistochemical analysis. Breast cancer risk factors, assessed by interview, were related to serum PRL levels among controls using analysis of variance. Mean serum PRL levels by tumour characteristics are reported. These associations also were evaluated using polytomous logistic regression. RESULTS: Prolactin levels were associated with nulliparity in premenopausal (P=0.05) but not in postmenopausal women. Associations in postmenopausal women included an inverse association with increasing body mass index (P=0.0008) and direct association with use of recent/current hormone therapy (P=0.0006). In case-only analyses, higher PRL levels were more strongly associated with lobular compared with ductal carcinoma among postmenopausal women (P=0.02). Levels were not different by tumour size, grade, node involvement or oestrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2 status. CONCLUSIONS: Our analysis demonstrates that PRL levels are higher among premenopausal nulliparous as compared with parous women. Among postmenopausal women, levels were higher among hormone users and lower among obese women. These results may have value in understanding the mechanisms underlying several breast cancer risk factor associations.

Effect modification of endocrine disruptors and testicular germ cell tumour risk by hormone-metabolizing genes.

It has been hypothesized that the increased prevalence of testicular germ cell tumours (TGCT) may be attributable to endocrine disrupting chemicals, such as persistent organic pollutants (POPs); these may be modulated by hormone-metabolizing enzymes. Using data from 568 cases and 698 controls enrolled in the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants Study, we examined associations between TGCT and POPs, including p,p'-dichlorodiphenyldichloroethylene, chlordane-related compounds and polychlorinated biphenyls (PCBs), modified by polymorphisms in five hormone-metabolizing genes (CYP17A1, CYP1A1, HSD17B1, HSD17B4 and AR). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models that stratified associations of POP exposure and TGCT risk by genotype. Two polymorphisms in CYP1A1, rs1456432 and rs7495708, modified the association between trans-nonachlor and total chlordanes and TGCT risk. Among men with a minor allele for rs1456432, those with the highest quartiles had an increased risk of TGCT (OR = 1.90, 95% CI, 1.01-3.56) compared with those with the lowest; there was no increased risk among men with the homozygous major allele genotype (p-interactions = 0.024). Similar results were seen for rs7495708. HSD17B4 rs384346 modified the associations between TGCT risk and PCB-118 and PCB-138 concentrations: the 45-55% reductions in TGCT risk for men with the highest quartiles compared with the lowest quartiles were only present in those who had a major homozygous allele genotype (p-interactions < 0.04). Thus, there are suggestions that certain CYP1A1 and HSD17B4 polymorphisms may modify the associations between POPs and TGCT risk. With false discovery rate values >0.2, however, caution is advisable when interpreting the findings of this study.

Wet method for measuring starch gelatinization temperature using electrical conductivity.

The objective of the present study was to develop a method for obtaining the gelatinization temperature of starches by using electrical conductivity. Native starches from corn, rice, potato, and wheat were prepared with different proportions of water and heated from room temperature to 90 degrees C, in a device especially designed for monitoring the electrical conductivity as a function of temperature. The results showed a linear trend of the electrical conductivity with the temperature until it reaches the onset gelatinization temperature. After that point, the electrical conductivity presented an increment or decrement depending on the water content in the sample and it was related to starch swelling and gelatinization phenomena. At the end gelatinization temperature, the conductivity becomes stable and linear, indicating that there are no more changes of phase. The starch gelatinization parameter, which was evaluated in the 4 types of starches using the electrical conductivity, was compared with those obtained by using differential scanning calorimeter (DSC). The onset temperature at which the electrical conductivity increased or decreased was found to be similar to that obtained by DSC. Also, the final temperature at which the electrical conductivity returned to linearity matched the end gelatinization temperature of the DSC. Further, a wet method for measuring the onset, peak, and end gelatinization temperatures as a function of temperature using the electrical conductivity curves is presented for a starch-water suspension.

Physical properties and composition of femurs of rat fed with diets based on corn tortillas made from different processes.

In this study the effect of calcium absorption on some physical properties and composition of rat femurs was evaluated, comparing rats fed with raw whole corn (RC), tortillas made from extruded masa with 0.25% lime content (TEWL) and without lime (TE), and nixtamal tortillas (NT). The diets were formulated to contain the same amount of protein, oil, fiber, vitamins and minerals other than calcium. In all diets 0.20% calcium was added. At the end of the trials, the femurs were extracted, weighed and measured for ash, calcium and phosphorus content, some physical dimensions, and the crystallinity percentage. The femurs of rats fed with TEWL and NT were heavier, thicker, longer and had higher calcium content. On the other hand, the force required to break the femur of rats fed on ETWL and NT was 1.25 kg greater than that required to break the femurs of rats fed with RC. Higher crystallinity percentage values were observed in the femurs of the rats fed with NT (37.66%) and TEWL (36.98%) as compared to a 30.31% value obtained with the RC.

[Sexual behavior and drug abuse in homosexuals, prostitutes and prisoners in Tijuana, Mexico]. / Comportamiento sexual y abuso de drogas en homosexuales, prostitutas y prisioneros en Tijuana, Mexico.

PIP: Results are presented of a sociodemographic and epidemiologic survey conducted between July-October 1988 in Tijuana, Mexico, among 3 subgroups believed to be at high risk of HIV infection. 383 female and 32 male prostitutes recruited at the Municipal Medical Services clinic in Tijuana, 376 male and 34 female prisoners recruited ate the State Penitentiary, 233 male homosexuals and bisexuals recruited in bars and other meeting places, and 11 drug addicts treated at a detoxification program were successfully interviewed. Although only 11 iv drug addicts were located and agreed to participate, 5 prostitutes, 85 prisoners, and 5 homosexual/bisexual reported histories of iv drug use. The homosexual/bisexual group was relatively younger and better educated,and had higher incomes than the other groups. The average age was 25.6 for homosexual/bisexuals, 29.5 for prostitutes, and 29 for prisoners. 82.7% of homosexual/bisexuals, 46.3% of prostitutes, and 44.4% of prisoners were single. Among prostitutes and prisoners, respectively, 6.5 and 25.9% were married and 22.2 and 18/5% were in consensual unions. The average number of years of schooling were 10.3 for homosexual/bisexuals, 5.6 for prostitutes, and 6.3 for prisoners. Male prostitutes reported the highest average number of sexual partners in the past year (261 +or- 341), prisoners reported the greatest frequency of iv drug users as sexual partners, and homosexual/bisexuals reported the highest frequency of receptive anal intercourse. 35% of respondents reported a history of sexually transmitted diseases. 36% of female prostitutes and 4% of prisoners reported using condoms regularly during vaginal intercourse. 25% of homosexual/bisexuals reported using condom regularly during anal intercourse. 31% of respondents reported having been tested previously for HIV antibodies,but only 41% of those knew the results. 72 homosexual/bisexuals, 56 prostitutes, and 126 prisoners reported having had sexual relations in the US. 80% of respondents reported consuming alcohol, 64% cigarettes, and 28% illegal drugs. The most frequently used illegal drug was marijuana. 68% of the 106 identified iv drug users continued to use drugs. The rest reported having used them since 1978. The introduction of HIV into these subpopulations has been slow but steady. Infection rates in this sample were .5% for prostitutes, 1.2% for prisoners, 11.6% for homosexual/bisexuals, and 1.9% for the 106 iv drug users.^ieng