Dietary Factors Differ Between Young-Onset and Older-Onset Colorectal Cancer Patients.

We aimed to evaluate differences in dietary factors between young-onset (diagnosed at ages <50) and older-onset colorectal cancer (CRC). CRC patients diagnosed from 1998 to 2018 reported to the Puget Sound Surveillance, Epidemiology, and End Results registry were recruited using mail and telephone. Consented patients completed questionnaires assessing demographics, medical history, and CRC risk factors, including dietary factors. We used multi-variable logistic regression to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) comparing dietary intake in young-onset vs. older-onset CRC. Analyses included 1,087 young- and 2,554 older-onset CRC patients. Compared to older-onset CRC, young-onset CRC patients had lower intake of vegetables (OR for highest intake vs. lowest = 0.59 CI: 0.55, 0.64) and fruit (OR for highest intake vs. lowest = 0.94 CI: 0.88, 0.99) and higher intake of processed meat (OR for highest intake vs. lowest = 1.82 CI: 1.11, 2.99) and spicy food (OR for highest intake vs. lowest = 1.69 CI: 1.09, 2.61). There was no statistically significant difference between young- and older-onset CRC patients for red meat consumption. Dietary patterns differed between young- and older-onset CRC; young-onset CRC patients had lower intake of vegetables and fruit and higher intakes of processed meat and spicy food.

Colorectal cancer pre-diagnostic symptoms are associated with anatomic cancer site.

BACKGROUND: Signs and red flag symptoms in colorectal cancer (CRC) patients who are below the recommended screening age are often overlooked, leading to delayed diagnosis and worse prognosis. This study investigates how patient pre-diagnostic symptoms are associated with anatomic site of their cancer and whether the association varies by age at CRC diagnosis. METHODS: We ascertained CRC patients' experienced symptoms and screening through medical abstractions from an ongoing population-based study of CRC patients identified through a SEER cancer registry (N = 626). We used logistic regression to estimate odds ratios and 95% confidence intervals for the association between symptoms and CRC anatomic site. Additional analyses were stratified by age at diagnosis. Early-onset was defined as less than 50 years of age at CRC diagnosis. RESULTS: Participants who experienced blood in stool were more likely (odds ratio (95% confidence interval)) to have rectal (vs. colon) cancer (4.37 (3.02, 6.33)), as were patients who experienced changes to stool (1.78 (1.21, 2.60)). Patients diagnosed with colon cancer were more likely to present with abdominal pain (0.30 (0.19, 0.47)), anemia (0.40 (0.21, 0.75)), other symptoms (0.33 (0.19, 0.55)) and no symptoms (0.68 (0.44, 1.04)). When stratifying by age at diagnosis, we found that the association between blood in stool and rectal tumor location was particularly pronounced for patients with early-onset CRC (6.48 (2.73, 15.41)). CONCLUSIONS: Common pre-diagnostic red flag symptoms are associated with CRC anatomic site. These findings can inform best practices for gastroenterologist triage of care and early evaluation of CRC and are of key importance given the rise of early-onset (pre-screening age) CRC. TRIAL REGISTRATION: Not applicable to this study and analysis.

Peer PrEP referral + HIV self-test delivery for PrEP initiation among young Kenyan women: study protocol for a hybrid cluster-randomized controlled trial.

BACKGROUND: Oral HIV pre-exposure prophylaxis (PrEP) for HIV prevention is highly effective, but uptake remains low in Africa, especially among young women who are a priority population for HIV prevention services. HIV self-testing (HIVST) has been proven to increase HIV testing in diverse populations but has been underutilized to support linkage to HIV prevention services. Most young women who initiate PrEP in Africa do so through informal peer referral. We wanted to test a model of formalized peer referral enhanced with HIVST delivery among young Kenyan women. METHODS: The Peer PrEP Trial is a two-arm hybrid effectiveness-implementation cluster-randomized controlled trial being conducted in central Kenya. Eligible participants (i.e., peer providers, n = 80) are women (≥ 16-24 years) refilling or initiating PrEP at public healthcare clinics who can identify at least four peers who could benefit from PrEP and not enrolled in another HIV study. Peer providers will be 1:1 randomized to (1) formal peer PrEP referral + HIVST delivery, where they will be encouraged to refer four peers (i.e., peer clients, ≥ 16-24 years) using educational materials and HIVST kits (two per peer client), or (2) informal peer PrEP referral, where they are encouraged to refer four peer clients using informal word-of-mouth referral. In both arms, peer providers will deliver a standard PrEP referral card with information on nearby public clinics delivering PrEP services. Peer providers will complete surveys at baseline and 3 months; peer clients will complete surveys at 3 months. Our primary outcome is PrEP initiation among peer clients, as reported by peer providers at 3 months. Secondary outcomes include PrEP continuation (any refilling), HIV testing (past 3 months), sexual behaviors (past month), and PrEP adherence (past month) among peer clients, as reported by both peer providers and clients at 3 months. Implementation outcomes will include participants' perceived acceptability, appropriateness, and feasibility of the intervention as well assessments of the intervention's fidelity and cost. DISCUSSION: Evidence from this trial will help us understand how HIVST could support health systems by facilitating linkage to PrEP services among young women who could benefit in Kenya and similar settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT04982250. Registered on July 29, 2021.

T cell-inflamed gene expression profile is associated with favorable disease-specific survival in non-hypermutated microsatellite-stable colorectal cancer patients.

BACKGROUND: The anti-tumor immune response plays a key role in colorectal cancer (CRC) progression and survival. The T cell-inflamed gene expression profile (GEP) is a biomarker predicting response to checkpoint inhibitor immunotherapy across immunogenic cancer types, but the prognostic value in CRC is unknown. We evaluated associations with disease-specific survival, somatic mutations, and examined its differentially expressed genes and pathways among 84 sporadic CRC patients from the Seattle Colon Cancer Family Registry. METHODS: Gene expression profiling was performed using Nanostring's nCounter PanCancer IO 360 panel. Somatic mutations were identified by a targeted DNA sequencing panel. RESULTS: The T cell-inflamed GEP was positively associated with tumor mutation burden and microsatellite instability high (MSI-H). Higher T cell-inflamed GEP had favorable CRC-specific survival (hazard ratio [HR] per standard deviation unit = 0.50, p = 0.004) regardless of hypermutation or MSI status. Analysis of recurrently mutated genes having at least 10 mutation carriers, suggested that the T cell-inflamed GEP is positively associated with RYR1, and negatively associated with APC. However, these associations were attenuated after adjusting for hypermutation or MSI status. We also found that expression of genes RPL23, EPCAM, AREG and ITGA6, and the Wnt signaling pathway was negatively associated with the T cell-inflamed GEP, which might indicate immune-inhibitory mechanisms. CONCLUSIONS: Our results show that the T cell-inflamed GEP is a prognostic biomarker in non-hypermutated microsatellite-stable CRC. This also suggests that patient stratification for immunotherapy within this CRC subgroup should be explored further. Moreover, reported immune-inhibitory gene expression signals may suggest targets for therapeutic combination with immunotherapy.

Examining the Use of HIV Self-Testing to Support PrEP Delivery: a Systematic Literature Review.

PURPOSE OF REVIEW: HIV self-testing (HIVST) has the potential to expand access to and uptake of HIV pre-exposure prophylaxis (PrEP) delivery. We conducted a systematic literature review to understand the evidence on HIVST use for PrEP delivery. RECENT FINDINGS: After screening 1055 records, we included eight: three randomized trials and five values and preferences studies. None measured PrEP initiation. Most studies occurred in Sub-Saharan Africa (7/8) and included different populations. One trial found that HIVST use between quarterly clinic visits as part of an adherence package with biofeedback slightly increased adherence; the other two trials found that HIVST use between or in lieu of quarterly clinic visits had no significant or non-inferior effects on adherence. HIVST to support PrEP delivery was acceptable, feasible, and preferred. HIVST use for PrEP continuation largely resulted in similar outcomes to standard-of-care delivery and was perceived acceptable and feasible. Further research is needed to optimize HIVST use within PrEP programming.

Colorectal Cancer Anatomical Site and Sleep Quality.

PURPOSE: Sleep quality in relation to anatomic site among colorectal cancer (CRC) patients is not well understood, though discerning the relationship could contribute to improved survivorship care. METHODS: We ascertained sleep quality (Pittsburgh Sleep Quality Index) and other personal characteristics within an ongoing population-based study of CRC patients identified through a cancer registry (N = 1453). Differences in sleep quality by CRC site were analyzed using chi-square and ANOVA tests. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of tumor site with sleep quality concerns, adjusting for patient attributes and time since diagnosis. RESULTS: Sleeping problems were reported by 70% of CRC patients. Overall, participants with rectal (vs. colon) cancer were more likely (OR (95% CI)) to report general trouble sleeping (1.58 (1.19, 2.10)). Rectal cancer patients were also more likely than colon cancer patients to report changes in sleep patterns after cancer diagnosis (1.38 (1.05, 1.80)), and trouble sleeping specifically due to getting up to use the bathroom (1.53 (1.20, 1.96)) or pain (1.58 (1.15, 2.17)), but were less likely to report trouble sleeping specifically due to issues with breathing/coughing/snoring (0.51 (0.27, 0.99)). CONCLUSION: Overall, rectal cancer patients were more likely to have sleep complications compared to colon cancer patients. This suggests sleep-focused survivorship care may be adapted according to CRC site to ensure patients receive appropriate support.

Year-round influenza immunisation during pregnancy in Nepal: a phase 4, randomised, placebo-controlled trial.

BACKGROUND: Influenza immunisation during pregnancy is recommended but not widely implemented in some low-income regions. We assessed the safety and efficacy in mothers and infants of year-round maternal influenza immunisation in Nepal, where influenza viruses circulate throughout the year. METHODS: In this phase 4, randomised, placebo-controlled trial, we enrolled two consecutive sequential annual cohorts of pregnant women from the Sarlahi district in southern Nepal. We randomised mothers 1:1 to receive seasonally recommended trivalent inactivated influenza vaccine or saline placebo in blocks of eight, stratified by gestational age at enrolment (17-25 weeks vs 26-34 weeks). Women were eligible if they were married, 15-40 years of age, 17-34 weeks' gestation at enrolment, and had not previously received any influenza vaccine that season. We collected serum samples before and after immunisation, and cord blood from a subset of women and infants. Staff masked to allocation made home visits every week from enrolment to 6 months after delivery. Midnasal swabs for respiratory virus PCR testing were collected during maternal acute febrile respiratory infections, and from infants with any respiratory symptom. We assessed vaccine immunogenicity, safety, and three primary outcomes: the incidence of maternal influenza-like illness in pregnancy and 0-180 days postpartum, the incidence of low birthweight (<2500 g), and the incidence of laboratory-confirmed infant influenza disease from 0 to 180 days. This trial is registered with ClinicalTrials.gov, number NCT01034254. FINDINGS: From April 25, 2011, to Sept 9, 2013, we enrolled 3693 women in two cohorts of 2090 (1041 assigned to placebo and 1049 to vaccine) and 1603 (805 assigned to placebo and 798 to vaccine), with 3646 liveborn infants (cohort 1, 999 in placebo group and 1010 in vaccine group; cohort 2, 805 in placebo group and 798 in vaccine group). Immunisation reduced maternal febrile influenza-like illness with an overall efficacy of 19% (95% CI 1 to 34) in the combined cohorts; 9% efficacy (-16 to 29) in the first cohort, and 36% efficacy (9 to 55) in the second cohort. For laboratory-confirmed influenza infections in infants aged 0-6 months, immunisation had an overall efficacy for the combined cohorts of 30% (95% CI 5 to 48); in the first cohort, the efficacy was 16% (-19 to 41), and in the second cohort it was 60% (26 to 88). Maternal immunisation reduced the rates of low birthweight by 15% (95% CI 3-25) in both cohorts combined. The rate of small for gestational age infants was not modified by immunisation. The number of adverse events was similar regardless of immunisation status. Miscarriage occurred in three (0·2%) participants in the placebo group versus five (0·3%) in the vaccine group, stillbirth occurred in 31 (1·7%) versus 33 (1·8%), and congenital defects occurred in 18 (1·0%) versus 20 (1·1%). Five women died in the placebo group and three died in the vaccine group. The number of infant deaths at age 0-6 months was similar in each group (50 in the placebo group and 61 in the vaccine group). No serious adverse events were associated with receipt of immunisation. INTERPRETATION: Year-round maternal influenza immunisation significantly reduced maternal influenza-like illness, influenza in infants, and low birthweight over the entire course of the study, indicating the strategy could be useful in subtropical regions. FUNDING: Bill & Melinda Gates Foundation.

Prevalence and risk factors for low vitamin D status among breastfeeding mother-infant dyads in an environment with abundant sunshine.

PURPOSE: Evaluation of vitamin D (vD) status and risk factors for low vD among breastfeeding mother-infant dyads in a population at high risk for vD deficiency. SUBJECTS AND METHODS: We measured serum 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone at 1 month postpartum in 60 consecutive exclusively breastfeeding Arab mother-infant dyads enrolled in a high dose vD supplementation study to prevent vD deficiency in Doha, Qatar, (latitude 25°N) during summer months. Data were collected on demography, sun exposure, and vD supplementation. Comparison with a US cohort was evaluated. vD deficiency was defined as serum 25(OH)D <50 nmol/L and severe deficiency categorized as 25(OH)D <25 nmol/L in mothers and infants. RESULTS: Mean maternal age was 29 years and 77% had college or university education. Maternal median 25(OH)D was 32.5 nmol/L and 78% were vD-deficient and 20% had 25(OH)D <25 nmol/L. Only 42% of mothers had reportedly taken vD supplements postpartum and median dietary vD intake (119 IU/day) and calcium (490 mg/day) were low. Maternal median sun index score (sun exposure [hours/week] × body surface area exposed while outdoors) was 0. Maternal 25(OH)D correlated with percent body surface area exposure while outdoors (rs=0.37, P=0.004). Infant median 25(OH)D was 20 nmol/L and 83% were deficient, while 58% had 25(OH)D <25 nmol/L. Infant 25(OH)D correlated with maternal levels (rs=0.41, P=0.001). None of the infants received vD supplement at 1 month of age and median sun index score was 0. Infant's parathyroid hormone showed negative correlations with 25(OH)D (rs=-0.28, P=0.03). Sun exposure, vD supplementation rate, and vD status were lower in Doha than Cincinnati, US cohort. CONCLUSION: vD deficiency is common in breastfeeding mother-infant dyads in this sunny environment and is associated with sun avoidance and low vD intake. We suggest corrective vD supplement of breastfeeding mothers and their infants, which should preferably start during pregnancy.