Fat intake modifies association between cigarette smoking and lung cancer in a prospective cohort study: A potential explanation for the lung cancer paradox.

BACKGROUND & AIMS: It remains unclear why the association between cigarette smoking and lung cancer was substantially stronger in Western countries than in Asian countries. As experimental studies have revealed that fat intake modulates tobacco carcinogen metabolism and the growth of transplanted or carcinogen-induced lung tumors in mice, the present study sought to investigate whether the association between cigarette smoking and lung cancer was modified by intake of total fat and types of fat (saturated, monounsaturated, and polyunsaturated fats) in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. METHODS: During a median follow-up of 8.9 years, 1,425 cases of lung cancer were documented from 100,864 participants eligible for the present analysis. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: After adjustment for established or suspected confounders, the strength of the association between cigarette smoking and lung cancer was remarkably larger among individuals with high fat intake. HRs (95% CIs) comparing current with never smokers were 23.0 (13.4, 39.6), 32.7 (20.3, 52.8), and 59.8 (30.2, 118.2) for the tertile 1 (≤13.48 g/day), tertile 2 (13.49-21.89 g/day), and tertile 3 (≥21.90 g/day) of saturate fat intake, respectively. A similar pattern of the non-significant interaction was observed when the accumulated amount of cigarette smoking (1-19, 20-39, and ≥40 vs. 0 pack-years) was entered into the regression models. CONCLUSIONS: The present study showed that lung cancer risk associated with both the status and accumulated amount of cigarette smoking was remarkably stronger in individuals with high intakes of fat, particularly saturated fat. However, this interaction was not statistically significant and thus warrants further investigations in other studies.

Treatment patterns of galcanezumab versus standard of care preventive migraine medications over 24 months: a US retrospective claims study.

OBJECTIVE: To describe long-term (24-month) treatment patterns of patients initiating galcanezumab versus standard of care (SOC) preventive migraine treatments including anticonvulsants, beta-blockers, antidepressants, and onabotulinumtoxinA using administrative claims data. METHODS: This retrospective cohort study, which used Optum de-identified Market Clarity data, included adults with migraine with ≥1 claim for galcanezumab or SOC preventive migraine therapy (September 1, 2018 - March 31, 2020) and continuous database enrollment for 12 months before (baseline) and 24 months after (follow-up) the index date (date of first claim). Baseline patient demographics, clinical characteristics, and treatment patterns were analyzed after 24-month follow-up, including adherence (measured as the proportion of days covered [PDC]), persistence, discontinuation (≥60-day gap), restart, and treatment switch. Propensity score matching (1:1) was used to balance the galcanezumab and SOC cohorts. RESULTS: The study included 2307 matched patient pairs with 24-month follow-up. The mean age across cohorts was 44.5 years (females: ∼87%). Patients in the galcanezumab versus SOC cohort demonstrated greater treatment adherence (PDC: 48% vs. 38%), with more patients considered adherent (PDC ≥80%: 26.6% vs. 20.7%) and persistent (322.1 vs. 236.4 d) (all p < .001). After 24-month follow-up, fewer galcanezumab-treated patients had discontinued compared with SOC-treated patients (80.1% vs. 84.7%; p < .001), of which 41.3% and 39.6% switched to a non-index medication, respectively. The most prevalent medication patients switched to in both cohorts was erenumab. Significantly greater proportions of patients who initiated galcanezumab versus SOC medications switched to fremanezumab (p < .001) and onabotulinumtoxinA (p = .016). CONCLUSION: Patients who initiated galcanezumab for migraine prevention had higher treatment adherence and persistence compared with those who initiated SOC medications after 24-month follow-up.

Only few patients (3 − 13%) with migraine, who qualify for preventive treatment, are using them. Conventional preventive treatments have not been developed specifically for migraine treatment, and more than half of the patients stop using them prematurely. Calcitonin gene-related peptide monoclonal antibodies such as galcanezumab, fremanezumab, and erenumab are newer treatments that provide migraine-specific preventive treatment. Prior studies have compared 6- to 12-month migraine medication use by patients starting galcanezumab versus those starting traditional standard of care (SOC) migraine preventive medications. We compared long-term (24-month) migraine medication use in patients starting galcanezumab versus those starting SOC migraine preventive medications to confirm if the results are sustained over a longer period. Over 24 months, patients who used galcanezumab followed the prescribed treatment regimen to a greater extent compared with those who used SOC medications (48% vs. 38%, respectively). Additionally, patients using galcanezumab continued treatment for a longer time compared with those using SOC. Over 24 months, about 85% of patients stopped taking SOC medications, while around 80% of patients stopped taking galcanezumab. Our findings indicate that patients with migraine are more likely to continue using galcanezumab as a preventive treatment for a longer period compared with SOC medications. This study helps identify gaps in the preventive treatment of migraine and provides insights on how they are not being used enough.

Comparison of Treatment Patterns in Patients with Migraine Initiating Calcitonin Gene-Related Peptide Monoclonal Antibodies: A Retrospective Real-World US Study.

Background: Calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) are indicated for migraine prevention in the United States. Limited data comparing real-world treatment patterns for CGRP mAbs are available. Objective: To compare the treatment patterns among patients with migraine initiating galcanezumab, fremanezumab, and erenumab. Methods: This retrospective study included adult patients with one or more claims for a self-injectable CGRP mAb (galcanezumab, fremanezumab, or erenumab), with continuous enrollment in medical and pharmacy benefits for 12 months pre-index and 6 and 12 months post-index using MerativeTM MarketScan® Commercial and Medicare databases from May 2017 through March 2021. Propensity-score matching was used to address confounding by observed covariates. Outcomes analyzed included proportion of days covered (PDC), medication-possession ratio (MPR), persistence (≤60-day gap), treatment discontinuation, and switch to a non-index drug. Descriptive X2 and t-test analyses were conducted. Results: At the 12-month follow-up, matched galcanezumab and fremanezumab cohorts each comprised 2674 patients and the galcanezumab and erenumab cohorts 3503 each. The mean (SD) PDC and MPR were both 0.6 (0.3) across all cohorts. Based on PDC ≥0.80 and MPR ≥0.80, a greater proportion of galcanezumab vs fremanezumab (46.2% vs 43.7%, p=0.053; 46.8% vs 44.3%, p=0.053) and galcanezumab vs erenumab (46.2% vs 44%, p=0.156; 46.7% vs 44.5%, p=0.262), respectively, initiators were adherent. Compared to galcanezumab, fremanezumab (248.0 days vs 236.5 days, p=0.001), and erenumab (247.8 days vs 241.7 days, p=0.061) initiators had lower mean persistence. Galcanezumab initiators were less likely to discontinue treatment than fremanezumab (47.8% vs 51.7%, p=0.005) and erenumab (47.7% vs 50.2%, p=0.040) initiators. Across cohorts, most switchers initiated onabotulinum toxin A as subsequent treatment. Similar results were observed for 6-month follow-up cohorts. Conclusion: Patients with migraine who initiated treatment with galcanezumab showed higher persistence and lower treatment discontinuation rates than those initiating either fremanezumab or erenumab.

Associations between Two Dietary Quality Scores and Pancreatic Cancer Risk in a US National Prospective Cohort Study.

OBJECTIVE: Most previous studies investigated the associations between intake of individual nutrients and risk of disease, which failed to consider the potential interactions and correlations between various nutrients contained in food. Although dietary quality scores provide a comprehensive evaluation of the entire diet, it remains elusive whether they are associated with the risk of pancreatic cancer. METHODS: Dietary intake data collected with the Dietary Questionnaire (DQX) and Diet History Questionnaire (DHQ) were used to calculate HEI-2015 and DQI-R scores for participants in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. A high score indicates an increased intake of adequacy components and a decreased intake of moderation components. This study included 252 cases of pancreatic cancer documented from 58,477 persons during a median follow-up of 12.2 years in the DQX cohort and 372 cases of pancreatic cancer ascertained from 101,721 persons during a median follow-up of 8.9 years in the DHQ cohort. Cox proportional hazards regression analysis was performed to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the associations between the two dietary quality scores and pancreatic cancer risk. RESULTS: After adjustment for confounders, HEI-2015 and DQI-R scores were not significantly associated with pancreatic cancer risk. However, a significantly lower risk was observed for overweight persons with a higher HEI-2015 score in the DQX cohort (HR [95% CI] comparing the highest with lowest tertile: 0.52 [0.32, 0.85], p for trend = 0.009) and those with higher scores of some individual components. CONCLUSION: Collectively, overall dietary quality is not associated with an altered risk of pancreatic cancer in this US population.

Previous studies evaluating the roles of individual nutrients in the etiology of pancreatic cancer fails to consider the potential interactions and correlations between various nutrients contained in food. We investigated the associations between overall dietary quality scores (HEI-2015 and DQI-R) and pancreatic cancer risk in a large prospective cohort study. The findings of this study can help inform a novel and practical approach to primary prevention of this deadly disease through dietary modification and intervention.

Treatment Patterns, Healthcare Resource Utilization, and Direct Costs Among Patients Initiating Concomitant Use of a Calcitonin Gene-Related Peptide Monoclonal Antibody (CGRP mAb) and Novel Acute Medication in the United States.

Purpose: To describe treatment patterns, all-cause and migraine-related healthcare resource utilization (HCRU), and direct costs among people with migraine treated with concomitant calcitonin gene-related peptide monoclonal antibody (CGRP mAb) and novel acute migraine medications (ubrogepant, rimegepant, lasmiditan) in the United States (US). Patients and Methods: This retrospective, observational cohort study utilized data from the IBM MarketScan® Research Databases and included adults initiating CGRP mAb or novel acute migraine medication as index medications between May 01, 2018, and Feb 28, 2021. All-cause and migraine-related HCRU (number of visits) and costs at baseline (12 months pre-index) and at follow-up (12 months post-index) were descriptively analyzed; differences between values at follow-up and baseline were reported. Results: Of 4,167 included in the analysis (mean [SD] age: 43.7 [11.2] years), 89.2% were women, and 59.7% had chronic migraine. Adherence to the indexed CGRP mAb was 47% (using proportion of days covered [PDC]) and 80.1% (using medication possession ratio [MPR]); mean (SD) persistence was 273.4 (115.3) days). At follow-up, 43.9% of the patients discontinued their index preventive medication of which 80.2% switched to a different preventive migraine medication; 17.0% restarted their index preventive medication. Reductions in all-cause inpatient HCRU, all-cause inpatient and outpatient costs, and migraine-related outpatient HCRU were observed at follow-up vs. baseline, whereas increases in all-cause outpatient HCRU, all-cause medication costs, migraine-related inpatient HCRU, and migraine-related inpatient, outpatient, and medication costs were observed. Conclusion: In this study, observed treatment patterns with the indexed CGRP mAb were consistent with prior reports. Concomitant treatment with CGRP mAb and novel acute migraine medications led to reductions in some outcomes of HCRU and direct costs, however, increases were also observed. Treatment utilization, reductions in HCRU and cost savings identified in this study in favor of concomitant CGRP mAb and novel acute medications may help clinicians and other healthcare decision makers assessing appropriate therapeutic options for migraine management.

Prediagnostic BMI trajectories in relation to pancreatic cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

OBJECTIVE: It remains elusive whether prediagnostic BMI trajectory is associated with pancreatic cancer. METHODS: This study investigated this question among 145,489 participants who gave rise to 696 incident cases of pancreatic cancer over a median follow-up of 12 years in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. At baseline, participants were asked to recall their weight at ages 20, 50, and 55 to 74 years (at enrollment), as well as their height. RESULTS: At age 50 years, people with obesity had a significantly increased risk of pancreatic cancer compared with those with a normal weight after adjustment for confounders (hazard ratio [95% CI]: 1.27 [1.01-1.60]). Individuals who had overweight at age 20 years experienced a marginally significant elevated risk of pancreatic cancer (hazard ratio [95% CI]: 1.22 [0.99-1.50]). Compared with individuals who maintained a steady normal weight during follow-up, no significantly altered risk of pancreatic cancer was observed for those whose weight status changed from normal weight to overweight, from normal weight to obesity, and from overweight to obesity. CONCLUSIONS: The present study revealed that prediagnostic adulthood BMI trajectory was not associated with pancreatic cancer risk, but overweight at young adulthood and obesity at middle adulthood may confer an elevated risk of this malignancy.

Direct cost and healthcare resource utilization of patients with migraine before treatment initiation with calcitonin gene-related peptide monoclonal antibodies by the number of prior preventive migraine medication classes.

OBJECTIVE: This study compared all-cause direct cost and healthcare resource utilization (HCRU) among preventive migraine medication (PMM)-naïve patients and patients with up to 3 PMM category switches before initiating calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs). METHODS: This was a retrospective analysis of the IBM Marketscan database. Patients who initiated injectable CGRP mAbs between May 2018 and December 2019 (index period) were included in 4 groups based on the number of prior non-CGRP PMM classes used during the 24-month pre-index period: P0 = none; P1 = one; P2 = two; P3 ≥ three. All-cause direct cost and HCRU for groups were compared without adjustment and after generalized propensity score (GPS) matching. RESULTS: Of the 23,288 patients included (mean age ± standard deviation [SD] 45.4 ± 12.0 years), 85.6% were females, and the mean Charlson Comorbidity Index was 0.69 ± 1.2. P3 group had the highest average annual unadjusted total healthcare costs per patient ($50,274±$76,629); the highest costs attributed to procedure/imaging-related expenses ($20,105±$36,401) and pharmacy ($11,633±$29,763). P0 group had the lowest cost ($25,288±$41,427). Pairwise comparison of GPS matched costs showed significantly greater average annual direct costs per patient in the P3 group vs. P0 (p = .003), P1 (p = .014), and P2 (p = .021) groups. GPS matched HCRU also increased with the number of prior PMM classes used. Anti-epileptics (48.9%) were the most commonly used PMM class, with triptans (75.2%) being the most common acute medication class. CONCLUSIONS: Total direct healthcare cost and HCRU increased significantly with increasing use of PMM classes with the greatest cost difference existing between the P0 and the P3 groups.

Medications used for the prevention of migraine (PMM) are underused as they might cause adverse effects, intolerance, or may lack efficacy. This leads to the discontinuation of the current treatment and switching to other treatments. Calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) are a new class of drugs for the prevention of migraine. Since 2018, four CGRP mAbs have been approved for use in the prevention of migraine. It is known that patients who use more preventive migraine treatments incur greater total direct (caused by a number of medical visits or increased healthcare resource utilization, surgery, drugs, equipment, etc.) annual healthcare costs and healthcare resource utilization (HCRU) in patients with migraine. In the current study, the annual average direct cost and HCRU were compared between patients who had not used preventive medicine and patients who had used 1, 2, or ≥3 preventive medicines for migraine before starting CGRP mAbs. We observed that the healthcare costs and HCRU increased with the use of a higher number of preventive medicines for migraine. Patients who started using injectable CGRP mAbs after at least 3 preventive medicines had the highest healthcare costs and HCRU compared with other groups.

Intake of Calcium, Magnesium, and Phosphorus and Risk of Pancreatic Cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

ObjectiveFew epidemiological studies have investigated the associations between calcium, magnesium, and phosphorus intake and pancreatic cancer. We examined these associations in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.MethodsDiet was assessed using the Dietary Questionnaire (DQX) at baseline in the intervention arm and the Dietary History Questionnaire (DHQ) in 1999 or around the third anniversary of randomization in both the intervention and control arms. During a median follow-up of 12.2 years, 279 cases of pancreatic cancer occurred from 58,477 participants who completed DQX; 380 cases arose from 101,622 participants who responded to DHQ over a median follow-up of 8.9 years. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI).ResultsTotal calcium intake was inversely associated with pancreatic cancer [HR (95% CI) for the fourth vs. the first quartiles in the DHQ cohort: 0.67 (0.47, 0.96); p-trend: 0.035]. An inverse association was also observed for total magnesium intake [HR (95% CI) for the fourth vs. the first quartiles in the DQX cohort: 0.61 (0.37, 1.00); p-trend: 0.023]. Reduced risk associated with total calcium intake was confined to subjects with a high fat intake (>73 g/day) in the DHQ cohort (p-interaction: 0.16).ConclusionsThere was not a significant association between dietary phosphorus intake and pancreatic cancer risk in both cohorts. Total intake of calcium and magnesium are associated with a lower pancreatic cancer risk. The effect of total calcium intake was modified by fat intake.

Associations between intake of calcium, magnesium and phosphorus and risk of pancreatic cancer: a population-based, case-control study in Minnesota.

Experimental studies suggest that abnormal levels of Ca, Mg and phosphorus are implicated in pancreatic carcinogenesis. We investigated the associations between intakes of these minerals and the risk of pancreatic cancer in a case-control study conducted in 1994-1998. Cases of pancreatic cancer (n 150) were recruited from all hospitals in the metropolitan area of the Twin Cities and Mayo Clinic, Minnesota. Controls (n 459) were randomly selected from the general population and frequency matched to cases by age, sex and race. All dietary variables were adjusted for energy intake using the residual method prior to data analysis. Logistic regression was performed to evaluate the associations between intake of three nutrients examined and the risk of pancreatic cancer. Total intake of Ca (936 v. 1026 mg/d) and dietary intake of Mg (315 v. 331 mg/d) and phosphorus (1350 v. 1402 mg/d) were significantly lower in cases than in controls. After adjustment for confounders, there were not significant associations of total and dietary intakes of Ca, Mg and phosphorus with the risk of pancreatic cancer. In addition, no significant interactions exist between intakes of these minerals and total fat on pancreatic cancer risk. In conclusion, the present study does not suggest that intakes of Ca, Mg and phosphorus were significantly associated with the risk of pancreatic cancer.

Vitamin K intake and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial.

Background: Vitamin K inhibits prostate cancer cells, and an altered expression of vitamin K-dependent proteins in prostate tumors has been linked to their aggressiveness and progression. However, little is known about the effect of vitamin K intake on prostate cancer in human populations. Objectives: We evaluated the associations of dietary intake of phylloquinone (vitamin K-1), menaquinones (vitamin K-2), and total vitamin K with the development of prostate cancer among participants in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial. Design: Dietary intake of vitamin K was assessed with the Dietary Questionnaire (DQX) at baseline and the Dietary History Questionnaire (DHQ) at the third anniversary of randomization by using high-performance liquid chromatography-based food-composition data obtained from the USDA and published studies. During a median follow-up of 11.8 y, 2978 cases of prostate cancer (including 490 advanced cases) were identified from the 28,356 men who completed DQX. Similarly, 2973 cases of prostate cancer (including 647 advanced cases) were documented from the 48,090 men who completed DHQ. Cox proportional hazards regression was used to estimate prostate cancer risk in relation to the dietary intake of vitamin K. Results: After adjustment for confounders, dietary intakes of phylloquinone, menaquinones, and total vitamin K, assessed with either the DQX or DHQ, were not significantly associated with the risk of advanced, nonadvanced, and total prostate cancer. These results remained virtually the same when vitamin K intake was modeled as a categorical (divided into quintiles) or continuous (per IQR increase) variable or after outliers of total vitamin K intake (defined as a value that falls above the sum of third quartile and twice the IQR) were excluded. Conclusions: The present study does not suggest that vitamin K intake influences the occurrence of total and advanced prostate cancer in the general US population.

Intake of methyl-related nutrients and risk of pancreatic cancer in a population-based case-control study in Minnesota.

BACKGROUND/OBJECTIVES: Folate, vitamin B6, vitamin B12, and methionine are involved in DNA synthesis and methylation and thus may modulate pancreatic cancer risk. We investigated these associations in a population-based case-control study conducted in 1994-1998. SUBJECTS/METHODS: Cases (n = 150) were identified from all hospitals in the metropolitan areas of the Twin Cities and the Mayo Clinic, Minnesota. Controls (n = 459) were selected randomly from the general population and were frequency matched to cases by age, sex, and race. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for risk of pancreatic cancer in relation to intake of nutrients considered. RESULTS: Dietary intake of folate was associated with a reduced pancreatic cancer risk [OR (95% CI) for quartile (Q) 4 vs. Q1: 0.31 (0.12-0.78)]. A composite score (range from 2 to 8), reflecting combined dietary intake of folate and vitamin B6, was also inversely associated with pancreatic cancer risk [OR (95% CI) for Q4 vs. Q1: 0.24 (0.08-0.70)]. Null associations were found for intake of vitamin B12 and methionine. CONCLUSIONS: Dietary folate intake was associated with a reduced pancreatic cancer risk, and this association became stronger when dietary intake of folate and vitamin B6 was combined in analysis.