A Bayesian pharmacokinetics integrated phase I-II design to optimize dose-schedule regimes.

The schedule of administering a drug has profound impact on the toxicity and efficacy profiles of the drug through changing its pharmacokinetics (PK). PK is an innate and indispensable component of the dose-schedule optimization. Motivated by this, we propose a Bayesian PK integrated dose-schedule finding (PKIDS) design to identify the optimal dose-schedule regime by integrating PK, toxicity, and efficacy data. Based on the causal pathway that dose and schedule affect PK, which in turn affects efficacy and toxicity, we jointly model the three endpoints by first specifying a Bayesian hierarchical model for the marginal distribution of the longitudinal dose-concentration process. Conditional on the drug concentration in plasma, we jointly model toxicity and efficacy as a function of the concentration. We quantify the risk-benefit of regimes using utility-continuously updating the estimates of PK, toxicity, and efficacy based on interim data-and make adaptive decisions to assign new patients to appropriate dose-schedule regimes via adaptive randomization. The simulation study shows that the PKIDS design has desirable operating characteristics.

Immunogenicity, safety, and persistence induced by triple- and standard-strength four-dose hepatitis B vaccination regimens in hemodialysis patients: A multicenter, randomized, parallel-controlled trial in Six cities in Shanxi Province.

BACKGROUND: Hemodialysis (HD) patients represent a high-risk group for hepatitis B infection. It is crucial to administer hepatitis B vaccination and stimulate higher and more sustained levels of anti-HBs. Our aim is to enhance the immunogenicity and persistence by implementing high-dose and prolonged hepatitis B vaccine schedule regimen in HD patients. METHODS: We conducted this multicenter, randomized, parallel-controlled trial between July 2020 and February 2023 at 11 hospitals in Shanxi province, China. A total of 504 HD patients were enrolled. All participants randomly allocated in a ratio of 1:1:1 to receive recombinant HBV vaccine of 3 standard doses (20 µg) at 0-1-6 months (IM20×3 group), 4 standard doses at 0-1-2-6 months (IM20×4 group), or 4 triple doses (60 µg) at 0-1-2-6 months (IM60×4 group). RESULTS: The vaccine-elicited antibody response peaked at month 7. The follow-up outcomes ranging from month 7 to 30 revealed that the response rates of anti-HBs decreased from 85.9% (134/156) to 33.0% (33/100) in IM20×3 group, from 92.5% (135/146) to 53.9% (56/104) in IM20×4 group and from 95.4% (145/152) to 57.3% (55/96) in IM60×4 group. The duration of vaccine-induced response with 75% of patients maintained protective antibody were 21.0 months in IM20×3 group, 25.7 months in IM20×4 group (vs. IM20×3 group, P=0.056) and 29.2 months in IM60×4 group (vs. IM20×3 group, P=0.034). All the adverse reactions were mild. CONCLUSIONS: The four-triple-dose hepatitis B vaccination regimens could enhance the immunogenicity and 2-year duration in HD patients.The trial was registered with Clinical Trials.gov, number NCT03962881. https://classic.clinicaltrials.gov/ct2/show/NCT03962881?term=NCT03962881&draw=2&rank=1.

Cost-effectiveness of 4CMenB vaccination against gonorrhea: importance of dosing schedule, vaccine sentiment, targeting strategy, and duration of protection.

BACKGROUND: Observational evidence suggests the 4CMenB meningococcal vaccine may partially protect against gonorrhea, with one dose being two-thirds as protective as two. We examined the cost-effectiveness of vaccinating men-who-have-sex-with-men (MSM) in England, with one- or two-dose primary vaccination. METHODS: Integrated transmission-dynamic health-economic modeling explored the effects of targeting strategy, first- and second-dose uptake levels, and duration of vaccine protection, using observational estimates of vaccine protection. RESULTS: Vaccination with one or two primary doses is always cost-saving, irrespective of uptake, although vaccine sentiment is an important determinant of impact and cost-effectiveness. The most impactful and cost-effective targeting is offering "Vaccination-according-to-Risk" (VaR), to all patients with gonorrhea plus those reporting high numbers of sexual partners. If VaR is not feasible to implement then the more-restrictive strategy of "Vaccination-on-Diagnosis" (VoD) with gonorrhea is cost-effective, but much less impactful. Under conservative assumptions, VaR(2-dose) saves £7.62M(95%CrI:1.15-17.52) and gains 81.41(28.67-164.23) QALYs over 10 years; VoD(2-dose) saves £3.40M(0.48-7.71) and gains 41.26(17.52-78.25) QALYs versus no vaccination. Optimistic versus pessimistic vaccine-sentiment assumptions increase net benefits by ∼30%(VoD) or ∼60%(VaR). CONCLUSIONS: At UK costs, targeted 4CMenB vaccination of MSM gains QALYs and is cost-saving at any uptake level. Promoting uptake maximizes benefits and is an important role for behavioral science.

Assessing the Impact of Pneumococcal Conjugate Vaccine Immunization Schedule Change From 3+0 to 2+1 in Australian Children: A Retrospective Observational Study.

BACKGROUND: In mid-2018, the Australian childhood 13-valent pneumococcal conjugate vaccine schedule changed from 3+0 to 2+1, moving the third dose to 12 months of age, to address increasing breakthrough cases of invasive pneumococcal disease (IPD), predominantly in children aged >12 months. This study assessed the impact of this change using national IPD surveillance data. METHODS: Pre- and postschedule change 3-dose 13-valent pneumococcal conjugate vaccine breakthrough cases were compared by age group, serotype, and clinical syndrome. Annual rates of breakthrough cases were calculated (per 100 000) using respective birth cohort sizes and 3-dose vaccine coverage. Using time-series modelling, observed IPD rates in children aged <12 years were compared to that expected if the 3+0 schedule were continued. FINDINGS: Over 2012-2022, rate of 3-dose breakthrough cases in children aged >12 months was 2.8 per 100 000 (n = 557; 11 birth cohorts). Serotype 3 replaced 19A as predominant breakthrough serotype (respectively, 24% and 65% in 2013 to 60% and 20% in 2022) followed by 19F. In breakthrough cases, the most frequent clinical phenotype was bacteremic pneumonia (69%), with meningitis accounting for 3%-4%. In cohorts eligible for 2+1 versus 3+0 schedules, rate of breakthrough cases was lower for all vaccine serotypes, except type 3 (incidence rate ratio, 0.50 [95% confidence interval, .28-.84] and 1.12 [0.71-1.76], respectively). Observed compared to expected IPD was 51.7% lower (95% confidence interval, -60.9 to -40.7%) for vaccine serotypes, but the change for nonvaccine types was not significant 12% (-9.6 to 39.7). INTERPRETATIONS: The 2+1 schedule is likely superior to 3+0 for overall IPD control, a finding that may be worth consideration for other countries considering or using 3+0 PCV schedules.

Preconception sleep duration, non-daytime work schedules, and incidence of spontaneous abortion: a prospective cohort study.

STUDY QUESTION: To what extent do self-reported sleep duration and non-daytime work schedules in either partner affect the rate of spontaneous abortion (SAB)? SUMMARY ANSWER: Incidence of SAB had little association with female sleep duration and a modest positive association with male short sleep duration, female work at night, and discrepant work schedules among partners. WHAT IS KNOWN ALREADY: Several studies have reported an association between short sleep duration in either partner and reproductive health outcomes, including fecundability. Moreover, certain types of female occupational exposures during pregnancy have been associated with an increased risk of SAB. No studies have evaluated SAB risk in relation to male sleep and work schedules, or joint exposures within a couple. STUDY DESIGN, SIZE, DURATION: This prospective cohort study included 9357 female participants and 2602 of their male partners residing in North America (June 2013 to April 2023). PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants enrolled when they were attempting pregnancy and completed self-administered baseline questionnaires about their average sleep duration and work schedules. Among those who conceived, we ascertained SAB and gestational age at loss via follow-up questionnaires. We used multivariable Cox proportional hazards models with gestational weeks as the time scale to estimate hazard ratios (HRs) and 95% CIs relating SAB with sleep duration and non-daytime work schedules for female and male participants, and the couple. We used inverse probability weighting to account for potential selection bias due to the possibility of differential participation of male partners with respect to the exposures. MAIN RESULTS AND THE ROLE OF CHANCE: Compared to female participants with recommended sleep (7-8.9 h), those reporting short sleep duration (<6 h) did not have a higher rate of SAB (HR 0.88, 95% CI 0.69, 1.13). Short self-reported sleep duration among male participants was modestly associated with a higher rate of SAB (adjusted and weighted HR 1.30, 95% CI 0.96, 1.75). Female night work at night (adjusted HR 1.19, 95% CI 1.02, 1.38) and male non-daytime work (adjusted and weighted HR 1.26, 95% CI 1.00, 1.59) were associated with modestly higher rates of SAB, whereas female rotating shift work was not (adjusted HR 0.91, 0.78, 1.05) compared with daytime workers. Couples in which work schedules were discrepant had an elevated rate of SAB if the male partner worked a non-daytime shift (adjusted and weighted HR 1.46, 95% CI 1.13, 1.88) compared with couples in which both members worked during the day. The corresponding HR if only the female partner worked a non-daytime shift was 1.21 (95% CI 0.92, 1.58). LIMITATIONS, REASONS FOR CAUTION: Data on sleep duration and work schedules were based on self-report, which is vulnerable to misclassification, particularly since participants were asked to report their average sleep duration during the past month. Work exposures were heterogeneous, as many different types of employment may require night and shift work and may have different associations with SAB. WIDER IMPLICATIONS OF THE FINDINGS: Our findings are consistent with previous research indicating that some types of female employment schedules may be associated with SAB incidence. This is the first study to indicate a relationship between SAB and male employment schedules, indicating that discrepant work schedules within a couple might be relevant. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development grants R01HD105863 (PIs: L.A.W. and M.L.E.), R01HD086742 (PIs: L.A.W. and E.E.H.), and R21HD072326 (PI: L.A.W.). PRESTO has received in-kind donations from Swiss Precision Diagnostics and Kindara.com for primary data collection. L.A.W. is a consultant for AbbVie, Inc. and the Gates Foundation. M.L.E. is an advisor for and holds stock in Ro, Hannah, Dadi, Underdog, Vseat, & Doveras. The other authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Can we do better with Mylotarg? Model-based assessment of opportunities to improve therapeutic index.

Late-stage clinical trial failures increase the overall cost and risk of bringing new drugs to market. Determining the pharmacokinetic (PK) drivers of toxicity and efficacy in preclinical studies and early clinical trials supports quantitative optimization of drug schedule and dose through computational modeling. Additionally, this approach permits prioritization of lead candidates with better PK properties early in development. Mylotarg is an antibody-drug conjugate (ADC) that attained U.S. Food and Drug Administration (FDA) approval under a fractionated dosing schedule after 17 years of clinical trials, including a 10-year period on the market resulting in hundreds of fatal adverse events. Although ADCs are often considered lower risk for toxicity due to their targeted nature, off-target activity and liberated payload can still constrain dosing and drive clinical failure. Under its original schedule, Mylotarg was dosed infrequently at high levels, which is typical for ADCs because of their long half-lives. However, our PK modeling suggests that these regimens increase maximum plasma concentration (Cmax)-related toxicities while producing suboptimal exposures to the target receptor. Our analysis demonstrates that the benefits of dose fractionation for Mylotarg tolerability should have been obvious early in the drug's clinical development and could have curtailed the proliferation of ineffective Phase III studies. We also identify schedules likely to be even more efficacious without compromising on tolerability. Alternatively, a longer-circulating Mylotarg formulation could obviate the need for dose fractionation, allowing superior patient convenience. Early-stage PK optimization through quantitative modeling methods can accelerate clinical development and prevent late-stage failures.

Temporal trends in medication and service use patterns for mental health issues among men with prostate cancer.

OBJECTIVE: Prostate cancer can significantly impact mental wellbeing, creating uncertainty and morbidity. This study described patterns of psychotropic medication and mental health service use, as a proxy measure for mental health problems, 5 years before and 5 years after prostate cancer diagnosis. METHODS: Population-based registry data were linked with Pharmaceutical Benefits Scheme and Medicare Benefits Schedule data for all prostate cancer patients diagnosed in South Australia between 2012 and 2020 (n = 13,693). We estimated the proportion and rates of psychotropic medication and mental health service use before and after diagnosis. Multivariable adjusted interrupted time series analyses (ITSA) were conducted to uncover temporal patterns. RESULTS: Fifteen percent of men commenced psychotropic medications and 6.4% sought out mental health services for the first time after diagnosis. Psychotropic medication use rose from 34.5% 5 years before to 40.3% 5 years after diagnosis, including an increase in use of antidepressants (from 20.7% to 26.0%) and anxiolytics (from 11.3% to 12.8%). Mental health service use increased from 10.2% to 12.1%, with the increase mostly being general practice mental health visits (from 7.8% to 10.6%). Multivariable ITSA indicated a significant rise in medication and service utilisation immediately before and in the first 2 years following prostate cancer diagnosis. CONCLUSION: There is a clear increase in psychotropic medication use and mental health service use around the time of prostate cancer diagnosis. Mental health outcomes of men with prostate cancer may be improved with early mental health screening, particularly during the diagnosis process, to enable early intervention.

Analysis of the yearly transition function in measles disease modeling.

Globally, there were an estimated 9.8 million measles cases and 207 500 measles deaths in 2019. As the effort to eliminate measles around the world continues, modeling remains a valuable tool for public health decision-makers and program implementers. This study presents a novel approach to the use of a yearly transition function that formulates mathematically the vaccine schedules for different age groups while accounting for the effects of the age of vaccination, the timing of vaccination, and disease seasonality on the yearly number of measles cases in a country. The methodology presented adds to an existing modeling framework and expands its analysis, making its utilization more adjustable for the user and contributing to its conceptual clarity. This article also adjusts for the temporal interaction between vaccination and exposure to disease, applying adjustments to estimated yearly counts of cases and the number of vaccines administered that increase population immunity. These new model features provide the ability to forecast and compare the effects of different vaccination timing scenarios and seasonality of transmission on the expected disease incidence. Although the work presented is applied to the example of measles, it has potential relevance to modeling other vaccine-preventable diseases.

Confirming the Causal Role of Consistent Contexts in Developing a Walking Habit: A Randomized Comparison With Varied Contexts.

BACKGROUND: Physical activity interventions using habit development may help people increase and then maintain physical activity increases over time. Enacting behavior in consistent contexts is a central component of habit development, yet its causal role in habit development in health behaviors has not been confirmed. PURPOSE: This study tests the causal role of consistent context in habit development in health behavior, using a randomized control trial of a planning intervention to develop a walking habit in 127 insufficiently active, working, midlife adults in a real-world setting. METHODS: We compare participants who plan walking in consistent contexts with controls who plan walking in varied contexts and with controls not required to plan on a change in average daily steps (measured using an accelerometer) and inhabit automaticity during a 4-week intervention and at a 4-week follow-up. RESULTS: As expected, consistent and varied context planners increased walking during the intervention, but only consistent context planners developed (and maintained) habit automaticity. Counter to expectations, consistent context planners did not show walking maintenance. However, across conditions, participants who developed more habit automaticity during the intervention also maintained walking more (decreased less). Having a routine daily schedule moderated some effects. Notably, no-plan controls with greater routine developed more habit automaticity, mediated by walking in more consistent contexts. CONCLUSIONS: This study confirms the causal role of consistent contexts in developing a walking habit, in a real-world setting, with an important but challenging population for physical activity interventions and identifies a facilitating condition common for many: a routine schedule.

Developing an exercise habit may help people increase and then maintain physical activity. This study tests and confirms the role of exercising in consistent contexts as a cause of forming a daily walking habit. We use a randomized control trial of a 4-week planning intervention, with a follow-up 4 weeks after the intervention. Participants were 127 insufficiently active, working, midlife adults. We compared participants asked to plan their daily walks in consistent contexts from day-to-day, with participants asked to plan their walks in varied contexts and with participants not required to plan. As expected, consistent and varied context planners increased their daily walking steps (measured using an accelerometer) during the intervention compared to participants not required to plan. However, only consistent context planners developed (and then maintained) a daily walking habit, that is, where taking daily walks felt relatively automatic. Unexpectedly, consistent context planners did not show walking maintenance. However, across all participants, those who developed a stronger walking habit during the intervention maintained their walking more after the intervention ended. Lastly, having an existing routine daily schedule helped some participants. Those who were not asked to plan and had a more routine daily schedule also developed a daily walking habit.

Among-individual variation in flowering phenology affects flowering synchrony and mating opportunity.

PREMISE: The timing and pattern of a plant's flowering can have important consequences for reproductive success. Variation in flowering phenology may influence the number of prospective mates, the risk of mating with lower quality individuals, and the likelihood of self-pollination. Here we use a common garden experiment to explore within- and among-population variation in phenology. Our work provides new insights into how flowering phenology shapes mating opportunity and flowering synchrony in a self-compatible perennial. METHODS: To quantify variation in flowering phenology we raised progeny from nine populations of Mimulus ringens in a common garden. For each individual, we measured phenological traits including age at flowering onset, daily floral display size, total flower number, and flowering synchrony with other members of the population, and related these traits to mating opportunity. We also tested how individual flowering schedules influence the magnitude of synchrony. RESULTS: Flowering phenology and synchrony varied substantially within and among populations. From day to day, plants often oscillated between large and small daily floral displays. Additionally, flowering schedules of individual plants strongly influenced flowering synchrony and, along with the number of flowering days, markedly affected plants' mating opportunity. CONCLUSIONS: Phenological traits such as flowering synchrony can affect the quantity of mating opportunities and may be important targets of natural selection. Our results highlight the need for studies that quantify flowering patterns of individuals as well as populations.

Optimizing the Time and Dose of Melatonin as a Sleep-Promoting Drug: A Systematic Review of Randomized Controlled Trials and Dose-Response Meta-Analysis.

Previous studies have reported inconsistent results about exogenous melatonin's sleep-promoting effects. A possible explanation relies on the heterogeneity in administration schedule and dose, which might be accountable for differences in treatment efficacy. In this paper, we undertook a systematic review and meta-analysis of double-blind, randomized controlled trials performed on patients with insomnia and healthy volunteers, evaluating the effect of melatonin administration on sleep-related parameters. The standardized mean difference between treatment and placebo groups in terms of sleep onset latency and total sleep time were used as outcomes. Dose-response and meta-regression models were estimated to explore how time of administration, dose, and other treatment-related parameters might affect exogenous melatonin's efficacy. We included 26 randomized controlled trials published between 1987 and 2020, for a total of 1689 observations. Dose-response meta-analysis showed that melatonin gradually reduces sleep onset latency and increases total sleep time, peaking at 4 mg/day. Meta-regression models showed that insomnia status (ß = 0.50, p < 0.001) and time between treatment administration and the sleep episode (ß = -0.16, p = 0.023) were significant predictors of sleep onset latency, while the time of day (ß = -0.086, p < 0.01) was the only significant predictor of total sleep time. Our results suggest that advancing the timing of administration (3 h before the desired bedtime) and increasing the administered dose (4 mg/day), as compared to the exogenous melatonin schedule most used in clinical practice (2 mg 30 min before the desired bedtime), might optimize the efficacy of exogenous melatonin in promoting sleep.

Ensuring universal access to quality care for persons with presumed tuberculosis reaching the private sector: lessons from Kerala.

BACKGROUND: More than half of the people with Tuberculosis (TB) symptoms in India seek care from the private sector. People with TB getting treatment from private sector in India are considered to be at a higher risk for receiving suboptimal quality of care in terms of incorrect diagnosis and treatment, lack of treatment adherence support with a high loss to follow-up rate that could eventually increase their risk of drug resistance. The current study aims at documenting the approach and efforts taken by the Kerala state to partner with the private health care delivery providers for ensuring quality TB care to the people with presumed TB reaching them. METHODS: A case study approach was adopted with review of all available literature followed by five Key Informant Interviews to understand the case through a primary descriptive exploration. Grounded theory approach was used to generating the single theory of the case itself that explains it. RESULTS: Kerala state has taken a variety of interventions to ensure universal access to TB care for citizens reaching the private sector with documented improvement in the quality of TB care. Key learnings from these initiatives were (i) patients need to be at the centre of partnerships, (ii) good governance is essential for ensuring Universal Health Coverage in a mixed health system, (iii) data intelligence is required to guide partnerships, (iv) identification of the correct 'problems' is crucial for effective design of partnerships and (v) a platform for meaningful dialogue of key stakeholders is needed. CONCLUSION: Kerala experience demonstrated that if governments take a proactive role in engaging the private sector, in an informed and evidence-based way, they can leverage the advantages of the private sector while protecting the public health interest.

Comparison of current relative value unit-based prices and utility between common surgical procedures, including orthopedic surgeries, in South Korea.

BACKGROUND: The medical pricing system strongly influences physicians' job satisfaction and patient health outcomes. This study aimed to investigate the current relative value unit (RVU)-based pricing and utility of patients in commonly performed surgical procedures in South Korea. METHODS: Fifteen common surgical procedures were selected from OECD statistics, and three additional orthopedic procedures were examined. The current pricing of each surgical procedure was retrieved from the Korea National Health Insurance Service, and the corresponding utilities were obtained as quality-adjusted life year (QALY) gains from previous studies. The relationship between the current prices (RVUs) and the patients' utility (incremental QALY gains/year) was analyzed. Subgroup analysis was performed between fatal and non-fatal procedures and between orthopedic and non-orthopedic procedures. RESULTS: A significant negative correlation (r = - 0.558, p < 0.001) was observed between RVU and incremental QALY among all 18 procedures. The fatal subgroup had a significantly higher RVU than the non-fatal subgroup (p < 0.05), while the former had a significantly lower incremental QALY than the latter (p < 0.001). Orthopedic procedures showed higher incremental QALY values than non-orthopedic procedures, but they did not show higher prices (RVU). CONCLUSIONS: This paradoxical relationship between current prices and patient utility is attributed to the higher pricing of surgical procedures for fatal and urgent conditions. Orthopedic surgery has been found to be a cost-effective treatment strategy. These findings could contribute to a better understanding of the potential role of incremental QALY in pursuing value-based purchasing or reasonable modification of the current medical fee schedule.

Cetuximab every 2 weeks versus standard weekly dosing administration schedule.

Cetuximab every 2 weeks (Q2W) dosing schedule is approved by the US FDA and by the Japanese Pharmaceuticals and Medical Devices Agency in patients with metastatic colorectal cancer and squamous cell carcinoma of the head and neck. Phase II trials have found comparable efficacy and safety for the weekly (Q1W) and Q2W schedules, and real-world studies have shown noninferiority of the Q2W compared with the Q1W schedule. Several guidelines recommend cetuximab Q2W administration as an alternative to the Q1W dosing schedule. Cetuximab Q2W can be administered with a Q2W dose of chemotherapy, making it a more convenient option to the Q1W schedule, potentially resulting in reduced costs for administration, increased flexibility for clinical staff and improved patient adherence.

Cetuximab is a drug for patients with colorectal cancer or cancer of the head and neck. It is usually administered once a week. However, studies have shown that cetuximab given once every 2 weeks instead has similar clinical benefits and side effects. Based on this evidence, the every 2 weeks dosing schedule has been approved for use in USA and Japan. The every 2 weeks dosing schedule is a convenient alternative to the weekly schedule. It may result in fewer hospital visits, improved patient quality of life, reduced healthcare costs and more flexibility for medical staff. This review summarizes the current evidence and benefits for the every 2 weeks dosing schedule.

Changes in work schedule affect headache frequency among Norwegian nurses: a 3-year-follow-up study.

OBJECTIVES: To explore whether changes in work schedule, number of night shifts and number of quick returns were related to changes in headache frequencies. METHODS: A longitudinal study with questionnaire data from 2014 (baseline) and 2017 (follow-up) on work schedule (day only, shift work without nights and shift work with nights), number of night shifts, number of quick returns (less than 11 hours in-between shifts) and validated headache diagnoses among 1104 Norwegian nurses. Associations were explored by adjusted multivariate regression analyses. RESULTS: The median age at baseline was 37 years (IQR 31-43) and 90.5% were women. In the adjusted logistic regression analysis of changed work schedule between baseline and follow-up, changing from night work was associated with increased odds for reversion from headache >1 days/month to no headache at all last year (OR 2.77 (1.29; 5.95)). Changes towards less night shifts (>10) or quick returns (>10) during the last year were associated with increased odds of reversion of headache to no headache (OR 2.23 (1.20; 4.17) and OR 1.90 (1.04; 3.49)). Only decrease in number of night shifts (>10) during the last year reduced risk of onset of any new headache between baseline and follow-up (OR of 0.39 (0.18; 0.84)). CONCLUSION: Changing from night work and reducing the number of night shifts and quick returns were associated with less headache in this 3-year-follow-up of Norwegian nurses. This adds to the growing body of evidence that night work may have direct negative health consequences.

Feasibility of application-based psychomotor vigilance testing to assess fatigue in doctors working night shifts and correlation with smartwatch assessed shift intensity.

OBJECTIVES: To assess: (1) the feasibility of novel data collection methods (wearable technology and an application-based psychomotor vigilance test (PVT)), (2) the impact of night shift working on fatigue, both objective and perceived, for doctors working night shifts in acute hospital specialties and (3) the effects of shift intensity and naps obtained on participant fatigue. METHODS: We adopted an innovative, multimodal approach to data collection allowing assessment of objective and perceived measures of fatigue, in addition to markers of shift intensity. This comprised 5 min PVT for objective quantification of fatigue (via the validated, smartphone-based NASA PVT+ application), wearable electronic devices (Fitbit Versa2) for assessment of shift intensity (step counts and active minutes) and questionnaires to elicit perceptions of fatigue and shift intensity. RESULTS: Data was collected from 25 participants for a total of 145 night shifts. Objective fatigue (assessed by PVT performance) was significantly increased post night shift, with a PVT mean reaction time 257 ms pre shift versus 283 ms post shift (p<0.0001). However, differences in PVT pre and post shift were not affected by night shift intensity, nor breaks or naps taken on shift. Differences in psychomotor performance between doctors working in different specialties were also observed. CONCLUSIONS: The data collection methods used were found to be feasible with good participant engagement. Findings support existing evidence that night shift working in healthcare workers is associated with fatigue, with psychomotor impairment observed post shift. Lower shift intensity and napping did not appear to mitigate this effect.

Sex and race disparities in the association between work characteristics and vitamin D deficiency: findings from the National Health and Nutrition Examination Survey, 2005-2010.

OBJECTIVES: Vitamin D deficiency is highly prevalent worldwide; however, few large population-based studies have examined occupational risk factors. We examined associations between shift work, work schedule, hours worked, outdoor work, occupation and serum 25-hydroxyvitamin D (25(OH)D) levels in the US working population. METHODS: This cross-sectional study included 8601 workers from the 2005-2010 National Health and Nutrition Examination Survey (NHANES) cycles. NHANES occupational data were supplemented with measures of outdoor work from the Occupational Information Network. Serum 25(OH)D concentration in nanomoles per litre (nmol/L) was categorised as sufficient (≥75), insufficient (50-<75), moderately deficient (30-<50) and severely deficient (<30). Age-adjusted weighted multinomial and binary logistic regression were used to examine associations between work-related factors and vitamin D status with sex-race/ethnicity stratification. RESULTS: Shift workers had higher odds of severe vitamin D deficiency compared with day workers (OR: 1.64, 95% CI 1.22 to 2.19). Compared with those in white-collar occupations, those in natural resources were less likely to be deficient (OR: 0.31, 95% CI 0.19 to 0.52), while those in production were more likely to be deficient (OR: 2.25, 95% CI 1.48 to 3.43). Women working ≥40 hours/week compared with <40 hours/week were more likely to be moderately deficient (OR: 1.30, 95% CI 1.06 to 1.59). Black women working in sales were more likely to be deficient than those in management (OR: 1.53, 95% CI 1.03 to 2.27). Mexican American men working nights had the highest odds of deficiency (OR: 2.64, 95% CI 1.38 to 5.06). CONCLUSIONS: Work-related factors were associated with vitamin D status and there were race/ethnicity and sex differences. Targeted vitamin D screening and supplementation interventions may reduce these disparities.

Optimizing medication guidance support for patients with cancer pain: development and evaluation of a pharmaceutical care system for healthcare professionals.

BACKGROUND: Effective management of cancer pain critically depends on timely medication administration and adherence to precise medication guidelines. In the context of limited time and a busy healthcare environment, tailoring the optimal medication schedule for each patient with cancer pain presents a significant challenge for physicians and clinical pharmacists. METHODS: To address this challenge, we conducted a comprehensive analysis of healthcare professionals' needs in guiding cancer pain medication. By developing core features based on key user needs and continuously updating them, we have created the Universal Medication Schedule System (UMSS). We invited 20 physicians and pharmacists specializing in oncology or cancer pain to trial the system and assessed UMSS usage through distributed questionnaires. RESULTS: We identified five key needs of healthcare professionals in cancer pain medication guidance. Based on these needs, we (1) constructed a comprehensive drug information database, including basic information for 1135 drugs, 130,590 drug interaction data entries, and 1409 individual medication timing constraints, and (2) developed a web-based system that provides essential reference information such as drug interactions and dietary restrictions. It can create medication schedules and provide medication education tailored to the patient's daily routine. Participating evaluators unanimously agreed (100%) that the system aids in accurately assessing the risks of polypharmacy and quickly scheduling medication regimens. CONCLUSION: UMSS, by offering personalized medication schedule support, assists healthcare professionals in better managing patients' medication treatment plans. However, further improvements are needed in the automation of database updates and maintenance, as well as in integrating it with electronic health records.

Undergoing Lung Surgery (PSA-Lung) was appropriate for symptom assessment after discharge.

PURPOSE: To examine whether a 7-day or 24-h recall period of Perioperative Symptom Assessment for Patients Undergoing Lung Surgery (PSA-Lung) was appropriate for symptom assessment after discharge. METHODS: A total of 377 patients were recruited in a cohort study of patients who underwent lung surgery. We measured patient symptoms daily and weekly using the two recall period versions of the PSA-Lung scale, respectively. The psychometric properties of both versions were calculated. Spearman rank correlation coefficients and kappa (k) coefficients were used to measure the association between items score measured by the two version scales each week. Cohen's d effect size and mixed linear model were used to measure responsiveness to change over time. RESULTS: Spearman rank correlation coefficients between the symptom scores generated by the 7-day and 24-h versions (range 0.48-0.77; all P < 0.05). The correlations increased in patients in stable condition (weekly symptom change < 2). Cronbach's α coefficients for both ratings were > 0.87 and both had good test-retest reliability. The longitudinal analysis and Cohen's d effect sizes showed that both ratings had good ability to detect changes in all items. CONCLUSION: The 7-day retrospective scale was as effective as the 24-h retrospective scale in terms of psychometric performance. In the stage where the patient's symptoms change rapidly, it is recommended to use the 24-h retrospective scale for symptom monitoring. On the contrary, in a stable state, it can be considered to use the 7-day retrospective scale for monitoring to reduce the patient's burden.

Factors influencing menstrual regularity among female workers: a cross-sectional analysis study.

BACKGROUND: Regularity of menstrual cycles is an important indicator of women's health and fertility, and female workers are exposed to several factors, such as sleep disorders, stress, and shift work, that affect their menstrual regularity. This makes it necessary to comprehensively identify the determinants of menstrual regularity. Therefore, this study identified the factors affecting menstrual regularity among female workers from physiological, psychological, and situational dimensions based on the theory of unpleasant symptoms. METHODS: This was a secondary analysis of the 2010-2012 Korea National Health and Nutrition Examination Survey and utilized the data of 2418 female workers. Based on the theory of unpleasant symptoms, physiological factors included age, age at menarche, childbirth experience, body mass index, and sleep duration. Psychological factors included stress level, depressive mood, and suicidal ideation. Situational factors included education level, household income, consumption of alcohol, engagement in smoking, and work schedule. The χ²-test and hierarchical logistic regression analysis were performed, reflecting the complex sample design. RESULTS: Age at menarche, childbirth experience, and body mass index among physiological factors and education level and work schedule among situational factors were found to be related to menstrual regularity. A higher risk of menstrual irregularities was found among those who had given birth (versus those who had not), had a high age at menarche (versus those with a low age at menarche), were obese (versus those who had a normal body mass index), had elementary school-level or lesser educational achievements (versus those with college graduate-level or higher educational achievements), and who had a shift work schedule (versus those with a fixed schedule). CONCLUSIONS: Intervention is needed for female workers who have these risk factors, and special attention must be paid to female workers who have a shift work schedule. Additionally, since body mass index can be controlled, intervention concerning body mass index is necessary to reduce menstrual irregularity.