"It's always hard being a mom, but the pandemic has made everything harder": A qualitative exploration of the experiences of perinatal women during the COVID-19 pandemic.

BACKGROUND: Understanding the psychosocial impacts of the COVID-19 pandemic in vulnerable groups, such as pregnant and parenting women, is a critical research and clinical imperative. Although many survey-based perinatal health studies have contributed important information about mental health, few have given full voice about the experiences of pregnant and postpartum women during the prolonged worldwide pandemic using a qualitative approach. OBJECTIVE: The purpose of this study is to explore the lived experience of pregnant and postpartum women in the United States during the ongoing COVID-19 pandemic. DESIGN: Qualitative phenomenological study. SETTING: This study was conducted in the community, by recruiting women throughout the U.S. PARTICIPANTS: Fifty-four pregnant and postpartum women participated in qualitative interviews. METHODS: Data from one-on-one semi-structured interviews were analyzed using a team-based phenomenological qualitative approach. RESULTS: Two key themes were apparent: the pandemic has shined a light on the many typical struggles of motherhood; and, there is a lack of consistent, community-based or healthcare system resources available to address the complex needs of pregnant and postpartum women, both in general and during the pandemic. CONCLUSIONS: Going forward, as the world continues to deal with the current pandemic and possible future global health crises, health care systems and providers are encouraged to consider the suggestions provided by these participants: talk early and often to women about mental health; help pregnant and postpartum women create and institute a personal plan for early support of their mental health needs and create an easily accessible mental health network; conceptualize practice methods that enhance coping and resilience; practice in community-based and interdisciplinary teams (e.g., midwives, doulas, perinatal social workers/ psychotherapists) to ensure continuity of care and to foster relationships between providers and pregnant/ postpartum women; and consider learning from other countries' successful perinatal healthcare practices. REGISTRATION: Number (& date of first recruitment): not applicable. TWEETABLE ABSTRACT: Pregnant and postpartum women insist that mental health care must be overhauled, stating the pandemic has highlighted inherent cracks in the system.

Gender differences, UV exposure and risk of lentigo maligna in a nationwide healthcare population cohort study.

BACKGROUND: Our understanding of the relationship between ultraviolet (UV) radiation exposure and lentigo maligna (LM) has been largely derived from epidemiologic/clinical studies based on invasive melanoma. Recent studies have shown gender differences in melanocytic tumours incidence. OBJECTIVE: To examine the association of UV light with LM by gender remains unclear. METHODS: Two prospective cohort study [Nurses' Health Study (1980-2012)] and [Health Professionals Follow-up Study (1986-2010)] were analysed. All participants with LM or MIS, non-LM type were included in analysis. UV index at birth, age 15, and age 30 were calculated by gender. Lifetime UV flux was calculated. Hazard ratios (HRs) were calculated. RESULTS: A total of 110 485 women from NHS and 41 015 men from HPFS were examined. A total of 281 LM and 776 melanoma in situ (MIS), non-LM cases were reported. Risk of LM increased with increasing UV flux exposure in multivariate-adjusted models for men (P for trend = 0.04), but not for women (P for trend = 0.91). CONCLUSIONS: UV flux may be associated with LM in men but not in women.

Validation and comparison of quality-of-life measures for topical 5-fluorouracil treatment: results from a randomized controlled trial.

BACKGROUND: Topical 5-fluorouracil (5-FU) is commonly used for high-risk patients with keratinocyte carcinoma (KC). Skindex and Skin Cancer Index (SCI) are validated instruments to measure quality of life (QoL) of patients with KC and those who have had surgical treatment of KCs. AIM: To validate Skindex and SCI for topical 5-fluorouracil (5-FU) application and to compare the two QoL instruments. METHODS: We randomized 932 veterans at high risk for developing a KC to either topical 5-FU or vehicle control cream applied to the face and ears for up to 1 month. We collected their Skindex-29 and SCI scores at baseline and follow-up visits. RESULTS: Compared with controls, 5-FU reduced QoL, measured by the Skindex symptom, Skindex function and SCI social subscales (P < 0.001, P < 0.01, P = 0.02, respectively). At 1 month, significant changes in QoL in the 5-FU group were observed in the Skindex symptom (10.1, 95% CI 0.36-12.6), Skindex function (6.0, 95% CI 4.0-8.0) and SCI social (-3.5, 95% CI -6.2 to -0.8) subscales, while the other subscales of Skindex and SCI did not show significant changes. All three Skindex subscales at 1 month correlated with patient-reported symptom score and photograph-based toxicity score, whereas social subscale was the only one of the SCI subscales that correlated with patient-reported symptom and photograph-based toxicity scores. CONCLUSIONS: Our study validated Skindex symptom, Skindex function and SCI social subscales for QoL measurement during treatment with topical 5-FU. The study could not provide evidence for construct validity of the other subscales. Skindex was more responsive than SCI in the context of 5-FU treatment.

The global burden of melanoma: results from the Global Burden of Disease Study 2015.

BACKGROUND: Despite recent improvements in prevention, diagnosis and treatment, vast differences in melanoma burden still exist between populations. Comparative data can highlight these differences and lead to focused efforts to reduce the burden of melanoma. OBJECTIVES: To assess global, regional and national melanoma incidence, mortality and disability-adjusted life year (DALY) estimates from the Global Burden of Disease Study 2015. METHODS: Vital registration system and cancer registry data were used for melanoma mortality modelling. Incidence and prevalence were estimated using separately modelled mortality-to-incidence ratios. Total prevalence was divided into four disease phases and multiplied by disability weights to generate years lived with disability (YLDs). Deaths in each age group were multiplied by the reference life expectancy to generate years of life lost (YLLs). YLDs and YLLs were added to estimate DALYs. RESULTS: The five world regions with the greatest melanoma incidence, DALY and mortality rates were Australasia, North America, Eastern Europe, Western Europe and Central Europe. With the exception of regions in sub-Saharan Africa, DALY and mortality rates were greater in men than in women. DALY rate by age was highest in those aged 75-79 years, 70-74 years and ≥ 80 years. CONCLUSIONS: The greatest burden from melanoma falls on Australasian, North American, European, elderly and male populations, which is consistent with previous investigations. These substantial disparities in melanoma burden worldwide highlight the need for aggressive prevention efforts. The Global Burden of Disease Study results can help shape melanoma research and public policy.

Temporal trends in healthcare utilization following primary melanoma diagnosis among Medicare beneficiaries.

BACKGROUND: Little is known about the impact of primary melanoma diagnosis on healthcare utilization and changes in utilization over time. OBJECTIVES: To evaluate population-based temporal trends in healthcare utilization following primary melanoma diagnosis. METHODS: We conducted a before-and-after multiple time series study of Medicare beneficiaries aged ≥ 66 years with primary melanoma diagnoses between 2000 and 2009 using the Surveillance, Epidemiology, and End Results Medicare database. Primary exposure was time from primary melanoma diagnosis at 3-6 months and 6-24 months postdiagnosis. Covariates included tumour-, patient- and geographical-level characteristics and healthcare utilization in the 6 months before diagnosis. Poisson regression was used to estimate population-based risk-adjusted utilization rates for skin biopsies, benign skin excisions, internal medicine office visits and dermatology office visits. RESULTS: The study population included 56 254 patients with first diagnoses of primary melanoma. Most patients were ≥ 75 years old (56·8%), male (62·1%), and had in situ melanoma (42·4%) or localized invasive melanoma (45·9%). From 2000 to 2009, risk-adjusted skin biopsy rates 24 months postdiagnosis increased from 358·3 to 541·3 per 1000 person-years (P < 0·001), and dermatology visits increased from 989·0 to 1535·6 per 1000 person-years (P < 0·001). Benign excisions and internal medicine visits remained stable. In 2000, risk-adjusted skin biopsy rates 6 months postdiagnosis increased by 208·5 relative to the 6 months before diagnosis (148·7 vs. 357·2) compared with an observed absolute increase of 272·5 (290·9 vs. 563·1) in 2009. Trends in dermatology visits were similar. CONCLUSIONS: Utilization of skin biopsies and dermatology office visits following primary melanoma diagnosis has increased substantially over time. These results may inform optimization of care delivery for melanoma within the Medicare population.

Skin biopsy utilization and melanoma incidence among Medicare beneficiaries.

BACKGROUND: Melanoma incidence has increased in recent decades in the U.S.A. Uncertainty remains regarding how much of this increase is attributable to greater melanoma screening activities, potential detection bias and overdiagnosis. OBJECTIVES: To use a cross-sectional ecological analysis to evaluate the relationship between skin biopsy and melanoma incidence rates over a more recent time period than prior reports. METHODS: Examination of the association of biopsy rates and melanoma incidence (invasive and in situ) in SEER-Medicare data (including 10 states) for 2002-2009. RESULTS: The skin biopsy rate increased by approximately 50% (6% per year) throughout this 8-year period, from 7012 biopsies per 100 000 persons in 2002 to 10 528 biopsies per 100 000 persons in 2009. The overall melanoma incidence rate increased approximately 4% (< 1% per year) over the same time period. The incidence of melanoma in situ increased approximately 10% (1% per year), while the incidence of invasive melanoma increased from 2002 to 2005 then decreased from 2006 to 2009. Regression models estimated that, on average, for every 1000 skin biopsies performed, an additional 5·2 (95% confidence interval 4·1-6·3) cases of melanoma in situ were diagnosed and 8·1 (95% confidence interval 6·7-9·5) cases of invasive melanoma were diagnosed. When considering individual states, some demonstrated a positive association between biopsy rate and invasive melanoma incidence, others an inverse association, and still others a more complex pattern. CONCLUSIONS: Increased skin biopsies over time are associated with increased diagnosis of in situ melanoma, but the association with invasive melanoma is more complex.

Interval cancers after skin cancer screening: incidence, tumour characteristics and risk factors for cutaneous melanoma.

BACKGROUND: The rate of interval cancers is an established indicator for the performance of a cancer-screening programme. METHODS: We examined the incidence, tumour characteristics and risk factors of melanoma interval cancers that occurred in participants of the SCREEN project, which was carried out 2003/2004 in Schleswig-Holstein, Germany. Data from 350 306 SCREEN participants, who had been screened negative for melanoma, were linked to data of the state cancer registry. Melanoma interval cancers were defined as melanomas diagnosed within 4-24 months after SCREEN examination. Results were compared with melanomas of the pre-SCREEN era (1999-2002), extracted from the cancer registry. RESULTS: The overall relative incidence of melanoma interval cancers in terms of observed/expected ratio was 0.93 (95% CI: 0.82-1.05; in situ: 1.61 (1.32-1.95), invasive: 0.71 (0.60-0.84)). Compared with melanomas of the pre-SCREEN era, the interval melanomas were thinner and had a slightly greater proportion of lentigo maligna melanomas whereas nodular melanomas were less frequent. INTERPRETATION: The results indicate a moderate performance of the SCREEN intervention with an excess of in situ melanomas. In part, the findings might be due to specifics of the SCREEN project, in particular a short-term follow-up of patients at high risk for melanoma.

Current perspective on actinic keratosis: a review.

Actinic keratoses (AKs) are common, with prevalence in the U.S.A. estimated at almost 40 million in 2004 and annual costs of > $1 billion (U.S.D.). However, there is no universally accepted definition of AK and thus it is difficult to identify reliably. AKs are lesions of epidermal keratinocytic dysplasia that result from chronic sun exposure and have the ability to progress to invasive squamous cell carcinoma (SCC), but clinicians disagree about whether AKs are premalignant lesions, superficial SCCin situ or epiphenomena of chronically sun-damaged skin. Yearly AK to SCC progression rates of 0·6% were reported in an elderly population with multiple prior keratinocyte carcinomas (KCs); and rates of spontaneous AK regression have been reported to be > 50%, but regressed lesions often reappear. As AKs have both cosmetic consequences and potential for malignant transformation, there are multiple reasons for treatment. There is no current agreement on the most efficacious treatment, but 5-fluorouracil has been shown to both prevent and treat AKs, and imiquimod and photodynamic therapy may have the best cosmetic outcomes. AKs may be treated to improve appearance and relieve symptoms, but the keratinocytic dysplasia that gives rise to malignancy, and sometimes appears as an AK, may be what actually threatens patient health. Thus, treatments should aim to decrease the risk of KC or facilitate KC diagnosis by reducing the potential for misidentification created when a KC appears in a field of AKs. Improved agreement among clinicians on AK definition may improve management.

Safety and clinical activity of vascular endothelial growth factor receptor (VEGFR)-tyrosine kinase inhibitors after programmed cell death 1 inhibitor treatment in patients with metastatic clear cell renal cell carcinoma.

BACKGROUND: Emerging agents blocking the programmed cell death 1 (PD-1) pathway show activity in metastatic clear cell renal cell carcinoma (mRCC). The aim of this study was to evaluate the efficacy and safety of vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR)-tyrosine kinase inhibitor (TKI) therapy after PD-1 inhibition. PATIENTS AND METHODS: Patients with mRCC treated with anti-PD-1 antibody (aPD-1) monotherapy or in combination (with VEGFR-TKI or ipilimumab) that subsequently received VEGFR-TKI were retrospectively reviewed. The efficacy end points were objective response rate (ORR) and progression-free survival (PFS) stratified by the type of prior PD-1 regimen. Safety by the type and PD-1 exposure was also evaluated. RESULTS: Seventy patients were included. Forty-nine patients received prior therapy with immune checkpoint inhibitors (CPIs) alone and 21 had combination therapy of aPD-1 and VEGFR-TKI. Overall, ORR to VEGFR-TKI after PD-1 inhibition was 28% (19/68) and the median PFS was 6.4 months (mo) (4.3-9.5). ORR to VEGFR-TKI after aPD-1 in combination with VEGFR-TKI was lower than that in patients treated with VEGFR-TKI after CPI alone (ORR 10% versus 36%, P = 0.039). In the multivariable analysis, patients treated with prior CPI alone were more likely to achieve an objective response than those treated with aPD-1 in combination with VEGFR-TKI (OR = 5.38; 95% CI 1.12-26.0, P = 0.03). There was a trend toward numerically longer median PFS in the VEGFR-TKI after the CPI alone group, 8.4 mo (3.2-12.4) compared with 5.5 mo (2.9-8.3) for those who had VEGFR-TKI after aPD-1 in combination with VEGFR-TKI (P = 0.15). The most common adverse events (AEs) were asthenia, hypertension, and diarrhea. CONCLUSIONS: The efficacy and safety of VEGFR-TKIs after PD-1 inhibition were demonstrated in this retrospective study. The response rate was lower and the median progression-free survival was shorter in those patients who received prior PD-1 in combination with VEGFR-TKI. PD-1 exposure does not seem to significantly influence the safety of subsequent VEGFR-TKI treatment.

Indoline-3-propionate and 3-aminopropyl carbamates reduce lung injury and pro-inflammatory cytokines induced in mice by LPS.

BACKGROUND AND PURPOSE: In the search for safer and effective anti-inflammatory agents, we investigated the effect of methyl indoline-3-propionate and indoline-3-(3-aminopropyl) carbamates on LPS-induced lung injury and pro-inflammatory cytokines in mice. Their mechanism of action was determined in murine peritoneal macrophages. EXPERIMENTAL APPROACH: Lung injury was induced by intratracheal infusion of LPS and assessed by the change in lung weight and structure by light microscopy after staining by haematoxylin and eosin. In LPS-activated macrophages, MAPK proteins and IκBα were measured by Western blotting and the transcription factors, AP-1 and NF-κB by electromobility shift assay. Cytokines in the plasma and spleen of mice injected with LPS were measured by elisa-based assay. KEY RESULTS: AN917 and AN680 (1-10 pM) decreased TNF-α protein in macrophages by inhibiting phosphorylation of p38 MAPK, IκBα degradation and activation of AP-1 and NF-κB without affecting cell viability. In vivo, these compounds (10 µmol · kg(-1)) markedly decreased lung injury induced by LPS and the elevation of TNF-α and IL-6 in lung, plasma and spleen. Activation of α-7nACh receptors contributed to the reduction of TNF-α by AN917, which inhibited AChE in the spleen by 35%. CONCLUSION AND IMPLICATIONS: Indoline carbamates are potent inhibitors of pro-inflammatory mediators in murine macrophages and in mice injected with LPS, acting via the p38 MAPK, AP-1 and NF-κB cascades. Indirect α-7nACh receptor activation by AN917, through inhibition of AChE, contributes to its anti-inflammatory effect. Indoline carbamates may have therapeutic potential for lung injury and other diseases associated with chronic inflammation without causing immunosuppression.