A single-component, light-assisted uncaging switch for endoproteolytic release.

Proteases function as pivotal molecular switches, initiating numerous biological events. Notably, potyviral protease, derived from plant viruses, has emerged as a trusted proteolytic switch in synthetic biological circuits. To harness their capabilities, we have developed a single-component photocleavable switch, termed LAUNCHER (Light-Assisted UNcaging switCH for Endoproteolytic Release), by employing a circularly permutated tobacco etch virus protease and a blue-light-gated substrate, which are connected by fine-tuned intermodular linkers. As a single-component system, LAUNCHER exhibits a superior signal-to-noise ratio compared with multi-component systems, enabling precise and user-controllable release of payloads. This characteristic renders LAUNCHER highly suitable for diverse cellular applications, including transgene expression, tailored subcellular translocation and optochemogenetics. Additionally, the plug-and-play integration of LAUNCHER into existing synthetic circuits facilitates the enhancement of circuit performance. The demonstrated efficacy of LAUNCHER in improving existing circuitry underscores its significant potential for expanding its utilization in various applications.

History of Rectal Product Use and Country of Residence Influence Preference for Rectal Microbicide Dosage Forms Among Young Sexual and Gender Minorities: A Multi-country Trial Comparing Placebo Douche, Suppository, and Insert Products.

The DESIRE Study (MTN-035) explored product preference among three placebo rectal microbicide (RM) formulations, a rectal douche (RD), a suppository, and an insert, among 210 sexually active transgender people and men who have sex with men in five counties: the United States, Peru, Thailand, South Africa, and Malawi. Participants used each product prior to receptive anal sex (RAS) for 1 month, following a randomly assigned sequence, then selected their preferred product via computer assisted self-interview. In-depth interviews examined reasons for preference. We compared product preference and prior product use by country to explore whether geographic location and experience with the similar products impacted preference. A majority in the United States (56%) and Peru (58%) and nearly half in South Africa (48%) preferred the douche. Most in Malawi (59%) preferred the suppository, while half in Thailand (50%) and nearly half in South Africa (47%) preferred the insert. Participants who preferred the douche described it as quick and easy, already routinized, and serving a dual purpose of cleansing and protecting. Those who preferred the insert found it small, portable, discreet, with quick dissolution. Those who preferred the suppository found the size and shape acceptable and liked the added lubrication it provided. Experience with product use varied by country. Participants with RD experience were significantly more likely to prefer the douche (p = 0.03). Diversifying availability of multiple RM dosage forms can increase uptake and improve HIV prevention efforts globally.

RESUMEN: El estudio DESIRE (MTN-035) exploró la preferencia de producto entre tres formulaciones de microbicida rectal (MR) de placebo, una ducha rectal, un supositorio y un inserto, entre 210 personas transgénero y hombres que tienen sexo con hombres en cinco países: los Estados Unidos, Perú., Tailandia, Sudáfrica y Malawi. Los participantes utilizaron cada producto antes del sexo anal receptive (SAR) durante un mes, siguiendo una secuencia asignada al azar, luego seleccionaron su producto preferido mediante una autoentrevista asistida por computadora. Las entrevistas en profundidad examinaron los motivos de preferencia. Comparamos la preferencia de producto y el uso previo del producto por país para explorar si la ubicación geográfica y la experiencia con la forma farmacéutica impactaron la preferencia. Una mayoría en los Estados Unidos (56%) y Perú (58%) y casi la mitad en Sudáfrica (48%) prefirieron la ducha rectal. La mayoría en Malawi (59%) prefirió el supositorio, mientras que la mitad en Tailandia (50%) y casi la mitad en Sudáfrica (47%) prefirió el inserto. Los participantes que prefirieron la ducha rectal la describieron como rápida y fácil, ya parte de su rutina y que tenía el doble propósito de limpiar y proteger. Los que prefirieron el inserto lo consideraron pequeño, portátil, discreto y de rápida disolución. Los que prefirieron el supositorio encontraron que tenía un tamaño y forma aceptables y proveía lubricación adicional. La experiencia con el uso del producto varió según el país. Los participantes con experiencia con duchas rectales tenían significativamente más probabilidades de preferir la ducha rectal (p = 0,03). Diversificar la disponibilidad de múltiples formas farmacéuticas de MR puede aumentar la aceptación y mejorar los esfuerzos de prevención del VIH a nivel mundial.

Paradata: Measuring Engagement in Digital HIV Interventions for Sexual and Gender Minorities.

PURPOSE OF REVIEW: The goal of this review was to examine online engagement using paradata (i.e., intervention usage metrics) as part of the reporting of online behavioral HIV prevention and care interventions' findings. We underscore the importance of these data in examining intervention engagement and effectiveness. RECENT FINDINGS: We focused on studies indexed in PubMed and published between April 1, 2017, and June 30, 2023, that reported the development and testing of online behavioral interventions for HIV prevention and/or care. Of the 689 extracted citations, 19 met the study criteria and provided engagement data - only six studies tested the association between engagement and intervention outcomes. Of these, four studies found a positive association between participants' engagement and improvements in HIV-related outcomes. Increasing attention is being paid to the collection and reporting of paradata within HIV online behavioral interventions. While the current evidence suggests a dose-response relationship due to user engagement on HIV outcomes, greater efforts to systematically collect, report, and analyze paradata are warranted.

Co-occurring Epidemic Conditions Among Southern U.S. Black Men Who Have Sex with Men in an Online eHealth Intervention.

Black men who have sex with men (BMSM) face disproportionately higher risks for adverse sexual health outcomes compared to their non-Hispanic White counterparts. This disparity can be attributable to overlapping and intersecting risk factors at the individual and structural levels and can be understood through syndemic theory. Using longitudinal data from the HealthMPowerment trial (n = 363), six conditions related to stigma syndemics were indexed as a cumulative risk score: high alcohol use, polydrug use, depression and anxiety symptomology, and experiences of racism and sexual minority stigma. Using Poisson regression, we found a positive association between baseline risk scores and sexual risk behavior (b: 0.32, SE: 0.03, p < 0.001). Using a Generalized Estimating Equation, we also found a 0.23 decrease in the within-participant risk scores at 3-month follow-up (SE: 0.10, p < 0.020). Future work examining how care and prevention trials improve health outcomes in this population is needed.

Design, synthesis, and biological evaluation of novel HSP27 inhibitors to sensitize lung cancer cells to clinically available anticancer agents.

Expression of heat shock protein (HSP) correlates with the oncogenic status of malignant cells and plays an important role in tumorigenesis. HSP27 is constitutively expressed at specific stages of cancer development, and several clinical trials have reported correlations between HSP27 expression and tumor progression, metastasis, and chemoresistance in various types of cancer cells. These findings indicate that HSP27 is a major drug target, particularly in chemo-resistant cancers. As part of our ongoing efforts to improve the previously identified J2, a HSP27 cross-linker, we, in this study, report the identification of NK16 as a novel inducer of abnormal HSP27 dimers that did not affect the expression of HSP90 in an NCI-H460 lung cancer cell model. When NCI-H460 cells were treated with NK16 in combination with the anticancer drug cisplatin or paclitaxel, cleavage of PARP and caspase-3 was increased compared to administration of cisplatin or paclitaxel alone. Similar results were obtained in an NCI-H460-xenografted mouse model, in which tumor growth was suppressed more by co-administration of NK16 and paclitaxel than by paclitaxel alone. We propose NK16 as a meaningful strategy to improve the anticancer efficacy of cisplatin and paclitaxel.

Current and Future Perspectives of HIV Prevention Research Among Young Sexual Minority Men in South Korea.

Social stigma within Korean society hinders structural efforts to reduce HIV disparities among sexual minority men (SMM). To date, however, there have been limited intervention efforts to reduce HIV disparities among SMM in Korea. Therefore, the current mixed-methods study (n = 180) explored young Korean SMM's perspectives on the acceptability of HIV prevention mHealth interventions to inform effective strategies for future intervention studies. We then analyzed participants' comments and suggestions on HIV research and examined associations with the acceptability of mHealth interventions. Through our textual coding and analysis, we identified four primary themes for comments and suggestions for HIV research in Korea: the centrality of stigma, health service accessibility, informational accessibility, and cultural adaptation. Our study suggests culturally adapted HIV intervention addressing stigma, health service accessibility, and information accessibility and mHealth interventions disseminating information and resources for stigmatized young SMM in Korea.

Regional disparities in food security and depression among single-person households in the Republic of Korea.

BACKGROUND: Single-person households constitute over 40% of all households in the Republic of Korea and are more vulnerable to food insecurity and depression than multi-person households. There is a lack of research on examining whether regional characteristics are associated with the degree of food insecurity and depression among single-person households. This study aimed to examine the regional disparities in food security and depression among single-person households in the Republic of Korea. METHODS: A total of 227,873 adults from the 2019 Korean Community Health Survey was included in the analysis. According to population density and poverty rate, the residence of the participants was classified into four regions: metropolitan areas with high population density were classified into areas with low poverty rates (Region 1) and high poverty rates (Region 2), and provinces with low population density were classified into areas with low poverty rates (Region 3) and high poverty rates (Region 4). Using a single item of household food security, those who had experienced a lack of food due to financial difficulties over the past year were classified as food insecure. Depression was measured using the Patient Health Questionnaire-9. Odds ratios and 95% confidence intervals (CI) for the risk of food insecurity and depression according to regional characteristics were calculated after adjusting for potential confounding variables. RESULTS: After adjusting for confounding variables, single-person households in regions with high population density, Regions 1 and 2, had 1.16 times (95% CI = 1.04-1.30) and 1.43 times (95% CI = 1.27-1.61) higher odds of food insecurity, respectively, compared to those in Region 4. Single-person households in regions with low poverty rates, Regions 1 and 3, had 1.54 times (95% CI = 1.34-1.77) and 1.21 times (95% CI = 1.01-1.46) higher odds of depression, respectively, than those in Region 4. Among those who lived alone, the middle-aged, having low income, receiving livelihood benefits, or having a low educational attainment had higher odds of experiencing both food insecurity and depression than their counterparts. CONCLUSIONS: As the risk of food insecurity and depression in single-person households differs according to regional characteristics, local governments need to implement policies for single-person households in consideration of these distinct characteristics.

A latent trajectory analysis of young sexual and gender minorities' adherence to three rectal microbicide placebo formulations (MTN-035; a randomized crossover trial).

BACKGROUND: Rectal microbicides (RM) are biomedical HIV prevention products that aim to prevent or reduce the transmission of HIV and other sexually transmitted infections (STIs). RM modalities may be beneficial for populations who have complex lifestyles, difficulties adhering to pre-exposure prophylaxis (PrEP) regimens, and/or have limited access to care. MTN-035 (DESIRE; Developing and Evaluating Short-Acting Innovations for Rectal Use), a randomized crossover trial, aimed to evaluate the safety and acceptability of, and adherence to, three placebo RM modalities (douche, insert, and suppository) prior to receptive anal intercourse. METHODS: We conducted latent trajectory analysis to identify clusters of individuals who shared similar trajectories in acceptability and adherence for each product (douche, insert, and suppository) over time. We analyzed weekly short messaging service (SMS) use reports for each modality as reported by enrolled sexual and gender minority (SGM) participants. RESULTS: Two trajectories for each product were identified: a "protocol compliant" trajectory (i.e., at least one product use occasion per week) and "high use" trajectory (i.e., more than three product use occasions per week). Participants with high use were more likely to lack access to PrEP and have higher intentions to utilize RM modalities compared to those who were protocol compliant. CONCLUSIONS: This study highlighted high adherence to RM modalities among SGM. As research into viable HIV prevention modalities continues to evolve, tailored intervention strategies are needed to support the uptake of and adherence to alternative prevention modalities that are behaviorally congruent with targeted users. TRIAL REGISTRATION: NCT03671239 (14/09/2018).

A Latent Profile Analysis of Online Dating Patterns Among Single Young Men Who Have Sex with Men.

Despite the increased use of geosocial networking applications for finding sexual partners among young men who have sex with men (YMSM), few studies have examined the intricate patterns of online dating behaviors. In order to advance understanding of online dating patterns among YMSM, various factors, including how frequently and how much time is spent within partner-seeking sites, need to be examined concurrently. Therefore, we used latent profile analysis to identify online dating patterns and logistic regressions to examine their associations with sexual behaviors and relationship characteristics among single YMSM (N = 180; ages 18-24). We found three online dating patterns: discouraged users (N = 93, 52%), date seekers (N = 67, 37%), and instant lovers (N = 20, 11%). Discouraged users were less likely to seek sexual sensational activities, while date seekers were more likely to seek sexual sensational activities. Moreover, instant lovers were less likely to pursue committed romantic relationships, while they reported a higher number of condomless anal intercourse. Given that online dating patterns are not homogeneous, HIV prevention interventions may benefit from tailored approaches based on YMSM's different online dating profiles.

An Identity-Affirming Web Application to Help Sexual and Gender Minority Youth Cope With Minority Stress: Pilot Randomized Controlled Trial.

BACKGROUND: Efficacious mental health interventions for sexual and gender minority youth have had limited reach, given their delivery as time-intensive, in-person sessions. Internet-based interventions may facilitate reach to sexual and gender minority youth; however, there is little research examining their efficacy. OBJECTIVE: This study aims to describe the results of a pilot randomized controlled trial of imi, a web application designed to improve mental health by supporting lesbian, gay, bisexual, transgender, queer, and other sexual and gender minority identity affirmation, coping self-efficacy, and coping skill practice. METHODS: Sexual and gender minority youth (N=270) aged 13 to 19 (mean 16.5, SD 1.5) years and living in the United States were recruited through Instagram advertisements. Approximately 78% (210/270) of the sample identified as racial or ethnic minorities. Participants were randomized in a 1:1 fashion to the full imi intervention web application (treatment; 135/270, 50%) or a resource page-only version of the imi site (control; 135/270, 50%). The imi application covered four topical areas: gender identity; lesbian, gay, bisexual, transgender, queer, and other sexual and gender minority identity; stress and coping; and internalized homophobia and transphobia. Participants explored these areas by engaging with informational resources, exercises, and peer stories at a self-guided pace. Both arms were assessed via web-based surveys at baseline and 4-week follow-up for intervention satisfaction, stress appraisals (ie, challenge, threat, and resource), coping skills (ie, instrumental support, positive reframing, and planning), and mental health symptoms among other outcomes. Main intent-to-treat analyses compared the arms at week 4, controlling for baseline values on each outcome. RESULTS: Survey retention was 90.4% (244/270) at week 4. Participants in the treatment arm reported greater satisfaction with the intervention than participants in the control arm (t241=-2.98; P=.003). The treatment arm showed significantly greater improvement in challenge appraisals (ie, belief in one's coping abilities) than the control (Cohen d=0.26; P=.008). There were no differences between the arms for threat (d=0.10; P=.37) or resource (d=0.15; P=.14) appraisals. The treatment arm showed greater increases in coping skills than the control arm (instrumental support: d=0.24, P=.005; positive reframing: d=0.27, P=.02; planning: d=0.26, P=.02). Mental health symptoms improved across both the treatment and control arms; however, there were no differences between arms. Within the treatment arm, higher engagement with imi (≥5 sessions, >10 minutes, or >10 pages) predicted greater improvement in stress appraisals (all P values <.05). CONCLUSIONS: The results provide initial evidence that asynchronous psychosocial interventions delivered via a web application to sexual and gender minority youth can support their ability to cope with minority stress. Further research is needed to examine the long-term effects of the imi application. TRIAL REGISTRATION: ClinicalTrials.gov NCT05061966; https://clinicaltrials.gov/ct2/show/NCT05061966.

Approaches to Promoting Linkage to and Retention in HIV Care in the United States: a Scoping Review.

PURPOSE OF REVIEW: Linkage to and retention in HIV care, as conceptualized in the HIV care continuum, remain critical steps towards achieving and maintaining viral suppression. We evaluated recently published (Jan 2018-Nov 2020) peer-reviewed clinical trials of linkage to and retention in care outcomes in the United States. RECENT FINDINGS: We identified 12 trials evaluating linkage to and retention in care outcomes in the United States. Most trials did not adhere to standardized definitions or metrics for linkage to or retention in HIV care, hindering comparisons between studies. Four interventions indicated improvements on linkage to or retention in HIV care at follow-up, relying on behavioral incentives and/or case management as key intervention strategies. We recommend the adoption standardize metrics across linkage and retention trials, and the future use of implementation science frameworks to identify implementation facilitators and barriers, and evaluate key strategies associated with improvements in linkage to and retention in care.

A Multidimensional Model of Sexual Empowerment Among Young Black Men Who have Sex with Men: A Latent Profile Analysis.

Sexual empowerment is a key strategy in HIV prevention intervention design, yet its measurement has been conceptualized as homogeneous. To date, no studies have examined whether young Black men who have sex with men (YBMSM) exhibit heterogeneity across sexual empowerment. Using baseline data from a randomized controlled trial (N = 275, HIV-negative YBMSM), we classified YBMSM into sexual empowerment profiles based on five indicators using a latent profile analysis and assessed the associations between the sexual empowerment profiles and stigma-related experiences using multinomial logistic regression. Three profiles were identified: psychologically empowered with safer sex intentions (profile 1); psychologically disempowered with safer sex intentions (profile 2); and psychologically disempowered without safer sex intentions (profile 3). YBMSM reporting fewer stigma-related experiences were more likely to be profile 1 than profile 2 and profile 3. To empower YBMSM, interventions based on sexual empowerment profile targeting the psychological/behavioral aspects of empowerment and addressing stigma are needed.

Assessing the Role of Gay Community Attachment, Stigma, and PrEP Stereotypes on Young Men Who Have Sex with Men's PrEP Uptake.

Negative stereotypes about pre-exposure prophylaxis (PrEP) hinder PrEP uptake among young men who have sex with men (YMSM). Prior research suggests community homophobia may be linked to negative PrEP attitudes. Conversely, individuals with high gay community attachments (GCA) may have more access to credible PrEP information/resources. Among 285 YMSM recruited online, we estimated structural equation models to test competing conceptual models that inform pathways from perceived stigmas, GCA, and negative PrEP stereotype endorsements to PrEP uptake. In Model A, perceived stigma was directly associated with PrEP uptake, partially mediated by stereotype endorsement (ß = - 0.05; 95% CI [- 0.09, - 0.01]) and GCA (ß = - 0.06; 95% CI [- 0.11, 0.02]). In Model B, perceived stigma was associated with PrEP uptake (ß = - 0.07; 95% CI [- 0.14, - 0.01]) through stereotype endorsement among high GCA YMSM. Complemented by anti-stigma initiatives, PrEP outreach for YMSM should utilize sex-positive messaging and disentangle negative PrEP stereotypes within gay-centric social spaces.

RESUMEN: Los estereotipos negativos sobre la profilaxis pre-exposición (PrEP) dificultan su uso entre hombres jóvenes que tienen sexo con otros hombres (YMSM). Investigaciones anteriores sugieren que la homofobia comunitaria puede estar relacionada a las actitudes negativas sobre PrEP. En cambio, personas con alto apego a la comunidad gay (GCA) pueden tener más acceso a información y recursos creíbles sobre PrEP. Entre los 285 YMSM reclutados en línea, estimamos varios modelos de ecuaciones estructurales para contrastar las asociaciones entre los estigmas percibidos, la GCA, los estereotipos negativos sobre PrEP, y el uso de PrEP entre diversos modelos conceptuales. En el Modelo A, el estigma percibido se asoció directamente con el uso de PrEP, siendo parcialmente mediado por el endoso a estereotipos (ß = − 0.05; IC del 95% [− 0.09, − 0.01]) y GCA (ß = − 0.06; IC del 95% [− 0.11, 0.02]). En el Modelo B, el estigma percibido se asoció con el uso de PrEP (ß = − 0.07; IC del 95% [− 0.14, − 0.01]) a través de los estereotipos entre YMSM con puntajes altos en GCA. Complementado con iniciativas contra el estigma, el alcance de la PrEP para YMSM debe utilizar mensajes de sexo positivo y desenredar los estereotipos negativos de PrEP dentro de los espacios sociales centrados en la comunidad gay.

Is "Geriatric" Assessment Just for Older Patients?

Geriatric assessment (GA) is used in oncology to identify deficits in older patients with cancer that may affect treatment choice. We examine GA in 550 patients with early breast cancer, including both younger (<65 years) and older women (aged 65 years or older), to assess the potential value of this tool in younger, presumed "healthier" patients. Although older women have more GA-identified deficits overall, younger patients are more anxious. Suboptimal physical function was problematic across the age spectrum. GA domains can identify major deficits in younger patients beyond those likely to be uncovered in routine investigation.

Weight trajectories in women receiving systemic adjuvant therapy for breast cancer.

BACKGROUND: Weight gain after breast cancer (BC) diagnosis is a well-known phenomenon; however, it is not a universal phenomenon and identification of patients at highest risk for weight gain is needed. This study investigates weight trajectories in early BC patients at 2 years post-primary treatment, examining potential contributing factors such as age, race, and receipt of chemotherapy, anti-HER-2 therapy, and endocrine treatment (ET). METHODS: A single institution cohort of newly diagnosed women age 21 and older with early breast cancer patients (Stage 0-3) were identified by retrospective chart review (diagnosis year 1995 to 2016). Log-binomial regression models for net weight changes at 2 years post-primary treatment including patient demographic, clinical, and treatment characteristics. RESULTS: The final sample of 625 patients included 29% who were non-White and 37% who were pre-menopausal at diagnosis. Body mass index (BMI) at diagnosis was calculated and found to be normal in 33% (BMI 18 to < 25), overweight in 27% (BMI 25 to < 30), and obese in 40% (BMI 30 and higher). At 2 years, compared to weight at diagnosis, 31% had lost > 2 kg, 34% had stable weight ± 2 kg, and 35% had gained > 2 kg. Factors associated with > 2 kg weight gain were menopausal status (pre-menopausal HR 1.65, 95% CI 1.34-2.04, p < .0001), receiving any chemotherapy (HR 1.36, 95% CI 1.04-1.77), and anthracycline-based chemotherapy followed by ET (HR 1.60, CI 1.01-2.45). Anti-HER-2 therapy and transition from pre- to post-menopausal during the 2-year study period were not significant factors in weight gain. In multivariate analysis, menopausal status remained the only significant variable related to weight gain when adjusted for treatment. For all treatment combinations, pre-menopausal women had significantly more weight gain. CONCLUSIONS AND RELEVANCE: Weight gain, weight loss, and stable weight in women with early breast cancer vary greatly by treatment plan. However, pre-menopausal patients have the highest risk for weight gain.

The impact of a randomized dietary and physical activity intervention on chronic inflammation among obese African-American women.

Lifestyle interventions may reduce inflammation and lower breast cancer (BrCa) risk. This randomized trial assessed the impact of the Sistas Inspiring Sistas Through Activity and Support (SISTAS) study on plasma C-reactive protein (CRP), interleukin-6 (IL-6) and Dietary Inflammatory Index (DII). This unblinded, dietary and physical activity trial was implemented in 337 obese (body mass index [BMI] ≥30 kg/m2) African American (AA) women recruited between 2011 and 2015 in South Carolina through a community-based participatory approach with measurements at baseline, 3 months, and 12 months. Participants were randomized into either intervention (n = 176) or wait-list control group (n = 161). Linear mixed-effect models were used for analyses of CRP and IL-6. Baseline CRP was significantly higher in those with greater obesity, body fat percentage, and waist circumference (all p <.01). No difference was observed between groups for CRP or IL-6 at 3 or 12 months; however, improvements in diet were observed in the intervention group compared to the control group (p = .02) at 3 months but were not sustained at 12 months. Although the intervention was not successful at reducing levels of CRP or IL-6, a significant decrease was observed in DII score for the intervention group, indicating short-term positive dietary change.

Patient-reported and clinician-reported chemotherapy-induced peripheral neuropathy in patients with early breast cancer: Current clinical practice.

BACKGROUND: In the current study, the authors investigated the incidence of moderate to severe chemotherapy-induced peripheral neuropathy (CIPN) for chemotherapy regimens commonly used in current clinical practice for the treatment of patients with early breast cancer. Patient-reported and clinician-assessed CIPN severity scores were compared, and risk factors for CIPN severity were identified. METHODS: Patients completed a Patient-Reported Symptom Monitoring form and oncologists completed a Common Terminology Criteria for Adverse Events form. CIPN reports were collected prospectively during regularly scheduled infusion visits throughout the duration of chemotherapy. RESULTS: The sample included 184 women with a mean age of 55 years; approximately 73% were white. The 4 chemotherapy regimens used were doxorubicin and cyclophosphamide plus paclitaxel (60 patients); docetaxel and cyclophosphamide (50 patients); docetaxel, carboplatin, and anti-human epidermal growth factor receptor 2 (HER2) (24 patients); and doxorubicin and cyclophosphamide plus paclitaxel and carboplatin (18 patients). All patients treated with doxorubicin and cyclophosphamide plus paclitaxel and doxorubicin and cyclophosphamide plus paclitaxel and carboplatin received paclitaxel; all patients treated with docetaxel and cyclophosphamide and docetaxel, carboplatin, and anti-HER2 received docetaxel. The chemotherapy dose was reduced in 52 patients (28%); in 15 patients (29%), this reduction was due to CIPN. Chemotherapy was discontinued in 26 patients (14%), 8 because of CIPN. Agreement between patient-reported and clinician-assessed CIPN severity scores was minimal (weighted Cohen kappa, P = .34). Patient-reported moderate to severe CIPN was higher for paclitaxel (50%) compared with docetaxel (17.7%) (P < .001). Pretreatment arthritis and/or rheumatism (relative risk [RR], 1.58; 95% CI, 1.06-2.35 [P = .023]) and regimens containing paclitaxel (RR, 2.88; 95% CI, 1.72-4.83 [P < .0001]) were associated with higher CIPN severity. Being married (RR, 0.57; 95% CI, 0.37-0.887 [P = .01]) was found to be associated with lower CIPN severity. CONCLUSIONS: The discrepancy between patient-reported and clinician-assessed CIPN underscores the need for both patient and clinician perspectives regarding this common, dose-limiting, and potentially disabling side effect of chemotherapy.

Patient-Reported Toxicities During Chemotherapy Regimens in Current Clinical Practice for Early Breast Cancer.

BACKGROUND: This study explores the incidence of patient-reported major toxicity-symptoms rated "moderate," "severe," or "very severe"-for chemotherapy regimens commonly used in early breast cancer. PATIENTS AND METHODS: Female patients aged 21 years or older completed a validated Patient-Reported Symptom Monitoring instrument and rated 17 symptoms throughout adjuvant or neoadjuvant chemotherapy. Fisher's exact tests compared differences in percentages in symptom ratings, and general linear regression was used to model the incidence of patient-reported major toxicity. RESULTS: In 152 patients, the mean age was 54 years (range, 24-77), and 112 (74%) were white; 51% received an anthracycline-based regimen. The proportion of patients rating fatigue, constipation, myalgia, diarrhea, nausea, peripheral neuropathy, and swelling of arms or legs as a major toxicity at any time during chemotherapy varied significantly among four chemotherapy regimens (p < .05). The mean (SD) number of symptoms rated major toxicities was 6.3 (3.6) for anthracycline-based and 4.4 (3.5) for non-anthracycline-based regimens (p = .001; possible range, 0-17 symptoms). Baseline higher body mass index (p = .03), patient-reported Karnofsky performance status ≤80 (p = .0003), and anthracycline-based regimens (p = .0003) were associated with greater total number of symptoms rated major toxicities (alternative model: chemotherapy duration, p < .0001). Twenty-six percent of dose reductions (26 of 40), 75% of hospitalizations (15 of 20), and 94% of treatment discontinuations (15 of 16) were in anthracycline-based regimens. CONCLUSION: Capturing multiple toxicity outcomes throughout chemotherapy enables oncologists and patients to understand the range of side effects as they discuss treatment efficacies. Continuous symptom monitoring may aid in the timely development of interventions that minimize toxicity and improve outcomes. IMPLICATIONS FOR PRACTICE: This study investigated patient-reported toxicities for 17 symptoms recorded prospectively during adjuvant and neoadjuvant chemotherapy regimens for early breast cancer. An analysis of four commonly used chemotherapy regimens identified significant differences among regimens in both individual symptoms and total number of symptoms rated moderate, severe, or very severe. Longer chemotherapy regimens, such as anthracycline-based regimens followed by paclitaxel, had higher proportions of symptoms rated major toxicities. The inclusion of patient perspectives on multiple toxicity outcomes at the same time at multiple time points during chemotherapy has the potential for improving patient-provider communication regarding symptom management, patient satisfaction, and long-term clinical outcomes.

Associations of functional, psychosocial, medical, and socio-demographic factors with cognitive screening in chemotherapy naïve patients with breast cancer.

OBJECTIVE: To describe associations of functional, psychosocial, medical, and socio-demographic factors with performance on a cognitive screening test in chemotherapy naïve patients with breast cancer. METHODS: Women with breast cancer were recruited between 2009 and 2018. The Blessed Orientation Memory Concentration Test (BOMC) was administered prior to chemotherapy. Associations between baseline BOMC and functional (Karnofsky Self-Reported Performance Rating Scale (KPS), Time Up and Go Test (TUG), Medical Outcomes Study (MOS) Physical Function, Instrumental Activities of Daily Living (IADL)), psychosocial (Mental Health Inventory-13, MOS Social Activity Limitation and Social Support Survey), medical, and socio-demographic variables were assessed using linear regression analysis. RESULTS: In a sample of 331 women with breast cancer, the mean age was 65.2 years and 68.6% were 65 and older. Mean BOMC score was 3.60 on a scale from 0 (best) to 28 (worst). After controlling for demographic factors, worse BOMC screening test results were associated with KPS < 80 (P = 0.01), IADL<14 (P = 0.02), TUG ≥14 seconds (P = 0.001), worse MOS Physical Function (P = 0.0006), depressive symptoms (P = 0.04), and social activity limitations (P = 0.01). CONCLUSION: In a sample of women with breast cancer, pre-treatment cognitive screening scores did not reveal profound cognitive impairment. BOMC screening scores were associated with multiple measures of physical function, but further research is needed to determine a clinically meaningful cut point in the BOMC for screening of cancer-related cognitive impairment.

Impact of dietary protein intake and obesity on lean mass in middle-aged individuals after a 12-year follow-up: the Korean Genome and Epidemiology Study (KoGES).

The present study investigated the association between protein intake and lean mass according to obesity status over a 12-year period. Data on 4412 participants aged 40-69 years were obtained from the Korean Genome and Epidemiology Study. The usual dietary protein intake of these participants was assessed at baseline using a semi-quantitative FFQ. Body composition was measured using bioelectrical impedance analysis at baseline and after a 12-year follow-up. Linear mixed-effects models were used to examine the associations between lean mass after a 12-year follow-up and protein intake at baseline. After adjusting for covariates and lean mass at baseline, comparisons between the highest and lowest tertiles revealed that dietary protein intake was positively associated with lean mass in both men (ß = 0·79, P = 0·001) and women (ß = 0·28, P = 0·082) after the 12-year period; however, those differences were attenuated after additional adjustment for fat mass at baseline and were stronger in the normal-weight group (men, ß = 0·85, P = 0·002; women, ß = 0·97, P < 0·001) but were not detected in the obese group. In the obese group, age (men, ß = 4·08, P < 0·001; women, ß = 2·61, P < 0·001) and regular physical activity (men, ß = 0·88, P = 0·054; women, ß = 0·76, P < 0·001) were significantly associated with lean mass after 12 years of follow-up. The results of the present study showed that protein intake may contribute to the prevention of ageing-related lean mass loss; however, the impact of this intake may vary depending on obesity status. Therefore, the maintenance of a healthy body weight during ageing through enhanced protein intake is likely to confer health benefits.