Pragmatic design and inclusion of patient-partner representatives improves participant experience in clinical research.

Objectives: Patient engagement in the design and implementation of clinical trials is necessary to ensure that the research is relevant and responsive to patients. The PREP-IT trials, which include 2 pragmatic trials that evaluate different surgical preparation solutions in orthopaedic trauma patients, followed the patient-centered outcomes research (PCOR) methodology throughout the design, implementation, and conduct. We conducted a substudy within the PREP-IT trials to explore participants' experiences with trial participation. Methods: At the final follow-up visit (12 months after their fracture), patients participating in the PREP-IT trials were invited to participate in the substudy. After providing informed consent, participants completed a questionnaire that asked about their experience and satisfaction with participating in the PREP-IT trials. Descriptive statistics are used to report the findings. Results: Four hundred two participants participated in the substudy. Most participants (394 [98%]) reported a positive experience, and 376 (94%) participants felt their contributions were appreciated. The primary reasons for participation were helping future patients with fracture (279 [69%]) and to contribute to science (223 [56%]). Two hundred seventeen (46%) participants indicated that their decision to participate was influenced by the minimal time commitment. Conclusions: Most participants reported a positive experience with participating in the PREP-IT trials. Altruism was the largest motivator for participating in this research. Approximately half of the participants indicated that the pragmatic, low-participant burden design of the trial influenced their decision to participate. Meaningful patient engagement, a pragmatic, and low-burden protocol led to high levels of participant satisfaction.

Targeted Glioblastoma Treatment via Synthesis and Functionalization of Gold Nanoparticles With De Novo-Engineered Transferrin-Like Peptides: Protocol for a Novel Method.

BACKGROUND: Glioblastoma multiforme (GBM) is an aggressive brain tumor with limited treatment options due to the blood-brain barrier's (BBB's) impedance and inherent resistance to chemotherapy. Gold nanoparticles (AuNPs) functionalized with transferrin-like peptides show promise in overcoming these challenges, enhancing drug delivery to the brain, and reducing chemotherapy resistance. OBJECTIVE: The primary goal of this study is to establish a detailed protocol for synthesizing and stabilizing AuNPs, functionalizing them with de novo-engineered transferrin-like peptides, and conjugating them with the chemotherapeutic agent temozolomide. This strategy aims to improve drug delivery across the BBB and circumvent chemotherapy resistance. The secondary objective includes an assessment of the safety and potential for in vivo use of the synthesized nanoparticle complex. METHODS: The proposal involves multiple steps with rigorous quality control of AuNP synthesis, stabilization with surfactants, and polyethylene glycol coating. The engineered transferrin-like peptides will be synthesized and attached to the AuNPs' surface, followed by the attachment of temozolomide and O6-methylguanine-DNA methyltransferase inhibitors. The resulting complex will undergo in vitro testing to assess BBB penetration, efficacy against GBM cells, and potential toxicity. RESULTS: Initial preliminary experiments and simulations suggest successful synthesis and stabilization of AuNPs and effective attachment of transferrin-like peptides. We propose peptide attachment verification using Fourier transform infrared spectroscopy and surface plasmon resonance. Additionally, we will conduct pH stability tests to ensure our functionalized AuNPs retain their properties in acidic brain tumor microenvironments. CONCLUSIONS: The proposed functionalization of AuNPs with de novo-engineered transferrin-like peptides represents a novel approach to GBM treatment. Our strategy opens new avenues for drug delivery across the BBB and chemotherapy resistance reduction. While we primarily focus on in vitro studies and computational modeling at this stage, successful completion will lead to further development, including in vivo studies and nanoparticle design optimization. This proposal anticipates inspiring future research and funding in neuro-oncology, presenting a potentially innovative and effective treatment option for GBM. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/49417.

Research in the USA on COVID-19's long-term effects: measures needed to ensure black, indigenous and Latinx communities are not left behind.

The SARS-CoV-2 (COVID-19) pandemic continues to expose underlying inequities in healthcare for black, indigenous and Latinx communities in the USA. The gaps in equitable care for communities of colour transcend the diagnosis, treatment and vaccinations related to COVID-19. We are experiencing a continued gap across racial and socioeconomic lines for those who suffer prolonged effects of COVID-19, also known as 'Long COVID-19'. What we know about the treatment for Long COVID-19 so far is that it is complex, requires a multidisciplinary approach and there is still much research needed to fully understand the effects. In this paper, we discuss pragmatic considerations for including affected communities, relevant stakeholders, and leaders from communities of colour in the planning and implementation of Long COVID-19 research.

Epidemiological profile of dog attacks to patients under 14 years old assisted at the pediatric referral emergency unit of a tertiary hospital in Campinas, Brazil.

Introduction: Accidents involving dog attacks are very common, which makes this type of accident a global public health issue. The estimates point to 20% of the victims of such accidents seeking care in health units, and half of them being children. In addition to acute injuries, dog attacks might result in fractures, infections, scars, and psychological traumas. This study aimed to describe the epidemiological profile of dog attacks to children under 14 years old assisted in a pediatric emergency service in Brazil. Methods: The database of the Information and Toxicological Assistance Center of Campinas was surveyed to identify cases of children under 14 years old assisted after a dog attack in a 9-years period. Demographic data, number and type of lesions, type of exposure, part of the body affected, dog origin and condition, and the accident location and cause were analyzed. The data were presented in a descriptive way, and the age groups were classified as follows: 0-3 years old, 4-6 years old, and 7-14 years old. The different age groups were compared one to another regarding the markers evaluated using the chi-square test and the Fisher's exact test. A 0.05 alpha was adopted in all analyses. Results: The number of children assisted in the study period totaled 1,012. The 7-14-year-old group was the most affected (n = 498; 49.2%), male patients were also majority (n = 660; 65.2%). Most injuries were found on the head/neck area (n = 378; 37.4%). However, the older the patients were, the higher the frequency of lesions on upper and lower limbs was, as well as attacks occurred in external environments, thus involving animals that could not be observed. A significant increase in accidents with provoked causes was observed in younger patients. Conclusion: Accidents involving dog attacks are more likely to happen among boys. Younger children run higher risks of becoming victims of these accidents inside homes, being attacked by pets, and showing a greater incidence of head and neck lesions. Older children present more injuries on their limbs, which are caused by dogs that cannot be observed.

Storytelling training to promote stakeholder engagement in research dissemination.

Storytelling is increasingly recognized as a culturally relevant, human-centered strategy and has been linked to improvements in health knowledge, behavior, and outcomes. The Community Engagement Program of the Johns Hopkins Institute for Clinical and Translational Research designed and implemented a storytelling training program as a potentially versatile approach to promote stakeholder engagement. Data collected from multiple sources, including participant ratings, responses to open-ended questions, and field notes, consistently pointed to high-level satisfaction and acceptability of the program. As a next step, the storytelling training process and its impact need to be further investigated.

Developing patient-centered outcomes research infrastructure in a rural community through patient and stakeholder engagement and education during the COVID-19 pandemic.

In addition to facing numerous healthcare disparities, rural America is chronically underrepresented in clinical research. This gap was made more evident during the COVID-19 pandemic. St Lawrence Health, located in rural Upstate New York, established its Clinical and Rural Health Research Department in 2015 to help close this gap. The research department then launched the DISRUPTS (Developing InfraStructure for Research to Utilize Patient-centered Techniques at St Lawrence Health System) program to build the infrastructure to conduct Patient-Centered Outcomes Research (PCOR). Together with a diverse committee, the team used proven methods and frameworks to develop a model for engagement, content creation, and education delivery that was successfully used to create educational programs on PCOR and COVID-19. The resulting DISRUPTS webinars had a combined total of over 450 live attendees and over 1,110 views on recordings. Furthermore, nearly one-third of those who participated in the COVID-19 vaccines webinar indicated they were more likely to receive a COVID-19 vaccine after taking part. DISRUPTS can serve as an important model for other rural communities that aim to increase access to and engagement in PCOR, and which hope to improve outreach and education efforts in their communities.

Pragmatic patient engagement in designing pragmatic oncology clinical trials.

Oncology trials are the cornerstone of effective and safe therapeutic discoveries. However, there is increasing demand for pragmatism and patient engagement in the design, implementation and dissemination of oncology trials. Many researchers are uncertain about making trials more practical and even less knowledgeable about how to meaningfully engage patients without compromising scientific rigor to meet regulatory requirements. The present work provides practical guidance for addressing both pragmaticism and meaningful patient engagement. Applying evidence-based approaches like PRECIS-2-tool and the 10-Step Engagement Framework offer practical guidance to make future trials in oncology truly pragmatic and patient-centered. Consequently, such patient-centered trials have improved participation, faster recruitment and greater retention, and uptake of innovative technologies in community-based care.

Implementing stakeholder engagement to explore alternative models of consent: An example from the PREP-IT trials.

INTRODUCTION: Cluster randomized crossover trials are often faced with a dilemma when selecting an optimal model of consent, as the traditional model of obtaining informed consent from participant's before initiating any trial related activities may not be suitable. We describe our experience of engaging patient advisors to identify an optimal model of consent for the PREP-IT trials. This paper also examines surrogate measures of success for the selected model of consent. METHODS: The PREP-IT program consists of two multi-center cluster randomized crossover trials that engaged patient advisors to determine an optimal model of consent. Patient advisors and stakeholders met regularly and reached consensus on decisions related to the trial design including the model for consent. Patient advisors provided valuable insight on how key decisions on trial design and conduct would be received by participants and the impact these decisions will have. RESULTS: Patient advisors, together with stakeholders, reviewed the pros and cons and the requirements for the traditional model of consent, deferred consent, and waiver of consent. Collectively, they agreed upon a deferred consent model, in which patients may be approached for consent after their fracture surgery and prior to data collection. The consent rate in PREP-IT is 80.7%, and 0.67% of participants have withdrawn consent for participation. DISCUSSION: Involvement of patient advisors in the development of an optimal model of consent has been successful. Engagement of patient advisors is recommended for other large trials where the traditional model of consent may not be optimal.

Nucleophilic Neutralization of Organophosphates: Lack of Selectivity or Plenty of Versatility?

Neutralization of organophosphates is an issue of public health and safety, involving agrochemicals and chemical warfare. A promising approach is the nucleophilic neutralization, scope of this review, which focuses on the molecular nucleophiles: hydroxide, imidazole derivatives, alpha nucleophiles, amines and other nucleophiles. A reactivity mapping is given correlating the pathways and reaction efficiency with structural dependence of the nucleophile (basicity) and the organophosphate (electrophilic centers, P=O/P=S shift, leaving and non-leaving group). Reactions extremely unfavorable (>20 years) can be reduced to seconds with various nucleophiles, some which are catalytic. Although there is no universal nucleophile, a lack of selectivity in some cases accounts for plenty of versatility in other reactions. The ideal neutralization requires a solid mechanistic understanding, together with balancing factors such as milder conditions, fast process, selectivity and less toxic products.

Patient and Provider Acceptability of a Patient Preauthorized Concealed Opioid Reduction.

OBJECTIVE: Limited research of how to best taper opioids brings about an ethical and clinical dilemma. Experiments using overt and concealed administration of opioids have demonstrated the benefits of a concealed reduction to eliminate negative expectations and prolong analgesic benefits. This may allow for opioid tapering without significant increases in pain. Based on this, we investigated patient and provider acceptance of a concealed opioid reduction for chronic pain. METHODS: We conducted a cross-sectional survey via REDcap with 74 patients, who are currently taking or have taken high dose opioids, and 49 providers using a validated questionnaire based on two hypothetical clinical trials comparing a patient preauthorized concealed opioid reduction vs standard tapering. RESULTS: We found that patients and providers have positive attitudes toward a concealed reduction of opioid dosages. More than 60% of providers and patients surveyed viewed the hypothetical clinical trial as helpful to reduce pain, side effects, and withdrawal symptoms. Sixty-one percent of patients and 77.6% of providers recognized that there would be differences in pain relief depending upon which group the hypothetical participants would be enrolled in. CONCLUSIONS: Patients and providers appear to understand the benefits of a concealed opioid reduction. Our findings support future randomized controlled trials that compare concealed and overt opioid tapering in patients with chronic pain. More research is needed to understand the difference in attitudes between research and clinical practice and to test the acceptability of a concealed reduction following a participation in an active clinical trial.

Analysis of oral health conditions and risk factors for dental caries in patients with sickle cell disease / Condições de saúde bucal e análise de fatores de risco de cárie dentária de pacientes portadores de doença falciforme

ABSTRACT Objective: To analyze the oral health conditions and risk factors for caries in patients with sickle cell disease. Methods: An observational, cross-sectional study was conducted in the clinic of the Association of Persons with Hemoglobinopathies of Alagoas, in the city of Maceió-AL, Brazil. The sample composed of 43 patients were included by census sampling. The ICDAS/DMFT/dmf-t caries indices were used, and simplified oral hygiene, salivary flow and buffer capacity tests were performed. Patients were interviewed to check their level of knowledge about oral hygiene and diet. Spearman correlation and ANOVA statistical tests were applied (p<0.05). Results: The mean DMFT was 15.49±4.43; oral hygiene regular (IHOS=2.22±0.18); mean salivary flow 0.92±0.26, and mean buffer capacity 4.60±0.32. Correlation was found between salivary flow and buffer capacity (p = 0.009). Patients with the highest caries prevalence, in the age-ranges 6 to 12, and 20 to 26 years, had the lowest buffer capacity values (p = 0.04). Interviews showed that 58% did not use dental floss, 88% consumed cariogenic snacks, 100% reported never having received guidance from dentists about the cariogenic potential of foods and 60% reported the use of anticholinergic medications to reduce drooling (Tramal® and morphine) during pain crises. Conclusion: These patients presented extremely high caries prevalence, with predominance of carious teeth. The salivary parameters analyzed and level of knowledge about oral hygiene and cariogenic diet presented, showed that patients with sickle cell disease belonged to a group with risk for development of dental caries.

RESUMO Objetivo: Analisar as condições de saúde bucal e fatores de risco de cárie de pacientes com doença falciforme. Métodos: A pesquisa observacional e transversal foi realizada na Associação de Pessoas com Hemoglobinopatias de Alagoas situada na cidade de Maceió-AL. Amostra composta por 43 pacientes incluídos por amostragem censitária. Foram utilizados os índices de cárie ICDAS/CPOD/ceod e de higiene oral simplificado, testes de fluxo salivar e capacidade tampão. Os pacientes foram entrevistados para a verificação do nível de conhecimento sobre higiene bucal e dieta. Foram aplicados os testes de correlação de Spearman e ANOVA (p<0,05). Resultados: O CPOD médio foi de 15,49±4,43, higiene oral regular (IHOS=2,22±0,18), fluxo salivar médio de 0,92±0,26 e capacidade tampão média de 4,60±0,32. Existiu correlação entre o fluxo salivar e capacidade tampão (p= 0,009). Os pacientes com maiores prevalências de cárie, nas faixas etárias de 6 a 12 anos e 20 a 26 anos, possuíam os mais baixos valores de capacidade tampão (p= 0,04). A entrevista mostrou que 58% não utilizavam fio dental, 88% lanchavam alimentos cariogênicos, 100% relataram nunca ter recebido orientações do cirurgião dentista sobre o potencial cariogênico dos alimentos e 60% relataram que utilizavam medicamentos redutores de salivação (Tramal® e morfina) durante as crises álgicas. Conclusão: Os pacientes apresentaram uma prevalência de cárie muito alta, com a predominância de dentes cariados. Os parâmetros salivares analisados e o nível de conhecimento, sobre higiene bucal e dieta cariogênica apresentados, mostraram que pacientes com doença falciforme pertencem a um grupo de risco de desenvolvimento de cárie dentária.

Perfil epidemiológico de puérperas com quadro de depressão pós-parto em unidades de saúde de um município da Serra Catarinense, SC / Epidemiological profile of puerperal patients with postpartum depression in health units of a city in the Santa Catarina mountain range

Introdução: Foi realizada uma pesquisa acerca do perfil epidemiológico de depressão pós-parto em um município de médio porte da Serra Catarinense, SC. Teve como principal objetivo traçar e analisar o perfil epidemiológico da população de puérperas atendidas pelas Unidades de Saúde pesquisadas. É uma patologia que pode comprometer os cuidados da mulher consigo mesma e com o recém-nascido, implicando em vários aspectos psicossociais entre mãe e bebê. A prevalência de depressão pós-parto parece variar tanto em números quanto em apresentação dos sintomas de acordo com as diferentes populações. Metodologia: A pesquisa deu-se por corte transversal dos dados obtidos através da aplicação da Escala de Depressão Pós-natal de Edimburgo, de um questionário estruturado e análise das informações encontradas nas pacientes puérperas atendidas pelas unidades pesquisadas. Foram incluídas na pesquisa pacientes que tiverem dado a luz em um período menor ou igual a 6 meses, de qualquer faixa etária e que sejam atendidas pelas Unidades de Saúde pesquisadas durante o período da coleta de dados. Resultados: Os resultados foram obtidos a partir de uma amostra de 40 entrevistas feitas em três unidades de saúde. A prevalência de possíveis diagnósticos de depressão pós-parto foi de 40%, e os principais fatores relacionados foram tabagismo, nível elevado de estresse e má relação com o pai da criança. Sugerem-se novas pesquisas com mais sujeitos e maior tempo de amostragem para que mais diferenças significativas possam ser examinadas (AU)

Introduction: A survey was carried out on the epidemiological profile of postpartum depression in a medium-sized city of the Santa Catarina mountain range. Its main aim was to find and analyze the epidemiological profile of the population of puerperal patients seen at the Health Units surveyed. Postpartum depression is a disorder that can compromise the mother's care with herself and the newborn, implying in several psychosocial aspects between mother and baby. The prevalence of postpartum depression seems to vary both in numbers and in the presentation of symptoms according to the different populations. Methods: A cross-sectional study of the obtained data was performed by administering the Edinburgh Postnatal Depression Scale and a structured questionnaire, and by analyzing the information from the puerperal patients visiting the units surveyed. Included in the study were patients who had given birth within a period of less than or equal to 6 months of any age group and who were seen at the Health Units surveyed during the data collection period. Results: The results were obtained from a sample of 40 interviews carried out in three health units. The prevalence of possible diagnoses of postpartum depression was 40% and the main related factors were smoking, high stress level, and poor relation with the child's father. Further research with more subjects and longer sampling time is suggested so that more significant differences can be examined (AU)

Supramolecular phosphate transfer catalysis by pillar[5]arene.

A kinetic study on dinitrophenylphosphate monoester hydrolysis in the presence of a cationic pillararene, P5A, has been carried out. Formation of the supramolecular complex between phosphate ester and P5A has been studied by NMR showing complexation-induced upfield proton shifts indicative of aromatic ring inclusion in the pillararene cavity. Molecular dynamic calculations allow structure characterization for the 1 : 1 and 1 : 2 complexes. As a result of the supramolecular interaction both the acidity of DNPP and its hydrolysis rate constants are increased. Catalysis results from combination of both electrostatic stabilization reducing the negative electron density on the PO3(=) oxygens and monoester dianion destabilization by the steric effects of close NMe3(+) groups hindering the hydrogen-bonding with water and destabilising the monoester dianion.

Atlas culinário da literatura brasileira: alimentação e cultura / Culinary atlas of brazilian literature: food and culture

Introdução: Acredita-se que pensar a alimentação e seu aspecto cultural no território brasileiro, como salienta a Política Nacional de Alimentação e Nutrição, possa ser uma tarefa apoiada pela literatura. Pensar na literatura a partir do geoespaço pode fornecer uma reflexão sobre a alimentação no território brasileiro. Objetivo: Analisar a relação entre território e alimentação em obras da Literatura brasileira. Métodos: A metodologia foi elaborada em três fases: (1) explorar as obras para ordená-las no mapa; (2) sintetizar essa literatura em cada mancha; e, (3) produzir uma reflexão sobre o que essa literatura expressa com relação a alimentação no território brasileiro. Resultados: Foram mapeados um total de 28 autores. Desses, conseguiu-se identificar 47 obras de interesse. Elencam-se, a partir delas, características para cada uma das manchas propostas a priori: (1) na culinária da "Costa" litorânea uma tendência à abertura para inovação, influências que chegavam via mar, sendo também fortemente marcada injustiças, geradas por séculos pelos latifúndios da monocultura; (2) na culinária do "Recôncavo baiano" um protagonismo de enfrentamentos culturais históricos, bem como da fome, fruto desta intensa cultura de subjugação e dominação; (3) na culinária "Caipira" a expressão de uma geoculinária indoors dos comedores familiares, com seus conflitos protagonizados em cena; (4) na culinária "Amazônica" o remanescente do homem que com a natureza coabita e dela extrai seu meio de vida, utilizando-a integralmente; (5) na culinária "Meridional", representada por uma longa faixa de terra, com expressões intensamente heterogêneas, da fome à abundância. Conclusão: Percebeu-se que sete manchas expressariam melhor o componente cultural alimentar no território, o quanto os autores expressam de seu território em suas produções artísticas, o que levanta o tópico das cartografias imaginárias e/ou heterotopias. Além disso, fala-se de uma geoculinária literária que pode auxiliar na tarefa de promover alimentação adequada e saudável (AU).

Introduction: It is believed that thinking about food and its cultural aspect in Brazilian territory, as highlighted by the National Food and Nutrition Policy, can be a task supported by literature. Thinking about literature from geospatial can provide a reflection on the food in the Brazilian territory. Objective: The objective of this research is to analyze the relationship between territory and food in works of Brazilian Literature. Methods: For this was thought of in three phases: (1) explore the works to order them on the map; (2) synthesize this literature in each spot; And, (3) produce a reflection on what this literature expresses about food in Brazilian territory. Results: A total of 28 authors were mapped as results. Of these, 47 works of interest were mapped. The characteristics of each of the spots proposed a priori are listed: (1) in Costa cuisine a tendency towards openness to innovation, influences that came via sea, and also marked injustices, generated for centuries by the latifundia of the Monoculture; (2) in the cuisine of the Recôncavo a protagonism of historical cultural confrontations, as well as hunger, fruit of this intense culture of subjugation and domination; (3) in the Caipira cuisine the expression of a geoculinary indoors of the family eaters, with their conflicts staged on the scene; (4) in the Amazonian cuisine the remnant of the man who cohabits with nature and from it extracts his way of life, using it integrally; (5) in southern cuisine, represented by a long strip of land, with intensely heterogeneous expressions, from hunger to abundance. Conclusion: It was noticed that seven spots would better express the food cultural component in the territory, as the authors express of their territory in their artistic productions, which raises the topic of imaginary and/or heterotopian cartographies. In addition, there is talk of a literary geoculinary that can assist in the task of promoting adequate and healthy food (AU).

Randomized, double-blind, placebo-controlled, multicenter phase II study of the efficacy and safety of apricoxib in combination with either docetaxel or pemetrexed in patients with biomarker-selected non-small-cell lung cancer.

PURPOSE: Overexpression of COX-2 correlates with advanced stage and worse outcomes in non-small-cell lung cancer (NSCLC), possibly as a result of elevated levels of COX-2-dependent prostaglandin E2 (PGE2). Exploratory analyses of studies that used COX-2 inhibitors have demonstrated potentially superior outcome in patients in whom the urinary metabolite of PGE2 (PGE-M) is suppressed. We hypothesized that patients with disease defined by PGE-M suppression would benefit from the addition of apricoxib to second-line docetaxel or pemetrexed. PATIENTS AND METHODS: Patients with NSCLC who had disease progression after one line of platinum-based therapy, performance status of 0 to 2, and normal organ function were potentially eligible. Only patients with a ≥ 50% decrease in urinary PGE-M after 5 days of treatment with apricoxib could enroll. Docetaxel 75 mg/m(2) or pemetrexed 500 mg/m(2) once every 21 days per the investigator was administered with apricoxib or placebo 400 mg once per day. The primary end point was progression-free survival (PFS). Exploratory analysis was performed regarding baseline urinary PGE-M and outcomes. RESULTS: In all, 101 patients completed screening, and 72 of the 80 who demonstrated ≥ 50% suppression were randomly assigned to apricoxib or placebo. Toxicity was similar between the arms. No improvement in PFS was seen with apricoxib versus placebo. The median PFS for the control arm was 97 days (95% CI, 52 to 193 days) versus 85 days (95% CI, 67 to 142 days) for the experimental arm (P = .91). CONCLUSION: Apricoxib did not improve PFS, despite biomarker-driven patient selection.

Chemotherapy dose reduction due to chemotherapy induced peripheral neuropathy in breast cancer patients receiving chemotherapy in the neoadjuvant or adjuvant settings: a single-center experience.

PURPOSE: Taxanes are a cornerstone treatment in early and advanced stage breast cancer and in other common solid tumor malignancies; however, the development of chemotherapy induced peripheral neuropathy (CIPN) often necessitates dose-reduction, which may hamper the effectiveness of the drug and compromise survival outcomes especially when used in the adjuvant setting. Limited literature is available on the prevalence and severity of dose reduction due to CIPN. We sought to determine the frequency and severity of CIPN-induced dose reduction in early stage breast cancer patients who received taxane-based chemotherapy in the neoadjuvant or adjuvant settings. METHODS: We conducted a retrospective single-institution breast cancer clinic chart review of 123 newly diagnosed breast cancer patients and treated with taxane-based neoadjuvant/adjuvant chemotherapy at the University of Maryland Greenebaum Cancer Center between January 2008 and December 2011. RESULTS: Forty-nine of 123 (40%; 95% CI: 31-49%) patients required dose reduction. Twenty-one (17%; 95% CI: 11-25%) of these patients were dose-reduced specifically due to CIPN that developed during treatment. The median relative dose intensity (received dose/planned dose) for the 21 CIPN-induced dose reduction patients was 73.4% (range, 68.0-94.0%). Patients with diabetes appeared to have a higher risk of taxane-induced dose reduction (p-value=0.01). African-American patients and those treated with paclitaxel (rather than docetaxel) experienced a higher-risk of CIPN-induced dose reduction (p-values are <0.001 and 0.001, respectively). CONCLUSIONS: The incidence of CIPN-associated dose reduction in our patient population was 17%. African-American patients, diabetics and subjects treated with paclitaxel had a higher risk for CIPN-associated dose reduction in our study.

A pilot study of acupuncture in treating bortezomib-induced peripheral neuropathy in patients with multiple myeloma.

BACKGROUND: Peripheral neuropathy is the dose limiting toxicity of bortezomib in patients with multiple myeloma (MM). OBJECTIVES: To examine the safety, feasibility and efficacy of acupuncture in reducing bortezomib-induced peripheral neuropathy (BIPN) symptoms. METHODS: Patients with MM experiencing persistent BIPN ≥grade 2 despite adequate medical intervention and discontinuation of bortezomib received 10 acupuncture treatments for 10 weeks (2×/week for 2 weeks, 1×/week for 4 weeks, and then biweekly for 4 weeks). Responses were assessed by the Clinical Total Neuropathy Score (TNSc), Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) questionnaire, and the Neuropathy Pain Scale (NPS). Repeated-measures analysis of variance was used to test for monotonic decline in scores on each of the measures. Serial serum levels of proinflammatory and neurotrophic cytokines were obtained at baseline and weeks 1, 2, 4, 8, and 14. RESULTS: Twenty-seven patients with MM were enrolled in the trial. There were no adverse events associated with the acupuncture treatments. TNSc data were deemed invalid and therefore were not reported. At weeks 10 and 14, FACT/GOG-Ntx and NPS showed significant reduction suggesting decreased pain, and improved function (P values were <.0001 for both FACT/GOG-Ntx and NPS at weeks 10 and 14). However, nerve conduction studies did not significantly change between baseline assessment and end of study. There was no correlation in serum cytokines for responders versus none responders. CONCLUSIONS: Acupuncture is safe, feasible and produces subjective improvements in patients' symptoms. A follow-up randomized controlled trial is warranted.

Patient-reported outcomes in women with breast cancer enrolled in a dual-center, double-blind, randomized controlled trial assessing the effect of acupuncture in reducing aromatase inhibitor-induced musculoskeletal symptoms.

BACKGROUND: Aromatase inhibitors (AIs) have been associated with decrements in patient-reported outcomes (PROs). The objective of this study was to assess whether real acupuncture (RA), compared with sham acupuncture (SA), improves PROs in patients with breast cancer who are receiving an adjuvant AI. METHODS: Postmenopausal women with a stage 0 through III breast cancer who received an AI and had treatment-associated musculoskeletal symptoms were randomized to receive 8 weekly RA versus SA in a dual-center, randomized controlled trial. The National Surgical Adjuvant Breast and Bowel Project (NSABP) menopausal symptoms questionnaire, the Center for Epidemiological Studies Depression (CESD) scale, the Hospital Anxiety and Depression Scale (HADS), the Pittsburgh Sleep Quality Index (PSQI), the hot flash daily diary, the Hot Flash-Related Daily Interference Scale (HFRDI), and the European quality-of-life survey (EuroQol) were used to assess PROs at baseline and at 4weeks, 8 weeks, and 12 weeks. RESULTS: The intention-to-treat analysis included 23 patients in the RA arm and 24 patients in the SA arm. There were no significant differences in baseline characteristics between the 2 groups. Compared with baseline, scores in the RA arm improved significantly at week 8 on the CESD (P = .022), hot flash severity (P = .006), hot flash frequency (P = .011), the HFRDI (P = .014), and NSABP menopausal symptoms (P = .022); scores in the SA arm improved significantly on the EuroQol (P = .022),the HFRDI (P = .043), and NSABP menopausal symptoms (P = .005). Post-hoc analysis indicated that African American patients (n = 9) benefited more from RA than SA compared with non-African American patients (n = 38) in reducing hot flash severity (P < .001) and frequency (P < .001) scores. CONCLUSIONS: Both RA and SA were associated with improvement in PROs among patients with breast cancer who were receiving AIs, and no significant difference was detected between arms. Racial differences in response to acupuncture warrant further study.