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Purpose: The purpose of this narrative review was to assess the limited literature on fetal anomalies diagnosed in the second trimester of pregnancy and parental decision-making and identify sources of information deemed as facilitators and barriers to medical decisions., Methods: This was a literature review of source material and information about fetal anomalies diagnosed in the second trimester of pregnancy, decision-making, decision tools or aids, and sources of information for anomalies. The search string used explored related peer-reviewed publications and systematic reviews between 2007 and 2024. We also reviewed references from publications meeting inclusion criteria. The search was conducted between June 2022 and February 2024. Exclusion criteria included conference abstracts, non-peer reviewed literature, and articles not available in English language. A total of 77 publications were identified by searching multiple databases using a predefined search string. The search encompassed full text articles from 2007 to 2024 and 11 full-text publications were ultimately included in the review. A list of 45 co-occurring keywords was generated from the included texts, with each keyword having a minimum of two co-occurrences., Results: Key themes identified included (1) the role of the clinician and need for development of professional knowledge and empathy surrounding discussion of fetal anomalies with patients; (2) information gathering, with individuals reporting use of multiple strategies to obtain information; while the majority found information satisfying, they preferred more details on diagnosis, long-term outcomes of the fetus/child and management of the pregnancy or termination process; and (3) decision-making, the path and process of how individuals made decisions about the pregnancy including quality of life, future fertility, and seeking other people's experiences., Conclusion: Many factors contribute to an individual's decision-making after a diagnosis of a fetal anomalies diagnosed in the second trimester of pregnancy, ranging from personal beliefs and goals to shared experiences of others and access to care. Understanding how sources of information may be deemed both as facilitators and barriers to different individuals during the decision-making process is important for healthcare providers in order to understand how to most effectively support patients. There is a dearth of information on training healthcare professionals to provide support to patients facing these decisions., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To examine processes, barriers, and facilitators to sperm banking counseling and decision-making for adolescent males newly diagnosed with cancer from the perspective of clinicians who completed Oncofertility communication training. We also identify opportunities for improvement to inform future interventions and implementation., Methods: A survey (N=104) and subsequent focus groups (N=15) were conducted with non-physician clinicians practicing in pediatric oncology who completed Oncofertility communication training., Results: Most survey participants were confident in communicating about the impact of cancer on fertility (n=87, 83.7%) and fertility preservation options (n=80, 76.9%). Most participants reported never/rarely using a sperm banking decision tool (n=70, 67.3%), although 98.1% (n=102) said a decision tool with a family-centered approach would be beneficial. Primary themes in the subsequent focus groups included variable processes/workflows (inconsistent approaches to consult initiation; involvement of adolescents, caregivers, and various clinician types; assessment of puberty/sexual experience), structural and psychosocial barriers (cost and logistics, developmental, cultural, clinical acuity/prognosis), and facilitators (educational materials, alternative options for banking). Opportunities and strategies for improvement (including fertility preservation in existing research protocols; additional staffing/resources; oncologist education and buy-in; and development of decision tools) were informed by challenges identified in the other themes., Conclusion: Barriers to adolescent sperm banking remain, even among clinicians who have completed Oncofertility training. Although training is one factor necessary to facilitate banking, structural and psychosocial barriers persist. Given the complexities of offering sperm banking to pediatric populations, continued efforts are needed to mitigate structural barriers and develop strategies to facilitate decision-making before childhood cancer treatment., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The metalloid arsenic (As) induces oxidative stress is a well-known fact. However, the extent of variation of oxidative stress according to different exposure levels of As in groundwater and the mechanism responsible for As mediated oxidative stress is yet to be elucidated in a human population of West Bengal. In the present study, we have investigated the impact of low level (> 10 ≤ 50 µg/L) and high-level groundwater As (> 50 µg/L) on cellular redox status, DNA damage, and repair mechanisms in chronically exposed rural women of West Bengal. Prediction models of ordinary least square regression of nail As, forced vital capacity (FVC) %, and that of forced expiratory volume during the first one second (FEV1) % deciphered that accumulation of As in nails may predict hemoglobin deficiency. Moreover, consumption of As-laced water tends to decrease FEV1% and FVC%. A strong positive correlation was observed between water and nail As level and reactive oxygen species (ROS) generation. ROS, perturbed nuclear factor erythroid 2-related factor 2(Nrf2)/ Kelch-like ECH-associated protein 1 (Keap1) redox regulation, compromised antioxidant defense machinery-superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione transferase (GST), induced DNA damage, and suppressed DNA repair proteins-poly ADP ribose polymerase1(PARP1)/ X-ray repair cross-complementing protein 1(XRCC1)/ 8-oxoguanine glycosylase (OGG1) in a dose-dependent manner. All the low and high As areas had very high cancer risk values for the exposed population. It has been predicted that if the As level in the drinking water of a 40-year adult increases by 2 ug/L, the likelihood of the cancer risk will increase by 10%, keeping the body weight and amount of water intake constant. Thus, long-term exposure to either low or high As is seriously affecting the lives of asymptomatic women who are vulnerable to developing carcinogenic changes after a period of latency., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Patients with a chronic disease are more vulnerable in the labor market, and work-related support in clinical care would enhance the timely support greatly needed in each phase of their working life. This paper describes the development of a generic stay-at-work intervention to provide work-related support in clinical care to patients with a chronic disease., Methods: Steps 1-4 of Intervention Mapping (IM) were combined with action research principles. A needs assessment (Step 1) involved the project group formation, a literature review, qualitative studies with healthcare professionals (HCPs; n = 9) and patients (n = 10), consultation with financial staff and testing, and resulted in objectives (Step 2). Guided by methods and applications (Step 3), the intervention was developed, tested and finalized (Step 4)., Results: The needs assessment revealed the importance of behavioral change in HCPs, including changing attitude, self-efficacy, and social influence. For that purpose, a pathway and training sessions were developed. Testing these unveiled the need for practical tools and intervision. The final intervention comprises a care pathway as part of working routines, including screening, risk stratification, and tailored support. Practical tools, training sessions, and intervision for HCPs were developed., Conclusions: Combining IM with action research principles resulted in a generic stay-at-work intervention in clinical care via behavioral change in HCPs. A generic care pathway, practical tools, training sessions, and intervision were developed. More specific alignment to specific patient groups is possible. To implement the intervention in another hospital, the local context, (financial) resources, and the national legislation should be considered., (© 2022. The Author(s).)

Comparative effectiveness of behavioral interventions to mitigate the impacts of degeneration-based cognitive decline is not well understood. To better address this gap, we summarize the studies from the Healthy Action to Benefit Independence & Thinking (HABIT®) program, developed for persons with mild cognitive impairment (pwMCI) and their partners. HABIT® includes memory compensation training, computerized cognitive training (CCT), yoga, patient and partner support groups, and wellness education. Studies cited include (i) a survey of clinical program completers to establish outcome priorities; (ii) a five-arm, multi-site cluster randomized, comparative effectiveness trial; (iii) and a three-arm ancillary study. PwMCI quality of life (QoL) was considered a high-priority outcome. Across datasets, findings suggest that quality of life was most affected in groups where wellness education was included and CCT withheld. Wellness education also had greater impact on mood than CCT. Yoga had a greater impact on memory-dependent functional status than support groups. Yoga was associated with better functional status and improved caregiver burden relative to wellness education. CCT had the greatest impact on cognition compared to yoga. Taken together, comparisons of groups of program components suggest that knowledge-based interventions like wellness education benefit patient well-being (e.g., QoL and mood). Skill-based interventions like yoga and memory compensation training aid the maintenance of functional status. Notably, better adherence produced better outcomes. Future personalized intervention approaches for pwMCI may include different combinations of behavioral strategies selected to optimize outcomes prioritized by patient values and preferences., (© 2022. The American Society for Experimental NeuroTherapeutics, Inc.)

The impact of chronic low-level groundwater arsenic (As) exposure [in the range above the WHO-recommended limit of 10 μg/L but ≤50 μg/L (permissible limit of As for many Asian countries)] was investigated for cross talk of inflammatory changes and expression of phagocytic receptors of exposed rural women (N, 45) from districts of 24 Parganas (south) and in matched control groups (N, 43) [As ≤10 μg/L] from the same district. Systemic inflammation was evident from the upregulated levels of pro-inflammatory mediators like tumor necrosis factor-α (TNF-α); interleukins (ILs) like IL-6, IL-8, and IL-12; and C-reactive protein (CRP) in the sera and upregulated expression of protein kinase B phosphorylated at ser473 (pAKTser473)/nuclear factor-κB (NF-κB)/TNF-α axis in the leukocytes of exposed women with respect to control. We found that low-dose As exposure apart from inflicting inflammation altered the expression of phagocytic receptors-Fcγ receptors (FcγRs) and complement receptors (CRs). The leukocytes of the low-As-exposed women exhibited suppression of CD64, CD35, and CD11b and increased expression of CD16 with respect to control. Groundwater As showed a negative correlation with CD64 expression on monocytes [Pearson's r, -0.8205; 95% confidence interval (CI), -0.8789 to -0.7379] and granulocytes [r, -0.7635; 95% CI, -0.8388 to -0.6595] and a positive correlation with CD16 on granulocytes [r, 0.8363; 95% CI, 0.7599 to 0.8899]. A negative correlation of groundwater As was also observed with expression of CD35 on granulocytes [r, -0.8780; 95% CI, -0.9185 to -0.8192] and monocytes [r, -0.7778; 95% CI, -0.8490 to -0.6790] and CD11b on monocytes [r, -0.6035; 95% CI, -0.7218 to -0.4511]. Therefore, it may be indicated that chronic low-level As exposure (11-50 μg/L) not only evoked chronic inflammatory changes but also suppressed the expression of FcγRs and CRs in the exposed women. This, in turn, may lead to susceptibility towards pathogenic infections or in long run may even contribute towards chronic inflammatory diseases including cancer.

Background: Accumulating evidence shows evidence of efficacy with the combination of vorinostat and bortezomib in solid tumors. We previously examined a once-daily continuous dosing schedule of vorinostat in combination with bortezomib which was well tolerated in cycles 1 and 2; however, there was concern regarding the tolerability through multiple cycles. This study was conducted to evaluate an intermittent dosing schedule of vorinostat with bortezomib., Methods: Vorinostat was initially administered orally twice daily on days 1-14 with bortezomib IV on days 1, 4, 8, and 11 of a 21 day cycle. Two DLTs (elevated ALT and fatigue) were observed at dose level 1, thus the protocol was amended to administer vorinostat intermittently twice daily on days 1-4 and 8-11., Results: 29 patients were enrolled; 13 men and 16 women. Common cancer types included sarcoma, pancreatic, colorectal, GIST, and breast. The most common Grade 3-4 toxicities at any dose level included thrombocytopenia, fatigue, increased ALT, elevated INR, and diarrhea. DLTs in the intermittent dosing scheduled included thrombocytopenia and fatigue. The Cmax and AUC for the intermittent dosing regimen were similar to those observed in the daily dosing. In this heavily pretreated population, stable disease was observed in patients with sarcoma, colorectal adenocarcinoma and GIST., Conclusions: The MTD was established at vorinostat 300 mg BID on days 1-4 and 8-11 and bortezomib 1.3 mg/m(2) IV on days 1, 4, 8, and 11 of a 21 day cycle. Tolerability was not improved with the intermittent dosing schedule of vorinostat when compared to continuous dosing.

Background: A phase I study to assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics (PK) and antitumor activity of vorinostat in combination with bortezomib in patients with advanced solid tumors., Methods: Patients received vorinostat orally once daily on days 1-14 and bortezomib intravenously on days 1, 4, 8 and 11 of a 21-day cycle. Starting dose (level 1) was vorinostat (400 mg) and bortezomib (0.7 mg/m(2)). Bortezomib dosing was increased using a standard phase I dose-escalation schema. PKs were evaluated during cycle 1., Results: Twenty-three patients received 57 cycles of treatment on four dose levels ranging from bortezomib 0.7 mg/m(2) to 1.5 mg/m(2). The MTD was established at vorinostat 400 mg daily and bortezomib 1.3 mg/m(2). DLTs consisted of grade 3 fatigue in three patients (1 mg/m(2),1.3 mg/m(2) and 1.5 mg/m(2)) and grade 3 hyponatremia in one patient (1.5 mg/m(2)). The most common grade 1/2 toxicities included nausea (60.9%), fatigue (34.8%), diaphoresis (34.8%), anorexia (30.4%) and constipation (26.1%). Objective partial responses were observed in one patient with NSCLC and in one patient with treatment-refractory soft tissue sarcoma. Bortezomib did not affect the PKs of vorinostat; however, the Cmax and AUC of the acid metabolite were significantly increased on day 2 compared with day 1., Conclusions: This combination was generally well-tolerated at doses that achieved clinical benefit. The MTD was established at vorinostat 400 mg daily × 14 days and bortezomib 1.3 mg/m(2) on days 1, 4, 8 and 11 of a 21-day cycle.

Purpose: To assess the safety, maximum-tolerated dose (MTD), and dose-limiting toxicities (DLT), of motexafin gadolinium (MGd), given in combination with doxorubicin, in patients with advanced solid tumors., Study Design: The combination of MGd and doxorubicin was administered every 28 days (cycle 1) and then every 21 days (subsequent cycles). The dose of MGd, given daily for 3 days, was escalated from 1.0 mg/kg/d to 3.3 mg/kg/d, while the dose of doxorubicin was held at 30 mg/m²., Results: Fifteen patients received 37 cycles of treatment, for a median of 2 cycles per patient (range 0-6 cycles). Three patients (20%) completed 6 cycles of therapy. The MTD was identified as MGd, 2 mg/kg/day and doxorubicin, 30 mg/m². Dose limiting toxicities included grade 3 hypertension, pneumonia, bacteremia, and elevated GGT. Serious adverse events also included pulmonary embolism and urinary tract infection requiring hospitalization. There was no exacerbation of cardiac toxicity. No patients attained a response to treatment. Six patients (54%) had stable disease. The median time to disease progression, or to last assessment, was 49 days (range 8-195 days)., Conclusions: The combination of MGd and doxorubicin was fairly well tolerated. However, due to emerging preclinical data suggesting that MGd inhibits ribonucleotide reductase, further development of the combination of MGd plus doxorubicin is not recommended.

Purpose: To assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), safety, and tolerability of MN-209, a novel vascular disrupting agent, in patients with advanced solid tumors., Study Design: MN-029 was administered weekly for three consecutive weeks out of four; two cycles were planned. Dose escalation proceeded by 100% per toxicity criteria. Intra-patient dose escalation was permitted., Results: Twenty patients received a total of 151 infusions of MN-029. No DLTs or grade 4 toxicities occurred. The most common adverse events were nausea, vomiting, arthralgias, and headache. One patient developed acute substernal chest pain 4 days after his first dose of MN-029 and was removed from the study. An MTD was not determined. The recommended phase II dose was identified as 180 mg/m(2)/week. One patient with advanced pancreatic cancer attained a partial response lasting 10 weeks., Conclusions: MN-029 was well tolerated in this schedule. Further development of this class of agents is warranted, especially in combination with other anti-cancer treatments.

Objective: To assess the efficacy and toxicity of the combination of interferon-alpha and doxycycline in patients with metastatic renal cell carcinoma and to assess the effect of this treatment on serum vascular endothelial growth factor (VEGF) levels., Patients and Methods: Seventeen patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and life expectancy greater than 4 months with radiologically evident advanced renal cell carcinoma were enrolled. Eight patients had prior nephrectomy and 10 patients were treated within 4 months of their diagnosis. Treatment consisted of interferon-alpha up to 9 million units subcutaneously three times per week and doxycycline 300 mg orally twice per day for weeks one and three of each four-week cycle. Toxicity was evaluated on a biweekly basis and response on a bimonthly basis. VEGF plasma levels were assessed monthly as a measure of potential antiangiogenic effect., Results: No objective responses were seen. The mean duration of study was 2.6 cycles (range: 0.8-6.0 cycles). Three patients (17%) tolerated therapy and displayed stable disease for greater than four months. Five patients withdrew from study before the first response evaluation. Ten patients experienced grade 2 gastrointestinal toxicity requiring dose reduction of doxycycline. Eight patients experienced grade 2 fatigue requiring dose reduction of interferon. VEGF plasma levels were initially suppressed in patients who demonstrated progressive disease but not in patients with stable disease., Conclusion: This regimen of doxycycline and interferon-alpha was not efficacious as treatment for renal cell carcinoma. Plasma VEGF levels were significantly decreased during the first two cycles of treatment, but this does not correlate with clinical outcome.

Background: This phase I study was conducted to determine maximal tolerated dose (MTD) and dose-limiting toxicities (DLT) in patients with advanced solid tumors treated with the polyamine analog N1, N14-diethylhomospermine (DEHSPM)., Methods: Patients were treated with DEHSPM administered as a subcutaneous (SC) injection daily for five consecutive days repeated every 4 weeks. Three dose levels were examined starting at 12.5 mg/m2/day, escalating to 37.5 mg/m2/day., Results: A total of 15 patients were enrolled. Dose limiting toxicities (grade 3 or 4) included nausea, vomiting, constipation, ileus, elevations of aspartate aminotransferase (AST) and alkaline phosphatase, hyperbilirubinemia, and ventricular bigeminy., Conclusion: DEHSPM given as a SC injection is overall well tolerated at lower doses, but significant toxicities were observed at the 37.5mg/m2/day dose level. MTD was established at 25 mg/m2/day but further investigation with this study drug is not recommended secondary to the potential for neurotoxicities and hepatic damage as a result of cumulative doses.

Objective: We conducted a phase II multicenter trial of perillyl alcohol in patients with advanced hormone refractory prostate cancer (HRPC). The primary endpoint was to evaluate the 6-month progression-free survival given the potential cytostatic nature of the drug. Secondary objectives included assessing acute and chronic toxicities, as well as measuring objective response rates., Methods: Patients with metastatic androgen-independent prostate cancer that failed at least one prior chemotherapeutic or experimental regimen were eligible. Perillyl alcohol was administered orally at 1200 mg/m2/dose four times daily and continued until disease progression or development of unacceptable toxicity., Results: Fifteen patients were eligible. Six patients received less than one cycle (4 weeks) of drug, four of which stopped because of drug intolerance. Only six patients received more than two cycles of therapy and were considered evaluable for response. Main toxicity included grade 1-2 gastrointestinal intolerance (nausea/vomiting in 60% of the patients) and fatigue (47%). One patient developed a grade 4 hypokalemia that was felt likely attributable to the drug. No objective responses were seen. All patients either progressed or withdrew from the study secondary to drug intolerance before the 6-month time period., Conclusion: Perillyl alcohol administered at this dose and formulation did not have any objective clinical activity in this patient population.

Purpose: The objectives of this trial were to assess the maximal tolerated dose and toxicity of the combination of oral eniluracil and 5-fluorouracil and intravenous gemcitabine., Patients and Methods: Patients with histologically confirmed, incurable malignancy (solid tumor or lymphoma) refractory to standard therapy or for which no standard therapy exists were enrolled. The treatment plan consisted of weekly gemcitabine for three weeks with twice daily dosing of 5-FU and eniluracil for 21 days beginning on day one of gemcitabine. Cycles repeated on an every four week schedule. The initial cohort received gemcitabine 800 mg/m2, oral 5-FU 0.6 mg/m2 and eniluracil 6.0 mg/m2., Results: Twenty-six patients were enrolled. Eight patients received less than 2 cycles of therapy. Hematologic and gastrointestinal toxicity predominated, with 48% of courses resulted in grade one or two neutropenia. Hematologic toxicity was dose limiting. One treatment related death occurred., Conclusions: The combination of eniluracil, 5-fluorouracil and gemcitabine offers an oral alternative for 5-FU administration. The recommended phase II dose is gemcitabine 1000 mg/m2, 5FU 1.2 mg/m2 and eniluracil 12 mg/m2.

The objectives of the study were: (a) to determine pharmacists' perceptions of the importance of Healthy People (HP) 2000 objectives for their patients and community; and (b) to analyze pharmacists' perceived perceptions about recent trends in the characteristics of patients. Three hundred one useful questionnaire were collected from pharmacists who either own or manage a pharmacy located in New Jersey's 67 cities eligible for financial assistance. Pharmacists consider health objectives which are directly linked to health care such as preventing, detecting, and controlling hypertension, heart disease, stroke, cancer, diabetes, and disabling conditions, to be very important. Pharmacists agree to some extent that their patients are now more willing to accept pharmacy counseling services with their prescriptions than before. In conclusion, pharmacists considered objectives related to preventive services to be the most important for HP 2000 objectives, and health promotion and health protection to be less important. The findings of this study will enhance the understanding of pharmacists' perceptions of community health issues and will be beneficial to attain the objectives of HP 2010.