Jacobs Institute of Women's Health
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Haematologic outcomes and associated clinical characteristics among patients receiving Olaparib therapy in the UAE: a retrospective chart review
No full textBACKGROUND: Poly ADP ribose polymerase (PARP) inhibitors, such as Olaparib (Lynparza), are pivotal in treating certain cancers, particularly those linked to BReast CAncer gene (BRCA) mutations. Despite its established efficacy, Olaparib use is associated with various adverse events (AEs), notably haematologic toxicities, such as anaemia. This retrospective chart review study aimed to examine haematologic outcomes and associated factors in patients treated with Olaparib at a tertiary hospital in the UAE. METHODS: We reviewed the medical charts of patients prescribed Olaparib and focused on haematologic indices at a baseline of 1-month, 3-month and 6-month follow-up periods. Data were analysed to determine the AEs frequency, transfusions need and potential associated patients\u27 clinical characteristics. RESULTS: This study included all patients who received Olaparib (n = 66). Most patients were females (n = 61; 92.4%) and the vast majority were non-smokers (97%) and free of hepatic disease. Themean age of the patients was 57.03-year-old (SD) = 12.06 years), and body mass index (BMI) was 28.16 (SD = 6.40) kg/m. A high rate of anaemia (70.8%) was detected among the patients during their Olaparib therapy. Approximately, one-third of the patients developed neutropenia and thrombocytopenia. Transfusion was needed in almost half of the patients. Glomerular filtration rate (GFR) and neutropenia were significantly correlated with moderate-severe anaemia (OR = 0.097, 95% CI: 0.011-0.88, p value = .038) and (OR = 9.04, 95% CI: 1.024-79.78, p value = .048), respectively. CONCLUSIONS: Our findings highlight the side effects of Olaparib therapy in terms of haematology which could be avoided. Further studies are needed to better understand the therapeutic management of Olaparib and the mitigation of haematologic complications
Harmonizing excellence: Crafting the nexus of competencies, standards, and degree demands in nurse practitioner education
No full textNurse practitioner (NP) programs have a long history of producing safe and competent NPs; however, bold, transformative leadership is needed to set a minimum standard for quality NP education to support a 21st-century healthcare system. This paper is a call to action for leaders in NP education to transition NP education to the DNP degree utilizing the 2022 National Task Force Standards for Quality NP Education and a competency-based approach as defined in the 2021 AACN Essentials. There is now an opportunity to redesign healthcare systems with quality and equity as a primary consideration and DNP-prepared NPs are positioned to lead this redesign. The 2022 NTF Standards include several critical changes in clinical hours, oversight of clinical sites, and preparation of NP students to enter clinical sites. By emphasizing competency attainment within NP programs, the 2021 AACN Essentials ensure that NP graduates are practice-ready
Proteomic analysis identifies novel biological pathways that may link dietary quality to type 2 diabetes risk: evidence from African American and Asian cohorts
No full textBACKGROUND: Diet affects the development of chronic diseases such as type 2 diabetes, but the underlying biological mechanisms are only partly understood. OBJECTIVES: This study aimed to identify proteomic markers of the Alternative Healthy Eating Index (AHEI) and the Dietary Approaches to Stop Hypertension (DASH) diet and their association with type 2 diabetes risk. METHODS: We examined the associations between the AHEI and DASH diet quality scores and 1317 plasma proteins in African American participants of the Jackson Heart Study (JHS, n = 1878). These findings were validated in a Singapore Multi-Ethnic Cohort (n = 2395) and examined in relation to type 2 diabetes incidence (n = 539 cases). We adjusted for multiple testing by using false discovery rate-adjusted q values. RESULTS: We identified 13 proteins consistently associated with the AHEI or DASH scores with the strongest associations for the AHEI score and epidermal growth factor receptor (β:0.089; SE: 0.017; q \u3c 0.001) and for the DASH score and tissue factor (β: -0.114; SE: 0.022; q \u3c 0.001). Most of these proteins were related to inflammation, thrombosis, adipogenesis, and glucose metabolism. Concentrations of myeloperoxidase, epidermal growth factor receptor, hepatocyte growth factor receptor, coagulation factor Xa, contactin 4, kynureninase, neurogenic locus notch homolog protein 1, and vesicular integral-membrane protein VIP36 were associated with the risk of type 2 diabetes in the Asian cohort. The diabetes odds ratio for a 2-fold higher protein abundance concentration ranged from 0.03 (95% CI: 0.01, 0.08) for neurogenic locus notch homolog protein 1 to 3.04 (95% CI: 2.13, 4.33) for kynureninase. Furthermore, genetic markers for myeloperoxidase and hepatocyte growth factor receptor were significantly associated with diabetes risk. CONCLUSIONS: Our study across geographically and ethnically diverse populations identified robust protein biomarkers for healthy dietary patterns. Furthermore, our findings suggest novel biological mechanisms linking dietary patterns with type 2 diabetes development
Food purchase diversity is associated with market food diversity and diets of children and their mothers but not fathers in rural Tanzania: Results from the EFFECTS baseline survey
No full textRural households in East Africa rely on local markets, but the influence of market food diversity and household food purchase diversity on diets has not been well-characterized. We quantify the associations among market food diversity, household food purchase diversity and dietary diversity of mothers, fathers and children in rural Tanzania. This study uses baseline data from a randomized controlled trial, Engaging Fathers for Effective Child Nutrition and Development in Tanzania. We used the 10 food groups for women\u27s dietary diversity to assess the seasonal availability of nutritious foods in 79 markets. Using data from 957 rural households in two districts in Mara, Tanzania, we measured household food purchase diversity over the previous month and dietary diversity among children (6-23 months), mothers and fathers. Overall, 63% of markets sold all 10 food groups throughout the year, indicating high-market food diversity and minimal seasonality. However, only 33% of women and 35% of children met dietary diversity recommendations. Households that reported higher purchasing power (0.14, p \u3c 0.001), lived within 30 min of a market (0.36, p = 0.001) and had access to a highly diverse market (0.37, p = 0.01) purchased a higher diversity of foods. In turn, food purchase diversity was positively associated with the dietary diversity of mothers (p \u3c 0.001) and children 9-23 months (p \u3c 0.001) but not fathers (p = 0.56). Interventions must account for food availability and access in local markets, and promoting diverse food purchases may be an effective strategy to improve women\u27s and children\u27s diets in rural areas
Anatomical correlates for the newly discovered meningeal layer in the existing literature: A systematic review
No full textThe existence of a previously unrecognized subarachnoid lymphatic-like membrane (SLYM) was reported in a recent study. SLYM is described as an intermediate leptomeningeal layer between the arachnoid and pia mater in mouse and human brains, which divides the subarachnoid space (SAS) into two functional compartments. Being a macroscopic structure, having missed detection in previous studies is surprising. We systematically reviewed the published reports in animals and humans to explore whether prior descriptions of this meningeal layer were reported in some way. A comprehensive search was conducted in PubMed/Medline, EMBASE, Google Scholar, Science Direct, and Web of Science databases using combinations of MeSH terms and keywords with Boolean operators from inception until 31 December 2023. We found at least eight studies that provided structural evidence of an intermediate leptomeningeal layer in the brain or spinal cord. However, unequivocal descriptions for this layer all along the central nervous system were scarce. Obscure names like the epipial, intermediate meningeal, outer pial layers, or intermediate lamella were used to describe it. Its microscopic/ultrastructural details closely resemble the recently reported SLYM. We further examined the counterarguments in current literature that are skeptical of the existence of this layer. The potential physiological and clinical implications of this new meningeal layer are significant, underscoring the urgent need for further exploration of its structural and functional details
Safety Profile of Preoperative Meningioma Embolization: A Meta-Analysis Comparing Embolic Agents and Carotid Systems Embolized
No full textBACKGROUND: Meningiomas can be embolized to facilitate safe tumor resection. However, the procedure may be associated with complications that have not been well-characterized. We aimed to compare the safety of liquid versus particulate agents and to assess the safety of embolization using internal carotid artery (ICA) branches. METHODS: Studies evaluating outcomes of preoperative meningioma embolization from 1974 to 2024 were systematically searched on PubMed, Embase, and Scopus. Data on embolic agents used, feeder arteries embolized, and complication outcomes were extracted. Complication rates were statistically compared using Z-scores calculated from the standard errors of the pooled rates. RESULTS: The meta-analysis encompassed 3,069 patients from 50 studies. Embolization appears safe with an overall complication rate of 3.2% (95% CI: 2.4-4.0%) and a permanent neurological deficit rate of only 1.2% (0.8-1.6%). Overall complication rates were comparable between liquid (4.1%, 1.8-6.5%) and particulate agents (2.7%, 1.7-3.6%) (P = 0.28). The rate of tumor edema causing neurologic deficits was slightly higher for liquid agents (2.4%, 0.6-4.2%) compared to particulate agents (0.5%, 0.2-0.8%) (P = 0.041). No significant differences were observed in hemorrhagic (liquid 2.3%, particulate 0.7%; P = 0.087) or ischemic complications (liquid 1.6%, particulate 1.1%; P = 0.53). For the carotid systems embolized, the pooled complication rate for ICA branches embolization (5.2%, 1.1-9.2%) was comparable to the pooled complication rate of external carotid artery embolization (2.5%, 1.8-3.2%) (P = 0.20). CONCLUSIONS: Preoperative embolization is a safe adjunct for meningioma resection, with similarly low complication rates for liquid and particulate agents. Furthermore, embolization of ICA branches can be as safe as external carotid artery branches in select cases
Two Non-myeloablative HLA-Matched Related Donor Allogeneic Hematopoietic Cell Transplant Regimens in Patients with Severe Sickle Cell Disease
No full textBACKGROUND: Non-myeloablative (NMA) conditioning is increasingly being used with success in matched related donor (MRD) and alternative donor allogeneic hematopoietic cell transplant (allo-HCT) in individuals with sickle cell disease (SCD). Advantages include decrease toxicity and applicability in patients otherwise unable to tolerate conditioning regimens due to end organ damage or age. OBJECTIVE(S): We aimed to add to published data outcomes of two similar NMA protocols Protocol 1 (clinicaltrials.gov ID: NCT00061568) and Protocol 2 (clinicaltrials.gov ID: NCT02105766)) in mainly adult patients with SCD to evaluate safety, toxicity, and success of these regimens in individuals at high-risk for poor transplant-related outcomes. We also evaluated the tolerability and outcomes of Protocol 2, which included pre-conditioning immuno-depletion, in patients at even higher risk of T-cell mediated rejection or plasma/B-cell mediated anti-donor erythrocyte antibody production-the latter due to ABO incompatibility or recipient red blood cell alloimmunization to a donor antigen. Lastly, we evaluated the incidence and trajectory of mixed donor myeloid chimerism over time following allo-HCT. STUDY DESIGN: In this retrospective analysis of the two prospective phase 2 NMA transplant protocols, 91 individuals with SCD or transfusion-dependent beta thalassemia underwent MRD allo-HCT at the National Heart, Lung, and Blood Institute; regimens contained alemtuzumab, low dose radiation, and sirolimus for graft-versus-host disease (GVHD) prophylaxis with or without preconditioning immuno-depletion with pentostatin and oral cyclophosphamide (Protocol 2). RESULTS: In the total cohort of 91 transplant recipients, outcomes were favorable with timely neutrophil and platelet engraftment (median: 21 days (range, 7-67) and 21 days (10-112), respectively), minimal high-grade acute and no chronic GVHD, overall survival of 90%, sickle-free survival of 85%, and mixed donor myeloid chimerism in 43% at a median follow up of 7.3 years (range, 0.8-20). Most patients with mixed myeloid chimerism at 2-years post-HCT remained stable in their values. In analyzing each protocol separately, outcomes were comparable except for higher cytomegalovirus reactivation requiring treatment in Protocol 2, without associated increase in graft failure. In the combined cohort, graft failure occurred in 11 patients and hematologic malignancy or abnormal cytogenetics on bone marrow evaluation developed in 7 recipients. On a sub-analysis of factors that may implicate transplant outcomes, the number of RBC units transfused post-HCT was significantly higher in recipients with pre-HCT history of alloimmunization to donor red blood cell antigens. There was no difference in RBC units transfused, duration of transfusion, or in red cell engraftment in those with major ABO incompatibility; pre-conditioning immune-depletion and pre-treatment with rituximab were likely helpful. CONCLUSION: Both NMA allo-HCT protocols were successful in achieving adequate engraftment and sickle-free survival with minimal toxicity, including in individuals with mixed donor myeloid chimerism. The addition of pre-conditioning immuno-depletion was well-tolerated and reduced graft failure rate in high-risk recipients
Menopausal hormone therapy for breast cancer patients: what is the current evidence?
No full textIMPORTANCE AND OBJECTIVES: Many breast cancer survivors struggle with menopausal symptoms due to oncological treatment-induced hormone deficiency, or because they experience menopause some years after completing treatment, but have limited menopause treatment options. Estrogen replacement therapy is the most effective treatment for menopausal symptoms, but is not recommended after breast cancer because it can increase the risk of relapse. Our objectives were to review the evidence and develop a consensus statement to define the role of menopausal hormone therapy after breast cancer, and to highlight evidence gaps to inform future research. METHODS: A 25-member multidisciplinary panel developed the consensus statements using a modified Delphi methodology. The panel consisted of 18 senior doctors who voted (5 GP menopause specialists, 5 gynecologists, 4 medical oncologists, 3 breast surgical oncologists, and 1 breast radiologist), and 7 members who did not vote (4 patient representatives, 1 medical oncologist, 1 urologist and 1 administrator). Consensus was defined as ≥70% agreement with low-to-moderate variation in extent of agreement (mean absolute deviation from median of ≤0.75). We reviewed current evidence relating to use of vaginal and systemic menopausal hormone therapy ( MHT , also known as hormone therapy, HT or hormone replacement therapy, HRT ) after breast cancer diagnosis, and adjuvant endocrine (anti-estrogen) therapy, and developed a narrative synthesis. Finally, four additional breast cancer specialists peer-reviewed the manuscript. DISCUSSION AND CONCLUSIONS: The panel agreed that some women may choose to take MHT, (off-label use) and accept an increased risk of relapse in exchange for relief from menopausal symptoms and an improved quality of life, and that preferences may vary according to individual circumstances and the absolute risk of relapse. All respondents agreed or strongly agreed with statements supporting shared decision making and individualized menopause care (MADM 0.29).In our review of the literature, we found mainly moderate quality evidence concerning use of vaginal and systemic estrogen after breast cancer, and high quality evidence concerning the benefits of anti-estrogen therapy for estrogen receptor positive breast cancer. Based on the available data, we recommend that shared decisions are based on (1) an individual\u27s menopausal symptoms and impact on quality of life, (2) the potential increase in an individual\u27s risk of relapse by use of menopausal hormone therapy, and (3) patient preferences, views and treatment goals. Clinicians and patients can use our findings to make informed menopause treatment choices after breast cancer. We strongly recommend registering all patients considering MHT after breast cancer in a clinical study (eg, MENopausal hormone therapy and Outcomes After Breast Cancer, the MENO-ABC trial)
Mediterranean Diet and Patients With Psoriasis: The MEDIPSO Randomized Clinical Trial
No full textIMPORTANCE: Despite growing interest on the role of diet in the prevention and treatment of psoriasis, randomized clinical trials are lacking. The Mediterranean diet is known for its anti-inflammatory and cardiometabolic benefits, which may be relevant to psoriasis pathophysiology. OBJECTIVE: To assess whether a 16-week Mediterranean diet intervention would improve psoriasis severity in patients with mild to moderate disease. DESIGN, SETTING, AND PARTICIPANTS: MEDIPSO (Impact of the Mediterranean Diet on Patients With Psoriasis), an open-label, single-center, single-blinded (evaluator) randomized clinical trial, was conducted from February 2024 to March 2025 at a dermatology referral clinic in Madrid, Spain. Participants were adults with mild to moderate psoriasis (Psoriasis Area and Severity Index [PASI] of 2-10, with higher scores indicating maximal disease) receiving stable topical therapy. INTERVENTIONS: Participants were randomized 1:1 to the intervention or control group. The intervention group received a 16-week, dietitian-guided Mediterranean diet program, including nutritional counseling, educational materials, and weekly provision of extra virgin olive oil. The control group received standard low-fat dietary advice without dietitian supervision. MAIN OUTCOMES AND MEASURES: The primary outcome was the change in the PASI from baseline to week 16. Secondary outcomes included changes in Mediterranean diet adherence, anthropometric and metabolic parameters, serum inflammatory cytokines, and patient-reported outcomes. Estimated marginal means (EMMs) at baseline and for the change from baseline to week 16 were reported, with the intervention effect presented as the between-group difference. RESULTS: Among 45 individuals screened, 38 participants were enrolled and randomized (mean [SD] age, 46.4 [12.8] years; 25 males [65.8%]); 19 were randomized to the intervention group and 19 were randomized to the control group; 37 individuals (97.4%) completed the study. The EMM PASI change at week 16 was -3.4 (95% CI, -4.4 to -2.4) in the intervention group and 0.0 (95% CI, -1.0 to 1.0) in the control group; the between-group EMM difference was -3.4 (95% CI, -4.8 to -2.0; P \u3c .001). Nine of 19 participants in the Mediterranean diet group (47.4%) achieved PASI 75 (a 75% reduction in PASI) compared with none in the control group. A significant reduction in EMM hemoglobin A1c (glycated hemoglobin) was observed in the intervention group as compared with the control group (between-group EMM difference, -4.1 mmol/mol [95% CI, -6.9 to -1.3 mmol/mol]; P = .01). CONCLUSIONS AND RELEVANCE: This randomized clinical trial found that a 16-week Mediterranean diet intervention significantly improved psoriasis severity in patients with mild to moderate disease receiving stable topical therapy. These findings suggest that incorporating dietary strategies may be beneficial as an adjunctive therapy in psoriasis management. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06257641