High-dose IV magnesium in mesothelioma patients receiving surgery with hyperthermic intraoperative cisplatin: Pilot studies and design of a phase II randomized clinical trial.

INTRODUCTION: Hyperthermic intraoperative cisplatin (HIOC) is associated with acute kidney injury (AKI). Administration of high-dose magnesium attenuates cisplatin-induced AKI (CP-AKI) in animal models but has not been rigorously examined in humans. METHODS: We tested the feasibility and safety of different doses of magnesium in mesothelioma patients receiving HIOC. In Pilot Study 1, we administered a 36-h continuous infusion of magnesium at 0.5 g/h, targeting serum magnesium levels between 3 and 4.8 mg/dL. In Pilot Study 2A, we administered a 6 g bolus followed by an infusion starting at 2 g/h, titrated to achieve levels between 4 and 6 mg/dL. We eliminated the bolus in Pilot Study 2B. RESULTS: In Pilot Study 1, all five patients enrolled completed the study; however, median postoperative Mg levels were only 2.4 mg/dL. In Pilot Study 2A, two of four patients (50%) were withdrawn due to bradycardia during the bolus. In Pilot Study 2B, two patients completed the study whereas two developed postoperative bradycardia attributed to the magnesium. CONCLUSIONS: A 0.5 g/h infusion for 36 h did not achieve therapeutic magnesium levels, while an infusion at 2 g/h was associated with bradycardia. These studies informed the design of a randomized clinical trial testing whether intravenously Mg attenuates HIOC-associated AKI.

Kidney function in patients with ovarian cancer treated with poly (ADP-ribose) polymerase (PARP) inhibitors.

BACKGROUND: Poly (ADP-ribose) polymerase inhibitors (PARPi) have revolutionized the treatment of ovarian cancer; however, real-world data on kidney function among patients treated with PARPi are lacking. METHODS: We identified adults treated with olaparib or niraparib between 2015 and 2021 at a major cancer center in Boston, MA, USA. We determined the incidence of any acute kidney injury (AKI), defined as at least a 1.5-fold rise in serum creatinine from baseline in the first 12 months following PARPi initiation. We calculated the percentage of patients with any AKI and sustained AKI and adjudicated the etiologies by manual chart review. We compared trajectories in estimated glomerular filtration rate (eGFR) among PARPi-treated and carboplatin and paclitaxel-treated patients with ovarian cancer, matched by baseline eGFR. RESULTS: Of 269 patients, 60 (22.3%) developed AKI, including 43 of 194 (22.1%) olaparib-treated patients and 17 of 75 (22.7%) niraparib-treated patients. Only 9 of 269 (3.3%) had AKI attributable to the PARPi. Of the 60 patients with AKI, 21 (35%) had sustained AKI, of whom 6 had AKI attributable to the PARPi (2.2% of the whole cohort). eGFR declined within 30 days post-PARPi initiation by 9.61 (SD = 11.017) mL/min per 1.73 m2 but recovered by 8.39 (SD = 14.05) mL/min per 1.73 m2 within 90 days after therapy cessation. There was no difference in eGFR at 12 months post-therapy initiation in patients receiving PARPi or controls receiving carboplatin and paclitaxel (P = .29). CONCLUSIONS: AKI is common following PARPi initiation as is a transient decline in eGFR; however, sustained AKI directly attributable to the PARPi and long-term eGFR decline are uncommon.

Awareness and attitudes towards advance care planning in primary care: role of demographic, socioeconomic and religiosity factors in a cross-sectional Lebanese study.

OBJECTIVE: To assess awareness and attitudes towards engaging in advance care planning (ACP) and their relationship with demographic, socioeconomic and religiosity factors among Lebanese middle-aged to older-aged adults in primary care. DESIGN: A cross-sectional survey study. SETTING: Tertiary referral hospital in Beirut, Lebanon. PARTICIPANTS: A total of 215 middle-aged to older-aged adults. RESULTS: Out of 215 participants, 18.6% of participants knew about ACP; 94% favoured truth-telling; 87.4% favoured healthcare autonomy; 77.2% favoured documenting their own health values and preferences; and 29.3% were willing to undergo life-prolonging interventions. Among participants who were aware of ACP, 67.5% preferred ACP documentation and 85% had negative attitudes towards life-sustaining interventions. Women were more aware about ACP than men. Those who were willing to undergo life-prolonging interventions were found to be men and had higher religiosity scores. CONCLUSION: Large deficit in ACP awareness was evident despite the high preference for healthcare autonomy. Medical and public health efforts should strive to enhance patients' ACP awareness and engagement in ACP while considering factors relevant to gender, culture and religiosity.

Knowledge and attitude towards Alzheimer's disease and related dementias in a low- to middle-income country: a cross-sectional survey among Lebanese middle-aged and older adults.

BACKGROUND: Despite the growing burden of Alzheimer's disease and related dementias (ADRD) in low- to middle-income countries (LMICs) and prior findings of important gaps in research on ADRD knowledge, very few studies have assessed ADRD knowledge in these populations. This study evaluates the knowledge and attitudes towards ADRD among Lebanese middle-aged and older adults. METHOD: Participants aged ≥ 40 (n = 215) attending primary care clinics at a large medical centre in Lebanon completed the Alzheimer's Disease Knowledge Scale (ADKS), an attitude scale, and the Duke University Religion Index. RESULTS: ADRD knowledge accuracy was 61.5% (mean score = 18.6 out of 30 (SD = 3.05)). Items with the least correct answers were related to caregiving and risk factors (≤9% and ≤28%). Overall, participants had tolerant views concerning ADRD; the least positive views were regarding living with people with ADRD. Older age, lower educational attainment, and higher religiosity scores were associated with poorer knowledge and attitudes. CONCLUSION: Results highlight the need for awareness and preventive efforts that address misconceptions about modifiable risk factors and living with ADRD, especially given that the burden of caregiving for older adults often falls on family members in Lebanon and other LMIC countries.