Nevin Manimala

Haematologica. 2024 Mar 28. doi: 10.3324/haematol.2023.284520. Online ahead of print.

ABSTRACT

There is little long-term outcome data on the efficacy of autologous hematopoietic stem cell transplantation (ASCT) in light chain deposition disease (LCDD). We identified 51 LCDD patients in the EBMT registry who had undergone upfront ASCT between 1995 and 2021. The median serum creatinine was 280 μmol/L and 45% required renal replacement therapy (RRT) at time of transplant. The melphalan dose was 100mg/m2 in 23%, 140mg/m2 in 55% and 200 mg/m2 in 21%. The rate of very good partial response or better improved from 41% pre-transplant to 66% at Day +100 post-ASCT. In RRT-independent patients, there was a modest improvement in renal function within the first 3 months; the median eGFR increased from 44 to 51 ml/min/1.73 m2. There was no further change between 3 and 12 months post- ASCT. No patient who was RRT-independent at ASCT became RRT dependent by Day + 100 post-ASCT. Median follow-up post-ASCT was 84 months (IQR: 46-122). At 6-years post ASCT, overall survival (OS) was 88% (95% CI: 78-98%) and PFS was 44% (95% CI: 28-60%). The 2-year cumulative incidence of relapse and non-relapse mortality (NRM) was 17% (95% CI: 6-27%) and 2% (95% CI: 0-6%), respectively. The cumulative incidence of renal transplantation at 4 years after ASCT was 27% (95% CI 13-41) with renal transplantation performed between 6.3 and 52.9 months post-ASCT (median 24.7 months). ASCT represents a feasible option for LCDD patients even if RRT dependent at time of transplant. Outcomes are favourable with low NRM and good long-term OS.

PMID:38546696 | DOI:10.3324/haematol.2023.284520

JAMA Netw Open. 2024 Mar 4;7(3):e244008. doi: 10.1001/jamanetworkopen.2024.4008.

ABSTRACT

IMPORTANCE: Reducing acute care use is an important strategy for improving value. Patients with cancer are at risk for unplanned emergency department (ED) visits and hospital stays (HS). Clinical trial patients have homogeneous treatment; despite this, structural barriers to care may independently impact acute care use.

OBJECTIVE: To examine whether ED visits and HS within 12 months of trial enrollment are more common among Medicare enrollees who live in areas of socioeconomic deprivation or have Medicaid insurance.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included patients with cancer who were 65 years or older and treated in SWOG Cancer Research Network trials from 1999 to 2018 using data linked to Medicare claims. Data were collected from 1999 to 2019 and analyzed from 2022 to 2024.

MAIN OUTCOMES AND MEASURES: Outcomes were ED visits, HS, and costs in the first year following enrollment. Neighborhood socioeconomic deprivation was measured using patients’ zip code linked to the Area Deprivation Index (ADI), measured on a 0 to 100 scale for increasing deprivation and categorized into tertiles (T1 to T3). Type of insurance was classified as Medicare with or without commercial insurance vs dual Medicare and Medicaid. Demographic, clinical, and prognostic factors were captured from trial records. Multivariable regression was used, and the association of ADI and insurance with each outcome was considered separately.

RESULTS: In total, 3027 trial participants were analyzed. The median (range) age was 71 (65-98) years, 1280 (32.3%) were female, 221 (7.3%) were Black patients, 2717 (89.8%) were White patients, 90 (3.0%) had Medicare and Medicaid insurance, and 660 (22.3%) were in the areas of highest deprivation (ADI-T3). In all, 1094 patients (36.1%) had an ED visit and 983 patients (32.4%) had an HS. In multivariable generalized estimating equation, patients living in areas categorized as ADI-T3 were more likely to have an ED visit (OR, 1.34; 95% CI, 1.10-1.62; P = .004). A similar but nonsignificant pattern was observed for HS (OR, 1.36; 95% CI, 0.96-1.93; P = .08). Patients from areas with the highest deprivation had a 62% increase in risk of either an ED visit or HS (OR, 1.62; 95% CI, 1.25-2.09; P < .001). Patients with Medicare and Medicaid were 96% more likely to have an ED visit (OR, 1.96; 95% CI, 1.56-2.46; P < .001).

CONCLUSIONS AND RELEVANCE: In this cohort of older patients enrolled in clinical trials, neighborhood deprivation and economic disadvantage were associated with an increase in ED visits and HS. Efforts are needed to ensure adequate resources to prevent unplanned use of acute care in socioeconomically vulnerable populations.

PMID:38546646 | DOI:10.1001/jamanetworkopen.2024.4008

JAMA Netw Open. 2024 Mar 4;7(3):e244013. doi: 10.1001/jamanetworkopen.2024.4013.

ABSTRACT

IMPORTANCE: Cardiovascular benefits of mild to moderate alcohol consumption need to be validated in the context of behavioral changes. The benefits of reduced alcohol consumption among people who drink heavily across different subtypes of cardiovascular disease (CVD) are unclear.

OBJECTIVE: To investigate the association between reduced alcohol consumption and risk of major adverse cardiovascular events (MACEs) in individuals who drink heavily across different CVD subtypes.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed data from the Korean National Health Insurance Service-Health Screening database and self-reported questionnaires. The nationally representative cohort comprised Korean citizens aged 40 to 79 years who had national health insurance coverage on December 31, 2002, and were included in the 2002 to 2003 National Health Screening Program. People who drank heavily who underwent serial health examinations over 2 consecutive periods (first period: 2005-2008; second period: 2009-2012) were included and analyzed between February and May 2023. Heavy drinking was defined as more than 4 drinks (56 g) per day or more than 14 drinks (196 g) per week for males and more than 3 drinks (42 g) per day or more than 7 drinks (98 g) per week for females.

EXPOSURES: Habitual change in heavy alcohol consumption during the second health examination period. People who drank heavily at baseline were categorized into 2 groups according to changes in alcohol consumption during the second health examination period as sustained heavy drinking or reduced drinking.

MAIN OUTCOMES AND MEASURES: The primary outcome was the occurrence of MACEs, a composite of nonfatal myocardial infarction or angina undergoing revascularization, any stroke accompanied by hospitalization, and all-cause death.

RESULTS: Of the 21 011 participants with heavy alcohol consumption at baseline (18 963 males [90.3%]; mean [SD] age, 56.08 [6.16] years) included in the study, 14 220 (67.7%) sustained heavy drinking, whereas 6791 (32.2%) shifted to mild to moderate drinking. During the follow-up of 162 378 person-years, the sustained heavy drinking group experienced a significantly higher incidence of MACEs than the reduced drinking group (817 vs 675 per 100 000 person-years; log-rank P = .003). Reduced alcohol consumption was associated with a 23% lower risk of MACEs compared with sustained heavy drinking (propensity score matching hazard ratio [PSM HR], 0.77; 95% CI, 0.67-0.88). These benefits were mostly accounted for by a significant reduction in the incidence of angina (PSM HR, 0.70; 95% CI, 0.51-0.97) and ischemic stroke (PSM HR, 0.66; 95% CI, 0.51-0.86). The preventive attributes of reduced alcohol intake were consistently observed across various subgroups of participants.

CONCLUSIONS AND RELEVANCE: Results of this cohort study suggest that reducing alcohol consumption is associated with a decreased risk of future CVD, with the most pronounced benefits expected for angina and ischemic stroke.

PMID:38546645 | DOI:10.1001/jamanetworkopen.2024.4013

JAMA Otolaryngol Head Neck Surg. 2024 Mar 28. doi: 10.1001/jamaoto.2023.4739. Online ahead of print.

ABSTRACT

IMPORTANCE: Sex differences in head and neck cancer (HNC) incidence suggest a potential contribution of sex hormones.

OBJECTIVE: To assess the role of exogenous estrogen exposure in the development of HNC in female patients.

DESIGN, SETTINGS, AND PARTICIPANTS: This large multicenter cohort study using clinical records from the TriNetX real-world database included 20 years of data (through May 31, 2023) from 87 health care organizations. The TriNetX database was searched for medical records for female patients with and without exogenous estrogen exposure according to their chronological age. Cohort 1 included 731 366 female patients aged 18 to 45 years old with regular oral contraceptive (OC) intake and cohort 2 included 3 886 568 patients in the same age group who did not use OC. Cohort 3 comprised 135 875 female patients at least 50 years old receiving hormone replacement therapy (HRT), whereas cohort 4 included 5 875 270 patients at least 50 years old without HRT. Propensity score matching was performed for the confounders age, alcohol dependence, and nicotine dependence. Data analyses were performed in May 2023.

MAIN OUTCOME AND MEASURES: Diagnosis of HNC (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision: C00-C14), and after propensity score matching (1:1 nearest-neighbor greedy matching), a risk analysis to investigate risk differences and risk ratios (RRs) with a 95% CI.

RESULTS: Among the 718 101 female patients in each of cohorts 1 and 2 (mean [SD] age at diagnosis, 25.9 [6.7] years), those with OC intake had a higher risk of an HNC diagnosis (RR, 1.47; 95% CI, 1.21-1.78) than those without OC use. Among the 131 835 female patients in each of cohorts 3 and 4 (mean [SD] age, 67.9 [12.0] years), those with postmenopausal HRT intake had a lower risk of an HNC diagnosis (RR, 0.77; 95% CI, 0.64-0.92) than those without HRT use.

CONCLUSIONS AND RELEVANCE: The findings of this cohort study illustrate a positive association between OC and a negative association between HRT and the development of HNC in female patients. Given the limitations of the TriNetX database, future research should include detailed information on the intake of OC and HRT and reproductive health information (eg, age at menarche/menopause, number of pregnancies) to more accurately define the strength and direction of the possible association between exogeneous estrogen exposure and the development of HNC in female patients.

PMID:38546631 | DOI:10.1001/jamaoto.2023.4739

Personal Disord. 2024 Mar 28. doi: 10.1037/per0000657. Online ahead of print.

ABSTRACT

The goal of this study was to compare the predictive validity of the alternative model for personality disorders (AMPD) versus the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) Section II categorical model regarding clinician judgments about mental health outcomes. To do so, we instructed a national sample of 136 mental health professionals to provide clinical judgments on a random subset of four (out of a possible 12) case vignettes. For each case, they made a variety of diagnostic judgments corresponding to each model, as well as clinical outcome judgments (e.g., prognosis). Our analyses included hierarchical and individual regressions to compare the predictive value of each diagnostic system toward these clinical outcome judgments. We found that the AMPD predictors consistently added unique variance beyond the Section II predictors, whereas the Section II predictors were rarely incremental above the AMPD. Further, the AMPD judgments predicted outcome judgments very consistently (98.3% of regressions) compared to the Section II predictors (70% of regressions), and the single Criterion A judgment (level of personality functioning) was the strongest overall predictor. Finally, the categorical borderline personality disorder diagnoses from the two systems performed similarly in predicting clinical outcomes and agreed in 79% of cases. We interpreted our results to suggest that the AMPD is at least as effective, and by some measures more effective, than the DSM-5 categorical model at predicting clinician’s judgment of outcomes in clinical cases. We conclude by discussing the value of this evidence in relation to the broader AMPD literature, as well as possible paths forward for the diagnosis of personality disorders. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

PMID:38546613 | DOI:10.1037/per0000657

JAMA Oncol. 2024 Mar 28. doi: 10.1001/jamaoncol.2023.7304. Online ahead of print.

ABSTRACT

IMPORTANCE: Biologic features may affect pathologic complete response (pCR) and event-free survival (EFS) after neoadjuvant chemotherapy plus ERBB2/HER2 blockade in ERBB2/HER2-positive early breast cancer (EBC).

OBJECTIVE: To define the quantitative association between pCR and EFS by intrinsic subtype and by other gene expression signatures in a pooled analysis of 3 phase 3 trials: CALGB 40601, NeoALTTO, and NSABP B-41.

DESIGN, SETTING, AND PARTICIPANTS: In this retrospective pooled analysis, 1289 patients with EBC received chemotherapy plus either trastuzumab, lapatinib, or the combination, with a combined median follow-up of 5.5 years. Gene expression profiling by RNA sequencing was obtained from 758 samples, and intrinsic subtypes and 618 gene expression signatures were calculated. Data analyses were performed from June 1, 2020, to January 1, 2023.

MAIN OUTCOMES AND MEASURES: The association of clinical variables and gene expression biomarkers with pCR and EFS were studied by logistic regression and Cox analyses.

RESULTS: In the pooled analysis, of 758 women, median age was 49 years, 12% were Asian, 6% Black, and 75% were White. Overall, pCR results were associated with EFS in the ERBB2-enriched (hazard ratio [HR], 0.45; 95% CI, 0.29-0.70; P < .001) and basal-like (HR, 0.19; 95% CI, 0.04-0.86; P = .03) subtypes but not in luminal A or B tumors. Dual trastuzumab plus lapatinib blockade over trastuzumab alone had a trend toward EFS benefit in the intention-to-treat population; however, in the ERBB2-enriched subtype there was a significant and independent EFS benefit of trastuzumab plus lapatinib vs trastuzumab alone (HR, 0.47; 95% CI, 0.27-0.83; P = .009). Overall, 275 of 618 gene expression signatures (44.5%) were significantly associated with pCR and 9 of 618 (1.5%) with EFS. The ERBB2/HER2 amplicon and multiple immune signatures were significantly associated with pCR. Luminal-related signatures were associated with lower pCR rates but better EFS, especially among patients with residual disease and independent of hormone receptor status. There was significant adjusted HR for pCR ranging from 0.45 to 0.81 (higher pCR) and 1.21-1.94 (lower pCR rate); significant adjusted HR for EFS ranged from 0.71 to 0.94.

CONCLUSIONS AND RELEVANCE: In patients with ERBB2/HER2-positive EBC, the association between pCR and EFS differed by tumor intrinsic subtype, and the benefit of dual ERBB2/HER2 blockade was limited to ERBB2-enriched tumors. Immune-activated signatures were concordantly associated with higher pCR rates and better EFS, whereas luminal signatures were associated with lower pCR rates.

PMID:38546612 | DOI:10.1001/jamaoncol.2023.7304

JAMA Ophthalmol. 2024 Mar 28. doi: 10.1001/jamaophthalmol.2024.0363. Online ahead of print.

ABSTRACT

IMPORTANCE: Effects of genetic variants on primary angle-closure disease remained uncertain.

OBJECTIVE: To systematically review the associations of common single-nucleotide variants (SNVs) and rare coding variants with primary angle-closure disease, its subtypes (including primary angle-closure glaucoma, primary angle-closure suspect, and primary angle-closure) and progression.

DATA SOURCES: Eligible studies from PubMed, Embase, and Web of Science were retrieved up to April 3, 2023. SNV information was extracted from eligible reports and 2 genome-wide association studies summary statistics, UK BioBank and FinnGen.

STUDY SELECTION: Studies providing analyzable genotype or allele data in a case-control design for primary angle-closure disease association and longitudinal case-only design for primary angle-closure disease progression.

DATA EXTRACTION AND SYNTHESIS: PRISMA guidelines were used for literature screening and the Newcastle Ottawa Scale for data quality assessment. Pooled effect size with 95% CIs of SNV associations were calculated using fixed- or random-effect models according to I2 statistics.

MAIN OUTCOMES AND MEASURES: SNVs reported in 2 or more studies were meta-analyzed to generate pooled odds ratios and P values. Common and rare coding variants from single reports were summarized.

RESULTS: Sixty-nine citations were eligible for meta-analysis on overall primary angle-closure disease, involving 206 SNVs in 64 genes or loci. Seventeen SNVs in 15 genes or loci showed associations with primary angle-closure disease, and 15 SNVs in 13 genes or loci showed associations with primary angle-closure glaucoma. Two SNVs, ABCA1 rs2422493 and ZNRF3 rs3178915, were associated only with primary angle-closure disease. Two SNVs, PCMTD1-ST18 rs1015213 and COL11A1 rs3753841, were associated with primary angle-closure suspect, and 1 SNV, MMP9 rs3918249, was associated with primary angle-closure. This systematic review and meta-analysis newly confirmed 7 genes or loci associated with primary angle-closure glaucoma: ATOH7, CALCRL, FBN1, IL6, LOXL1, MMP19, and VAV3. Common and rare coding variants in 16 genes or loci that have been associated with primary angle-closure disease were cataloged. Stratification analysis revealed different primary angle-closure disease-associated genes in different ethnic populations. Only 1 study regarding the genetic association of primary angle-closure glaucoma progression was identified.

CONCLUSIONS AND RELEVANCE: This study revealed the genetic complexity of primary angle-closure disease, involving common SNVs and rare coding variants in more than 30 genes or loci, with ethnic and phenotypic diversities. Further replication, genotype-phenotype correlation, and pathway analyses are warranted.

PMID:38546604 | DOI:10.1001/jamaophthalmol.2024.0363

Am J Orthopsychiatry. 2024 Mar 28. doi: 10.1037/ort0000732. Online ahead of print.

ABSTRACT

Black and Latinx people are disproportionately impacted by HIV, COVID-19, and other syndemic health crises with similar underlying social determinants of health. Lessons learned from the HIV pandemic and COVID-19 response have been invoked to improve health equity at the systemic level in the face of other emergent health crises. However, few have examined the potential translation of strategies between syndemics at the individual level. The current mixed-methods study examined strategies used to manage HIV during the COVID-19 pandemic and the extent to which they were helpful in managing COVID-19 vulnerability among Black and Latinx people living with HIV. Participants (n = 30) were interviewed by telephone and completed demographic, mental health, alcohol and substance use, health literacy, and clinical measures in October and November 2020 in Los Angeles County. Rapid qualitative analysis, descriptive statistics, and mixed-methods merging were used to analyze the data. Qualitative results demonstrated that participants found HIV self-management strategies translated to aspects of the COVID-19 pandemic including hygiene and social distancing and coping with a health-related stressor. Although telemedicine provided continuity of HIV care for most participants, technology access and literacy posed a potential barrier, particularly to those facing other sociodemographic marginalization (i.e., low education, disability). Findings suggest providers can encourage leveraging individual HIV self-management strategies in response to other public health crises. However, these interventions must be culturally responsive and address intersecting social determinants of health. Future research should examine mechanisms that predict individual translation of HIV management strategies to other health concerns. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

PMID:38546560 | DOI:10.1037/ort0000732

JAMA Oncol. 2024 Mar 28. doi: 10.1001/jamaoncol.2023.7333. Online ahead of print.

ABSTRACT

IMPORTANCE: Despite the clear potential benefits of neoadjuvant therapy, the optimal neoadjuvant regimen for patients with high-risk resectable melanoma (HRRM) is not known.

OBJECTIVE: To compare the safety and efficacy of dual checkpoint inhibitors with anti-programmed cell death protein-1 (anti-PD1) therapy in a neoadjuvant setting among patients with HRRM.

DESIGN, SETTING, AND PARTICIPANTS: In this pooled analysis of clinical trials, studies were selected provided they investigated immune checkpoint inhibitor treatment, were published between January 2018 and March 2023, and were phase 1, 2, or 3 clinical trials. Participant data included in the analysis were derived from trials evaluating the efficacy and safety of anti-PD1 monotherapy and the combination of anti-cytotoxic T lymphocyte-associated protein-4 with anti-PD1 in the neoadjuvant setting, specifically among patients with HRRM.

INTERVENTIONS: Patients were treated with either anti-PD1 monotherapy; dual checkpoint inhibition (DCPI) with a conventional dose of 3-mg/kg ipilimumab and 1-mg/kg nivolumab; or DCPI with an alternative-dose regimen of 1-mg/kg ipilimumab and 3-mg/kg nivolumab.

MAIN OUTCOMES AND MEASURES: The main outcomes were radiologic complete response (rCR), radiologic overall objective response (rOOR), and radiologic progressive disease. Also, pathologic complete response (pCR), the proportion of patients undergoing surgical resection, and occurrence of grade 3 or 4 immune-related adverse events (irAEs) were considered.

RESULTS: Among 573 patients enrolled in 6 clinical trials, neoadjuvant therapy with DCPI was associated with higher odds of achieving pCR compared with anti-PD1 monotherapy (odds ratio [OR], 3.16; P < .001). DCPI was associated with higher odds of grade 3 or 4 irAEs compared with anti-PD1 monotherapy (OR, 3.75; P < .001). When comparing the alternative-dose ipilimumab and nivolumab (IPI-NIVO) regimen with conventional-dose IPI-NIVO, no statistically significant difference in rCR, rOOR, radiologic progressive disease, or pCR was noted. However, the conventional-dose IPI-NIVO regimen was associated with increased grade 3 or 4 irAEs (OR, 4.76; P < .001). Conventional-dose IPI-NIVO was associated with greater odds of achieving improved rOOR (OR, 1.95; P = .046) and pCR (OR, 2.99; P < .001) compared with anti-PD1 monotherapy. The alternative dose of IPI-NIVO also was associated with higher odds of achieving rCR (OR, 2.55; P = .03) and pCR (OR, 3.87; P < .001) compared with anti-PD1 monotherapy. The risk for grade 3 or 4 irAEs is higher with both the conventional-dose (OR, 9.59; P < .001) and alternative-dose IPI-NIVO regimens (OR, 2.02; P = .02) compared with anti-PD1 monotherapy.

CONCLUSION AND RELEVANCE: In this pooled analysis of 6 clinical trials, although DCPI was associated with increased likelihood of achieving pathological and radiologic responses, the associated risk for grade 3 or 4 irAEs was significantly lower with anti-PD1 monotherapy in the neoadjuvant setting for HRRM. Additionally, compared with alternative-dose IPI-NIVO, the conventional dose of IPI-NIVO was associated with increased risk for grade 3 or 4 irAEs, with no significant distinctions in radiologic or pathologic efficacy.

PMID:38546551 | DOI:10.1001/jamaoncol.2023.7333

Can J Diet Pract Res. 2024 Mar 28:1-6. doi: 10.3148/cjdpr-2023-026. Online ahead of print.

ABSTRACT

Purpose: The Canadian federal government has expressed an intention to work with provinces and territories to develop a national school food program (SFP). This study aimed to explore caregivers’ perception of attributes important to include in a future SFP.Methods: An online cross-sectional survey was conducted. Fifteen elementary schools from high, medium, or low median income neighbourhoods in Saskatoon were invited to participate. School principals sent a survey link to students’ caregivers. The 37-item survey included an item with 15 statements asking caregivers to rate the importance of various components of a SFP. Descriptive statistics and exploratory factor analysis were conducted.Results: A total of 510 caregivers completed the survey (response rate of 52%). The factor analysis indicated four key components of a future SFP: (1) learning opportunities on growing and preparing food, (2) offering healthy food following Canada’s Food Guide, (3) affordability of the meals offered, and (4) cultural adaptability of the meal program. Over 90% of caregivers thought providing healthy meals and ample time to eat meals to be very important.Conclusion: Our results indicate caregivers support multicomponent meal programs that, along with providing nutritious food, help children build healthy habits and sustainable food systems. These findings will help dietitians understand caregivers’ perspectives to inform the design of a national SFP.

PMID:38546536 | DOI:10.3148/cjdpr-2023-026