Tag: pubmed

BMC Cancer. 2022 Sep 21;22(1):1002. doi: 10.1186/s12885-022-10078-5.

ABSTRACT

BACKGROUND: Approximately 40% of hormone receptor positive/human epidermal receptor 2 negative (HR + /HER2-) metastatic breast cancer (mBC) patients harbor phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations. However, associations between PIK3CA mutation status and clinical outcomes among patients with HR + /HER2- mBC have been heterogeneous across clinical trials. This meta-analysis was conducted to survey recently available trial data to assess the prognostic effects of PIK3CA among patients with HR + /HER2- mBC. METHODS: Randomized clinical trials reporting progression-free survival (PFS) or overall survival (OS) stratified by PIK3CA status in HR + /HER2- mBC were identified via systematic literature review. Trial arms receiving phosphatidylinositol 3-kinase (PI3K)-targeted therapies were excluded. Meta-regression analysis was used to estimate the association between PIK3CA status and PFS and OS among included studies.

RESULTS: The analyzed data included 3,219 patients from 33 study arms across 11 trials (PIK3CA mutated: 1,386, wild type: 1,833). PIK3CA mutation was associated with shorter median PFS (difference [95% CI] (months): -1.8 [-3.4, -0.1], I² = 35%) and shorter median OS (-8.4 [-13.4, -3.5], I² = 58%, N = 1,545). Findings were similar for PFS rates at 6 months (odds ratio [95% CI]: 0.74 [0.59, 0.94], I² = 42%, N = 3,160) and 12 months (0.76 [0.59, 0.99], I² = 42%, N = 2,468) and directionally consistent but not statistically significant at 18 months (N = 1,726).

CONCLUSIONS: Pooling evidence across multiple studies, PIK3CA mutation was associated with shorter PFS and OS. These findings suggest a negative prognostic value of PIK3CA mutations in patients with HR + /HER2- mBC.

PMID:36131248 | DOI:10.1186/s12885-022-10078-5

BMC Prim Care. 2022 Sep 21;23(1):245. doi: 10.1186/s12875-022-01851-3.

ABSTRACT

BACKGROUND: The COVID-19 pandemic caused widespread changes to healthcare, but few studies focus on ambulatory care during the early phase of the pandemic. We characterize veterans’ ambulatory care experience, specifically access and satisfaction, early in the pandemic.

METHODS: We employed a semi-structured telephone interview to capture quantitative and qualitative data from patients scheduled with a primary care provider between March 1 – June 30, 2020. Forty veterans were randomly identified at a single large urban Veterans Health Administration (VHA) medical center. The interview guide utilized 56 closed and open-ended questions to characterize veterans’ perceptions of access to and satisfaction with their primary care experience at VHA and non-VHA primary care sources. We also explored the context of veterans’ daily lives during the pandemic. We analyzed quantitative data using descriptive statistics and verbatim quotes using a matrix analysis.

RESULTS: Veterans reported completing more appointments (mean 2.6 (SD 2.2)) than scheduled (mean 2.3 (SD 2.2)) mostly due to same-day or urgent visits, with a shift to telephone (mean 2.1 (SD 2.2)) and video (mean 1.5 (SD 0.6)). Among those who reported decreased access to care early in the pandemic (n = 27 (67%)), 15 (56%) cited administrative barriers (“The phone would hang up on me”) and 9 (33%) reported a lack of provider availability (“They are not reaching out like they used to”). While most veterans (n = 31 (78%)) were highly satisfied with their VHA care (mean score 8.6 (SD 2.0 on a 0-10 scale), 9 (23%) reported a decrease in satisfaction since the pandemic. The six (15%) veterans who utilized non-VHA providers during the period of interest reported, on average, higher satisfaction ratings (mean 9.5 (SD 1.2)). Many veterans reported psychosocial effects such as the worsening of mental health (n = 6 (15%)), anxiety concerning the virus (n = 12 (30%)), and social isolation (n = 8 (20%), “I stay inside and away from people”).

CONCLUSIONS: While the number of encounters reported suggest adequate access and satisfaction, the comments regarding barriers to care suggest that enhanced approaches may be warranted to improve and sustain veteran perceptions of adequate access to and satisfaction with primary care during times of crisis.

PMID:36131246 | DOI:10.1186/s12875-022-01851-3

BMC Genomics. 2022 Sep 21;23(1):663. doi: 10.1186/s12864-022-08884-z.

ABSTRACT

BACKGROUND: There is a need to match characteristics of tobacco users with cessation treatments and risks of tobacco attributable diseases such as lung cancer. The rate in which the body metabolizes nicotine has proven an important predictor of these outcomes. Nicotine metabolism is primarily catalyzed by the enzyme cytochrone P450 (CYP2A6) and CYP2A6 activity can be measured as the ratio of two nicotine metabolites: trans-3′-hydroxycotinine to cotinine (NMR). Measurements of these metabolites are only possible in current tobacco users and vary by biofluid source, timing of collection, and protocols; unfortunately, this has limited their use in clinical practice. The NMR depends highly on genetic variation near CYP2A6 on chromosome 19 as well as ancestry, environmental, and other genetic factors. Thus, we aimed to develop prediction models of nicotine metabolism using genotypes and basic individual characteristics (age, gender, height, and weight).

RESULTS: We identified four multiethnic studies with nicotine metabolites and DNA samples. We constructed a 263 marker panel from filtering genome-wide association scans of the NMR in each study. We then applied seven machine learning techniques to train models of nicotine metabolism on the largest and most ancestrally diverse dataset (N=2239). The models were then validated using the other three studies (total N=1415). Using cross-validation, we found the correlations between the observed and predicted NMR ranged from 0.69 to 0.97 depending on the model. When predictions were averaged in an ensemble model, the correlation was 0.81. The ensemble model generalizes well in the validation studies across ancestries, despite differences in the measurements of NMR between studies, with correlations of: 0.52 for African ancestry, 0.61 for Asian ancestry, and 0.46 for European ancestry. The most influential predictors of NMR identified in more than two models were rs56113850, rs11878604, and 21 other genetic variants near CYP2A6 as well as age and ancestry.

CONCLUSIONS: We have developed an ensemble of seven models for predicting the NMR across ancestries from genotypes and age, gender and BMI. These models were validated using three datasets and associate with nicotine dosages. The knowledge of how an individual metabolizes nicotine could be used to help select the optimal path to reducing or quitting tobacco use, as well as, evaluating risks of tobacco use.

PMID:36131240 | DOI:10.1186/s12864-022-08884-z

Spine Deform. 2022 Sep 21. doi: 10.1007/s43390-022-00586-6. Online ahead of print.

ABSTRACT

PURPOSE: To compare direct costs of index and revision operations of thoracic posterior spinal instrumented fusion (TPSIF) and thoracic anterior spinal tethering (TAST) for adolescent idiopathic thoracic scoliosis in children.

METHODS: Children (ages 11-18 years) who underwent TPSIF and TAST (2/2013-9/2019) were reviewed. Follow-up < 2 years and cervical instrumentation and/or instrumentation of a lumbar level at L3 or below were exclusion criteria. Patient demographics, radiographic curve magnitude, index operations and postoperative data, as well as indications for revisions/readmissions were collected. Direct costs were identified and compared for index and revision operations during follow-up.

RESULTS: One hundred and four patients were included (TPSIF: 78; TAST: 25). TAST procedures were performed in children significantly younger and for smaller curve magnitudes. They had significantly fewer levels instrumented, shorter operating room (OR) times, and less estimated blood loss (EBL). After operation, a significantly higher percentage of TAST were admitted to ICU. Hospital length of stay (LOS) was similar between groups. Index operations’ average direct costs were significantly higher for TAST than TPSIF ($52,947 v. $46,641; p = 0.02). Major cost drivers for both groups were implants, OR services, post-anesthesia care unit (PACU), and room/board. Revisions following TAST were more frequent than for TPSIF (36 v. 11.5%). Majority of TPSIF revisions were for junctional deformity. Curve progression and overcorrection were most common reason for TAST revisions. Average direct costs for revisions/readmissions were similar between groups (TPSIF: $28,485 v. TAST: $27,590; p = 0.46).

CONCLUSIONS: Index operations’ average direct costs were statistically similar between TPSIF and TAST for adolescent idiopathic scoliosis. Major cost drivers were implants, OR services, PACU, and room/board. TAST index operations’ direct costs and associated direct costs for implants and room/board were significantly higher, while their anesthesia and OR services were significantly lower than TPSIF. TAST revisions were for overcorrection and curve progression, while TPSIF revisions were most commonly for junctional deformity. Overall average direct costs for revisions were similar despite revision rates being higher for TAST.

LEVEL OF EVIDENCE: III.

PMID:36131225 | DOI:10.1007/s43390-022-00586-6

Eur J Health Econ. 2022 Sep 22. doi: 10.1007/s10198-022-01521-2. Online ahead of print.

ABSTRACT

BACKGROUND: Oseltamivir is usually not often prescribed (or reimbursed) for non-high-risk patients consulting for influenza-like-illness (ILI) in primary care in Europe. We aimed to evaluate the cost-effectiveness of adding oseltamivir to usual primary care in adults/adolescents (13 years +) and children with ILI during seasonal influenza epidemics, using data collected in an open-label, multi-season, randomised controlled trial of oseltamivir in 15 European countries.

METHODS: Direct and indirect cost estimates were based on patient reported resource use and official country-specific unit costs. Health-Related Quality of Life was assessed by EQ-5D questionnaires. Costs and quality adjusted life-years (QALY) were bootstrapped (N = 10,000) to estimate incremental cost-effectiveness ratios (ICER), from both the healthcare payers’ and the societal perspectives, with uncertainty expressed through probabilistic sensitivity analysis and expected value for perfect information (EVPI) analysis. Additionally, scenario (self-reported spending), comorbidities subgroup and country-specific analyses were performed.

RESULTS: The healthcare payers’ expected ICERs of oseltamivir were €22,459 per QALY gained in adults/adolescents and €13,001 in children. From the societal perspective, oseltamivir was cost-saving in adults/adolescents, but the ICER is €8,344 in children. Large uncertainties were observed in subgroups with comorbidities, especially for children. The expected ICERs and extent of decision uncertainty varied between countries (EVPI ranged €1-€35 per patient).

CONCLUSION: Adding oseltamivir to primary usual care in Europe is likely to be cost-effective for treating adults/adolescents and children with ILI from the healthcare payers’ perspective (if willingness-to-pay per QALY gained > €22,459) and cost-saving in adults/adolescents from a societal perspective.

PMID:36131214 | DOI:10.1007/s10198-022-01521-2

Salud Publica Mex. 2022 Jul 8;64(4, jul-ago):424-428. doi: 10.21149/13402.

ABSTRACT

OBJECTIVE: To characterize the impact of Mexico’s Co-vid-19 vaccination campaign of older adults.

MATERIALS AND METHODS: We estimated the absolute change in sympto-matic cases, hospitalizations and deaths for vaccine-eligible adults (aged >60 years) and the relative change compared to vaccine-ineligible groups since the campaign started. Re-sults. By May 3, 2021, the odds of Covid-19 cases among adults over 60 compared to 50-59 year olds decreased by 60.3% (95%CI: 53.1, 66.9), and 2 003 cases (95%CI: 1 156, 3 130) were avoided. Hospitalizations and deaths showed similar trends.

CONCLUSIONS: Covid-19 events decreased after vaccine rollout among those eligible for vaccination.

PMID:36130378 | DOI:10.21149/13402

Salud Publica Mex. 2022 Aug 19;64(5, sept-oct):478-487. doi: 10.21149/13584.

ABSTRACT

OBJECTIVE: Evaluate spatially and temporally simultaneous presence of clusters of dengue and Zika clinical cases and their relationship with expected dengue transmission risk.

MATERIALS AND METHODS: A classification of dengue risk transmission was carried out for whole country, and spatial autocorrelation analyses to identify clusters of confirmed clinical cases of dengue and Zika from 2015 to 2018 was conducted using Moran’s Index statistics.

RESULTS: Clusters of both diseases were identified in dengue-high risk munici-palities at the beginning of the outbreak, but, at the end of the outbreak, Zika clusters occurred in dengue low-risk mu-nicipalities.

CONCLUSION: This study identified Zika clusters in low-risk dengue areas suggesting participation of several factors that favor virus introduction and dissemination, such as differences in entomological and control interventions, and the possibility of cross-immunity in the population.

PMID:36130361 | DOI:10.21149/13584

Chronic Obstr Pulm Dis. 2022 Sep 21. doi: 10.15326/jcopdf.2022.0307. Online ahead of print.

ABSTRACT

Accurately interpreting scores on patient-reported outcome (PRO) measures is essential to understanding and communicating treatment benefit. Over the years, terminology and methods for developing recommendations for PRO score interpretation in clinical trials have evolved, leading to some confusion in the field. The phrase “minimal clinically important difference (MCID)” has been simplified to MID and use of responder thresholds to interpret statistically significant treatment effects has increased. Anchor-based derivation methods continue to be the standard, with specific variations preferred by regulatory authorities for drug development programs. In the midst of these changes, the Evaluating Respiratory Symptoms in COPD (E-RS:COPD) was developed and qualified for use as an endpoint in COPD drug development programs. This paper summarizes the evolution of terminology and method preferences for the development of recommendations for interpreting scores from PRO measures used in clinical trials, and how these changes are reflected in the E-RS:COPD recommendations. The intent is to add clarity to discussions around PRO endpoints and facilitate use of the E-RS:COPD as a key efficacy endpoint in clinical trials of COPD.

PMID:36130315 | DOI:10.15326/jcopdf.2022.0307

Health Promot Int. 2022 Aug 1;37(4):daac127. doi: 10.1093/heapro/daac127.

ABSTRACT

This repeated cross-sectional study investigated physical activity and associated barriers and facilitators during the first two waves of COVID-19 restrictions in Ireland. An online, anonymous questionnaire collated data from adults during May (n = 1274) and November (n = 810) 2020. Statistical analysis used a combination of traditional significance testing and Bayesian lasso logistic regression. The pattern of physical activity changed significantly between waves (χ2 86.8 on 3df; p < 0.001). During wave 1 restrictions, the majority [46.1% (n = 587)] of participants reported being more active than usual, decreasing to 26.3% (n = 213) during wave 2. More participants reported that their activity levels were less than usual [W1 29% (n = 369); W2 35% (n = 283)] during wave 2. Adherence to physical activity guidelines decreased from 56.5% (n = 705) to 43.7% (n = 35). Being unable to access their usual means of exercise [OR, 95% OR intervals; W1 1.611 (1.370-1.904), W2 1.638 (1.3731.968)] and advice not to leave home [OR, 95% OR intervals; W1 1.401 (1.164-1.697), W2 1.367 (1.106-1.696)] predicted less activity than usual during both waves. Increased time [OR, 95% OR intervals; W1 2.326 (1.948-2.794), W2 1.809 (1.478-2.233)], and valuing physical activity as important [OR, 95% OR intervals; W1 1.192 (1.001-1.444), W2 1.253 (1.003-1.637)] predicted increased activity during both waves, whilst finding new ways to be active [OR, 95% OR intervals; 2.515 (1.641-3.887)] predicted more activity in wave 2 only. Increases in physical activity of Irish adults during the first phase of COVID-19 restrictions were not maintained during the second wave and barriers to physical activity persisted.

PMID:36130306 | DOI:10.1093/heapro/daac127

Hum Mol Genet. 2022 Sep 20:ddac224. doi: 10.1093/hmg/ddac224. Online ahead of print.

ABSTRACT

We aimed to determine the genetic diversity and molecular characteristics of the Huntington disease (HD) gene (HTT) in Spain. We performed an extended haplotype and exon one deep sequencing analysis of the HTT gene in a nationwide cohort of population-based controls (n = 520) and families with symptomatic individuals referred for HD genetic testing. This group included 331 HD cases and 140 carriers of intermediate alleles. Clinical and family history data were obtained when available. Spanish normal alleles are enriched in C haplotypes (40.1%), while A1 (39.8%) and A2 (31.6%) prevail among intermediate and expanded alleles, respectively. Alleles ≥50 CAG repeats are primarily associated with haplotypes A2 (38.9%) and C (32%), which are also present in 50% and 21.4%, respectively, of HD families with large intergenerational expansions. Non-canonical variants of exon one sequence are less frequent, but much more diverse, in alleles of ≥27 CAG repeats. The deletion of CAACAG, one of the six rare variants not observed among smaller normal alleles, is associated with haplotype C and appears to correlate with larger intergenerational expansions and early onset of symptoms. Spanish HD haplotypes are characterised by a high genetic diversity, potentially admixed with other non-Caucasian populations, with a higher representation of A2 and C haplotypes than most European populations. Differences in haplotype distributions across the CAG length range support differential germline expansion dynamics, with A2 and C showing the largest intergenerational expansions. This haplotype-dependent germline instability may be driven by specific cis-elements, such as the CAACAG deletion.

PMID:36130218 | DOI:10.1093/hmg/ddac224