Prevalence of pain in a sample of long-term survivors of head and neck cancer.

PURPOSE: The experience of long-term pain in head and neck cancer (HNC) survivors is important but has received less attention in the HNC literature. The present study sought to examine the prevalence of pain from 2 to 5 years postdiagnosis and its association with HNC-specific health-related quality of life. MATERIALS & METHODS: Prospective observational study at a single-institution tertiary care center. Pain was measured using a single item ranging from 0 to 10 with 0 representing no pain and 10 representing worst pain possible at 2 through 5 years postdiagnosis. HNC-specific HRQOL was measured using the Head and Neck Cancer Inventory (HNCI). RESULTS: Pain reports were consistent across time. At 2 years postdiagnosis (N = 581), 27.6 % experienced at least some pain with 14.3 % reporting moderate or severe pain. At 3 years postdiagnosis (N = 417), 21.4 % experienced at least some pain with 14.2 % indicating moderate or severe pain. At 4 years postdiagnosis (N = 334), 26.7 % experienced at least some pain with 15.9 % reporting moderate or severe pain. At 5 years postdiagnosis (N = 399), 30.5 % experienced at least some pain with 17.5 % indicating moderate or severe pain. In general, across all four HNCI domains, those in the moderate and severe pain categories largely failed to reach 70 which is indicative of high functioning on the HNCI. CONCLUSIONS: Pain is a considerable issue in long-term HNC survivors up to 5 years postdiagnosis. More research is needed to understand correlates of pain after treatment, including opportunities for screening and intervention, to improve outcomes and optimize recovery in HNC.

Prevalence and persistence of depressive symptoms during the first year postdiagnosis in a large sample of patients with head and neck cancer.

PURPOSE: The experience of persistent depressive symptomatology during the first year postdiagnosis has implications for recovery and adjustment by one year postdiagnosis. The present descriptive study sought to examine the prevalence and persistence of mild to moderate-severe depressive symptomology and associated disease-specific health-related quality of life (HRQOL) in patients with HNC. MATERIALS & METHODS: This study was a prospective observational study at a single-institution tertiary cancer center. Depressive symptomatology was measured using the Beck Depression Inventory (BDI), captured at diagnosis and 3-, 6-, 9-, and 12-months postdiagnosis. HNC-specific HRQOL was measured using the Head and Neck Cancer Inventory (HNCI). Four subgroups were defined by BDI scores over time: persistent-moderate/severe subgroup, persistent-mild subgroup, transient subgroup, and resilient subgroup. RESULTS: The distribution of patients (N = 946) was 65 (6.9 %) in the persistent-moderate/severe subgroup, 190 (20.1 %) in the persistent-mild subgroup, 186 (19.7 %) in the transient subgroup, and 505 (53.3 %) in the resilient subgroup. Across all four HNCI domains, patients in the persistent-moderate/severe subgroup failed to reach a score of 70 by 12-months postdiagnosis which is indicative of high functioning on the HNCI (aesthetics: M = 42.32, SD = 28.7; eating: M = 32.08, SD = 25.7; speech: M = 47.67, SD = 25.3; social disruption: M = 52.39, SD = 24.3). Patients in the persistent-mild subgroup failed to reach 70 in three of four domains. Patients in the resilient subgroup reached, on average, >70 on all HNCI domains. CONCLUSIONS: Depression is a considerable issue during the first year postdiagnosis. Avenues for screening and intervention should be incorporated into HNC patient care per clinical practice guidelines to optimize recovery and HRQOL.

Evaluating the Psychometric Properties of Patient-Reported Outcome Measures for Assessing Symptoms in Hemodialysis: A Systematic Review Using COSMIN Guidelines.

CONTEXT: Patient-reported outcome measures (PROMs) may have an important role in screening and monitoring for unpleasant symptoms in kidney failure. However, there is still little evidence on the psychometric properties of the measures available to assess physical and psychological symptoms in people on hemodialysis. This gap makes it difficult to decide which measure is the most appropriate for use in clinical practice and research with this population. OBJECTIVES: This systematic review aimed to critically appraise, compare, and summarize the quality of the measurement properties of PROMs used to assess symptoms in adults on hemodialysis. METHODS: The protocol for this review was registered in PROSPERO (CRD42023393441). The last database search update was performed on November 25, 2022. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines informed methodological quality assessment, data extraction, analysis, and synthesis. RESULTS: Twenty-seven primary studies reported the measurement properties of 16 PROMs used to assess physical and psychological symptoms in adults on hemodialysis. Results showed that most measures lacked the necessary psychometric evidence to attest their suitability for this study population, and few underwent rigorous validation procedures. Overall, caveats were found on methodological quality and evidence of content validity and structural validity, and little data was available on responsiveness, measurement error, and cross-cultural validity. CONCLUSION: The current systematic review provides the basis for identifying PROMs with potential utility for assessing symptoms in hemodialysis care. Several recommendations are presented to help guide future research aimed at improving the rigor of validation and/or translation procedures of existing (and future) measures using COSMIN guidelines.

Rewiring of Aminoacyl-tRNA Synthetase Localization and Interactions in Plants With Extensive Mitochondrial tRNA Gene Loss.

The number of tRNAs encoded in plant mitochondrial genomes varies considerably. Ongoing loss of bacterial-like mitochondrial tRNA genes in many lineages necessitates the import of nuclear-encoded counterparts that share little sequence similarity. Because tRNAs are involved in highly specific molecular interactions, this replacement process raises questions about the identity and trafficking of enzymes necessary for the maturation and function of newly imported tRNAs. In particular, the aminoacyl-tRNA synthetases (aaRSs) that charge tRNAs are usually divided into distinct classes that specialize on either organellar (mitochondrial and plastid) or nuclear-encoded (cytosolic) tRNAs. Here, we investigate the evolution of aaRS subcellular localization in a plant lineage (Sileneae) that has experienced extensive and rapid mitochondrial tRNA loss. By analyzing full-length mRNA transcripts (PacBio Iso-Seq), we found predicted retargeting of many ancestrally cytosolic aaRSs to the mitochondrion and confirmed these results with colocalization microscopy assays. However, we also found cases where aaRS localization does not appear to change despite functional tRNA replacement, suggesting evolution of novel interactions and charging relationships. Therefore, the history of repeated tRNA replacement in Sileneae mitochondria reveals that differing constraints on tRNA/aaRS interactions may determine which of these alternative coevolutionary paths is used to maintain organellar translation in plant cells.

Examination of Predictors of Pain at 12 Months Postdiagnosis in Head and Neck Cancer Survivors.

OBJECTIVE: Pain following the completion of treatment is important but has received less attention in the head and neck cancer (HNC) literature. The present study sought to examine the prevalence and predictors of pain measured 12 months postdiagnosis and its impact on HNC-specific health-related quality of life (HRQOL) in 1038 HNC survivors. STUDY DESIGN: Prospective observational study. SETTING: Single-institution tertiary care center. METHODS: Pain was measured using a single item ranging from 0 to 10 with 0 representing no pain and 10 representing the worst pain possible. Self-reported depressive symptomatology was measured using the Beck Depression Inventory and self-reported problem alcohol use was measured by the Short Michigan Alcoholism Screening Test. HNC-specific HRQOL was measured using the Head and Neck Cancer Inventory (HNCI). RESULTS: Hierarchical multivariable linear regression analyses indicated that in addition to pain at 3 months postdiagnosis (ß = .145, t = 3.18, sr2 = .019, p = .002), both depressive symptomatology (ß = .110, t = 2.49, sr2 = .011, p = .015) and problem alcohol use (ß = .092, t = 2.07, sr2 = .008, p = .039) were significant predictors of pain at 12 months postdiagnosis. Subgroup analyses suggest that across all 4 HNCI domains, those in the moderate and severe pain groups at 12 months postdiagnosis failed to reach 70 which is indicative of high functioning. CONCLUSION: Pain in patients with HNC is a considerable issue at 12 months postdiagnosis, deserving further attention. Behavioral factors such as depression and problem alcohol use may be associated with pain and require systematic screening over time to identify and treat issues that impact optimal long-term recovery from HNC, including disease-specific HRQOL.

Designing family-based interventions in kidney failure: The perspectives of the triad 'patients on haemodialysis/family caregivers/healthcare professionals.

OBJECTIVES: This study explored the perspectives of people undergoing in-centre haemodialysis, family caregivers, and healthcare professionals about the development and implementation of family-based interventions in renal care settings. DESIGN: A qualitative exploratory study was carried out combining purposive and snowball sampling techniques. METHODS: Semi-structured interviews were submitted to thematic analysis. RESULTS: A total of 82 individuals (27 adults on haemodialysis, 32 family caregivers, and 23 healthcare professionals) participated in this study. Five major themes were identified: (i) educational needs (improve disease and treatment-related knowledge; acquire better clarification on dialysis-related health behaviours); (ii) support needs (easier access to available community resources and professional psychological support; additional emotional and instrumental support from family members); (iii) expected barriers (concerns about participating in a group format; availability of the person on haemodialysis/family caregiver dyad; travel to the intervention site and associated costs); (iv) expected benefits (mutual emotional validation and support; improve family coping skills and involvement); and (v) preferences for content and format (interdisciplinary and moderated by health psychologists) and timing of the intervention (weekends and/or non-dialysis days). CONCLUSIONS: Findings suggested that interventions focused on the family system in kidney failure need to follow an interdisciplinary approach, combining psychosocial support with an educational component. Future research is needed to minimize barriers to the conjoint participation of the person on haemodialysis/caregiver dyad. This study identifies important intervention goals to inform the design of family-based interventions for people receiving haemodialysis and their family caregivers.

Mapping Patients' Perceived Facilitators and Barriers to In-Center Hemodialysis Attendance to the Health Belief Model: Insights from a Qualitative Study.

BACKGROUND: Previous research has shown that deliberate withdrawal, skipping, and/or shortening hemodialysis sessions has become a major health problem associated with poor clinical outcomes and early mortality in patients with end-stage renal disease (ESRD). However, patients' experiences with this treatment remain largely unexplored. This study aimed to explore patients' perceived facilitators and barriers to in-center hemodialysis attendance and map these findings to the Health Belief Model. METHODS: A qualitative exploratory study was conducted with a purposive sample. Semi-structured interviews were conducted and submitted to thematic analysis. RESULTS: Twenty-four patients (66.2 ± 12.3 years old; length of time on hemodialysis: 35.2 ± 51.5 months) were interviewed. Five major facilitators (social support, perceived benefits, self-efficacy, time on dialysis, and risk/susceptibility perception) and two barriers (lack of knowledge about ESRD and hemodialysis, and psychosocial costs) were identified. CONCLUSION: Adherence to the prescribed regimen of hemodialysis attendance is a complex and multidimensional phenomenon that involves an interaction between modifying factors (social support, disease and treatment knowledge, time on dialysis) and patients' perceived benefits, perceived risks, self-efficacy, and treatment costs. This study findings expand knowledge by suggesting that perceiving health benefits from the beginning of treatment, self-efficacy to deal with dialysis demands, and purpose in life are important facilitators of adherence to in-center hemodialysis sessions. Furthermore, it suggests that the impact of the hemodialysis regimen on the emotional well-being of family members is an important barrier. Future interventions should focus on skills training to promote self-efficacy and family coping with the demands of in-center hemodialysis, improve disease and treatment knowledge, and help balance perceived benefits with dialysis costs.

Examination of risk factors for discontinuation of follow-up care in patients with head and neck cancer.

BACKGROUND: Little research has examined discontinuation of follow-up care in patients with head and neck cancer. This exploratory study sought to examine key demographic, disease, and behavioral factors as possible correlates of discontinuation (N = 512). METHODS: Cross-sectional study examined correlates of discontinuation of follow-up care within 1 year. The primary outcome was defined as a disease-free survivor not returning to cancer clinic for two consecutive follow-up appointments within the first year of care and not reentering oncologic care at any point thereafter. Demographic, disease, and behavioral factors were examined using multivariable logistic regression. RESULTS: One hundred twenty-six (24.6%) patients discontinued by 12-month follow-up. Being unmarried (OR = 1.28, 95% CI = 1.01-1.63, p = 0.041) and having elevated depressive symptomatology (OR = 1.04, 95% CI = 1.01-1.07, p = 0.034) were significantly associated with discontinuation. Receipt of a single (vs. multimodal) treatment approached significance (OR = 1.71, 95% CI = 0.96-3.07, p = 0.071). CONCLUSION: Approximately one quarter of patients disengaged from important follow-up care within 1 year. Lack of social support, depressive symptomatology, and single treatment modality may be important correlates of discontinuation of care in patients with head and neck cancer. Additional studies of this outcome are needed. Improved understanding of correlates associated with discontinuation could facilitate the identification of at-risk patients and further development of interventions to keep patients engaged at a crucial time in the survivorship care trajectory.

Establishing the criterion validity of self-report measures of adherence in hemodialysis through associations with clinical biomarkers: A systematic review and meta-analysis.

Accurate measurement of adherence is crucial to rigorously evaluate interventions aimed at improving this outcome in patients undergoing in-center hemodialysis. Previous research has shown great variability in non-adherence rates between studies, mainly due to the use of different direct (e.g., clinical biomarkers) and indirect (e.g., questionnaires) measures. Although self-reported adherence in hemodialysis has been widely explored, it is still unclear which is the most accurate questionnaire to assess this outcome; therefore, the question of how to optimize adherence measurement in research and clinical practice has emerged as a key issue that needs to be addressed. This systematic review and meta-analysis aimed to explore the criterion validity of self-report measures of adherence in hemodialysis established through the association between test scores and clinical biomarkers (the criterion measure). The protocol was registered in PROSPERO (2021 CRD42021267550). The last search was performed on March 29th, 2022, on Web of Science (all databases included), Scopus, CINHAL, APA PsycInfo, and MEDLINE/PubMed. Twenty-nine primary studies were included, and thirty-eight associations were analyzed. The Hunter-Schmidt's meta-analysis was computed for the associations with more than two studies (n = 20). The results showed that six associations were large (16%), 11 were medium (29%) and the remaining were of small strength. The test scores from the End-Stage Renal Disease Adherence Questionnaire (range: 0.212

Social networks in the single cell.

This article comments on: Chustecki JM, Etherington RD, Gibbs DJ, Johnston IG. 2022. Altered collective mitochondrial dynamics in the Arabidopsis msh1 mutant compromising organelle DNA maintenance. Journal of Experimental Botany 73, 5428-5439. Plant mitochondrial DNA (mtDNA) can become damaged in many ways. A major repair mechanism is homologous recombination, which requires an undamaged DNA template. Presumably, this template comes from a different mitochondrion in the same cell. Plant mitochondria undergo fission and fusion to form transient networks which could allow the exchange of genetic information. To test this hypothesis, Chustecki et al. (2022) used msh1 mutants with defective DNA repair, and showed that mitochondrial interactions increased, revealing a link between the physical and genetic behavior of mitochondria.

Disparities in dialysis modality decision-making using a social-ecological lens: a qualitative approach.

BACKGROUND: Patients with end-stage kidney disease (ESKD) may choose to undergo dialysis in-center or at home, but uptake of home dialysis in the US has been minimal despite its benefits over in-center dialysis. Factors that may have led patients to select home dialysis over in-center dialysis are poorly understood in the literature, and interventions to improve selection of home dialysis have focused on patient knowledge and shared decision-making processes between patients and providers. The purpose of this study was to explore micro- and macro-level factors surrounding dialysis modality decision-making among patients undergoing in-center and home dialysis, and explore what leads patients to select home dialysis over in-center dialysis. METHODS: Semi-structured qualitative interviews were conducted in a dialysis clinic at a large Midwestern research hospital, from September 2019 to December 2020. Participants were 18 years or older, undergoing dialysis for ESKD, and had the cognitive ability to provide consent. Surveys assessing demographic and clinical information were administered to participants following their interviews. RESULTS: Forty patients completed interviews and surveys (20 [50%] in-center dialysis, 17 [43%] female, mean [SD] age, 59 [15.99] years). Qualitative findings suggested that healthcare access and engagement before entering nephrology care, after entering nephrology care, and following dialysis initiation influenced patients' awareness regarding their kidney disease status, progression toward ESKD, and dialysis options. Potential modifiers of these outcomes include race, ethnicity, and language barriers. Most participants adopted a passive-approach during decision-making. Finally, fatigue, concerns regarding one's dialyzing schedule, and problems with fistula/catheter access sites contributed to overall satisfaction with one's dialysis modality. CONCLUSIONS: Findings point to broader factors affecting dialysis selection, including healthcare access and racial/ethnic inequities. Providing dialysis information before entering nephrology and after dialysis initiation may improve patient agency in decision-making. Additional resources should be prioritized for patients of underrepresented backgrounds. Dialysis decision-making may be appropriately modeled under the social-ecological framework to inform future interventions.

Problem alcohol and tobacco use in head and neck cancer patients at diagnosis: associations with health-related quality of life.

PURPOSE: Problem alcohol and tobacco use in patients with head and neck cancer (HNC) frequently co-occur and each are associated with poor outcomes including health-related quality of life (HRQOL). The purpose of this descriptive exploratory study was to identify the prevalence of these co-occurring behaviors and associations with HNC-specific HRQOL within the first year of diagnosis in a large sample of patients with HNC. METHODS: Cross-sectional study examined prevalence of co-occurring problem alcohol and tobacco use at diagnosis in a large sample of patients with HNC (N = 1327). Problem alcohol use was assessed using the Short Michigan Alcoholism Screening Test (SMAST); patients were classified as current/previous/never smokers based on self-reported tobacco use. HNC-specific HRQOL was assessed using the Head and Neck Cancer Inventory (HNCI), measured at diagnosis and 3 and 12 months postdiagnosis. RESULTS: Three hundred twenty-five of 1327 (24.5%) scored 3 + on the SMAST at diagnosis, suggesting problem alcohol use and nearly 30% (28.4%) were current smokers. Of those with problem alcohol use, 173 (53.2%) were also current smokers. In total, 173 of 1327 (13.0%) exhibited both behaviors at diagnosis. Covariate-adjusted mean HNCI scores suggest that patients classified as both problem drinkers and current smokers have lower HRQOL scores during the first year postdiagnosis in multiple HNC-specific domains. CONCLUSION: HNC patients should be screened for alcohol and tobacco use at diagnosis. Multimodal behavioral health interventions may provide one avenue for improved access and outcomes, particularly for patients at distance, and deserve further study in HNC.

Health-related quality of life in head and neck cancer survivors: Evaluating the rural disadvantage.

PURPOSE: Head and neck cancer (HNC) survivors often experience distress and health-related quality of life (HRQOL) impairment. Research suggests that rural cancer patients may have poorer outcomes than urban patients. This study examined whether HNC patient emotional and HRQOL outcomes differ in those living in a rural versus urban location at 6 and 12 months postdiagnosis. METHODS: A total of 261 HNC patients were included from a longitudinal study of HNC outcomes. The majority were diagnosed with advanced stage cancer (51.3%); the most common cancer site was oral cavity (41.0%). Rurality was measured using the US Department of Agriculture Rural Urban Commuting Area codes. Depression was measured using the Beck Depression Inventory (BDI), general HRQOL using the Short Form-36 (SF-36), and HNC-specific HRQOL using the Head and Neck Cancer Inventory (HNCI). Analyses were 2 (group) × 3 (assessment) repeated measures ANCOVAs, controlling for demographic and clinical characteristics. FINDINGS: Approximately 45% of the sample lived in a rural location. Follow-up comparisons of significant overall models indicated that rural patients reported significantly more nonsomatic depression symptoms at 6-month follow-up. Rural patients were also more likely to report significantly poorer general mental HRQOL at 12-month follow-up, significantly poorer HNC-specific HRQOL related to eating at 6- and 12-month follow-up, and marginally worse aesthetics at 12-month follow-up. CONCLUSIONS: These findings are consistent with suggestions that rural HNC patients may be at heightened risk for depression symptoms and decrements in HRQOL. Patients should be screened and regularly monitored for issues with depression and HNC-specific HRQOL throughout the survivorship period.

Association of depressive symptomatology with problem alcohol use in rural head and neck cancer patients at diagnosis.

PURPOSE: Problem alcohol use is a risk factor for the development of head and neck cancer (HNC) and continued use is associated with poor outcomes; depressive symptoms may be associated with this behavior. DESIGN: Exploratory cross-sectional study examined depressive symptoms as a correlate of self-reported problem alcohol use at diagnosis. SAMPLE/METHODS: Multivariable linear regression examined depressive symptoms as a correlate of problem alcohol use in a sample of rural HNC patients (N = 249). FINDINGS: Over half (55.2%) of rural patients with potentially problem alcohol use exhibited mild to moderate depressive symptomatology. Regression models controlling for age, cancer site, stage, sex, tobacco use, and treatment modality indicated that depressive symptoms at diagnosis were associated with self-reported problem alcohol use scores at diagnosis (ß = .186, sr2 = .031, p < .01). Follow-up subgroup analyses demonstrated that depressive symptoms at diagnosis were significantly associated with self-reported problem alcohol use in male patients, those with advanced stage disease, and of older age. CONCLUSIONS/IMPLICATIONS: HNC patients should be screened for alcohol use and depression at diagnosis. Access to behavioral health treatment and/or referral options may be lacking in rural areas thus additional ways of connecting rural patients to specialty care should be explored. These may include telehealth and multimodal interventions to address complex behavioral health cases. Additional research in important patient subgroups such as older patients and those presenting with advanced disease is also warranted.

Caring for parents with end-stage renal disease: What do adult children face and how do they cope?

AIM: This study aimed to explore the stressors and coping strategies of adult children who care for their parents with end-stage renal disease (ESRD) undergoing in-centre haemodialysis. BACKGROUND: Given the growing number of older patients with ESRD, adult children are increasingly providing more care and assistance to their parents with this condition. However, little is still known about the experiences of caring for a parent undergoing haemodialysis. DESIGN: A qualitative exploratory study was conducted in accordance with the Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines. METHODS: Semi-structured face-to-face interviews with nineteen adult children (44.9 ± 11.7 years old) were carried out. Data were transcribed verbatim and subjected to thematic analysis. RESULTS: Four stressors (managing disease and treatment-related requirements, patients' reaction to treatment, lack of support from family members, and additional challenges to personal and family life) and five coping strategies (active coping and planning, seeking social support for emotional use, accepting the situation as it is, venting emotions, and maintaining interests outside caring) were identified. CONCLUSION: Caring for a parent undergoing haemodialysis is an experience with several challenges, marked by educational needs, emotional distress, lack of support from close relatives and the need to manage multiple responsibilities. RELEVANCE TO CLINICAL PRACTICE: Findings highlight the importance of developing interdisciplinary educational and supportive interventions to support this group of caregivers. These interventions should facilitate access to disease and treatment-related information, provide emotional support, and train coping skills to prevent burden and promote healthy adjustment to the demands of ESRD care.

A dedicated flavin-dependent monooxygenase catalyzes the hydroxylation of demethoxyubiquinone into ubiquinone (coenzyme Q) in Arabidopsis.

Ubiquinone (Coenzyme Q) is a vital respiratory cofactor and liposoluble antioxidant. In plants, it is not known how the C-6 hydroxylation of demethoxyubiquinone, the penultimate step in ubiquinone biosynthesis, is catalyzed. The combination of cross-species gene network modeling along with mining of embryo-defective mutant databases of Arabidopsis thaliana identified the embryo lethal locus EMB2421 (At1g24340) as a top candidate for the missing plant demethoxyubiquinone hydroxylase. In marked contrast with prototypical eukaryotic demethoxyubiquinone hydroxylases, the catalytic mechanism of which depends on a carboxylate-bridged di-iron domain, At1g24340 is homologous to FAD-dependent oxidoreductases that instead use NAD(P)H as an electron donor. Complementation assays in Saccharomyces cerevisiae and Escherichia coli demonstrated that At1g24340 encodes a functional demethoxyubiquinone hydroxylase and that the enzyme displays strict specificity for the C-6 position of the benzoquinone ring. Laser-scanning confocal microscopy also showed that GFP-tagged At1g24340 is targeted to mitochondria. Silencing of At1g24340 resulted in 40 to 74% decrease in ubiquinone content and de novo ubiquinone biosynthesis. Consistent with the role of At1g24340 as a benzenoid ring modification enzyme, this metabolic blockage could not be bypassed by supplementation with 4-hydroxybenzoate, the immediate precursor of ubiquinone's ring. Unlike in yeast, in Arabidopsis overexpression of demethoxyubiquinone hydroxylase did not boost ubiquinone content. Phylogenetic reconstructions indicated that plant demethoxyubiquinone hydroxylase is most closely related to prokaryotic monooxygenases that act on halogenated aromatics and likely descends from an event of horizontal gene transfer between a green alga and a bacterium.

Plant Mitochondria are a Riddle Wrapped in a Mystery Inside an Enigma.

A fundamental paradox motivates the study of plant mitochondrial genomics: the mutation rate is very low (lower than in the nucleus) but the rearrangement rate is high. A landmark paper published in Journal of Molecular Evolution in 1988 established these facts and revealed the paradox. Jeffrey Palmer and Laura Herbon did a prodigious amount of work in the pre-genome sequencing era to identify both the high frequency of rearrangements between closely related species, and the low frequency of mutations, observations that have now been confirmed many times by sequencing. This paper was also the first to use molecular data on rearrangements as a phylogenetic trait to build a parsimonious tree. The work was a technical tour-de-force, its findings are still at the heart of plant mitochondrial genomics, and the underlying molecular mechanisms that produce this paradox are still not completely understood.

Problem alcohol use among rural head and neck cancer patients at diagnosis: Associations with health-related quality of life.

OBJECTIVE: Problem alcohol use in persons with head and neck cancer (HNC) is associated with poor outcomes, including survival. Some evidence suggests that individuals living in rural areas may be at greater risk of problem alcohol use. The present exploratory cross-sectional study sought to examine problem alcohol use at diagnosis in a sample of HNC patients by rural versus urban status. METHODS: Self-reported problem alcohol use as measured by the Short Michigan Alcoholism Screening Test (SMAST) was examined in rural and urban HNC patients at diagnosis (N = 454). Multivariable linear regression analysis was conducted to examine correlates of problem alcohol use. Subgroup analyses examined HNC-specific health-related quality of life (HRQOL) by problem drinking status at diagnosis and 3- and 12-month postdiagnosis in rural patients. RESULTS: Multivariable linear regression analysis controlling for age, cancer site, cancer stage, depressive symptoms at diagnosis, and tobacco use at diagnosis indicated that rural residence was significantly associated with SMAST scores at diagnosis such that rural patients were more likely to report higher scores (ß = 0.095, sr2  = 0.010, p = 0.04). Covariate-adjusted subgroup analyses suggest that rural patients with self-reported problem alcohol use may exhibit deficits in HNC-specific HRQOL at diagnosis and 3- and 12-month postdiagnosis. CONCLUSIONS: HNC patients should be screened for problem alcohol use at diagnosis and counseled regarding the deleterious effects of continued drinking during treatment and beyond. Because access to treatment and referral options may be lacking in rural areas, additional ways of connecting rural patients to specialty care should be explored.

A cluster randomized trial to evaluate a centralized remote clinical pharmacy service in large, health system primary care clinics.

Background: We developed a remote cardiovascular risk service (CVRS) managed by clinical pharmacists to support primary care teams. The purpose of this study was to examine whether the CVRS could improve guideline adherence in primary care clinics with diverse geographic and patient characteristics. Methods: This study was a cluster-randomized trial initiated in 20 primary care clinics across the US. Clinics were stratified as high or low minority and then randomized to receive the intervention or maintain usual care for 12 months. The primary outcome was adherence to relevant The Guideline Advantage (TGA) criteria met. TGA is a compilation of criteria from practice guidelines intended to improve the quality of primary care. Post-hoc outcomes included changes in individual TGA measures. Results: A total of 401 study subjects were included in the analysis. Mean TGA scores remained the same in the intervention group (n=193, 0.72) and slightly decreased in the usual care group (n=208, 0.67 to 0.66) over the 12-month study period. There was no significant difference between the mean TGA scores in intervention and usual care groups for the overall population at 12 months (0.72 versus 0.66 respectively, p=0.10). For under-represented minority subjects, there was no significant difference between TGA scores at 12 months (n=186; 0.70 versus 0.67, respectively, p=0.50). In a post-hoc analysis of subjects uncontrolled at baseline, there was a significant improvement in systolic BP at 12 months in the intervention group versus usual care (model-based difference of -8.03mmHg, p=0.03). Conclusions: Improvements in individual TGA measures were limited, in part, due to higher than expected baseline TGA scores. Future studies of this model should focus on patients with uncontrolled conditions at high risk for cardiovascular events. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT02215408; https://clinicaltrials.gov/ct2/show/NCT02215408?id=NCT02215408.

Association of patient preferences on medication discussion in hypertension: Results from a randomized clinical trial.

Patient-centered care has received significant attention and is an integral component of high-quality healthcare. While it is often assumed that most prefer a patient-centered role orientation, such preferences exist along a continuum with some patients preferring a more provider-centered role. The present study examines patient preference data from a randomized clinical trial designed to test the efficacy of a patient activation intervention to promote thiazide prescribing for veteran patients with uncontrolled hypertension. Patient preferences for involvement in healthcare were assessed using the 9-item Sharing subscale of the Patient-Practitioner Orientation Scale (PPOS). The primary aim was to examine differences in discussion of thiazide use in the clinical encounter by those scoring high versus low on the PPOS. Five hundred ninety-five veteran patients were randomized to either one of three intervention groups or a usual care control group. The adjusted odds ratios (OR) for the three intervention groups relative to the control group indicated that thiazide discussion increased as a function of intervention intensity across both high and low PPOS groups. ORs for the most intensive intervention group were 3.72 (95% CI = 1.61-8.65, p < .01) for high PPOS patients and 6.71 (95% CI = 2.59-10.67, p < .001) for low PPOS patients. Results suggest that this patient activation intervention is effective for veteran patients representing a range of preferred involvement. Consideration of such preferences may be useful in tailoring future interventions in the healthcare context.