Exploring management and outcomes of elderly patients with glioblastoma using data from two randomised trials (GEINO1401/EX-TEM).

PURPOSE: The impact of age on optimal management of glioblastoma remains unclear. A recent combined analysis of two randomised trials, GEINO14-01 and EX-TEM, found no benefit from extending post-radiation temozolomide in newly diagnosed glioblastoma. Here, we explore the impact of age. METHODS: Relevant intergroup statistics were used to identify differences in tumour, treatment and outcome characteristics based on age with elderly patients (EP) defined as age 65 years and over. Survival was estimated using the Kaplan Meier method. RESULTS: Of the combined 205 patients, 57 (28%) were EP. Of these, 95% were ECOG 0-1 and 65% underwent macroscopic resection compared with 97% and 61% of younger patients (YP) respectively. There were numerically less MGMT-methylated (56% vs. 63%, p = 0.4) and IDH-mutated (4% vs. 13%, p = 0.1) tumours in EP vs. YP. Following surgery, EP were more likely to receive short course chemoradiation (17.5% vs. 6%, p = 0.017). At recurrence, EP tended to receive or best supportive care (28.3% vs. 15.4%, p = 0.09) or non-surgical options (96.2% vs. 84.6%, p = 0.06), but were less likely to receive bevacizumab (23.1% vs. 49.5%, p < 0.01). Median PFS was similar at 9.3months in EP and 8.5months in YP, with similar median OS at 20months. CONCLUSION: In this trial population of predominantly fit EP, survival was similar to YP despite a proportion receiving less aggressive therapy at diagnosis and recurrence. Advancing age does not appear to be an adverse prognostic factor for glioblastoma when patients are fit for treatment, and a less aggressive approach in selected patients may not compromise outcomes.

Precision medicine for psychotic disorders: objective assessment, risk prediction, and pharmacogenomics.

Psychosis occurs inside the brain, but may have external manifestations (peripheral molecular biomarkers, behaviors) that can be objectively and quantitatively measured. Blood biomarkers that track core psychotic manifestations such as hallucinations and delusions could provide a window into the biology of psychosis, as well as help with diagnosis and treatment. We endeavored to identify objective blood gene expression biomarkers for hallucinations and delusions, using a stepwise discovery, prioritization, validation, and testing in independent cohorts design. We were successful in identifying biomarkers that were predictive of high hallucinations and of high delusions states, and of future psychiatric hospitalizations related to them, more so when personalized by gender and diagnosis. Top biomarkers for hallucinations that survived discovery, prioritization, validation and testing include PPP3CB, DLG1, ENPP2, ZEB2, and RTN4. Top biomarkers for delusions include AUTS2, MACROD2, NR4A2, PDE4D, PDP1, and RORA. The top biological pathways uncovered by our work are glutamatergic synapse for hallucinations, as well as Rap1 signaling for delusions. Some of the biomarkers are targets of existing drugs, of potential utility in pharmacogenomics approaches (matching patients to medications, monitoring response to treatment). The top biomarkers gene expression signatures through bioinformatic analyses suggested a prioritization of existing medications such as clozapine and risperidone, as well as of lithium, fluoxetine, valproate, and the nutraceuticals omega-3 fatty acids and magnesium. Finally, we provide an example of how a personalized laboratory report for doctors would look. Overall, our work provides advances for the improved diagnosis and treatment for schizophrenia and other psychotic disorders.

Functional neurogenomic responses to acoustic threats, including a heterospecific referential alarm call and its referent, in the auditory forebrain of red-winged blackbirds.

In animal communication, functionally referential alarm calls elicit the same behavioral responses as their referents, despite their typically distinct bioacoustic traits. Yet the auditory forebrain in at least one songbird species, the black-capped chickadee Poecile atricapillus, responds similarly to threat calls and their referent predatory owl calls, as assessed by immediate early gene responses in the secondary auditory forebrain nuclei. Whether and where in the brain such perceptual and cognitive equivalence is processed remains to be understood in most other avian systems. Here, we studied the functional neurogenomic (non-) equivalence of acoustic threat stimuli perception by the red-winged blackbird Agelaius phoeniceus in response to the actual calls of the obligate brood parasitic brown-headed cowbird Molothrus ater and the referential anti-parasitic alarm calls of the yellow warbler Setophaga petechia, upon which the blackbird is known to eavesdrop. Using RNA-sequencing from neural tissue in the auditory lobule (primary and secondary auditory nuclei combined), in contrast to previous findings, we found significant differences in the gene expression profiles of both an immediate early gene, ZENK (egr-1), and other song-system relevant gene-products in blackbirds responding to cowbird vs. warbler calls. In turn, direct cues of threats (including conspecific intruder calls and nest-predator calls) elicited higher ZENK and other differential gene expression patterns compared to harmless heterospecific calls. These patterns are consistent with a perceptual non-equivalence in the auditory forebrain of adult male red-winged blackbirds in response to referential calls and the calls of their referents.

Comparative genomic analysis of Fischer F344 rat livers exposed for 90 days to 3-methylfuran or its parental compound furan.

Furan is a naturally forming compound found in heat-processed foods such as coffee, canned meats, and jarred baby food. It is concurrently found with analogues including 2-methylfuran (2-MF) and 3-methylfuran (3-MF), and toxicity studies demonstrate all are potent liver toxins. Toxicity studies found 3-MF is more toxic than either furan, or 2-MF. The present analysis assesses the transcriptional response in liver samples taken from male Fischer (F344) rats exposed to furan or 3-MF from 0 to 2.0 and 0-1.0 mg/kg bw/day, respectively, for 90 days. Transcriptional analyses found decreased liver function and fatty acid metabolism are common responses to both furan and 3-MF exposure. Furan liver injury promotes a ductular reaction through Hippo and TGFB signalling, which combined with increased immune response results in ameliorating perturbed bile acid homeostasis in treated rats. Failure to activate these pathways in 3-MF exposed rats and decreased p53 activity leads to cholestasis, and increased toxicity. Finally, BMD analysis indicate many of the most sensitive pathways affected by furan and 3-MF exposure relate to metabolism - malate dehydrogenase and glucose metabolism with BMDLs of 0.03 and 0.01 mg/kg bw/day for furan and 3-MF exposure, respectively, which agrees with BMDLs previously reported for apical and microarray data.

A combined analysis of two prospective randomised studies exploring the impact of extended post-radiation temozolomide on survival outcomes in newly diagnosed glioblastoma.

PURPOSE: The optimal duration of post-radiation temozolomide in newly diagnosed glioblastoma remains unclear, with no published phase III randomised trials. Standard-of-care stipulates 6 months. However, in routine care, it is often extended to 12 months, despite lacking robust supporting data. METHODS: GEINO14-01 (Spain) and EX-TEM (Australia) studies enrolled glioblastoma patients without progression at the end of 6 months post-radiation temozolomide. Participants were randomised 1:1 to six additional months of temozolomide or observation. Primary endpoint was 6-month progression free survival from date of randomisation (6mPFS). Secondary endpoints included overall survival (OS) and toxicity. 204 patients were required to detect an improvement in 6mPFS from 50 to 60% (80% power). Neither study recruited sufficient patients. We performed a combined analysis of individual patient data. RESULTS: 205 patients were recruited: 159 in GEINO14-01 (2014-2018) and 46 in EX-TEM (2019-2022). Median follow-up was 20.0 and 14.5 months. Baseline characteristics were balanced. There was no significant improvement in 6mPFS (57.2% vs 64.0%, OR0.75, p = 0.4), nor across any subgroups, including MGMT methylated; PFS (HR0.92, p = 0.59, median 7.8 vs 9.7 months); or OS (HR1.03, p = 0.87, median 20.1 vs 19.4 months). During treatment extension, 64% experienced any grade adverse event, mainly fatigue and gastrointestinal (both 54%). Only a minority required treatment changes: 4.5% dose delay, 7.5% dose reduction, 1.5% temozolomide discontinuation. CONCLUSION: For glioblastoma patients, extending post-radiation temozolomide from 6 to 12 months is well tolerated but does not improve 6mPFS. We could not identify any subset that benefitted from extended treatment. Six months should remain standard-of-care.

Hyperbaric Oxygen Therapy for Soft Tissue Injury in Open Musculoskeletal Trauma: A Prospective Study.

Background Non-union, chronic pain, functional disability, and infection are all things that have been associated with open fractures with severe soft tissue damage leading to the need for additional hospitalization, and sometimes even subsequent surgeries and weeks or months of rehabilitation. Open fractures and severe musculoskeletal injuries are occasionally treated with hyperbaric oxygen therapy (HBOT) in an effort to reduce the risk of complications and increase the likelihood of a successful recovery. Methods A prospective randomized controlled study was done between January 2019 and August 2022 at a tertiary health care center including 60 patients with a severe soft tissue injury (Grade II and III) divided into two groups - group-CT (30 patients who received conventional treatment) and group HT (30 patients, who received HBOT in addition to conventional treatment). The outcome was measured according to the Bates-Jensen Wound Assessment Tool. Results The wound size, depth, and granulation were significantly reduced in group-HT patients. In the final session, the patient's severity of the wound in group-HT was significantly reduced (P = 0.0001) compared to group-CT. Conclusions Patients who received HBOT reported a significant improvement in their wounds.

Qualitative analysis of healthcare provider perspectives to evaluating beta-lactam allergies.

BACKGROUND: There is a lack of understanding of the barriers reported by healthcare providers when evaluating beta-lactam allergies, but knowledge of these barriers is required for practical and effective implementation interventions. METHODS: Twenty-five healthcare providers, consisting of physicians, nurses and pharmacists practicing in the areas of intensive care, emergency medicine, infectious disease and general hospital practice, were interviewed between September 2021 and July 2023. Twenty-three of these providers were practising in the USA. A semi-structured interview guide grounded in the Theoretical Domain Framework was used for the interviews. Deductive and inductive analysis was performed on the interview transcripts, and translated into intervention recommendations using the Behaviour Change Wheel. RESULTS: Widely held beliefs included a lack of clear policy for the evaluation of allergies, confusing or missing documentation of allergy information, confidence in their own and their colleagues' ability to evaluate allergies when information is available, and pharmacists as the provider most equipped to evaluate beta-lactam allergies. CONCLUSIONS: Health systems should adopt and disseminate policies for the evaluation of beta-lactam allergies, and promote the use of pharmacists in the evaluation of drug allergies when possible. Allergy sections of electronic health records should be reworked to encourage unambiguous documentation of allergy reactions and support using previously tolerated beta-lactam antibiotics.

The Oral Microbiome and Cross-Kingdom Interactions during Pregnancy.

Pregnancy initiates a temporary transition in the maternal physiological state, with a shift in the oral microbiome and a potential increase in frequency of oral diseases. The risk of oral disease is higher among populations of Hispanic and Black women and those with lower socioeconomic status (low SES), demonstrating a need for intervention within these high-risk populations. To further our understanding of the oral microbiome of high-risk pregnant women, we characterized the oral microbiome in 28 nonpregnant and 179 pregnant low-SES women during their third trimester living in Rochester, New York. Unstimulated saliva and supragingival plaque samples were collected cross-sectionally, followed by assessment of the bacterial (16S ribosomal RNA) and fungal (18S ITS) microbiota communities. Trained and calibrated dentists performed oral examinations to determine the number of decayed teeth and plaque index. Initially, plaque from 28 nonpregnant women and 48 pregnant women were compared; these data showed significant differences in bacterial abundances based on pregnancy status. To further our understanding of the oral microbiome within the pregnant population, we next examined the oral microbiome within this population based on several variables. Streptococcus mutans, Streptococcus oralis, and Lactobacillus were associated with a greater number of decayed teeth. The composition of fungal communities differed between plaque and saliva, demonstrating 2 distinct "mycotypes" that were represented by a greater abundance of Candida in plaque and Malassezia in saliva. Veillonella rogosae, a common oral bacterium, was negatively associated with both plaque index and salivary Candida albicans colonization by culture data. This was further emphasized by in vitro inhibition of C. albicans by V. rogosae. Identification of interactions between the bacterial or fungal oral communities revealed that V. rogosae was positively associated with the oral commensal Streptococcus australis and negatively with the cariogenic Lactobacillus genus, suggesting V. rogosae as a potential biomarker of a noncariogenic oral microbiome.

The management of hepatocellular carcinoma. Current expert opinion and recommendations derived from the 24th ESMO/World Congress on Gastrointestinal Cancer, Barcelona, 2022.

This article summarises expert discussion on the management of patients with hepatocellular carcinoma (HCC), which took place during the 24th World Gastrointestinal Cancer Congress (WGICC) in Barcelona, July 2022. A multidisciplinary approach is mandatory to ensure an optimal diagnosis and staging of HCC, planning of curative and therapeutic options, including surgical, embolisation, ablative strategies, or systemic therapy. Furthermore, in many patients with HCC, underlying liver cirrhosis represents a challenge and influences the therapeutic options.

Towards precision medicine for anxiety disorders: objective assessment, risk prediction, pharmacogenomics, and repurposed drugs.

Anxiety disorders are increasingly prevalent, affect people's ability to do things, and decrease quality of life. Due to lack of objective tests, they are underdiagnosed and sub-optimally treated, resulting in adverse life events and/or addictions. We endeavored to discover blood biomarkers for anxiety, using a four-step approach. First, we used a longitudinal within-subject design in individuals with psychiatric disorders to discover blood gene expression changes between self-reported low anxiety and high anxiety states. Second, we prioritized the list of candidate biomarkers with a Convergent Functional Genomics approach using other evidence in the field. Third, we validated our top biomarkers from discovery and prioritization in an independent cohort of psychiatric subjects with clinically severe anxiety. Fourth, we tested these candidate biomarkers for clinical utility, i.e. ability to predict anxiety severity state, and future clinical worsening (hospitalizations with anxiety as a contributory cause), in another independent cohort of psychiatric subjects. We showed increased accuracy of individual biomarkers with a personalized approach, by gender and diagnosis, particularly in women. The biomarkers with the best overall evidence were GAD1, NTRK3, ADRA2A, FZD10, GRK4, and SLC6A4. Finally, we identified which of our biomarkers are targets of existing drugs (such as a valproate, omega-3 fatty acids, fluoxetine, lithium, sertraline, benzodiazepines, and ketamine), and thus can be used to match patients to medications and measure response to treatment. We also used our biomarker gene expression signature to identify drugs that could be repurposed for treating anxiety, such as estradiol, pirenperone, loperamide, and disopyramide. Given the detrimental impact of untreated anxiety, the current lack of objective measures to guide treatment, and the addiction potential of existing benzodiazepines-based anxiety medications, there is a urgent need for more precise and personalized approaches like the one we developed.

A Prospective Longitudinal Study of Early Childhood Caries Onset in Initially Caries-Free Children.

INTRODUCTION: Early childhood caries (ECC) is a complex oral disease that is prevalent in US children. OBJECTIVES: The purpose of this 2-y prospective cohort study was to examine baseline and time-dependent risk factors for ECC onset in initially caries-free preschool children. METHODS: A cohort of 189 initially caries-free children aged 1 to 3 y was recruited. At each 6-mo study visit, children were examined using the ICDAS index; salivary samples were collected to assess mutans streptococci (MS), lactobacilli, Candida species, salivary cortisol (prior and after a stressor), and salivary IgA. Diet and oral health behavior were assessed from parent report. Child and family stress exposure was assessed from measures of psychological symptoms, stressful life event exposure, family organization and violence exposure, and social support. Sociodemographic factors were also considered. A Kaplan-Meier estimator of survival function of time to ECC and a Cox proportional hazards model were used to identify predictors of ECC onset. RESULTS: Onset of ECC was associated with high salivary MS levels at baseline (log-rank test, P < 0.0001). Cox proportional hazards regression showed that the risk of dental caries significantly increased with salivary MS in log scale over the 6-mo period (hazard ratio, 1.08; P = 0.01). Other risk factors in the model did not reach statistical significance. CONCLUSION: Our results provide prospective evidence that an increase in salivary MS predicts ECC onset in young, initially caries-free children, confirming that a high salivary MS count likely plays a causal role in ECC onset, independent of covariates. KNOWLEDGE TRANSFER STATEMENT: These results suggest that we must focus on reducing salivary MS counts in young children and preventing or delaying MS colonization in infants and young children determined to be at risk for ECC.

Changing Parental Knowledge and Treatment Acceptance for ADHD: A Pilot Study.

This pilot study assessed the feasibility and potential effectiveness of a single-session workshop in modifying parental beliefs/knowledge about attention-deficit/hyperactivity disorder (ADHD) in children and impact on treatment acceptance/utilization. Concerns raised by school professionals about lack of treatment follow-through after ADHD diagnosis and parental misinformation about medication usage catalyzed this project. A single-group pre-post quasi-experimental design was used. Sixty-eight parents completed ADHD knowledge/belief scales and stress inventories, and pre-ADHD and post-ADHD information workshop. Follow-up calls were made after the workshop to assess treatment utilization. Parents/caregivers experienced significant knowledge and belief changes regarding medication efficacy, willingness to accept physician treatment recommendations, and rejection of non-empirically based treatments. Follow-up data showed that 41% of contacted participants met with physicians to discuss medication utilization and behavioral treatments. Brief, one-session psycho-educational workshops were feasible and impacted parental beliefs and behaviors regarding scientifically supported interventions for ADHD.

Surgical vs Non-surgical interventions for distal radius fractures: a quantitative analysis of Patient-Rated Wrist Evaluation measures.

Trials to assess differences in PRWE (Patient Related Wrist Evaluation) over time, for both surgical and non-surgical interventions post DRFs (distal radius fractures) are rare. The DASH (Disabilities of the Arm, Shoulder and Hand) questionnaire has been shown to be improved by a greater margin in the medium term for surgical interventions, than non surgical interventions. However, a study found that PRWE can be considered superior to the DASH questionnaire for DRFs, due to greater specificity to wrist pain and function. Conflicting data makes it difficult to determine surgical vs non-surgical superiority for DRF's over time with PRWE as a recovery metric. PubMed and Cochrane were searched for randomised controlled trials up to 31.8.23, reporting PRWE over 3, and 12 months. Data was extracted by 2 researchers. The differences in PRWE over time post surgical and non-surgical interventions was assessed using unpaired T testing. 1226 records were screened. 4 studies enrolling 817 participants met the eligibility criteria and were analysed. Significantly lower PRWE in surgical intervention has been identified at the 3 month mark (p<0.001). There was greater significant change in non-surgical intervention between months 3 and 12 (p<0.001). Change in PRWE over time may be a good indicator of functional outcomes in DRFs post surgical or non-surgical interventions. This could inform future clinical trial design and surgical decision-making. Further work is required to design even more user-friendly and digital patient- reported outcomes specifically for DRFs.

What are the similarities and differences in lung cancer symptom appraisal and help-seeking according to smoking status? A qualitative study with lung cancer patients.

OBJECTIVE: Lung cancer in never-smokers represents a growing proportion of patients. The relationship between smoking status, symptom appraisal and help-seeking behaviour is complex. Little is known about cancer symptom-related health behaviours according to smoking status. The aim of the study was to explore lung cancer patients' experiences of a lung cancer diagnosis, identifying differences by smoking history. METHOD: This was a qualitative study involving telephone interviews with 40 lung cancer patients (20 never smokers, 11 former smokers and 9 current smokers). We used framework analysis to analyse the data using the Common Sense Model of Illness Self-Regulation as a theoretical framework, developed after initial analysis. RESULTS: All patients were likely to delay seeking help for symptoms in primary care regardless of smoking history, but for different reasons. Smoking history was instrumental to how individuals perceived and responded to early symptoms of lung cancer. Differences in interpretation and coping responses to new symptoms seemed to be caused by the higher presence of comorbidities due to smoking, and perceptions of the current state of health. Individuals with a smoking history reported acting with urgency in seeking help and follow up, whereas patients who experienced low levels of concern were more easily reassured by clinicians, resulting in delays. CONCLUSIONS: Never and former smokers perceive, interpret, and respond to symptoms of lung cancer differently to smokers. However, few people attribute their lung symptoms to cancer initially, even with a smoking history. Interventions that drive increased urgency and vigilance in never smokers may be effective.

Preterm birth and infant diurnal cortisol regulation.

BACKGROUND: Hypothalamic-pituitary-adrenal (HPA) axis adaptation is a potential mechanism linking early life exposures with later adverse health. This study tested the hypothesis that preterm birth is associated with adaptation of diurnal cortisol regulation across infancy. METHODS: A secondary analysis was conducted of saliva cortisol measured morning, midday and evening, monthly, across infancy, as part of a birth cohort conducted in Linköping, Sweden. Diurnal cortisol regulation of infants born extremely preterm (n=24), very preterm (n=27) and at term (n=130) were compared across infancy through random coefficients regression models. RESULTS: Compared with infants born at term, infants born extremely preterm (-17.2%, 95% CI: -30.7 to -1.2), but not very preterm (1.7%, 95% CI: -14.1 to 20.4), had a flattened diurnal slope across infancy. CONCLUSIONS: Extremely preterm birth is associated with a flattened diurnal slope in infancy. This pattern of cortisol regulation could contribute to adverse metabolic and neurodevelopmental phenotypes observed in this population.

Saliva cortisol diurnal variation and stress responses in term and preterm infants.

OBJECTIVE: To determine if preterm birth is associated with adaptation of the hypothalamic-pituitary-adrenal (HPA) axis and whether HPA axis programming relates to the degree of prematurity (defined as extremely preterm birth at <28 weeks or very preterm birth at 28-32 weeks gestation). DESIGN: This study reports findings from a prospective birth cohort. Saliva cortisol concentrations were measured prevaccination and postvaccination, and in the morning and evening, at 4 months chronological age. SETTING: Infants born at a single Scottish hospital. PARTICIPANTS: 45 term-born, 42 very preterm and 16 extremely preterm infants. OUTCOMES: Cortisol stress response to vaccination (postvaccination minus prevaccination cortisol concentrations), diurnal slope (log-transformed morning minus log-transformed evening cortisol values) and mean log-transformed daily cortisol. RESULTS: Compared with infants born at term, infants born extremely preterm had a blunted cortisol response to vaccination (5.8 nmol/L vs 13.1 nmol/L, difference in means: -7.3 nmol/L, 95% CI -14.0 to -0.6) and a flattened diurnal slope (difference in geometric means: -72.9%, 95% CI -87.1 to -42.8). In contrast, the cortisol response to vaccination (difference in means -2.7 nmol/L, 95% CI -7.4 to 2.0) and diurnal slope at 4 months (difference in geometric means: -33.6%, 95% CI -62.0 to 16.0) did not differ significantly in infants born very preterm compared with infants born at term. CONCLUSIONS: Infants born extremely preterm have blunted cortisol reactivity and a flattened diurnal slope. These patterns of HPA axis regulation are commonly seen after childhood adversity and could contribute to later metabolic and neurodevelopmental phenotypes observed in this population.

Challenges and opportunities in productivity and sustainability of rice cultivation system: a critical review in Indian perspective.

Abstract: Rice-wheat cropping system, intensively followed in Indo-Gangetic plains (IGP), played a prominent role in fulfilling the food grains demand of the increasing population of South Asia. In northern Indian plains, some practices such as intensive rice cultivation with traditional method for long-term have been associated with severe deterioration of natural resources, declining factor productivity, multiple nutrients deficiencies, depleting groundwater, labour scarcity and higher cost of cultivation, putting the agricultural sustainability in question. Varietal development, soil and water management, and adoption of resource conservation technologies in rice cultivation are the key interventions areas to address these challenges. The cultivation of lesser water requiring crops, replacing rice in light-textured soil and rainfed condition, should be encouraged through policy interventions. Direct seeding of short duration, high-yielding and stress tolerant rice varieties with water conservation technologies can be a successful approach to improve the input use efficiency in rice cultivation under medium-heavy-textured soils. Moreover, integrated approach of suitable cultivars for conservation agriculture, mechanized transplanting on zero-tilled/unpuddled field and need-based application of water, fertilizer and chemicals might be a successful approach for sustainable rice production system in the current scenario. In this review study, various challenges in productivity and sustainability of rice cultivation system and possible alternatives and solutions to overcome such challenges are discussed in details.

The impact of cultural stress and gender norms on alcohol use severity among Latino immigrant men.

Alcohol misuse affects 15 million people in the United States. Compared to White men, Latino men have disproportionately higher rates of both alcohol misuse and negative alcohol-related consequences (e.g. drunk driving, liver disease, alcohol dependence, HIV/AIDS). This cross sectional study examined how cultural stressors [immigration stress and negative context of reception (NCR)] coupled with traditional Latino male gender norms (machismo and caballerismo) influences alcohol use severity (AUS) among adult Latino immigrant men. Data for the present study was collected between 2017 and 2018 from 279 Cuban, Central American, and South American adult Latino men who immigrated to the US approximately 10 years prior. Results from hierarchical multiple regression analysis revealed higher levels of perceived NCR (ß = 0.15, p = .01), and machismo (ß = 0.16, p = .02) were associated with greater AUS. Significant interaction effects were found between both cultural stressors and machismo [immigration stress x machismo (ß = 0.22, p < .001); NCR x machismo (ß = 0.22, p < .001)] whereby higher levels of machismo strengthened the association between cultural stress and AUS. Findings from the present study can inform culturally appropriate interventions aimed at mitigating alcohol use among Latino immigrant men.

Bone infection: a clinical priority for clinicians, scientists and educators.

Bone infection has received increasing attention in recent years as one of the main outstanding clinical problems in orthopaedic-trauma surgery that has not been successfully addressed. In fact, infection may develop across a spectrum of patient types regardless of the level of perioperative management, including antibiotic prophylaxis. Some of the main unknown factors that may be involved, and the main targets for future intervention, include more accurate and less invasive diagnostic options, more thorough and accurate debridement protocols, and more potent and targeted antimicrobials. The underlying biology dominates the clinical management of bone infections, with features such as biofilm formation, osteolysis and vascularisation being particularly influential. Based on the persistence of this problem, an improved understanding of the basic biology is deemed necessary to enable innovation in the field. Furthermore, from the clinical side, better evidence, documentation and outreach will be required to translate these innovations to the patient. This review presents the findings and progress of the AO Trauma Clinical Priority Program on the topic of bone infection.