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Multicenter clinical trials are essential for evaluating interventions but often face significant challenges in study design, site coordination, participant recruitment, and regulatory compliance. To address these issues, the National Institutes of Health’s National Center for Advancing Translational Sciences established the Trial Innovation Network (TIN). The TIN offers a scientific consultation process, providing access to clinical trial and disease experts who provide input and recommendations throughout the trial’s duration, at no cost to investigators. This approach aims to improve trial design, accelerate implementation, foster interdisciplinary teamwork, and spur innovations that enhance multicenter trial quality and efficiency. The TIN leverages resources of the Clinical and Translational Science Awards (CTSA) program, complementing local capabilities at the investigator’s institution. The Initial Consultation process focuses on the study’s scientific premise, design, site development, recruitment and retention strategies, funding feasibility, and other support areas. As of 6/1/2024, the TIN has provided 431 Initial Consultations to increase efficiency and accelerate trial implementation by delivering customized support and tailored recommendations. Across a range of clinical trials, the TIN has developed standardized, streamlined, and adaptable processes. We describe these processes, provide operational metrics, and include a set of lessons learned for consideration by other trial support and innovation networks.
Electronic health records (EHRs), increasingly available in low- and middle-income countries (LMICs), provide an opportunity to study transdiagnostic features of serious mental illness (SMI) and its trajectories.
Aims
Characterise transdiagnostic features and diagnostic trajectories of SMI using an EHR database in an LMIC institution.
Method
We conducted a retrospective cohort study using EHRs from 2005–2022 at Clínica San Juan de Dios Manizales, a specialised mental health facility in Colombia, including 22 447 patients with schizophrenia (SCZ), bipolar disorder (BPD) or severe/recurrent major depressive disorder (MDD). Using diagnostic codes and clinical notes, we analysed the frequency of suicidality and psychosis across diagnoses, patterns of diagnostic switching and the accumulation of comorbidities. Mixed-effect logistic regression was used to identify factors influencing diagnostic stability.
Results
High frequencies of suicidality and psychosis were observed across diagnoses of SCZ, BPD and MDD. Most patients (64%) received multiple diagnoses over time, including switches between primary SMI diagnoses (19%), diagnostic comorbidities (30%) or both (15%). Predictors of diagnostic switching included mentions of delusions (odds ratio = 1.47, 95% CI 1.34–1.61), prior diagnostic switching (odds ratio = 4.01, 95% CI 3.7–4.34) and time in treatment, independent of age (log of visit number; odds ratio = 0.57, 95% CI 0.54–0.61). Over 80% of patients reached diagnostic stability within 6 years of their first record.
Conclusions
Integrating structured and unstructured EHR data reveals transdiagnostic patterns in SMI and predictors of disease trajectories, highlighting the potential of EHR-based tools for research and precision psychiatry in LMICs.
Interprofessional teams in the pediatric cardiac ICU consolidate their management plans in pre-family meeting huddles, a process that affects the course of family meetings but often lacks optimal communication and teamwork.
Methods:
Cardiac ICU clinicians participated in an interprofessional intervention to improve how they prepared for and conducted family meetings. We conducted a pretest–posttest study with clinicians participating in huddles before family meetings. We assessed feasibility of clinician enrollment, assessed clinician perception of acceptability of the intervention via questionnaire and semi-structured interviews, and impact on team performance using a validated tool. Wilcoxon rank sum test assessed intervention impact on team performance at meeting level comparing pre- and post-intervention data.
Results:
Totally, 24 clinicians enrolled in the intervention (92% retention) with 100% completion of training. All participants recommend cardiac ICU Teams and Loved ones Communicating to others and 96% believe it improved their participation in family meetings. We exceeded an acceptable level of protocol fidelity (>75%). Team performance was significantly (p < 0.001) higher in post-intervention huddles (n = 30) than in pre-intervention (n = 28) in all domains. Median comparisons: Team structure [2 vs. 5], Leadership [3 vs. 5], Situation Monitoring [3 vs. 5], Mutual Support [ 3 vs. 5], and Communication [3 vs. 5].
Conclusion:
Implementing an interprofessional team intervention to improve team performance in pre-family meeting huddles is feasible, acceptable, and improves team function. Future research should further assess impact on clinicians, patients, and families.
Head and neck squamous cell carcinomas (HNSCCs) are aggressive tumours lacking a standardised timeline for treatment initiation post-diagnosis. Delays beyond 60 days are linked to poorer outcomes and higher recurrence risk.
Methods:
A retrospective review was conducted on patients over 18 with HNSCC treated with (chemo)radiation at a rural tertiary care centre (September 2020–2022). Data on patient demographics, oncologic characteristics, treatment details and delay causes were analysed using SPSS.
Results:
Out of 93 patients, 35.5% experienced treatment initiation delays (TTIs) over 60 days. Median TTI was 73 days for delayed cases, compared to 41.5 days otherwise. No significant differences in demographics or cancer characteristics were observed between groups. The primary reasons for the delay were care coordination (69.7%) and patient factors (18.2%). AJCC cancer stage showed a trend towards longer delays in advanced stages.
Conclusion:
One-third of patients faced delayed TTI, primarily due to care coordination and lack of social support. These findings highlight the need for improved multidisciplinary communication and patient support mechanisms, suggesting potential areas for quality improvement in HNSCC treatment management.
Spotted-wing drosophila, Drosophila suzukii, is a global pest of soft fruits that is capable of reproducing on a wide range of cultivated and wild plant species. In Canada, D. suzukii was first reported in British Columbia in 2009 and is now widespread across the country. Understanding the genetic structure of D. suzukii populations could be important for pest management if there are phenotypic differences between genetically distinct populations. For example, insect pest populations could respond differently to directional selection imposed by insecticides, differ in their host plant preferences, and vary in their susceptibility to biological control agents. Here, we used double-digest restriction site–associated DNA sequencing to examine large- and fine-scale patterns of the genetic structure of D. suzukii reared from fruit hosts in Canada. We found that this species has a large-scale spatial genetic structure; the flies collected formed two distinct genetic clusters, one of which was distinct to western Canada and the other to eastern Canada. At the local scale, D. suzukii populations showed no evidence of host-associated structuring in British Columbia, suggesting that pest management tactics may be best applied at the landscape level. Our results highlight the need to investigate phenotypic differences between western and eastern D. suzukii populations in Canada.
Text message-delivered interventions for chronic disease self-management have potential to reduce health disparities, yet limited research has explored implementing these interventions into clinical care. We partnered with safety net clinics to evaluate a texting intervention for type 2 diabetes called REACH (Rapid Encouragement/Education And Communications for Health) in a randomized controlled trial. Following evaluation, we explored potential implementation determinants and recommended implementation strategies.
Methods:
We interviewed clinic staff (n = 14) and a subset of intervention participants (n = 36) to ask about REACH’s implementation potential. Using the Consolidated Framework for Implementation Research (CFIR) as an organizing framework, we coded transcripts and used thematic analysis to derive implementation barriers and facilitators. We integrated the CFIR-ERIC (Expert Recommendations for Implementing Change) Matching Tool, interview feedback, and the literature to recommend implementation strategies.
Results:
Implementation facilitators included low complexity, strong evidence and quality, available clinic resources, the need for a program to support diabetes self-management, and strong fit between REACH and both the clinics’ existing workflows and patients’ needs and resources. The barriers included REACH only being available in English, a lack of interoperability with electronic health record systems, patients’ concerns about diabetes stigma, limited funding, and high staff turnover. Categories of recommended implementation strategies included training and education, offering flexibility and adaptation, evaluating key processes, and securing funding.
Conclusion:
Text message-delivered interventions have strong potential for integration in low-resource settings as a supplement to care. Pursuing implementation can ensure patients benefit from these innovations and help close the research to practice gap.
Background: We evaluated (1) the predictive accuracy and (2) multi-observer reliability of non-contrast CT markers of hematoma expansion (HE). Methods: In 124 patients with spontaneous intracerebral hemorrhage, two investigators documented the presence of six density (Barras density, hypodensity, black hole, swirl, blend, fluid level) and three shape (Barras shape, island, satellite) expansion markers, with discrepancies resolved by a third rater. We defined HE as any one of (1) >6 mL absolute or >33% relative growth of the intraparenchymal hematoma or (2) an absolute growth of >1 mL or new development of intraventricular hematoma. A subsample of 60 patients was used for the inter-observer reliability study in 13 raters. Seven raters participated in the intra-rater study. Results: The sensitivity of markers for HE varied between 4% (fluid level) and 78% (satellite), while specificity ranged from 37% (swirl) to 97% (black hole). Almost perfect inter-rater agreement was observed for the swirl (0.89) and fluid level (0.83) markers, while hypodensity (0.65) showed substantial agreement. Only the blend and fluid level markers achieved substantial intra-rater agreement (> 0.6) in all raters. Conclusions: Non-contrast CT markers of HE showed lower reliability and predictive accuracy than previously reported. Future studies should address means to improve NCCT-based HE prediction.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Benzodiazepine (BZD) prescription rates have increased over the past decade in the United States. Available literature indicates that sociodemographic factors may influence diagnostic patterns and/or prescription behaviour. Herein, the aim of this study is to determine whether the gender of the prescriber and/or patient influences BZD prescription.
Methods
Cross-sectional study using data from the Florida Medicaid Managed Medical Assistance Program from January 1, 2018 to December 31, 2018. Eligible recipients ages 18 to 64, inclusive, enrolled in the Florida Medicaid plan for at least 1 day, and were dually eligible. Recipients either had a serious mental illness (SMI), or non-SMI and anxiety.
Results
Total 125 463 cases were identified (i.e., received BZD or non-BZD prescription). Main effect of patient and prescriber gender was significant F(1, 125 459) = 0.105, P = 0 .745, partial η2 < 0.001. Relative risk (RR) of male prescribers prescribing a BZD compared to female prescribers was 1.540, 95% confidence intervals (CI) [1.513, 1.567], whereas the RR of male patients being prescribed a BZD compared to female patients was 1.16, 95% CI [1.14, 1.18]. Main effects of patient and prescriber gender were statistically significant F(1, 125 459) = 188.232, P < 0.001, partial η2 = 0.001 and F(1, 125 459) = 349.704, P < 0.001, partial η2 = 0.013, respectively.
Conclusions
Male prescribers are more likely to prescribe BZDs, and male patients are more likely to receive BZDs. Further studies are required to characterize factors that influence this gender-by-gender interaction.
Identify risk factors that could increase progression to severe disease and mortality in hospitalized SARS-CoV-2 patients in the Southeast region of the United States.
Design, setting, and participants:
Multicenter, retrospective cohort including 502 adults hospitalized with laboratory-confirmed COVID-19 between March 1, 2020, and May 8, 2020 within 1 of 15 participating hospitals in 5 health systems across 5 states in the Southeast United States.
Methods:
The study objectives were to identify risk factors that could increase progression to hospital mortality and severe disease (defined as a composite of intensive care unit admission or requirement of mechanical ventilation) in hospitalized SARS-CoV-2 patients in the Southeast United States.
Results:
In total, 502 patients were included, and 476 of 502 (95%) had clinically evaluable outcomes. The hospital mortality rate was 16% (76 of 476); 35% (177 of 502) required ICU admission and 18% (91 of 502) required mechanical ventilation. By both univariate and adjusted multivariate analyses, hospital mortality was independently associated with age (adjusted odds ratio [aOR], 2.03 for each decade increase; 95% confidence interval [CI], 1.56-–2.69), male sex (aOR, 2.44; 95% CI, 1.34–4.59), and cardiovascular disease (aOR, 2.16; 95% CI, 1.15–4.09). As with mortality, risk of severe disease was independently associated with age (aOR, 1.17 for each decade increase; 95% CI, 1.00–1.37), male sex (aOR, 2.34; 95% CI, 1.54–3.60), and cardiovascular disease (aOR, 1.77; 95% CI, 1.09–2.85).
Conclusions:
In an adjusted multivariate analysis, advanced age, male sex, and cardiovascular disease increased risk of severe disease and mortality in patients with COVID-19 in the Southeast United States. In-hospital mortality risk doubled with each subsequent decade of life.
Introduction. Individuals with psychotic-spectrum disorders may smoke due to the ameliorating effect of nicotine on the cognitive deficits that accompany these illnesses. Metacognitive remediation therapy (MCR) has been shown to produce improvements in cognitive functioning among individuals with psychotic-spectrum disorders and provides a foundation for a novel smoking cessation intervention for this population. Aims. To complete an open investigation of pharmacotherapy and a modified version of MCR [MCR to Quit (MCR-Q)] in promoting smoking cessation among individuals with psychotic-spectrum disorders. Methods. Forty-nine individuals with a psychotic-spectrum disorder and who currently smoke cigarettes participated in MCR-Q while also receiving evidence-based smoking cessation pharmacotherapy. Tobacco use was assessed as follows: (i) prior to MCR-Q, (ii) immediately after completing MCR-Q, and (iii) six weeks after completion of MCR-Q. Results/Findings. During participation in MCR-Q, nearly 80% of participants made a 24-hour quit attempt. Following the completion of MCR-Q, participants experienced reductions in level of nicotine dependency and exhaled carbon monoxide, with reductions in nicotine dependency sustained six weeks after completion of MCR-Q. Over the course of their participation in MCR-Q, participants reported strong therapeutic alliance with their MCR-Q therapist and high levels of intrinsic motivation with regard to completing MCR-Q exercises. Conclusions. The results from the current study suggest cautious optimism with regard to the use of MCR-Q in combination with medication for individuals with psychotic-spectrum disorders who want to quit smoking.
Background: Detection of unusual carbapenemase-producing organisms (CPOs) in a healthcare facility may signify broader regional spread. During investigation of a VIM-producing Pseudomonas aeruginosa (VIM-CRPA) outbreak in a long-term acute-care hospital in central Florida, enhanced surveillance identified VIM-CRPA from multiple facilities, denoting potential regional emergence. We evaluated infection control and performed screening for CPOs in skilled nursing facilities (SNFs) across the region to identify potential CPO reservoirs and improve practices. Methods: All SNFs in 2 central Florida counties were offered a facility-wide point-prevalence survey (PPS) for CPOs and a nonregulatory infection control consultation. PPSs were conducted using a PCR-based screening method; specimens with a carbapenemase gene detected were cultured to identify the organisms. Infection control assessments focused on direct observations of hand hygiene (HH), environmental cleaning, and the sink splash zone. Thoroughness of environmental cleaning was evaluated using fluorescent markers applied to 6 standardized high-touch surfaces in at least 2 rooms per facility. Results: Overall, 21 (48%) SNFs in the 2-county region participated; 18 conducted PPS. Bed size ranged from 40 to 391, 5 (24%) facilities were ventilator-capable SNFs (vSNFs), and 12 had short-stay inpatient rehabilitation units. Of 1,338 residents approached, 649 agreed to rectal screening, and 14 (2.2%) carried CPOs. CPO-colonized residents were from the ventilator-capable units of 3 vSNFs (KPC-CRE=7; KPC-CRPA=1) and from short-stay units of 2 additional facilities (VIM-CRPA, n = 5; KPC-CRE, n = 1). Among the 5 facilities where CPO colonization was identified, the prevalence ranged from 1.1% in a short-stay unit to 16.1% in a ventilator unit. All facilities had access to soap and water in resident bathrooms; 14 (67%) had alcohol-based hand rubs accessible. Overall, mean facility HH adherence was 52% (range, 37%–66%; mean observations per facility = 106) (Fig. 1). We observed the use of non–EPA-registered disinfectants and cross contamination from dirty to clean areas during environmental cleaning; the overall surface cleaning rate was 46% (n = 178 rooms); only 1 room had all 6 markers removed. Resident supplies were frequently stored in the sink splash zone. Conclusions: A regional assessment conducted in response to emergence of VIM-CRPA identified a relatively low CPO prevalence at participating SNFs; CPOs were primarily identified in vSNFs and among short-stay residents. Across facilities, we observed low adherence to core infection control practices that could facilitate spread of CPOs and other resistant organisms. In this region, targeting ventilator and short-stay units of SNFs for surveillance and infection control efforts may have the greatest prevention impact.
Two randomized, controlled trials of L-methylfolate augmentation of SSRIs for major depressive disorder (MDD) were conducted using a novel study design (sequential parallel comparison design- SPCD).
Objectives/aims
To evaluate the efficacy of L-methylfolate augmentation using the Hamilton Depression Rating Scale.
Methods
In study one (TRD-1), 148 outpatients with SSRI-resistant MDD were enrolled in a 60-day, SPCD study, divided into two 30-day periods (phases 1 and 2). Patients were randomized 2:3:3 to receive L-methylfolate (7.5mg/d in phase 1, 15mg/d in phase 2), placebo in phase 1 followed by L-methylfolate 7.5mg/d in phase 2, or placebo for both phases. Study two (TRD-2) involved 75 patients and was identical in design to TRD-1 except for the dose of L-methylfolate (15mg only).
Results
In the TRD-1 Study, L-methylfolate 7.5 mg/d was not found to be more effective than placebo. In phase 1 of the TRD-2 Study, 37% of patients on L-methylfolate 15mg/d responded and 18% of placebo patients responded, while in phase 2 among placebo non-responders, the response rates were 28% on L-methylfolate 15mg/d and 9.5% on placebo. When phases 1 and 2 were pooled according to the SPCD model, the difference in response rates was statistically significant in favor of L-methylfolate (p = 0.0399). The rates of spontaneously reported AEs and rates of study discontinuation appear r comparable between L-methylfolate and placebo in both studies. Rates of study discontinuation were also comparable
Conclusions
These studies suggest that L-methylfolate 15 mg/d may be a safe and effective augmentation strategy for inadequate response to SSRIs.
Disturbed sleep and activity are prominent features of bipolar disorder type I (BP-I). However, the relationship of sleep and activity characteristics to brain structure and behavior in euthymic BP-I patients and their non-BP-I relatives is unknown. Additionally, underlying genetic relationships between these traits have not been investigated.
Methods
Relationships between sleep and activity phenotypes, assessed using actigraphy, with structural neuroimaging (brain) and cognitive and temperament (behavior) phenotypes were investigated in 558 euthymic individuals from multi-generational pedigrees including at least one member with BP-I. Genetic correlations between actigraphy-brain and actigraphy-behavior associations were assessed, and bivariate linkage analysis was conducted for trait pairs with evidence of shared genetic influences.
Results
More physical activity and longer awake time were significantly associated with increased brain volumes and cortical thickness, better performance on neurocognitive measures of long-term memory and executive function, and less extreme scores on measures of temperament (impulsivity, cyclothymia). These associations did not differ between BP-I patients and their non-BP-I relatives. For nine activity-brain or activity-behavior pairs there was evidence for shared genetic influence (genetic correlations); of these pairs, a suggestive bivariate quantitative trait locus on chromosome 7 for wake duration and verbal working memory was identified.
Conclusions
Our findings indicate that increased physical activity and more adequate sleep are associated with increased brain size, better cognitive function and more stable temperament in BP-I patients and their non-BP-I relatives. Additionally, we found evidence for pleiotropy of several actigraphy-behavior and actigraphy-brain phenotypes, suggesting a shared genetic basis for these traits.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
There are a variety of causes of acute heart failure in children including myocarditis, genetic/metabolic conditions, and congenital heart defects. In cases with a structurally normal heart and a negative personal and family history, myocarditis is often presumed to be the cause, but we hypothesise that genetic disorders contribute to a significant portion of these cases. We reviewed our cases of children who presented with acute heart failure and underwent genetic testing from 2008 to 2017. Eighty-seven percent of these individuals were found to have either a genetic syndrome or pathogenic or likely pathogenic variant in a cardiac-related gene. None of these individuals had a personal or family history of cardiomyopathy that was suggestive of a genetic aetiology prior to presentation. All of these individuals either passed away or were listed for cardiac transplantation indicating genetic testing may provide important information regarding prognosis in addition to providing information critical to assessment of family members.
The majority of paediatric Clostridioides difficile infections (CDI) are community-associated (CA), but few data exist regarding associated risk factors. We conducted a case–control study to evaluate CA-CDI risk factors in young children. Participants were enrolled from eight US sites during October 2014–February 2016. Case-patients were defined as children aged 1–5 years with a positive C. difficile specimen collected as an outpatient or ⩽3 days of hospital admission, who had no healthcare facility admission in the prior 12 weeks and no history of CDI. Each case-patient was matched to one control. Caregivers were interviewed regarding relevant exposures. Multivariable conditional logistic regression was performed. Of 68 pairs, 44.1% were female. More case-patients than controls had a comorbidity (33.3% vs. 12.1%; P = 0.01); recent higher-risk outpatient exposures (34.9% vs. 17.7%; P = 0.03); recent antibiotic use (54.4% vs. 19.4%; P < 0.0001); or recent exposure to a household member with diarrhoea (41.3% vs. 21.5%; P = 0.04). In multivariable analysis, antibiotic exposure in the preceding 12 weeks was significantly associated with CA-CDI (adjusted matched odds ratio, 6.25; 95% CI 2.18–17.96). Improved antibiotic prescribing might reduce CA-CDI in this population. Further evaluation of the potential role of outpatient healthcare and household exposures in C. difficile transmission is needed.
Laser-based compact MeV X-ray sources are useful for a variety of applications such as radiography and active interrogation of nuclear materials. MeV X rays are typically generated by impinging the intense laser onto ~mm-thick high-Z foil. Here, we have characterized such a MeV X-ray source from 120 TW (80 J, 650 fs) laser interaction with a 1 mm-thick tantalum foil. Our measurements show X-ray temperature of 2.5 MeV, flux of 3 × 1012 photons/sr/shot, beam divergence of ~0.1 sr, conversion efficiency of ~1%, that is, ~1 J of MeV X rays out of 80 J incident laser, and source size of 80 m. Our measurement also shows that MeV X-ray yield and temperature is largely insensitive to nanosecond laser contrasts up to 10−5. Also, preliminary measurements of similar MeV X-ray source using a double-foil scheme, where the laser-driven hot electrons from a thin foil undergoing relativistic transparency impinging onto a second high-Z converter foil separated by 50–400 m, show MeV X-ray yield more than an order of magnitude lower compared with the single-foil results.
Both elevated blood pressure and/or depression increase the risk of cardiovascular disease and mortality. This study in treated elderly hypertensive patients explored the incidence of depression, its association (pre-existing and incident) with mortality and predictors of incident depression.
Methods:
Data from 6,083 hypertensive patients aged ≥65 years enrolled in the Second Australian National Blood Pressure study were used. Participants were followed for a median of 10.8 years (including 4.1 years in-trial) and classified into: “no depression,” “pre-existing” and “incident” depression groups based on either being “diagnosed with depressive disorders” and/or “treated with an anti-depressant drug” at baseline or during in-trial period. Further, we redefined “depression” restricted to presence of both conditions for sensitivity analyses. For the current study, end-points were all-cause and any cardiovascular mortality.
Results:
313 (5%) participants had pre-existing depression and a further 916 (15%) participants developed depression during the trial period (incidence 4% per annum). Increased (hazard-ratio, 95% confidence-interval) all-cause mortality was observed among those with either pre-existing (1.23, 1.01–1.50; p = 0.03) or incident (1.26, 1.12–1.41; p < 0.001) depression compared to those without. For cardiovascular mortality, a 24% increased risk (1.24, 1.05–1.47; p = 0.01) was observed among those with incident depression. The sensitivity analyses, using the restricted depression definition showed similar associations. Incident depression was associated with being female, aged ≥75 years, being an active smoker at study entry, and developing new diabetes during the study period.
Conclusions:
This elderly cohort had a high incidence of depression irrespective of their randomised antihypertensive regimen. Both pre-existing and incident depression were associated with increased mortality.