Quality improvement programmes (QIPs) are designed to enhance patient outcomes by systematically introducing evidence-based clinical practices. The CONQUEST QIP focuses on improving the identification and management of patients with COPD in primary care. The process of developing CONQUEST, recruiting, preparing systems for participation, and implementing the QIP across three integrated healthcare systems (IHSs) is examined to identify and share lessons learned.

This review is organized into three stages: 1) development, 2) preparing IHSs for implementation, and 3) implementation. In each stage, key steps are described with the lessons learned and how they can inform others interested in developing QIPs designed to improve the care of patients with chronic conditions in primary care.

Stage 1 was establishing and working with steering committees to develop the QIP Quality Standards, define the target patient population, assess current management practices, and create a global operational protocol. Additionally, potential IHSs were assessed for feasibility of QIP integration into primary care practices. Factors assessed included a review of technological infrastructure, QI experience, and capacity for effective implementation.

Stage 2 was preparation for implementation. Key was enlisting clinical champions to advocate for the QIP, secure participation in primary care, and establish effective communication channels. Preparation for implementation required obtaining IHS approvals, ensuring Health Insurance Portability and Accountability Act compliance, and devising operational strategies for patient outreach and clinical decision support delivery.

Stage 3 was developing three IHS implementation models. With insight into the local context from local clinicians, implementation models were adapted to work with the resources and capacity of the IHSs while ensuring the delivery of essential elements of the programme.

Developing and launching a QIP programme across primary care practices requires extensive groundwork, preparation, and committed local champions to assist in building an adaptable environment that encourages open communication and is receptive to feedback.

Syncope is common among pediatric patients and is rarely pathologic. The mechanisms for symptoms during exercise are less well understood than the resting mechanisms. Additionally, inert gas rebreathing analysis, a non-invasive examination of haemodynamics including cardiac output, has not previously been studied in youth with neurocardiogenic syncope.

This was a retrospective (2017–2023), single-center cohort study in pediatric patients ≤ 21 years with prior peri-exertional syncope evaluated with echocardiography and cardiopulmonary exercise testing with inert gas rebreathing analysis performed on the same day. Patients with and without symptoms during or immediately following exercise were noted.

Of the 101 patients (15.2 ± 2.3 years; 31% male), there were 22 patients with symptoms during exercise testing or recovery. Resting echocardiography stroke volume correlated with resting (r = 0.53, p < 0.0001) and peak stroke volume (r = 0.32, p = 0.009) by inert gas rebreathing and with peak oxygen pulse (r = 0.61, p < 0.0001). Patients with syncopal symptoms peri-exercise had lower left ventricular end-diastolic volume (Z-score –1.2 ± 1.3 vs. –0.36 ± 1.3, p = 0.01) and end-systolic volume (Z-score –1.0 ± 1.4 vs. −0.1 ± 1.1, p = 0.001) by echocardiography, lower percent predicted peak oxygen pulse during exercise (95.5 ± 14.0 vs. 104.6 ± 18.5%, p = 0.04), and slower post-exercise heart rate recovery (31.0 ± 12.7 vs. 37.8 ± 13.2 bpm, p = 0.03).

Among youth with a history of peri-exertional syncope, those who become syncopal with exercise testing have lower left ventricular volumes at rest, decreased peak oxygen pulse, and slower heart rate recovery after exercise than those who remain asymptomatic. Peak oxygen pulse and resting stroke volume on inert gas rebreathing are associated with stroke volume on echocardiogram.

It has been posited that alcohol use may confound the association between greater concussion history and poorer neurobehavioral functioning. However, while greater alcohol use is positively correlated with neurobehavioral difficulties, the association between alcohol use and concussion history is not well understood. Therefore, this study investigated the cross-sectional and longitudinal associations between cumulative concussion history, years of contact sport participation, and health-related/psychological factors with alcohol use in former professional football players across multiple decades.

Former professional American football players completed general health questionnaires in 2001 and 2019, including demographic information, football history, concussion/medical history, and health-related/psychological functioning. Alcohol use frequency and amount was reported for three timepoints: during professional career (collected retrospectively in 2001), 2001, and 2019. During professional career and 2001 alcohol use frequency included none, 1-2, 3-4, 5-7 days/week, while amount included none, 12, 3-5, 6-7, 8+ drinks/occasion. For 2019, frequency included never, monthly or less, 2-4 times/month, 2-3 times/week, >4 times/week, while amount included none, 1-2, 3-4, 5-6, 7-9, 10+ drinks/occasion. Scores on a screening measure for Alcohol Use Disorder (CAGE) were also available at during professional career and 2001 timepoints. Concussion history was recorded in 2001 and binned into five groups: 0, 1-2, 3-5, 6-9, 10+. Depression and pain interference were assessed via PROMIS measures at all timepoints. Sleep disturbance was assessed in 2001 via separate instrument and with PROMIS Sleep Disturbance in 2019. Spearman’s rho correlations tested associations between concussion history and years of sport participation with alcohol use across timepoints, and whether poor health functioning (depression, pain interference, sleep disturbance) in 2001 and 2019 were associated with alcohol use both within and between timepoints.

Among the 351 participants (Mage=47.86[SD=10.18] in 2001), there were no significant associations between concussion history or years of contact sport participation with CAGE scores or alcohol use frequency/amount during professional career, 2001, or 2019 (rhos=-.072-.067, ps>.05). In 2001, greater depressive symptomology and sleep disturbance were related to higher CAGE scores (rho=.209, p<.001; rho=.176, p<.001, respectively), while greater depressive symptomology, pain interference, and sleep disturbance were related to higher alcohol use frequency (rho=.176, p=.002; rho=.109, p=.045; rho=.132, p=.013, respectively) and amount/occasion (rho=.215, p<.001; rho=.127, p=.020; rho=.153, p=.004, respectively). In 2019, depressive symptomology, pain interference, and sleep disturbance were not related to alcohol use (rhos=-.047-.087, ps>.05). Between timepoints, more sleep disturbance in 2001 was associated with higher alcohol amount/occasion in 2019 (rho=.115, p=.036).

Increased alcohol intake has been theorized to be a consequence of greater concussion history, and as such, thought to confound associations between concussion history and neurobehavioral function later in life. Our findings indicate concussion history and years of contact sport participation were not significantly associated with alcohol use cross-sectionally or longitudinally, regardless of alcohol use characterization. While higher levels of depression, pain interference, and sleep disturbance in 2001 were related to greater alcohol use in 2001, they were not associated cross-sectionally in 2019. Results support the need to concurrently address health-related and psychological factors in the implementation of alcohol use interventions for former NFL players, particularly earlier in the sport discontinuation timeline.

Impulsivity is a central symptom of borderline personality disorder (BPD) and its neural basis may be instantiated in a frontoparietal network involved in response inhibition. However, research has yet to determine whether neural activation differences in BPD associated with response inhibition are attributed to attentional saliency, which is subserved by a partially overlapping network of brain regions.

Patients with BPD (n = 45) and 29 healthy controls (HCs; n = 29) underwent functional magnetic resonance imaging while completing a novel go/no-go task with infrequent odd-ball trials to control for attentional saliency. Contrasts reflecting a combination of response inhibition and attentional saliency (no-go > go), saliency processing alone (oddball > go), and response inhibition controlling for attentional saliency (no-go > oddball) were compared between BPD and HC.

Compared to HC, BPD showed less activation in the combined no-go > go contrast in the right posterior inferior and middle-frontal gyri, and less activation for oddball > go in left-hemispheric inferior frontal junction, frontal pole, superior parietal lobe, and supramarginal gyri. Crucially, BPD and HC showed no activation differences for the no-go > oddball contrast. In BPD, higher vlPFC activation for no-go > go was correlated with greater self-rated BPD symptoms, whereas lower vlPFC activation for oddball > go was associated with greater self-rated attentional impulsivity.

Patients with BPD show frontoparietal disruptions related to the combination of response inhibition and attentional saliency or saliency alone, but no specific response inhibition neural activation difference when attentional saliency is controlled. The findings suggest a neural dysfunction in BPD underlying attention to salient or infrequent stimuli, which is supported by a negative correlation with self-rated impulsiveness.

Haematopoietic stem cell transplantation is an important and effective treatment strategy for many malignancies, marrow failure syndromes, and immunodeficiencies in children, adolescents, and young adults. Despite advances in supportive care, patients undergoing transplant are at increased risk to develop cardiovascular co-morbidities.

This study was performed as a feasibility study of a rapid cardiac MRI protocol to substitute for echocardiography in the assessment of left ventricular size and function, pericardial effusion, and right ventricular hypertension.

A total of 13 patients were enrolled for the study (age 17.5 ± 7.7 years, 77% male, 77% white). Mean study time was 13.2 ± 5.6 minutes for MRI and 18.8 ± 5.7 minutes for echocardiogram (p = 0.064). Correlation between left ventricular ejection fraction by MRI and echocardiogram was good (ICC 0.76; 95% CI 0.47, 0.92). None of the patients had documented right ventricular hypertension. Patients were given a survey regarding their experiences, with the majority both perceiving that the echocardiogram took longer (7/13) and indicating they would prefer the MRI if given a choice (10/13).

A rapid cardiac MRI protocol was shown feasible to substitute for echocardiogram in the assessment of key factors prior to or in follow-up after haematopoietic stem cell transplantation.

Psychological stress is associated with accelerated cellular aging and increased risk for aging-related diseases, but the underlying molecular mechanisms are unclear.

We examined the effect of stress on a DNA methylation age predictor that was shown to correlate strongly with chronological age across human tissues (Horvath 2013). Genome-wide DNA methylation was measured in peripheral blood using the 450K Illumina array in three independent cohorts: the Grady Trauma Project/GTP (N=366); a panic disorder case/control sample recruited at the Max Planck Institute of Psychiatry/MPI-P (N=318); and the Conte Center for the Psychobiology of Early-Life Trauma/Conte (N=42). Age acceleration was calculated by subtracting chronological age from age predicted by DNA methylation. Psychiatric symptomatology and stressors were assessed using standard questionnaires.

DNA methylation age strongly correlated with chronological age in all samples (r=0.9, p=2.5x10^-133). Cumulative lifetime stress but not childhood or current stress predicted age acceleration in GTP (p=0.012) and MPI-P (p=0.021). Moreover, epigenetic age acceleration predicted depression (GTP: p=0.002; Conte: p=0.014) and panic disorder (p=0.007). In secondary analyses, we examined the effect of lifetime stress on individual CpGs of the DNA methylation age predictor. After correcting for multiple comparisons, we identified in both GTP and MPI-P a stress-regulated CpG near MCAM, a gene implicated in aging-related diseases, including cardiovascular disease and cancers.

Cumulative lifetime stress, but not childhood or current stress, and psychiatric phenotypes are associated with accelerated epigenetic aging. Our findings may explain the accelerated cellular aging and increased disease risk associated with chronic stress and psychiatric disorders.

Persons using the Internet generate large amounts of health-related data, which are increasingly used in modern health sciences.

We analysed the relation between annual prescription volumes (APV) of several antidepressants with marketing approval in Germany and corresponding web search query data generated in Google to test, if web search query volume may be a proxy for medical prescription practice.

We obtained APVs of several antidepressants related to corresponding prescriptions at the expense of the statutory health insurance in Germany from 2004–2013. Web search query data generated in Germany and related to defined search-terms (active substance or brand name) were obtained with Google Trends. We calculated correlations (Pearson's r) between the APVs of each substance and the respective annual “search share” values; coefficients of determination (R2) were computed to determine the amount of variability shared by the two variables.

Significant and strong correlations between substance-specific APVs and corresponding annual query volume were found for each substance during the observational interval: agomelatine (r = 0.968; R2 = 0.932; P = 0.01), bupropion (r = 0.962; R2 = 0.925; P = 0.01), citalopram (r = 0.970; R2 = 0.941; P = 0.01), escitalopram (r = 0.824; R2 = 0.682; P = 0.01), fluoxetine (r = 0.885; R2 = 0.783; P = 0.01), paroxetine (r = 0.801; R2 = 0.641; P = 0.01), and sertraline (r = 0.880; R2 = 0.689; P = 0.01).

Although the used data did not allow to perform an analysis with a higher temporal resolution our results suggest that web search query volume may be a proxy for corresponding prescription behaviour. However, further studies analysing other pharmacologic agents and prescription data that facilitates an increased temporal resolution are needed to confirm this hypothesis.

The authors have not supplied their declaration of competing interest.

Pathological gambling is a behavioural addiction with negative economic, social, and psychological consequences. Identification of contributing genes and pathways may improve understanding of aetiology and facilitate therapy and prevention. Here, we report the first genome-wide association study of pathological gambling. Our aims were to identify pathways involved in pathological gambling, and examine whether there is a genetic overlap between pathological gambling and alcohol dependence.

Four hundred and forty-five individuals with a diagnosis of pathological gambling according to the Diagnostic and Statistical Manual of Mental Disorders were recruited in Germany, and 986 controls were drawn from a German general population sample. A genome-wide association study of pathological gambling comprising single marker, gene-based, and pathway analyses, was performed. Polygenic risk scores were generated using data from a German genome-wide association study of alcohol dependence.

No genome-wide significant association with pathological gambling was found for single markers or genes. Pathways for Huntington's disease (P-value = 6.63 × 10−3); 5′-adenosine monophosphate-activated protein kinase signalling (P-value = 9.57 × 10−3); and apoptosis (P-value = 1.75 × 10−2) were significant. Polygenic risk score analysis of the alcohol dependence dataset yielded a one-sided nominal significant P-value in subjects with pathological gambling, irrespective of comorbid alcohol dependence status.

The present results accord with previous quantitative formal genetic studies which showed genetic overlap between non-substance- and substance-related addictions. Furthermore, pathway analysis suggests shared pathology between Huntington's disease and pathological gambling. This finding is consistent with previous imaging studies.

Drug-induced liver injury is a major problem of pharmacotherapy and is also frequent with anti-depressive psychopharmacotherapy.

However, there are only few studies using a consistent methodologic approach to study hepatotoxicity of a larger group of antidepressants.

We performed a quantitative signal detection analysis using pharmacovigilance data from the Uppsala monitoring center from the WHO that records adverse drug reaction data from worldwide sources; we calculated reporting odds ratios (ROR) as measures for disproportionality within a case-/non-case approach for several frequently prescribed anti-depressants.

Both positive controls, amineptine (ROR 38.4 [95% CI: 33.8–43.6]) and nefazodone (ROR 3.2 [95% CI: 3.0–3.5]), were statistically associated with hepatotoxicity. Following amineptine, agomelatine (ROR 6.4 [95% CI: 5.7–7.2]) was associated with the second highest ROR, followed by tianeptine (ROR 4.4 [95% CI: 3.6–5.3]), mianserin (ROR 3.6 [95% CI: 3.3–3.4]) and nefazodone.

In line with previous studies our results support the hypothesis that agomelatine and several other anti-depressants may be associated with relevant hepatotoxicity. However, the used data and applied method do not allow a quantitative evaluation of hepatotoxicity or assessment of substance–specific differences regarding the extent of hepatotoxicity.

The authors have not supplied their declaration of competing interest.