Daptomycin is preferred in outpatient parenteral antimicrobial therapy (OPAT) due to daily dosing. Elevations in creatine phosphokinase (CPK) of 3%–10% and musculoskeletal adverse events have been described with daptomycin, but data regarding risk factors and frequency of monitoring in the OPAT setting is limited. We evaluated the incidence and risk factors for CPK elevation and musculoskeletal adverse effects in patients receiving daptomycin OPAT.

This was a single-center, retrospective cohort study of adults on OPAT with daptomycin and at least two CPK values. The primary outcome was the incidence of CPK values greater than 500 U/L.

We included 127 patients. Most patients were male (55.1%), and the median age was 56 years (IQR 46–63). The most common indication was bone/joint infections (73.2%, n = 93). The median daptomycin dose was 7.4 mg/kg/day (IQR 6.1–8.1) and duration of therapy was 37 days (IQR 21–44). Fifteen patients (11.8%) experienced a CPK greater than 500 U/L within a median 13 days (IQR 9–16). Five patients (3.9%) developed rhabdomyolysis. Independent predictors of CPK>500 U/L included male sex (OR, 4.2 [95% CI, 1.05–16.61]; P = .0424) and cerebrovascular disease (OR, 11 [95% CI, 1.21–99.86]; P = .0332).

The incidence of CPK elevation was similar previously reported rates. This expands the literature to patients with daptomycin doses>6 mg/kg and prolonged durations of therapy. The incidence of CPK elevation and time to onset of 9–16 days supports the current recommendations for weekly lab monitoring.

Inappropriate diagnosis and treatment of urinary tract infections (UTIs) contribute to antibiotic overuse. The Inappropriate Diagnosis of UTI (ID-UTI) measure uses a standard definition of asymptomatic bacteriuria (ASB) and was validated in large hospitals. Critical access hospitals (CAHs) have different resources which may make ASB stewardship challenging. To address this inequity, we adapted the ID-UTI metric for use in CAHs and assessed the adapted measure’s feasibility, validity, and reliability.

Retrospective observational study

10 CAHs

From October 2022 to July 2023, CAHs submitted clinical information for adults admitted or discharged from the emergency department who received antibiotics for a positive urine culture. Feasibility of case submission was assessed as the number of CAHs achieving the goal of 59 cases. Validity (sensitivity/specificity) and reliability of the ID-UTI definition were assessed by dual-physician review of a random sample of submitted cases.

Among 10 CAHs able to participate throughout the study period, only 40% (4/10) submitted >59 cases (goal); an additional 3 submitted >35 cases (secondary goal). Per the ID-UTI metric, 28% (16/58) of cases were ASB. Compared to physician review, the ID-UTI metric had 100% specificity (ie all cases called ASB were ASB on clinical review) but poor sensitivity (48.5%; ie did not identify all ASB cases). Measure reliability was high (93% [54/58] agreement).

Similar to measure performance in non-CAHs, the ID-UTI measure had high reliability and specificity—all cases identified as ASB were considered ASB—but poor sensitivity. Though feasible for a subset of CAHs, barriers remain.

Elevated risk of psychosis for ethnic minority groups has generally been shown to be mitigated by high ethnic density. However, past survey studies examining UK Pakistani populations have shown an absence of protective ethnic density effects, which is not observed in other South Asian groups.

To assess the ethnic density effect at a local neighbourhood level, in the UK Pakistani population in East Lancashire.

Data was collected by the East Lancashire Early Intervention Service, identifying all cases of first episode psychosis (FEP) within their catchment area between 2012 and 2020. Multilevel Poisson regression analyses were used to compare incidence rates between Pakistani and White majority groups, while controlling for age, gender and area-level deprivation. The ethnic density effect was also examined by comparing incidence rates across high and low density areas.

A total of 455 cases of FEP (364 White, 91 Pakistani) were identified. The Pakistani group had a higher incidence of FEP compared to the White majority population. A clear effect of ethnic density on rates of FEP was shown, with those in low density areas having higher incidence rates compared to the White majority, whereas incidence rates in high density areas did not significantly differ. Within the Pakistani group, a dose-response effect was also observed, with risk of FEP increasing incrementally as ethnic density decreased.

Higher ethnic density related to lower risk of FEP within the Pakistani population in East Lancashire, highlighting the impact of local social context on psychosis incidence.

Children and adolescents with a history of adverse childhood experiences (ACEs) are more likely than their peers to develop mental health difficulties, but not enough is known about their help-seeking behaviours and preferences. We aimed to determine whether ACEs are associated with access to and perceived unmet need for mental health services and support amongst secondary school students.

We used multi-level logistic regression with data from the 2020 OxWell Student Survey to assess whether ACEs were associated with (1) prior access to mental health support and (2) perceived unmet need for mental health services in a community sample of English secondary school students. We assessed ACEs as a cumulative score from the Center for Youth Wellness Adverse Childhood Experiences Questionnaire: Teen Self-Report version and accounted for current mental health difficulties as measured by the 25-item Revised Children’s Anxiety and Depression Scale (RCADS).

Our analysis included 2018 students across 64 schools, of whom 29.9% (598/2002) reported prior access to mental health support. Of those not reporting prior access, 34.1% (469/1377) reported a perceived unmet need for services. In the unadjusted models, cumulative ACE scores were significantly positively associated with both prior access to mental health support (odds ratio (OR) = 1.36; 95% confidence interval (CI): 1.29–1.43) and perceived unmet need for mental health services (OR = 1.47; 95% CI: 1.37–1.59), meaning that students who had experienced adversity had a greater chance of having previously accessed support as well as perceiving an unmet need for services. After adjusting for mental health difficulties and other sociodemographic variables, cumulative ACE scores were positively associated with prior access (adjusted OR (aOR) = 1.25; 95% CI: 1.17–1.34 with a significant interaction between RCADS and ACE scores, aOR = 0.88; 95% CI: 0.84–0.93) as well as perceived unmet need (aOR = 1.32; 95% CI: 1.21–1.43 with a significant interaction between RCADS and ACE scores, aOR = 0.85; 95% CI: 0.78–0.91).

Although it is encouraging that adolescents with experience of adversity are more likely than their peers with similar levels of depression and anxiety symptoms to have accessed mental health support, there remains a concern that those who have not accessed support are more likely to perceive an as-yet unmet need for it. Mental health support must be available, accessible and acceptable to all who need it, especially for those groups that traditionally have not accessed services, including the more marginalised and vulnerable populations.

The UK Soft Drinks Industry Levy (SDIL) (announced in March 2016; implemented in April 2018) aims to incentivise reformulation of soft drinks to reduce added sugar levels. The SDIL has been applauded as a policy success, and it has survived calls from parliamentarians for it to be repealed. We aimed to explore parliamentary reaction to the SDIL following its announcement until two years post-implementation in order to understand how health policy can become established and resilient to opposition.

Searches of Hansard for parliamentary debate transcripts that discussed the SDIL retrieved 186 transcripts, with 160 included after screening. Five stages of Applied Thematic Analysis were conducted: familiarisation and creation of initial codebooks; independent second coding; codebook finalisation through team consensus; final coding of the dataset to the complete codebook; and theme finalisation through team consensus.

The United Kingdom Parliament

N/A

Between the announcement (16/03/2016) – royal assent (26/04/2017), two themes were identified 1: SDIL welcomed cross-party 2: SDIL a good start but not enough. Between royal assent – implementation (5/04/2018), one theme was identified 3: The SDIL worked – what next? The final theme identified from implementation until 16/03/2020 was 4: Moving on from the SDIL.

After the announcement, the SDIL had cross-party support and was recognised to have encouraged reformulation prior to implementation. Lessons for governments indicate that the combination of cross-party support and a policy’s documented success in achieving its aim can help cement the resilience of it to opposition and threats of repeal.

Normal pressure hydrocephalus (NPH) is characterized by pathologically enlarged ventricles without elevated cerebrospinal fluid (CSF) pressure along with a triad of clinical symptoms including gait disturbances, urinary incontinence, and cognitive impairment. NPH is evaluated with lumbar drain trials (LDTs) where CSF is removed over several days to determine if patients would benefit from ventricular shunting. Candidate selection and success for these surgeries remains challenging because other diseases such as Alzheimer’s disease (AD) share common features with NPH in cognitive impairment and enlarged ventricles. Prior research has found that 20%-40% of presumed NPH cases have AD pathology as determined by brain biopsy or autopsy. CSF biomarkers of AD can be altered in NPH and are not always conclusive, complicating the interpretation of results when formulating diagnoses and prognoses. Studies to refine the analyses of AD CSF biomarkers in NPH are needed. We aimed to examine the frequency of CSF biomarker results among patients presenting for NPH evaluations with LDTs.

62 patients presented for LDTs upon physician recommendations. CSF specimens were sent to Mayo Clinic Laboratories for Alzheimer Disease Evaluation (ADEVL) that utilizes Elecsys (Lenexa, KS) CSF electrochemiluminescence immunoassays (Roche Diagnostics, Basel, Switzerland) to measure levels of amyloid-beta 42 (Aβ42), total tau (t-tau), and phosphorylatedtau (p-tau), and p-tau:Aβ42 ratio. Results were classified based on interpretation through the Amyloid/Tau/Neurodegeneration (ATN) framework1: 1) AD - biomarker profile consistent with AD pathologic change, 2) non-AD profile - biomarker levels normal or inconsistent with AD pathologic change, or 3) indeterminate - biomarkers were incongruous with only one or two abnormal levels of Aβ42, t-tau, p-tau, or ptau: Aβ42. Indeterminate cases may represent altered protein levels due to CSF dynamics or AD-related pathologic change. In reviewing recent research on CSF dynamics and AD biomarkers in NPH2 a p-tau threshold of 15 pg/mL was derived and implemented such that cases with Aß42 <=1026 pg/mL and p-tau <15 pg/mL were designated as suspected non-AD, and those with Aß42 <=1026 pg/mL and p-tau >15 pg/mL were designated suspected AD.

Of the 62 LDT cases, 12 (19.35%) were classified as AD, 31 (50%) were indeterminate and 22 (35.48%) were non-AD. Of the 31 indeterminate cases, 21 (33.87% of the overall sample) were suspected non-AD and 7 (11.29% of the full sample) were categorized as suspected AD.

Our findings show that 20%-30% of patients presenting for LDT showed evidence for AD-type pathologic change, consistent with prior reports of AD pathology in cases of possible NPH. Half of all LDT cases had indeterminate AD CSF biomarker results, the interpretations of which were confounded by the potential alterations of CSF biomarkers levels due to NPH independent of AD. Our findings emphasize the need to establish better approaches to interpreting CSF AD biomarkers in evaluating NPH. Future research should examine the discriminative utility of CSF AD biomarkers and the selected p-tau threshold in indeterminate cases for predicting response to LDT and shunting.

Alterations in heart rate (HR) may provide new information about physiological signatures of depression severity. This 2-year study in individuals with a history of recurrent major depressive disorder (MDD) explored the intra-individual variations in HR parameters and their relationship with depression severity.

Data from 510 participants (Number of observations of the HR parameters = 6666) were collected from three centres in the Netherlands, Spain, and the UK, as a part of the remote assessment of disease and relapse-MDD study. We analysed the relationship between depression severity, assessed every 2 weeks with the Patient Health Questionnaire-8, with HR parameters in the week before the assessment, such as HR features during all day, resting periods during the day and at night, and activity periods during the day evaluated with a wrist-worn Fitbit device. Linear mixed models were used with random intercepts for participants and countries. Covariates included in the models were age, sex, BMI, smoking and alcohol consumption, antidepressant use and co-morbidities with other medical health conditions.

Decreases in HR variation during resting periods during the day were related with an increased severity of depression both in univariate and multivariate analyses. Mean HR during resting at night was higher in participants with more severe depressive symptoms.

Our findings demonstrate that alterations in resting HR during all day and night are associated with depression severity. These findings may provide an early warning of worsening depression symptoms which could allow clinicians to take responsive treatment measures promptly.

To inform strategies aimed at improving blood pressure (BP) control and reducing salt intake, we assessed educational inequalities in high blood pressure (HBP) awareness, treatment and control; physician’s advice on salt reduction; and salt knowledge, perceptions and consumption behaviours in Eastern Europe and Central Asia.

Data were collected in cross-sectional, population-based nationally representative surveys, using a multi-stage clustered sampling design. Five HBP awareness, treatment and control categories were created from measured BP and hypertension medication use. Education and other variables were self-reported. Weighted multinomial mixed-effects regression models, adjusted for confounders, were used to assess differences across education categories.

Nine Eastern European and Central Asian countries (Armenia, Azerbaijan, Belarus, Georgia, Kyrgyzstan, Republic of Moldova, Tajikistan, Turkey and Uzbekistan).

Nationally representative samples of 30 455 adults aged 25–65 years.

HBP awareness, treatment and control varied substantially by education. The coverage of physician’s advice on salt was less frequent among participants with lower education, and those with untreated HBP or unaware of their HBP. The education gradient was evident in salt knowledge and perceptions of salt intake but not in salt consumption behaviours. Improved salt knowledge and perceptions were more prevalent among participants who received physician’s advice on salt reduction.

There is a strong education gradient in HBP awareness, treatment and control as well as salt knowledge and perceived intake. Enhancements in public and patient knowledge and awareness of HBP and its risk factors targeting socio-economically disadvantaged groups are urgently needed to alleviate the growing HBP burden in low- and middle-income countries.

Outpatient antimicrobial therapy (OPAT) is managed by a variety of teams, but primarily through an infectious disease clinic. At our medical center, OPAT monitoring is performed telephonically by pharmacists through a collaborative practice agreement under the supervision of an infectious disease physician. The effect of telephonic monitoring of OPAT by pharmacists on patient outcomes is unknown.

This retrospective cohort study was conducted between July 2017 and July 2018 at a 350-bed academic medical center and included adult patients discharged home on IV antibiotics or oral linezolid. The experimental group comprised patients discharged with a consultation for the OPAT management program, whereas the control group comprised patients discharged home without a consultation. The primary outcome was 30-day readmission.

In total, 399 patients were included: 243 patients in the OPAT management program group and 156 patients in the control group. The 30-day readmission rates were similar in each cohort (20% vs 19%; P = .8193); however, the 30-day readmission rates were lower in the OPAT management program for patients discharged on vancomycin (19.4% vs 39.1%; P = .004).

We did not find a difference in 30-day readmissions between patients receiving pharmacy-driven OPAT management services and those who did not. Patients receiving vancomycin via OPAT had lower 30-day readmissions when included in the pharmacist-driven OPAT management program. Institutions with limited resources may consider reserving OPAT management services for patients receiving antimicrobials that require pharmacokinetic dosing and/or close monitoring.