This study estimates the maximum price at which mesenchymal stem cell (MSC) therapy is deemed cost-effective for septic shock patients and identifies parameters that are most important in making treatment decisions.

We developed a probabilistic Markov model according to the sepsis care trajectory to simulate costs and quality-adjusted life years (QALYs) of septic shock patients receiving either MSC therapy or usual care over their lifetime. We calculated the therapeutic headroom by multiplying the gains attributable to MSCs with willingness-to-pay (WTP) threshold and derived the maximum reimbursable price (MRP) from the expected net monetary benefit and savings attributable to MSCs. We performed scenario analyses to assess the impact of changes to assumptions on the study findings. A value of information analysis is performed to identify parameters with greatest impact on the uncertainty around the cost-effectiveness of MSC therapy.

At a WTP threshold of $50,000 per QALY, the therapeutic headroom and MRP of MSC therapy were $20,941 and $16,748, respectively; these estimates increased with the larger WTP values and the greater impact of MSCs on in-hospital mortality and hospital discharge rates. The parameters with greatest information value were MSC's impact on in-hospital mortality and the baseline septic shock in-hospital mortality.

At a common WTP of $50,000/QALY, MSC therapy is deemed to be economically attractive if its unit cost does not exceed $16,748. This ceiling price can be increased to $101,450 if the therapy significantly reduces both in-hospital mortality and increases hospital discharge rates.

The aims of this study were to evaluate changes in inflammatory and oxidative stress levels following treatment with N-acetylcysteine (NAC) or mitochondrial-enhancing agents (CT), and to assess the how these changes may predict and/or moderate clinical outcomes primarily the Montgomery-Åsberg Depression Rating Scale (MADRS).

This study involved secondary analysis of a placebo-controlled randomised trial (n = 163). Serum samples were collected at baseline and week 16 of the clinical trial to determine changes in Interleukin-6 (IL-6) and total antioxidant capacity (TAC) following adjunctive CT and/or NAC treatment, and to explore the predictability of the outcome or moderator effects of these markers.

In the NAC-treated group, no difference was observed in serum IL-6 and TAC levels after 16 weeks of treatment with NAC or CT. However, results from a moderator analysis showed that in the CT group, lower IL-6 levels at baseline was a significant moderator of MADRS χ2 (df) = 4.90, p = 0.027) and Clinical Global Impression-Improvement (CGI-I, χ2 (df) = 6.28 p = 0.012). In addition, IL-6 was a non-specific but significant predictor of functioning (based on the Social and Occupational Functioning Assessment Scale (SOFAS)), indicating that individuals with higher IL-6 levels at baseline had a greater improvement on SOFAS regardless of their treatment (p = 0.023).

Participants with lower IL-6 levels at baseline had a better response to the adjunctive treatment with the mitochondrial-enhancing agents in terms of improvements in MADRS and CGI-I outcomes.

Prognostic staging is one of the most important current psychiatrical challenges.

Bipolar prognostic factors must be identified to assist in staging.

To assess prognostic factors, to describe any correlation with the disease outcome and to recommend that psychiatrists assess bipolar patients, determining their stage of disease in order to identify possible high-risk groups of patients.

We collected data from the clinical notes of 70 bipolar outpatients seen at the initial psychiatric assessment clinic about socio-demographic and clinical factors.

The sample comprised 16 bipolar I (22.9%) and 54 bipolar II (77.1%) outpatients; 60.9% reported anxiety, 71.7 % mixed state features and 72.7% rapid cycling. A comparison between 12 prognostic factors found that only the correlations between current illicit drug use/previous illicit drug use, current alcohol use/previous alcohol use, and current illicit drug use/anxiety were statistically significant; the correlation between previous illicit drug use/previous alcohol use, previous alcohol use/family history and mixed state features/anxiety were almost significant.

17 patients were assigned to a care coordinator; we found no statistically significant differences between the patients with or without a care coordinator on the basis of the presence of 12 possible prognostic factors.

In our sample, some patients were found not to have information available so we suggest that a questionnaire to remind clinicians of potentially useful information would be helpful to aid in prognostication. Specific features of the disease (family history, age at onset, features of depressive episodes and mixed state, rapid cycling) may be highlighted.

The Health of the Nation Outcomes Scales (HoNOS) has been widely used as an outcome measure in UK mental health settings for the past decade. The data-set gathered provides a unique opportunity to evaluate the effectiveness of the totality of mental healthcare in ‘real-world’ conditions; much of our clinical evidence currently comes from highly parameterised clinical trials investigating single interventions in highly selected patients.

To examine all outcomes measured by HoNOS for a range of diagnostic groups, evaluate the influence of patient demographics on those outcomes, and observe changes in patient groups over time.

Here we show the data from 6813 adult patients treated in Cambridgeshire between 2012 and 2017. Patients were split into three diagnostic groups: psychosis, non-psychosis and organic. Changes in HoNOS scores from initial assessment to discharge were tested and regressions were used to evaluate the influence of age, gender and ethnicity on the changes, as well as to model changes in the severity of initial presenting symptoms with time.

HoNOS scores significantly improve after treatment for psychotic, non-psychotic and organic conditions in adults and older adults. Age, but not gender or ethnicity, influenced change in HoNOS scores. Patients entering secondary mental health services had increased initial HoNOS scores over time.

The UK repository of HoNOS scores provides a significant and relatively underutilised resource that can be exploited to gain insights into mental illness and treatment effectiveness. This is likely to have many applications, including influencing the commissioning of services.

Consistent with pathophysiological models of psychosis, temporal disturbances in schizophrenia spectrum populations may reflect abnormal cortical (e.g. prefrontal cortex) and subcortical (e.g. striatum) cerebellar connectivity. However, few studies have examined associations between cerebellar connectivity and timing dysfunction in psychosis populations, and none have been conducted in youth at clinical high-risk (CHR) for psychosis. Thus, it is currently unknown if impairments in temporal processes are present in CHR youth or how they may be associated with cerebellar connectivity and worsening of symptoms.

A total of 108 (56 CHR/52 controls) youth were administered an auditory temporal bisection task along with a resting state imaging scan to examine cerebellar resting state connectivity. Positive and negative symptoms at baseline and 12 months later were also quantified.

Controlling for alcohol and cannabis use, CHR youth exhibited poorer temporal accuracy compared to controls, and temporal accuracy deficits were associated with abnormal connectivity between the bilateral anterior cerebellum and a right caudate/nucleus accumbens striatal cluster. Poor temporal accuracy accounted for 11% of the variance in worsening of negative symptoms over 12 months.

Behavioral findings suggest CHR youth perceive durations of auditory tones as shortened compared to objective time, which may indicate a slower internal clock. Poorer temporal accuracy in CHR youth was associated with abnormalities in brain regions involved in an important cerebellar network implicated in prominent pathophysiological models of psychosis. Lastly, temporal accuracy was associated with worsening of negative symptoms across 12 months, suggesting temporal dysfunction may be sensitive to illness progression.

Rehabilitation of memory after stroke remains an unmet need. Telehealth delivery may overcome barriers to accessing rehabilitation services.

We conducted a non-randomized intervention trial to investigate feasibility and effectiveness of individual telehealth (internet videoconferencing) and face-to-face delivery methods for a six-week compensatory memory rehabilitation program. Supplementary analyses investigated non-inferiority to an existing group-based intervention, and the role of booster sessions in maintaining functional gains. The primary outcome measure was functional attainment of participants’ goals. Secondary measures included subjective reports of lapses in everyday memory and prospective memory, reported use of internal and external memory strategies, and objective measures of memory functioning.

Forty-six stroke survivors were allocated to telehealth and face-to-face intervention delivery conditions. Feasibility of delivery methods was supported, and participants in both conditions demonstrated treatment-related improvements in goal attainment, and key subjective outcomes of everyday memory, and prospective memory. Gains on these measures were maintained at six-week follow-up. Short-term gains in use of internal strategies were also seen. Non-inferiority to group-based delivery was established only on the primary measure for the telehealth delivery condition. Booster sessions were associated with greater maintenance of gains on subjective measures of everyday memory and prospective memory.

This exploratory study supports the feasibility and potential effectiveness of telehealth options for remote delivery of compensatory memory skills training after a stroke. These results are also encouraging of a role for booster sessions in prolonging functional gains over time.

The C677T polymorphism in the folate metabolising enzyme methylenetetrahydrofolate reductase (MTHFR) is associated with hypertension. Riboflavin acts as a cofactor for MTHFR in one-carbon metabolism which generates methyl groups for utilisation in important biological reactions such as DNA methylation. Supplementation with riboflavin has previously been shown to lower blood pressure in individuals with the MTHFR 677TT genotype. The mechanism regulating this gene-nutrient interaction is currently unknown but may involve aberrant DNA methylation which has been implicated hypertension.

The aims of this study were to examine DNA methylation of hypertension-related genes in adults stratified by MTHFR C677T genotype and the effect of riboflavin supplementation on DNA methylation of these genes in individuals with the MTHFR 677TT genotype.

We measured DNA methylation using pyrosequencing in a set of candidate genes associated with hypertension including angiotensin II receptor type 1 (AGTR1), G nucleotide binding protein subunit alpha 12 (GNA12), insulin-like growth factor 2 (IGF2) and nitric oxide synthase 3 (NOS3). Stored peripheral blood leukocyte samples from participants previously screened for the MTHFR C677T genotype who participated in targeted randomised controlled trials (1.6mg/d riboflavin or placebo for 16 weeks) at Ulster University were accessed for this analysis (n = 120).

There were significant differences in baseline average methylation between MTHFR CC and TT genotypes at NOS3 (p = 0.026) and AGTR1 (p = 0.045) loci. Riboflavin supplementation in the TT genotype group resulted in altered average methylation at IGF2 (p = 0.025) and CpG site-specific alterations at the AGTR1 and GNA12 loci.

DNA methylation at genes related to hypertension were significantly different in individuals stratified by MTHFR genotype group. Furthermore, in MTHFR 677TT genotype individuals, there were concurrent alterations in DNA methylation at genes linked to hypertension in response to riboflavin supplementation. This is the largest study to date to demonstrate an interaction between DNA methylation of hypertension-related genes and riboflavin supplementation in adults with the MTHFR 677TT genotype. Further work using a genome-wide approach is required to better understand the role of riboflavin in altering DNA methylation in these genetically at-risk individuals.

American Indians experience substantial health disparities relative to the US population, including vascular brain aging. Poorer cognitive test performance has been associated with cranial magnetic resonance imaging findings in aging community populations, but no study has investigated these associations in elderly American Indians.

We examined 786 American Indians aged 64 years and older from the Cerebrovascular Disease and its Consequences in American Indians study (2010–2013). Cranial magnetic resonance images were scored for cortical and subcortical infarcts, hemorrhages, severity of white matter disease, sulcal widening, ventricle enlargement, and volumetric estimates for white matter hyperintensities (WMHs), hippocampus, and brain. Participants completed demographic, medical history, and neuropsychological assessments including testing for general cognitive functioning, verbal learning and memory, processing speed, phonemic fluency, and executive function.

Processing speed was independently associated with the presence of any infarcts, white matter disease, and hippocampal and brain volumes, independent of socioeconomic, language, education, and clinical factors. Other significant associations included general cognitive functioning with hippocampal volume. Nonsignificant, marginal associations included general cognition with WMH and brain volume; verbal memory with hippocampal volume; verbal fluency and executive function with brain volume; and processing speed with ventricle enlargement.

Brain-cognition associations found in this study of elderly American Indians are similar to those found in other racial/ethnic populations, with processing speed comprising an especially strong correlate of cerebrovascular disease. These findings may assist future efforts to define opportunities for disease prevention, to conduct research on diagnostic and normative standards, and to guide clinical evaluation of this underserved and overburdened population.

Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.

We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.

16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).

PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.