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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.
To evaluate the effect of school-based nutrition interventions (SBNI) involving schoolchildren and adolescents in sub-Saharan Africa (SSA) on child nutrition status and nutrition-related knowledge, attitudes and behaviour.
A systematic review on published school nutrition intervention studies of randomised controlled trials, controlled clinical trials, controlled before-and-after studies or quasi-experimental designs with control. Nine electronic bibliographic databases were searched. To be included, interventions had to involve changes to the school’s physical and social environments, to the school’s nutrition policies, to teaching curriculum to incorporate nutrition education and/or to partnership with parents/community.
Schools in SSA.
School-aged children and adolescents, aged 5–19 years.
Fourteen studies met our inclusion criteria. While there are few existing studies of SBNI in SSA, the evidence shows that food supplementation/fortification is very effective in reducing micronutrient deficiencies and can improve nutrition status. Secondly, school nutrition education can improve nutrition knowledge, but this may not necessarily translate into healthy nutrition behaviour, indicating that nutrition knowledge may have little impact without a facilitating environment. Results regarding anthropometry were inconclusive; however, there is evidence for the effectiveness of SBNI in improving cognitive abilities.
There is enough evidence to warrant further trials of SBNI in SSA. Future research should consider investigating the impact of SBNI on anthropometry and nutrition behaviour, focusing on the role of programme intensity and/or duration. To address the high incidence of micronutrient deficiencies in low- and middle-income countries, food supplementation strategies currently available to schoolchildren should be expanded.
A number of genomic conditions caused by copy number variants (CNVs) are associated with a high risk of neurodevelopmental and psychiatric disorders (ND-CNVs). Although these patients also tend to have cognitive impairments, few studies have investigated the range of emotion and behaviour problems in young people with ND-CNVs using measures that are suitable for those with learning difficulties.
A total of 322 young people with 13 ND-CNVs across eight loci (mean age: 9.79 years, range: 6.02–17.91, 66.5% male) took part in the study. Primary carers completed the Developmental Behaviour Checklist (DBC).
Of the total, 69% of individuals with an ND-CNV screened positive for clinically significant difficulties. Young people from families with higher incomes (OR = 0.71, CI = 0.55–0.91, p = .008) were less likely to screen positive. The rate of difficulties differed depending on ND-CNV genotype (χ2 = 39.99, p < 0.001), with the lowest rate in young people with 22q11.2 deletion (45.7%) and the highest in those with 1q21.1 deletion (93.8%). Specific patterns of strengths and weaknesses were found for different ND-CNV genotypes. However, ND-CNV genotype explained no more than 9–16% of the variance, depending on DBC subdomain.
Emotion and behaviour problems are common in young people with ND-CNVs. The ND-CNV specific patterns we find can provide a basis for more tailored support. More research is needed to better understand the variation in emotion and behaviour problems not accounted for by genotype.
Biodiversity loss may increase the risk of infectious disease in a phenomenon known as the dilution effect. Circumstances that increase the likelihood of disease dilution are: (i) when hosts vary in their competence, and (ii) when communities disassemble predictably, such that the least competent hosts are the most likely to go extinct. Despite the central role of competence in diversity–disease theory, we lack a clear understanding of the factors underlying competence, as well as the drivers and extent of its variation. Our perspective piece encourages a mechanistic understanding of competence and a deeper consideration of its role in diversity–disease relationships. We outline current evidence, emerging questions and future directions regarding the basis of competence, its definition and measurement, the roots of its variation and its role in the community ecology of infectious disease.
Dialysis patients may not have access to conventional renal replacement therapy (RRT) following disasters. We hypothesized that improvised renal replacement therapy (ImpRRT) would be comparable to continuous renal replacement therapy (CRRT) in a porcine acute kidney injury model.
Following bilateral nephrectomies and 2 hours of caudal aortic occlusion, 12 pigs were randomized to 4 hours of ImpRRT or CRRT. In the ImpRRT group, blood was circulated through a dialysis filter using a rapid infuser to collect the ultrafiltrate. Improvised replacement fluid, made with stock solutions, was infused pre-pump. In the CRRT group, commercial replacement fluid was used. During RRT, animals received isotonic crystalloids and norepinephrine.
There were no differences in serum creatinine, calcium, magnesium, or phosphorus concentrations. While there was a difference between groups in serum potassium concentration over time (P < 0.001), significance was lost in pairwise comparison at specific time points. Replacement fluids or ultrafiltrate flows did not differ between groups. There were no differences in lactate concentration, isotonic crystalloid requirement, or norepinephrine doses. No difference was found in electrolyte concentrations between the commercial and improvised replacement solutions.
The ImpRRT system achieved similar performance to CRRT and may represent a potential option for temporary RRT following disasters.
OBJECTIVES/GOALS: To determine if a multi-modal, interdisciplinary intervention delivered to a group of prediabetic patients will result in reduced rates of diabetes progression. This project is a retrospective evaluation that will exam the feasibility and possibly efficacy of this intervention. METHODS/STUDY POPULATION: We will evaluate outcomes of 50 participants for the clinic, aged 21-60 inclusive. Patients will have a Body Mass Index >25kg/m2 with a diagnosis of prediabetes. Patients must be non-pregnant, using approved contraception, and agree to not become pregnant for 1 year after enrollment. After enrollment, the initial treatment period is for 1 year and includes a 12 week low calorie diet plan, a 6-month intensive behavioral and lifestyle modification plan followed by a 6 month behavior reinforcement extension. Weight management medications may be used if appropriate for the patient from a clinical perspective during the 6-month intensive behavioral/lifestyle modification. RESULTS/ANTICIPATED RESULTS: It is anticipated that there will be decreased weight with a mean weight loss goal of approximately >10%. Furthermore, it is expect that there will be improvement of other markers of metabolic disease. These include improvement of lipid values (LDL-C, HDL-C, Triglycerides, Total Cholesterol) as well as blood pressure with expected blood pressures of below 130/80 in greater than 50% of participants. Finally, It is expected that 50% or greater participants will have improvement of glycemic control. It is anticipated that greater than 50% of participants will have improvement of glycemic control and achieve normoglycemia. These values will be determined based upon fasting glucose or A1c. DISCUSSION/SIGNIFICANCE OF IMPACT: The significance of this intervention is enormous. By demonstrating feasibility in this trial, we can work toward both assessing efficacy and possibly dissemination of this model program. If these interventions provide durable changes at scale, this could help slow the epidemic of obesity and obesity related comorbid conditions.
This study focuses on a draft letter by Ḥusayn b. ʿAbd al-Ṣamad al-ʿĀmilī (d. 984/1576) for his teacher Zayn al-Dīn al-ʿĀmilī (d. 965/1558); both were prominent Twelver Shiite jurists from the region of Jabal ʿĀmil in what is now Lebanon. Yūsuf Ṭabājah, who first published the text, argued that Ḥusayn wrote the letter while he was in Iraq c. 957/1550 and that it describes Zayn al-Dīn's legal work al-Rawḍah al-bahiyyah. It is argued here that the book in question is more likely Zayn al-Dīn's work Tamhīd al-qawāʿid, on legal and grammatical maxims, and that the letter dates to c. 958/1551. The text provides insight into the relationship between Ḥusayn and Zayn al-Dīn and the culture of scholarly correspondence.
Introduction: The novel Paramedics Providing Palliative Care at Home program has been developed to address the mismatch between traditional paramedic practice and patient's goals of care. Case-finding is key to estimate potential impact for systems looking to establish such programs, continuous quality improvement once operational, and for prospective identification of patients who might benefit from referral to palliative care. Typical paramedic charting templates do not provide direct identification of these cases. Our objective was to test the validity of a previously derived Palliative Support Composite Measure (PSCM) and two modifications. Methods: A priori Gold Standard criteria for determining whether a response was appropriate for a paramedic palliative care approach were identified by expert consensus. Excluding chief complaints and clinical conditions that were universally identified as not appropriate for paramedic palliative support, these criteria were applied by two trained chart abstractors to 500 consecutive charts to classify calls as appropriate for paramedic palliative support, or not. The PSCM and modifications (added criteria call location type and registration in a palliative care program, text mining terms) were applied to the same cohort, and sensitivity, specificity, positive and negative predicative (PPV/NPV) values calculated. Results: Of the 500 cases, 21 (4.2%) were classified as appropriate for paramedic palliative support by the Gold Standard (kappa 0.734). 9 cases with initial disagreement were reviewed with 8 ultimately being deemed to fit the palliative support criteria. The PSCM performed poorly (using the “potential palliative” cut point): sensitivity 71.4% (95%CI: 47.8-88.7), specificity 71.4% (95%CI: 67.1-75.4) and PPV of 9.9% (95%CI: 7.5-12.9) and NPV of 98.3% (95%CI: 96.7-99). The modified PSCM: sensitivity 61.9% (95% CI: 38.4-81.9), specificity 99% (95%CI: 97.6-99.7), PPV 72.2% (95%CI: 50.5-86.9) and NPV 98.3% (95%CI: 97.2-99). A Modified PSCM plus pall* text term performed similarly: sensitivity100% (83.9-100), specificity 97.3% (95% CI: 95.4-98.5), PPV 61.8% (95%CI: 48.6-73.4) and NPV100%. Conclusion: A modified PSCM provides moderate sensitivity, specificity and PPV, improved by the text term Pall* if feasible. This query will be helpful to systems considering a paramedic palliative care program or when one is already operational.
Introduced from Europe to North America in the early 19th century as an ornamental shrub and for medicinal purposes, common buckthorn (Rhamnus cathartica L.) has since spread and naturalized throughout regions of the United States and Canada. The purpose of this study was to investigate levels of genetic variation and population differentiation in R.cathartica in its introduced range in North America compared with its native range in Europe to better understand patterns of spread. By analyzing introduced and native populations using microsatellite markers, we found that introduced populations generally exhibited similar or slightly lower levels of genetic variation compared with native populations, consistent with a slight bottleneck effect. Introduced populations contained many different genotypes, indicating genetic admixture, rather than one or few genotypes. In a few cases, populations had been misidentified in the field and were glossy buckthorn (Frangula alnus Mill.; syn. Rhamnus frangula L.). Overall, there was no substantial genetic differentiation detected between native and introduced populations of R. cathartica. Invasive spread in this species is likely due to its past horticultural history as well as adaptive biological traits such as competitive behavior, potential allelopathy, and seed dispersal via birds.
Patients with non-Hodgkin's lymphoma and chronic lymphocytic leukaemia are at an elevated risk of further malignancy. Head and neck squamous cell carcinoma often presents with cervical lymph node metastasis, and can pose a diagnostic challenge in patients with non-Hodgkin's lymphoma or chronic lymphocytic leukaemia who may have pre-existing palpable neck nodes.
A retrospective case review of a health board was conducted to identify patients with head and neck squamous cell carcinoma with a previous diagnosis of non-Hodgkin's lymphoma or chronic lymphocytic leukaemia.
Four patients with head and neck squamous cell carcinoma that developed after non-Hodgkin's lymphoma or chronic lymphocytic leukaemia were identified. Two patients had a background of non-Hodgkin's lymphoma treated with chemotherapy. The remaining two patients had a background of chronic lymphocytic leukaemia under active surveillance. Three out of the four patients died within 30 months of diagnosis.
Head and neck squamous cell carcinoma following non-Hodgkin's lymphoma or chronic lymphocytic leukaemia is aggressive. A heightened clinical suspicion is essential to facilitate early diagnosis and treatment of head and neck squamous cell carcinoma in patients with dual pathology.
The ‘sick-quitter’ hypothesis states that mental disorders associated with alcohol abstinence are accounted for by people who stop consuming alcohol because of poor health.
We investigated the association between alcohol abstinence and symptoms of common mental disorder and personality disorder, distinguishing between lifelong abstinence and abstinence following previous consumption.
Analyses were based on the British National Survey of Psychiatric Morbidity 2000, which sampled 8580 residents aged 16 to 74 years. Heavy consumers of alcohol were excluded, using the Alcohol Use Disorders Identification Test Questionnaire. Symptoms of common mental disorder (depression/anxiety) were identified by the Clinical Interview Schedule. The screening questionnaire of the Structured Clinical Interview for Axis II Personality Disorders was used to identify potential personality disorder. Self-reported alcohol abstinence was divided into lifelong abstinence and previous consumption. Previous consumers were asked why they had stopped. Covariates included socioeconomic status, social activity and general health status.
After adjustment, alcohol abstinence was associated with both common mental disorder symptoms and any personality disorder, but only for previous consumers (respective odds ratios 1.70 (1.23-2.34) and 1.45 (1.09-1.94)). Associations were non-specific, being apparent for most individual mental disorder symptoms and personality disorder categories. More detailed analysis indicated that associations were limited to previous consumers who reported ceasing alcohol consumption for health reasons.
The results were consistent with the ‘sick-quitter’ hypothesis and should be taken into account when interpreting associations between moderate alcohol consumption and beneficial health outcomes.
Lipids appear to mediate depressive vulnerability in the elderly, however, sex differences and genetic vulnerability have not been taken into account in previous prospective studies.
Depression was assessed in a population of 1040 women and 752 men aged 65 years and over at baseline and after 7-year follow-up. Clinical level of depression (DEP) was defined as having either a score of 16 and above on the Centre for Epidemiology Studies Depression scale or a diagnosis of current major depression on the Mini International Neuropsychiatric Interview. Lipid levels, apolipoprotein E and serotonin transporter linked promoter region (5-HTTLPR) genotypes were evaluated at baseline.
Multivariate analyses adjusted by socio-demographic and behavioral variables, measures of physical health including ischemic pathologies, and genetic vulnerability indicated gender-specific associations between dyslipidemia and DEP, independent of the use of lipid lowering agents or apolipoprotein E status. Men with low LDL-cholesterol levels had twice the risk of prevalent and incident DEP whereas in women low HDL-cholesterol levels were found to be significantly associated with increased prevalent DEP (OR = 1.5) only. A significant interaction was observed between low LDL-cholesterol and 5-HTTLPR genotype, men with s/s or s/l genotype being at increased risk of DEP (OR = 6.0 and 2.7, respectively). No significant gene-environment interaction was observed for women.
DEP is associated with higher atherogenic risk in women (low HDL-cholesterol), whereas the reverse is observed in men (low LDL-cholesterol). Late-life depression may have a complex gender-specific etiology involving genetic vulnerability in men.
Autism Spectrum Disorders (ASDs) affect 1% of children and are associated with lifelong psychosocial impairments. The majority of children with ASD will experience co-occurring psychiatric disorders. In the UK, antipsychotics remain unlicensed for use in ASDs, however 10% of children with ASD receive antipsychotic treatment; the co-occurring disorders being targeted by these medications remains unclear.
To examine rates of antipsychotic medication use and identify associated co-occurring disorders among children with ASD receiving psychiatric care.
The sample consisted of 2844 children aged 2 to 17 with a NHS clinician recorded ICD-10 diagnoses for ASD between 2008–2013. Clinical variables extracted from their anonymised electronic patient records included disorder severity, medication use, co-occurring ICD-10 diagnoses, family characteristics, demographics and antipsychotic use.
Of the 2844 children (79% male), the majority (57%) had co-occurring psychiatric diagnoses. 313 (11%) received antipsychotic medication. The proportion of children aged 13 to 17 years and 6 to 12 years prescribed antipsychotics was 19% and 7% respectively. After controlling for socio-demographic factors, disorder severity, specialist treatment, inpatient duration, risk of self harm, violence to others, self injurious behaviour, maltreatment history, parental mental illness, caregiver anxiety, and neighbourhood deprivation, multivariate regression analysis revealed only hyperactivity disorders (O.R 1.94, 95%C.I. 1.32–2.86), psychotic disorders (O.R 5.12 95% C.I. 2.6–10.1), mood disorders (O.R 2.02, 95%C.I. 1.04–3.92) and intellectual disability (O.R 2.89 95% C.I. 1.89–4.71) were associated with anti-psychotic use.
The prescription of antipsychotic medications in this UK ASD clinical sample is strongly associated with specific co-occurring psychiatric disorders and intellectual disability.
There are often substantial delays before diagnosis and initiation of treatment in people bipolar disorder. Increased delays are a source of considerable morbidity among affected individuals.
To investigate the factors associated with delays to diagnosis and treatment in people with bipolar disorder.
Retrospective cohort study using electronic health record data from the South London and Maudsley NHS Foundation Trust (SLaM) from 1364 adults diagnosed with bipolar disorder. The following predictor variables were analysed in a multivariable Cox regression analysis on diagnostic delay and treatment delay from first presentation to SLaM: age, gender, ethnicity, compulsory admission to hospital under the UK Mental Health Act, marital status and other diagnoses prior to bipolar disorder.
The median diagnostic delay was 62 days (interquartile range: 17–243) and median treatment delay was 31 days (4–122). Compulsory hospital admission was associated with a significant reduction in both diagnostic delay (hazard ratio 2.58, 95% CI 2.18–3.06) and treatment delay (4.40, 3.63–5.62). Prior diagnoses of other psychiatric disorders were associated with increased diagnostic delay, particularly alcohol (0.48, 0.33–0.41) and substance misuse disorders (0.44, 0.31–0.61). Prior diagnosis of schizophrenia and psychotic depression were associated with reduced treatment delay.
Some individuals experience a significant delay in diagnosis and treatment of bipolar disorder, particularly those with alcohol/substance misuse disorders. These findings highlight a need to better identify the symptoms of bipolar disorder and offer appropriate treatment sooner in order to facilitate improved clinical outcomes. This may include the development of specialist early intervention services.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Psychiatric disorders, including eating disorders (EDs), have clinical outcomes that range widely in severity and chronicity. The ability to predict such outcomes is extremely limited. Machine-learning (ML) approaches that model complexity may optimize the prediction of multifaceted psychiatric behaviors. However, the investigations of many psychiatric concerns have not capitalized on ML to improve prognosis. This study conducted the first comparison of an ML approach (elastic net regularized logistic regression) to traditional regression to longitudinally predict ED outcomes.
Females with heterogeneous ED diagnoses completed demographic and psychiatric assessments at baseline (n = 415) and Year 1 (n = 320) and 2 (n = 277) follow-ups. Elastic net and traditional logistic regression models comprising the same baseline variables were compared in ability to longitudinally predict ED diagnosis, binge eating, compensatory behavior, and underweight BMI at Years 1 and 2.
Elastic net models had higher accuracy for all outcomes at Years 1 and 2 [average Area Under the Receiving Operating Characteristics Curve (AUC) = 0.78] compared to logistic regression (average AUC = 0.67). Model performance did not deteriorate when the most important predictor was removed or an alternative ML algorithm (random forests) was applied. Baseline ED (e.g. diagnosis), psychiatric (e.g. hospitalization), and demographic (e.g. ethnicity) characteristics emerged as important predictors in exploratory predictor importance analyses.
ML algorithms can enhance the prediction of ED symptoms for 2 years and may identify important risk markers. The superior accuracy of ML for predicting complex outcomes suggests that these approaches may ultimately aid in advancing precision medicine for serious psychiatric disorders.
The Great Migration from the South and the rise of racial residential segregation strongly shaped the twentieth-century experience of African Americans. Yet, little attention has been devoted to how the two phenomena were linked, especially with respect to the individual experiences of the migrants. We address this gap by using novel data that links individual records from the complete-count 1940 Census to those in the 2000 Census long form, in conjunction with information about the level of racial residential segregation in metropolitan areas in 1940 and 2000. We first consider whether migrants from the South and their children experienced higher or lower levels of segregation in 1940 relative to their counterparts who were born in the North or who remained in the South. Next, we extend our analysis to second-generation Great Migration migrants and their segregation outcomes by observing their location in 2000. Additionally, we assess whether second-generation migrants experience larger decreases in their exposure to segregation as their socioeconomic status increases relative to their southern and/or northern stayer counterparts. Our study significantly advances our understanding of the Great Migration and the “segregated century.”
This study aimed to examine the influence of the complexity of the story-book on caregiver extra-textual talk (i.e., interactions beyond text reading) during shared reading with preschool-age children. Fifty-three mother–child dyads (3;00–4;11) were video-recorded sharing two ostensibly similar picture-books: a simple story (containing no false belief) and a complex story (containing a false belief central to the plot, which provided content that was more challenging for preschoolers to understand). Book-reading interactions were transcribed and coded. Results showed that the complex stories facilitated more extra-textual talk from mothers, and a higher quality of extra-textual talk (as indexed by linguistic richness and level of abstraction). Although the type of story did not affect the number of questions mothers posed, more elaborative follow-ups on children's responses were provided by mothers when sharing complex stories. Complex stories may facilitate more and linguistically richer caregiver extra-textual talk, having implications for preschoolers’ developing language abilities.
Psychiatric disorders are associated with increased risk of ischaemic heart disease (IHD) and stroke, but it is not known whether the associations or the role of sociodemographic factors have changed over time.
To investigate the association between psychiatric disorders and IHD and stroke, by time period and sociodemographic factors.
We used Scottish population-based records from 1991 to 2015 to create retrospective cohorts with a hospital record for psychiatric disorders of interest (schizophrenia, bipolar disorder or depression) or no record of hospital admission for mental illness. We estimated incidence and relative risks of IHD and stroke in people with versus without psychiatric disorders by calendar year, age, gender and area-based deprivation level.
In all cohorts, incidence of IHD (645 393 events) and stroke (276 073 events) decreased over time, but relative risks decreased for depression only. In 2015, at the mean age at event onset, relative risks were 2- to 2.5-fold higher in people with versus without a psychiatric disorder. Age at incidence of outcome differed by cohort, gender and socioeconomic status. Relative but not absolute risks were generally higher in women than men. Increasing deprivation conveys a greater absolute risk of IHD for people with bipolar disorder or depression.
Despite declines in absolute rates of IHD and stroke, relative risks remain high in those with versus without psychiatric disorders. Cardiovascular disease monitoring and prevention approaches may need to be tailored by psychiatric disorder and cardiovascular outcome, and be targeted, for example, by age and deprivation level.