Harnessing the Regenerative Potential of Purified Bovine Dental Pulp and Dentin Extracellular Matrices in a Chitosan/Alginate Hydrogel.

When a tooth is diseased or damaged through caries, bioactive molecules are liberated from the pulp and dentin as part of the natural response to injury and these are key molecules for stimulating stem cell responses for tissue repair. Incorporation of these extracellular-matrix (ECM)-derived molecules into a hydrogel model can mimic in vivo conditions to enable dentin-pulp complex regeneration. Here, a chitosan/alginate (C/A) hydrogel is developed to sequester bovine ECM extracts. Human dental pulp cells (hDPCs) are cultured with these constructs and proliferation and cytotoxicity assays confirm that these C/A hydrogels are bioactive. Sequential z-axis fluorescent imaging visualizes hDPCs protruding into the hydrogel as it degraded. Alizarin red S staining shows that hDPCs cultured with the hydrogels display increased calcium-ion deposition, with dentin ECM stimulating the highest levels. Alkaline phosphatase activity is increased, as is expression of transforming growth factor-beta as demonstrated using immunocytochemistry. Directional analysis following phase contrast kinetic image capture demonstrates that both dentin and pulp ECM molecules act as chemoattractants for hDPCs. Data from this study demonstrate that purified ECM from dental pulp and dentin when delivered in a C/A hydrogel stimulates dental tissue repair processes in vitro.

Prevalence of depression and anxiety symptoms after stroke in young adults: A systematic review and meta-analysis.

BACKGROUND: Young adults with stroke have distinct professional and social roles making them vulnerable to symptoms of post-stroke depression (PSD) and post-stroke anxiety (PSA). Prior reviews have examined the prevalence of anxiety and depression in stroke populations. However, there are a lack of studies that have focused on these conditions in young adults. OBJECTIVE: We performed a systematic review and meta-analysis of observational studies that reported on symptoms of PSD, PSA and comorbid PSD/PSA in young adults aged 18 to 55 years of age. METHODS: MEDLINE, EMBASE, SCOPUS and PsycINFO were searched for studies reporting the prevalence of symptoms of PSD and/or PSA in young adults with stroke from inception until June 23, 2023. We included studies that evaluated depression and/or anxiety symptoms with screening tools or interviews following ischemic or hemorrhagic stroke. Validated methods were employed to evaluate risk of bias. RESULTS: 4748 patients from twenty eligible studies were included. Among them, 2420 were also evaluated for symptoms of PSA while 847 participants were evaluated for both PSD and PSA symptoms. Sixteen studies were included in the random effects meta-analysis for PSD symptoms, with a pooled prevalence of 31 % (95 % CI 24-38 %). Pooled PSA symptom prevalence was 39 % (95 % CI 30-48 %) and comorbid PSD with PSA symptom prevalence was 25 % (95 % CI 12-39 %). Varying definitions of 'young adult', combinations of stroke subtypes, and methods to assess PSD and PSA contributed to high heterogeneity amongst studies. CONCLUSIONS: We identified high heterogeneity in studies investigating the prevalence of symptoms of PSD and PSA in young adults, emphasizing the importance of standardized approaches in future research to gain insight into the outcomes and prognosis of PSD and PSA symptoms following stroke in young adults. Larger longitudinal epidemiological studies as well as studies on tailored interventions are required to address the mental health needs of this important population. FUNDING: None.

A practical guide to living evidence: Reducing the knowledge-to-practice gap.

Living evidence involves continuous evidence surveillance to incorporate new relevant evidence into systematic reviews and clinical practice guideline recommendations as soon as it becomes available. Thus, living evidence may improve the timeliness of recommendation updates and reduce the knowledge-to-practice gap. When considering a living evidence model, several processes and practical aspects need to be explored. Some of these include identifying the need for a living evidence model, funding, governance structure, time, team skills and capabilities, frequency of updates, approval and endorsement and publication and dissemination.

Individual patient data meta-analysis of the effects of fluoxetine on functional outcomes after acute stroke.

BACKGROUND: Three large randomized controlled trials of fluoxetine for stroke recovery have been performed. We performed an individual patient data meta-analysis (IPDM) on the combined data. METHODS: Fixed effects meta-analyses were performed on the combined data set, for the primary outcome (modified Rankin scale (mRS) at 6 months), and secondary outcomes common to the individual trials. As a sensitivity analysis, summary statistics from each trial were created and combined. FINDINGS: The three trials recruited a combined total of 5907 people (mean age 69.5 years (SD 12.3), 2256 (38%) females, 2-15 days post-stroke) from Australia, New Zealand, United Kingdom, Sweden, and Vietnam; and randomized them to fluoxetine 20 mg daily or matching placebo for 6 months. Data on 5833 (98.75%) were available at 6 months. The adjusted ordinal comparison of mRS was similar in the two groups (common OR 0.96, 95% CI 0.87 to 1.05, p = 0.37). There were no statistically significant interactions between the minimization variables (baseline probability of being alive and independent at 6 months, time to treatment, motor deficit, or aphasia) and pre-specified subgroups (including age, pathological type, inability to assess mood, proxy or patient consent, baseline depression, country). Fluoxetine increased seizure risk (2.64% vs 1.8%, p = 0.03), falls with injury (6.26% vs 4.51%, p = 0.03), fractures (3.15% vs 1.39%, p < 0.0001) and hyponatremia (1.22% vs 0.61%, p = 0.01) but reduced new depression (10.05% vs 13.42%, p < 0.0001). At 12 months, there was no difference in adjusted mRS (n = 5760; common OR 0.98, 95% CI 0.89 to 1.07). Sensitivity analyses gave the same results. INTERPRETATION: Fluoxetine 20 mg daily for 6 months did not improve functional recovery. It increased seizures, falls with injury, and bone fractures but reduced depression frequency at 6 months.

Mental health in the two years following hypertensive and normotensive pregnancy: The Postpartum, Physiology, Psychology and Paediatric follow-up (P4) cohort study.

BACKGROUND: Postpartum mental illnesses and hypertensive disorders of pregnancy (HDP) are both common, and both associated with adverse maternal and child health outcomes. However, the relationship between them is unclear. This study aimed to investigate prevalence and symptom severity of depression, anxiety, and post-traumatic stress disorder (PTSD) 2-years postpartum in women with normal blood pressure (NBP) during pregnancy versus preeclampsia or gestational hypertension (GH). METHODS: Two-years follow-up of the prospective Postpartum, Physiology, Psychology and Paediatric (P4) Cohort Study was conducted in metropolitan Australia. Prevalence and symptom severity of depression (Edinburgh Postnatal Depression Scale, EPDS > 12), anxiety (7-item Generalized Anxiety Disorder scale, GAD-7 ≥ 10) and PTSD (Posttraumatic stress Diagnostic Scale, PDS/PDS-5) were measured and calculated for women with NBP, preeclampsia and GH. RESULTS: Among 365 participants (NBP: n = 271, preeclampsia: n = 75, GH: n = 19), 2-years postpartum depression prevalence was 3.9% (95% CI 2.3-6.4%): 4.4% after NBP, and 2.7% after preeclampsia (p = 0.53). Anxiety prevalence was higher after GH than NBP (15.8% versus 3.3%, p = 0.02). Prevalence of any mental illness (depression/anxiety/PTSD) was 5.9% (95% CI 3.8-8.8%); 5.6% after NBP, 4.1% after PE, and 15.8% after GH (p = 0.15). Although PTSD prevalence was low (1.4%), and similar between groups (p = 0.97), around 3 times more women after PE (8.1%), compared to NBP (2.5%), recalled childbirth as traumatic (p = 0.003). CONCLUSIONS: Preeclampsia, although associated with persistent perceptions of traumatic childbirth, did not alter the risk of mental illnesses at 2-years postpartum. GH (albeit in a small subgroup) was associated with increased anxiety scores. Larger, multicentre studies are required to clarify relationships between HDP and postpartum mental illness. TRIAL REGISTRATION: Retrospectively registered on 18/11/2013 with the Australian and New Zealand Clinical Trials Registry. REGISTRATION NUMBER: ACTRN 12613 00,126 0718.

EMPOWERED trial: protocol for a randomised control trial of digitally supported, highly personalised and measurement-based care to improve functional outcomes in young people with mood disorders.

OBJECTIVES: Many adolescents and young adults with emerging mood disorders do not achieve substantial improvements in education, employment, or social function after receiving standard youth mental health care. We have developed a new model of care referred to as 'highly personalised and measurement-based care' (HP&MBC). HP&MBC involves repeated assessment of multidimensional domains of morbidity to enable continuous and personalised clinical decision-making. Although measurement-based care is common in medical disease management, it is not a standard practice in mental health. This clinical effectiveness trial tests whether HP&MBC, supported by continuous digital feedback, delivers better functional improvements than standard care and digital support. METHOD AND ANALYSIS: This controlled implementation trial is a PROBE study (Prospective, Randomised, Open, Blinded End-point) that comprises a multisite 24-month, assessor-blinded, follow-up study of 1500 individuals aged 15-25 years who present for mental health treatment. Eligible participants will be individually randomised (1:1) to 12 months of HP&MBC or standardised clinical care. The primary outcome measure is social and occupational functioning 12 months after trial entry, assessed by the Social and Occupational Functioning Assessment Scale. Clinical and social outcomes for all participants will be monitored for a further 12 months after cessation of active care. ETHICS AND DISSEMINATION: This clinical trial has been reviewed and approved by the Human Research Ethics Committee of the Sydney Local Health District (HREC Approval Number: X22-0042 & 2022/ETH00725, Protocol ID: BMC-YMH-003-2018, protocol version: V.3, 03/08/2022). Research findings will be disseminated through peer-reviewed journals, presentations at scientific conferences, and to user and advocacy groups. Participant data will be deidentified. TRIAL REGISTRATION NUMBER: ACTRN12622000882729.

Pharmacological, non-invasive brain stimulation and psychological interventions, and their combination, for treating depression after stroke.

BACKGROUND: Depression is an important morbidity associated with stroke that impacts on recovery, yet is often undetected or inadequately treated. OBJECTIVES: To evaluate the benefits and harms of pharmacological intervention, non-invasive brain stimulation, psychological therapy, or combinations of these to treat depression after stroke. SEARCH METHODS: This is a living systematic review. We search for new evidence every two months and update the review when we identify relevant new evidence. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review. We searched the Specialised Registers of Cochrane Stroke, and Cochrane Depression Anxiety and Neurosis, CENTRAL, MEDLINE, Embase, five other databases, two clinical trials registers, reference lists and conference proceedings (February 2022). We contacted study authors. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing: 1) pharmacological interventions with placebo; 2) non-invasive brain stimulation with sham stimulation or usual care; 3) psychological therapy with usual care or attention control; 4) pharmacological intervention and psychological therapy with pharmacological intervention and usual care or attention control; 5) pharmacological intervention and non-invasive brain stimulation with pharmacological intervention and sham stimulation or usual care; 6) non-invasive brain stimulation and psychological therapy versus sham brain stimulation or usual care and psychological therapy; 7) pharmacological intervention and psychological therapy with placebo and psychological therapy; 8) pharmacological intervention and non-invasive brain stimulation with placebo and non-invasive brain stimulation; and 9) non-invasive brain stimulation and psychological therapy versus non-invasive brain stimulation and usual care or attention control, with the intention of treating depression after stroke. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risk of bias, and extracted data from included studies. We calculated mean difference (MD) or standardised mean difference (SMD) for continuous data, and risk ratio (RR) for dichotomous data, with 95% confidence intervals (CIs). We assessed heterogeneity using the I² statistic and certainty of the evidence according to GRADE. MAIN RESULTS: We included 65 trials (72 comparisons) with 5831 participants. Data were available for: 1) 20 comparisons; 2) nine comparisons; 3) 25 comparisons; 4) three comparisons; 5) 14 comparisons; and 6) one comparison. We found no trials for comparisons 7 to 9. Comparison 1: Pharmacological interventions Very low-certainty evidence from eight trials suggests pharmacological interventions decreased the number of people meeting the study criteria for depression (RR 0.70, 95% CI 0.55 to 0.88; P = 0.002; 8 RCTs; 1025 participants) at end of treatment and very low-certainty evidence from six trials suggests that pharmacological interventions decreased the number of people with inadequate response to treatment (RR 0.47, 95% CI 0.32 to 0.70; P = 0.0002; 6 RCTs; 511 participants) compared to placebo. More adverse events related to the central nervous system (CNS) (RR 1.55, 95% CI 1.12 to 2.15; P = 0.008; 5 RCTs; 488 participants; very low-certainty evidence) and gastrointestinal system (RR 1.62, 95% CI 1.19 to 2.19; P = 0.002; 4 RCTs; 473 participants; very low-certainty evidence) were noted in the pharmacological intervention than in the placebo group. Comparison 2: Non-invasive brain stimulation Very low-certainty evidence from two trials show that non-invasive brain stimulation had little to no effect on the number of people meeting the study criteria for depression (RR 0.67, 95% CI 0.39 to 1.14; P = 0.14; 2 RCTs; 130 participants) and the number of people with inadequate response to treatment (RR 0.84, 95% CI 0.52, 1.37; P = 0.49; 2 RCTs; 130 participants) compared to sham stimulation. Non-invasive brain stimulation resulted in no deaths. Comparison 3: Psychological therapy Very low-certainty evidence from six trials suggests that psychological therapy decreased the number of people meeting the study criteria for depression at end of treatment (RR 0.77, 95% CI 0.62 to 0.95; P = 0.01; 521 participants) compared to usual care/attention control. No trials of psychological therapy reported on the outcome inadequate response to treatment. No differences in the number of deaths or adverse events were found in the psychological therapy group compared to the usual care/attention control group. Comparison 4: Pharmacological interventions with psychological therapy No trials of this combination reported on the primary outcomes. Combination therapy resulted in no deaths. Comparison 5: Pharmacological interventions with non-invasive brain stimulation Non-invasive brain stimulation with pharmacological intervention reduced the number of people meeting study criteria for depression at end of treatment (RR 0.77, 95% CI 0.64 to 0.91; P = 0.002; 3 RCTs; 392 participants; low-certainty evidence) but not the number of people with inadequate response to treatment (RR 0.95, 95% CI 0.69 to 1.30; P = 0.75; 3 RCTs; 392 participants; very low-certainty evidence) compared to pharmacological therapy alone. Very low-certainty evidence from five trials suggest no difference in deaths between this combination therapy (RR 1.06, 95% CI 0.27 to 4.16; P = 0.93; 487 participants) compared to pharmacological therapy intervention and sham stimulation or usual care. Comparison 6: Non-invasive brain stimulation with psychological therapy No trials of this combination reported on the primary outcomes. AUTHORS' CONCLUSIONS: Very low-certainty evidence suggests that pharmacological, psychological and combination therapies can reduce the prevalence of depression while non-invasive brain stimulation had little to no effect on the prevalence of depression. Pharmacological intervention was associated with adverse events related to the CNS and the gastrointestinal tract. More research is required before recommendations can be made about the routine use of such treatments.

ANTECEDENTES: La depresión tiene una morbilidad importante asociada con el accidente cerebrovascular que repercute en la recuperación, pero que a menudo no se detecta o se trata de manera inadecuada. OBJETIVOS: Evaluar los efectos beneficiosos y perjudiciales de las intervenciones farmacológicas, la estimulación cerebral no invasiva, la terapia psicológica o las combinaciones de éstas para tratar la depresión después del accidente cerebrovascular. MÉTODOS DE BÚSQUEDA: Esta es una revisión sistemática continua. Cada dos meses se busca nueva evidencia y la revisión se actualiza cuando se identifica evidencia nueva relevante. Consultar el estado actual de esta revisión en la Base de Datos Cochrane de Revisiones Sistemáticas (Cochrane Database of Systematic Reviews). Se realizaron búsquedas en los Registros especializados del Grupo Cochrane de Accidentes cerebrovasculares (Cochrane Stroke) y del Grupo Cochrane de Depresión, ansiedad y neurosis (Cochrane Depression, Anxiety and Neurosis), en CENTRAL, MEDLINE, Embase, otras cinco bases de datos, dos registros de ensayos clínicos, listas de referencias y resúmenes de congresos (febrero de 2022). Se estableció contacto con autores de estudios. CRITERIOS DE SELECCIÓN: Ensayos controlados aleatorizados (ECA) que compararan: 1) intervenciones farmacológicas con placebo; 2) estimulación cerebral no invasiva con estimulación simulada o atención habitual; 3) terapia psicológica con atención habitual o control de atención; 4) intervención farmacológica y terapia psicológica con intervención farmacológica y atención habitual o control de atención; 5) intervención farmacológica y estimulación cerebral no invasiva con intervención farmacológica y estimulación simulada o atención habitual; 6) estimulación cerebral no invasiva y terapia psicológica versus estimulación cerebral simulada o atención habitual y terapia psicológica; 7) intervención farmacológica y terapia psicológica con placebo y terapia psicológica; 8) intervención farmacológica y estimulación cerebral no invasiva con placebo y estimulación cerebral no invasiva; y 9) estimulación cerebral no invasiva y terapia psicológica versus estimulación cerebral no invasiva y atención habitual o control de atención, con la intención de tratar la depresión después del accidente cerebrovascular. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos autores de la revisión, de forma independiente, seleccionaron los estudios, evaluaron el riesgo de sesgo y extrajeron los datos de los estudios incluidos. Se calculó la diferencia de medias (DM) o la diferencia de medias estandarizada (DME) para los datos continuos, y la razón de riesgos (RR) para los datos dicotómicos, con intervalos de confianza (IC) del 95%. La heterogeneidad se evaluó mediante la estadística I² y la certeza de la evidencia según GRADE. RESULTADOS PRINCIPALES: Se incluyeron 65 ensayos (72 comparaciones) con 5831 participantes. Se dispuso de datos para: 1) 20 comparaciones; 2) nueve comparaciones; 3) 25 comparaciones; 4) tres comparaciones; 5) 14 comparaciones; y 6) una comparación. No se encontraron ensayos para las comparaciones 7 a 9. Comparación 1: Intervenciones farmacológicas Evidencia de certeza muy baja de ocho ensayos indica que las intervenciones farmacológicas disminuyeron el número de personas que cumplían los criterios del estudio para la depresión (RR 0,70; IC del 95%: 0,55 a 0,88; p = 0,002; ocho ECA; 1025 participantes) al final del tratamiento y evidencia de certeza muy baja de seis ensayos indica que las intervenciones farmacológicas disminuyeron el número de personas con respuesta inadecuada al tratamiento (RR 0,47; IC del 95%: 0,32 a 0,70; p = 0,0002; seis ECA; 511 participantes) en comparación con placebo. Se observaron más eventos adversos relacionados con el sistema nervioso central (SNC) (RR 1,55; IC del 95%: 1,12 a 2,15; p = 0,008; cinco ECA; 488 participantes; evidencia de certeza muy baja) y el sistema gastrointestinal (RR 1,62; IC del 95%: 1,19 a 2,19; p = 0,002; cuatro ECA; 473 participantes; evidencia de certeza muy baja) en el grupo de intervención farmacológica que en el grupo placebo. Comparación 2: Estimulación cerebral no invasiva Evidencia de certeza muy baja de dos ensayos muestra que la estimulación cerebral no invasiva tuvo poco o ningún efecto sobre el número de personas que cumplían los criterios del estudio para la depresión (RR 0,67; IC del 95%: 0,39 a 1,14; p = 0,14; dos ECA; 130 participantes) y el número de personas con respuesta inadecuada al tratamiento (RR 0,84; IC del 95%: 0,52 a 1,37; p = 0,49; dos ECA; 130 participantes) en comparación con la estimulación simulada. La estimulación cerebral no invasiva no provocó muertes. Comparación 3: Terapia psicológica Evidencia de certeza muy baja de seis ensayos indica que la terapia psicológica disminuyó el número de personas que cumplían los criterios del estudio para la depresión al final del tratamiento (RR 0,77; IC del 95%: 0,62 a 0,95; p = 0,01; 521 participantes) en comparación con atención habitual/control de atención. Ningún ensayo de terapia psicológica informó sobre el desenlace respuesta inadecuada al tratamiento. No se encontraron diferencias en el número de muertes o eventos adversos en el grupo de terapia psicológica en comparación con el grupo de control de atención/atención habitual. Comparación 4: Intervenciones farmacológicas con terapia psicológica Ningún ensayo de esta combinación informó sobre los desenlaces principales. El tratamiento combinado no provocó muertes. Comparación 5: Intervenciones farmacológicas con estimulación cerebral no invasiva La estimulación cerebral no invasiva con intervención farmacológica redujo el número de personas que cumplían los criterios del estudio para la depresión al final del tratamiento (RR 0,77; IC del 95%: 0,64 a 0,91; p = 0,002; tres ECA; 392 participantes; evidencia de certeza baja), pero no el número de personas con respuesta inadecuada al tratamiento (RR 0,95; IC del 95%: 0,69 a 1,30; p = 0,75; tres ECA; 392 participantes; evidencia de certeza muy baja) en comparación con el tratamiento farmacológico solo. Evidencia de certeza muy baja de cinco ensayos no indica diferencias en las muertes entre este tratamiento combinado (RR 1,06; IC del 95%: 0,27 a 4,16; p = 0,93; 487 participantes) en comparación con la intervención de tratamiento farmacológico y la estimulación simulada o la atención habitual. Comparación 6: Estimulación cerebral no invasiva con terapia psicológica Ningún ensayo de esta combinación informó sobre los desenlaces principales. CONCLUSIONES DE LOS AUTORES: Evidencia de certeza muy baja indica que los tratamientos farmacológicos, las terapias psicológicas y los tratamientos combinados pueden reducir la prevalencia de la depresión, mientras que la estimulación cerebral no invasiva tuvo poco o ningún efecto sobre la prevalencia de la depresión. Las intervenciones farmacológicas se asociaron con eventos adversos relacionados con el SNC y el sistema gastrointestinal. Se necesitan más estudios de investigación antes de poder hacer recomendaciones sobre el uso habitual de dichos tratamientos.

An Exploratory Analysis of Firefighter Reproduction through Survey Data and Biomonitoring.

Firefighters are occupationally exposed to chemicals that may affect fertility. To investigate this effect, firefighters were recruited to contribute blood, urine, breast milk or semen samples to (1) evaluate chemical concentrations and semen parameters against fertility standards and the general population; (2) assess correlations between chemical concentrations and demographics, fire exposure and reproductive history; and (3) consider how occupational exposures may affect reproduction. A total of 774 firefighters completed the online survey, and 97 firefighters produced 125 urine samples, 113 plasma samples, 46 breast milk samples and 23 semen samples. Blood, urine and breast milk samples were analysed for chemical concentrations (semivolatile organic compounds, volatile organic compounds, metals). Semen samples were analysed for quality (volume, count, motility, morphology). Firefighter semen parameters were below WHO reference values across multiple parameters. Self-reported rates of miscarriage were higher than the general population (22% vs. 12-15%) and in line with prior firefighter studies. Estimated daily intake for infants was above reference values for multiple chemicals in breast milk. More frequent fire incident exposure (more than once per fortnight), longer duration of employment (≥15 years) or not always using a breathing apparatus demonstrated significantly higher concentrations across a range of investigated chemicals. Findings of this study warrant further research surrounding the risk occupational exposure has on reproduction.

Development of the stroke patient concerns inventory: A modified Delphi study.

OBJECTIVES: Stroke survivors often have unmet physical, psychological and/or social concerns. Patient Concerns Inventories (PCIs) have been developed for other health conditions to address concerns. Our objective was to develop a PCI for stroke care. METHODS: This was a development study, including Modified Delphi study design, with academic and healthcare professionals with stroke care expertise. In Stage 1, a draft Stroke PCI (Version 1a) was created through identifying patient-reported concerns post-stroke from three previous studies and through expert panel discussions using Nominal Group Technique. In Stage 2, Version 1a was sent to 92 academic and healthcare professionals with stroke care expertise. Participants ranked their top 20 Stroke PCI items in order of importance and provided feedback. Rankings were converted into scores, and, with the feedback, used to amend the Stroke PCI. Two further rounds of feedback followed until consensus was reached between participants. A final draft of the Stroke PCI was created. RESULTS: In stage 1, 64 potential Stroke PCI items were generated. In Stage 2, 38 participants (41.3%) responded to the request to rank Stroke PCI items. The three highest ranked items were 'Risk of another stroke', 'Walking', 'Recovery'. After three rounds of feedback and amendments, the final draft of the Stroke PCI consisted of 53 items. CONCLUSIONS: A Stroke PCI has been developed using patient-reported concerns in previous studies and input from academic and healthcare professionals. Future work will involve gathering further feedback on the tool and exploring its acceptability and usability in a pilot study.

"I tried to get help about my addiction but he just gave me tablets:" male Aboriginal drug and alcohol rehabilitation clients' experiences and preferences speaking about substance use in primary care.

BACKGROUND: Primary healthcare (PHC) services are crucial in supporting people who use substances. The aims of this study were to explore the experiences of Aboriginal males in NSW in treatment for substance use about speaking about their substance use with PHC staff, and their preferences for accessing PHC about their substance use. METHODS: Semi-structured interviews with residential drug and alcohol rehabilitation treatment service clients. Thematic analysis was used to develop themes inductively and deductively. Two interviews were independently double coded by an Aboriginal researcher and the project was supported by an Aboriginal Advisory Group. RESULTS: Twenty male adults who self-identified as Aboriginal participated (mean age 27 years). Half reported visiting PHC and talking about their substance use before their residential service stay. Two major themes developed: (1) speaking up about substance use or mental health problems linked with substance use, (2) ways to improve access to PHC about substance use. Although some males were offered treatment, some were not, and others had concerns about the treatments offered. CONCLUSION: This research highlights opportunities to improve access and to better support Aboriginal males who use substances in PHC. Focus on culturally appropriate PHC and providing staff with training around substance use and treatment options may improve access. It is important to foster culturally appropriate services, develop PHC staff knowledge around substance use, focus on therapeutic relationships and have a range of treatment options available that can be tailored to individual circumstances.

Validation of the Longitudinal Interval Follow-Up Evaluation for the Long-Term Measurement of Mood Symptoms in Bipolar Disorder.

The long-term burden of symptoms is an important outcome in bipolar disorder (BD). A method which has minimal burden of assessment uses a retrospective interview, the Longitudinal Interval Follow-up Examination (LIFE), although this may be subject to problems with recall. This study examines the relationship between the retrospective LIFE scale and concurrently-rated mood rating scales in two clinical trials of 18 months of psychotherapy for patients with BD. The Montgomery-Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) were administered every eight to nine weeks and the LIFE was carried out every 6 months. Correlations between scores on mood rating scales and at equivalent times on the LIFE were examined, as well as of potential clinical moderators. There were significant correlations between LIFE depression ratings and concurrent MADRS score (r = 0.57) and between LIFE mania ratings and YMRS score (r = 0.40). In determining "mild depression" on the MADRS, a receiver operating characteristics (ROC) analysis showed an AUC of 0.78 for LIFE scores. Correlations, particularly for depression scores, were high even when the LIFE rating was several months before the interview, suggesting that the LIFE has validity in examining the burden of mood symptoms over time, with relatively little burden of assessment. Future research should examine the relationship between symptom burden and quality of life measured in this way.

The effectiveness of postpartum interventions aimed at improving women's mental health after medical complications of pregnancy: a systematic review and meta-analysis.

BACKGROUND: Postpartum mental disorders including depression and anxiety are common. Medical complications of pregnancy, such as preeclampsia and gestational diabetes, are thought to increase the risk of mental disorders postpartum. However, it is unclear which interventions may be effective for preventing and/or treating postpartum mental disorders following a medically complicated pregnancy. We aimed to systematically review published literature on the effectiveness of postpartum interventions to improve women's mental health after medical complications of pregnancy. METHODS: Systematic review (PROSPERO: CRD42021220030) was performed. ELIGIBILITY CRITERIA: (1) randomized controlled trials (RCTs), published 1st Jan 2001-12th August 2021 (2) outcome measures reported on postpartum mental disorders (3) participants had ≥ 1 medical complication during pregnancy (4) intervention entirely postpartum or contained a postpartum component (5) full-text available in English or Chinese. Risk of bias was assessed using the Revised Cochrane Criteria Risk of Bias. Random effects inverse-variance weighted meta-analysis was used to pool the individual standardized mean differences (SMD) in depression or anxiety scores between intervention and control groups. RESULTS: Of 5928 studies screened, 9 met inclusion criteria, and were based on non-pharmaceutical, combined lifestyle interventions that began shortly after childbirth, or as part of extended care packages beginning during pregnancy. Of these, 2 were rated as low risk of bias, 1 with some concerns, and 6 were at high risk. Meta-analysis was performed for 8 studies using standardized measures of depression and 7 for anxiety. There were statistically significant reductions in depression (SMD - 1.48; 95%CI: -2.41 to -0.55), and anxiety scores (SMD - 1.98; 95%CI: -3.03 to -0.94) in intervention versus control groups. Considerable heterogeneity was noted for pooled depression (I2 = 97.9%, p < 0.05), and anxiety (I2 = 96.8%, p < 0.05) results. CONCLUSION: Limited intervention studies aimed at improving postpartum mental disorders after medically complicated pregnancy were found, most with a high risk of bias. There was some evidence to suggest that postpartum depression and anxiety scores improved after early intervention. However, in general the current quality of evidence is low. Further, high-quality, interventional research is required in this understudied field.

Pharmaceutical interventions for emotionalism after stroke.

BACKGROUND: Antidepressants may be useful in the treatment of abnormal crying associated with stroke. This is an update of a Cochrane Review first published in 2004 and last updated in 2019. OBJECTIVES: To evaluate the benefits and harms of pharmaceutical treatment in people with emotionalism after stroke. SEARCH METHODS: We searched the Cochrane Stroke Group Register, CENTRAL, MEDLINE, Embase, four other databases, and three trials registers (May 2022). SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing psychotropic medication to placebo in people with stroke and emotionalism (also known as emotional lability, pathological crying or laughing, emotional incontinence, involuntary emotional expression disorder, and pseudobulbar affect). DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed risk of bias, extracted data from all included trials, and used GRADE to assess the certainty of the body of evidence. We calculated the mean difference (MD) or standardised mean difference (SMD) for continuous data and the risk ratio (RR) for dichotomous data, with 95% confidence intervals (CIs). We assessed heterogeneity using the I2 statistic. The primary emotionalism measures were the proportion of participants achieving at least a 50% reduction in abnormal emotional behaviour at the end of treatment, improved score on the Center for Neurologic Study - Lability Scale (CNS-LS) or Clinician Interview-Based Impression of Change (CIBIC), or diminished tearfulness. MAIN RESULTS: We did not identify any new trials for this update. We included seven trials with a total of 239 participants. Two trials had a cross-over design, but outcome data were not available from the first phase (precross-over) in an appropriate format for inclusion as a parallel randomised controlled trial (RCT). Thus, the results of the review are based on five trials with a total of 213 participants. It is uncertain whether fluoxetine increases the number of people who have a 50% reduction in emotionalism when compared to placebo (risk ratio (RR) 0.26, 95% CI 0.09 to 0.77; P = 0.02; 1 trial, 19 participants) because the certainty of evidence is very low. Sertraline may lead to little to no difference in Center for Neurologic Study - Lability Scale (CNS-LS) scores and Clinician Interview-Based Impression of Change (CIBIC) scores when compared to placebo (RR 0.20, 95% CI 0.03 to 1.50; P = 0.12; 1 trial, 28 participants; low-certainty evidence). Antidepressants probably increase the number of people who experience a reduction in tearfulness (RR 0.32, 95% CI 0.12 to 0.86; P = 0.02; 3 trials, 164 participants; moderate-certainty evidence). No trials were found that evaluated the impact of other pharmaceutical interventions. Only two trial authors systematically recorded and reported adverse events, resulting in limited data on the potential harms of treatment. Six trials reported death as an adverse event and found no difference between the groups (antidepressants versus placebo) in the number of deaths reported (RR 0.59, 95% CI 0.08 to 4.50; P = 0.61; 172 participants; moderate-certainty evidence). This review provides very low- to moderate-certainty evidence that antidepressants may reduce the frequency and severity of emotionalism. The included trials were small and had some degree of bias. AUTHORS' CONCLUSIONS: Antidepressants may reduce the frequency and severity of crying or laughing episodes when compared to placebo, based on very low-certainty evidence. Our conclusions must be qualified by several methodological deficiencies in the trials and interpreted with caution despite the effect being very large. The effect does not seem specific to one drug or class of drugs. More reliable data are required before appropriate conclusions can be made about the treatment of post-stroke emotionalism. Future trialists investigating the effect of antidepressants in people with emotionalism after stroke should consider developing and using a standardised method to diagnose emotionalism, determine severity, and assess change over time; provide treatment for a sufficient duration and follow-up to better assess rates of relapse or maintenance; and include careful assessment and complete reporting of adverse events.

Repeated Measures of Modified Rankin Scale Scores to Assess Functional Recovery From Stroke: AFFINITY Study Findings.

Background Function after acute stroke using the modified Rankin Scale (mRS) is usually assessed at a point in time. The analytical implications of serial mRS measurements to evaluate functional recovery over time is not completely understood. We compare repeated-measures and single-measure analyses of the mRS from a randomized clinical trial. Methods and Results Serial mRS data from AFFINITY (Assessment of Fluoxetine in Stroke Recovery), a double-blind placebo randomized clinical trial of fluoxetine following stroke (n=1280) were analyzed to identify demographic and clinical associations with functional recovery (reduction in mRS) over 12 months. Associations were identified using single-measure (day 365) and repeated-measures (days 28, 90, 180, and 365) partial proportional odds logistic regression. Ninety-five percent of participants experienced a reduction in mRS after 12 months. Functional recovery was associated with age at stroke <70 years; no prestroke history of diabetes, coronary heart disease, or ischemic stroke; prestroke history of depression, a relationship partner, living with others, independence, or paid employment; no fluoxetine intervention; ischemic stroke (compared with hemorrhagic); stroke treatment in Vietnam (compared with Australia or New Zealand); longer time since current stroke; and lower baseline National Institutes of Health Stroke Scale & Patient Health Questionnaire-9 scores. Direction of associations was largely concordant between single-measure and repeated-measures models. Association strength and variance was generally smaller in the repeated-measures model compared with the single-measure model. Conclusions Repeated-measures may improve trial precision in identifying trial associations and effects. Further repeated-measures stroke analyses are required to prove methodological value. Registration URL: http://www.anzctr.org.au; Unique identifier: ACTRN12611000774921.

Mixed methods evaluation to explore participant experiences of a pilot randomized trial to facilitate self-management of people living with stroke: Inspiring virtual enabled resources following vascular events (iVERVE).

INTRODUCTION: Despite digital health tools being popular for supporting self-management of chronic diseases, little research has been undertaken on stroke. We developed and pilot tested, using a randomized controlled design, a multicomponent digital health programme, known as Inspiring Virtual Enabled Resources following Vascular Events (iVERVE), to improve self-management after stroke. The 4-week trial incorporated facilitated person-centred goal setting, with those in the intervention group receiving electronic messages aligned to their goals, versus limited administrative messages for the control group. In this paper, we describe the participant experience of the various components involved with the iVERVE trial. METHODS: Mixed method design: satisfaction surveys (control and intervention) and a focus group interview (purposively selected intervention participants). Experiences relating to goal setting and overall trial satisfaction were obtained from intervention and control participants, with feedback on the electronic message component from intervention participants. Inductive thematic analysis was used for interview data and open-text responses, and closed questions were summarized descriptively. Triangulation of data allowed participants' perceptions to be explored in depth. RESULTS: Overall, 27/54 trial participants completed the survey (13 intervention: 52%; 14 control: 48%); and 5/8 invited participants in the intervention group attended the focus group. Goal setting: The approach was considered comprehensive, with the involvement of health professionals in the process helpful in developing realistic, meaningful and person-centred goals. Electronic messages (intervention): Messages were perceived as easy to understand (92%), and the frequency of receipt was considered appropriate (11/13 survey; 4/5 focus group). The content of messages was considered motivational (62%) and assisted participants to achieve their goals (77%). Some participants described the benefits of receiving messages as a 'reminder' to act. Overall trial satisfaction: Messages were acceptable for educating about stroke (77%). Having options for short message services or email to receive messages was considered important. Feedback on the length of the intervention related to specific goals, and benefits of receiving the programme earlier after stroke was expressed. CONCLUSION: The participant experience has indicated acceptance and utility of iVERVE. Feedback from this evaluation is invaluable to inform refinements to future Phase II and III trials, and wider research in the field. PATIENT OR PUBLIC CONTRIBUTION: Two consumer representatives sourced from the Stroke Foundation (Australia) actively contributed to the design of the iVERVE programme. In this study, participant experiences directly contributed to the further development of the iVERVE intervention and future trial design.

Lithium and Stroke Recovery: A Systematic Review and Meta-Analysis of Stroke Models in Rodents and Human Data.

BACKGROUND: Lithium has neuroprotective effects in animal models of stroke, but benefits in humans remain uncertain. This article aims to systematically review the available evidence of the neuroprotective and regenerative effects of lithium in animal models of stroke, as well as in observational and trial stroke studies in humans. METHODS: This systematic review and meta-analysis was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched Medline, Embase, and PsycINFO for preclinical and clinical studies published between January 2000 and September 2021. A random-effects meta-analysis was conducted from observational studies. RESULTS: From 1625 retrieved studies, 42 were included in the systematic review. Of those, we identified 36 rodent models of stroke using preinsult or postinsult treatment with lithium, and 6 studies were conducted in human samples, of which 4 could be meta-analyzed. The review of animal models was stratified according to the type of stroke and outcomes. Human data were subdivided into observational and intervention studies. Treatment of rodents with lithium was associated with smaller stroke volumes, decreased apoptosis, and improved poststroke function. In humans, exposure to lithium was associated with a lower risk of stroke among adults with bipolar disorder in 2 of 4 studies. Two small trials showed equivocal clinical benefits of lithium poststroke. CONCLUSIONS: Animal models of stroke show consistent biological and functional evidence of benefits associated with lithium treatment, whereas human evidence remains sparse and inconclusive. The potential role of lithium in poststroke recovery is yet to be adequately tested in humans.

Randomised controlled trial of Interpersonal and Social Rhythm Therapy and group-based Cognitive Remediation versus Interpersonal and Social Rhythm Therapy alone for mood disorders: study protocol.

BACKGROUND: Individuals with mood disorders frequently experience cognitive impairment, which impacts on the long-term trajectory of the disorders, including being associated with persisting difficulties in occupational and psychosocial functioning, residual mood symptoms, and relapse. Current first-line treatments for mood disorders do little to improve cognitive function. Targeting cognition in clinical research is thus considered a priority. This protocol outlines a prospectively-registered randomised controlled trial (RCT) which examines the impact of adding group-based Cognitive Remediation (CR) to Interpersonal and Social Rhythm Therapy (IPSRT-CR) for individuals with mood disorders. METHODS: This is a pragmatic, two-arm, single-blinded RCT comparing IPSRT-CR with IPSRT alone for adults (n = 100) with mood disorders (Major Depressive Disorder or Bipolar Disorder) with subjective cognitive difficulties, on discharge from Specialist Mental Health Services in Christchurch, New Zealand. Both treatment arms will receive a 12-month course of individual IPSRT (full dose = 24 sessions). At 6 months, randomisation to receive, or not, an 8-week group-based CR programme (Action-based Cognitive Remediation - New Zealand) will occur. The primary outcome will be change in Global Cognition between 6 and 12 months (treatment-end) in IPSRT-CR versus IPSRT alone. Secondary outcomes will be change in cognitive, functional, and mood outcomes at 6, 12, 18, and 24 months from baseline and exploratory outcomes include change in quality of life, medication adherence, rumination, and inflammatory markers between treatment arms. Outcome analyses will use an intention-to-treat approach. Sub-group analyses will assess the impact of baseline features on CR treatment response. Participants' experiences of their mood disorder, including treatment, will be examined using qualitative analysis. DISCUSSION: This will be the first RCT to combine group-based CR with an evidence-based psychotherapy for adults with mood disorders. The trial may provide valuable information regarding how we can help promote long-term recovery from mood disorders. Many issues have been considered in developing this protocol, including: recruitment of the spectrum of mood disorders, screening for cognitive impairment, dose and timing of the CR intervention, choice of comparator treatment, and choice of outcome measures. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, ACTRN12619001080112 . Registered on 6 August 2019.