The landscape of autosomal-recessive pathogenic variants in European populations reveals phenotype-specific effects.

The number and distribution of recessive alleles in the population for various diseases are not known at genome-wide-scale. Based on 6,447 exome sequences of healthy, genetically unrelated Europeans of two distinct ancestries, we estimate that every individual is a carrier of at least 2 pathogenic variants in currently known autosomal-recessive (AR) genes and that 0.8%-1% of European couples are at risk of having a child affected with a severe AR genetic disorder. This risk is 16.5-fold higher for first cousins but is significantly more increased for skeletal disorders and intellectual disabilities due to their distinct genetic architecture.

Tips for Testing Adults With Suspected Genetic Kidney Disease.

Genetic kidney disease is common but often unrecognized. It accounts for most cystic kidney diseases and tubulopathies, many forms of congenital abnormalities of the kidney and urinary tract (CAKUT), and some glomerulopathies. Genetic kidney disease is typically suspected where the disease usually has a genetic basis or there is another affected family member, a young age at onset, or extrarenal involvement, but there are also many exceptions to these "rules". Genetic testing requires the patient's written informed consent. When a patient declines testing, another later conversation may be worthwhile. Genetic testing not only indicates the diagnosis but also the inheritance pattern, likely at-risk family members, disease in other organs, clinical course, and possibly effective treatments. Sometimes genetic testing does not identify a pathogenic variant even where other evidence is strong. A variant of uncertain significance (VUS) may be reported but should not be used for clinical decision making. It may be reclassified after more information becomes available without necessarily retesting the patient. Patients should be provided with a copy of their genetic test report, the results explained, and at-risk family members offered "cascade" testing. A referral to a clinical geneticist or genetic counselor helps identify affected family members and in providing advice to assist with reproductive decisions.

Depressive symptoms in youth before and during the COVID-19 pandemic: longitudinal investigation of patterns dependent on age, sex, and family history of mental illness.

BACKGROUND: Cross-sectional studies report high levels of depressive symptoms during the COVID-19 pandemic, especially in youth and females. However, longitudinal research comparing depressive symptoms before and during the pandemic is lacking. Little is known about how the pandemic affected individuals with familial history of mental illness. The present study examines the impact of the pandemic on youth depressive symptoms, including offspring of parents with major mood and psychotic disorders. METHODS: Between March 2018 and February 2020, we measured depressive symptoms in 412 youth aged 5-25 years. We measured depressive symptoms again in 371 (90%) of these youth between April 2020 and May 2022. Two thirds (249) participants had a biological parent with a major mood or psychotic disorder. We tested the effect of the pandemic by comparing depression symptoms before and after March 2020. We examined age, sex, and family history as potential moderators. RESULTS: We found an overall small increase in youth depressive symptoms (b = 0.07, 95% CI -0.01 to 0.15, p = 0.062). This was driven by an increase in female youth without familial history of mental illness (b = 0.35, 95% CI 0.14 to 0.56, p = 0.001). There was no change in depressive symptoms among offspring of parents with mental illness or males. CONCLUSIONS: Our results provide reassurance about the wellbeing of children of parents with mental illness during a period of restricted access to resources outside the family. Rather than increasing symptoms in established risk groups, the pandemic led to a redistribution of depression burden towards segments of the youth population that were previously considered to be low-risk.

Increased hippocampal blood flow in people at clinical high risk for psychosis and effects of cannabidiol.

BACKGROUND: Hippocampal hyperperfusion has been observed in people at Clinical High Risk for Psychosis (CHR), is associated with adverse longitudinal outcomes and represents a potential treatment target for novel pharmacotherapies. Whether cannabidiol (CBD) has ameliorative effects on hippocampal blood flow (rCBF) in CHR patients remains unknown. METHODS: Using a double-blind, parallel-group design, 33 CHR patients were randomized to a single oral 600 mg dose of CBD or placebo; 19 healthy controls did not receive any drug. Hippocampal rCBF was measured using Arterial Spin Labeling. We examined differences relating to CHR status (controls v. placebo), effects of CBD in CHR (placebo v. CBD) and linear between-group relationships, such that placebo > CBD > controls or controls > CBD > placebo, using a combination of hypothesis-driven and exploratory wholebrain analyses. RESULTS: Placebo-treated patients had significantly higher hippocampal rCBF bilaterally (all pFWE<0.01) compared to healthy controls. There were no suprathreshold effects in the CBD v. placebo contrast. However, we found a significant linear relationship in the right hippocampus (pFWE = 0.035) such that rCBF was highest in the placebo group, lowest in controls and intermediate in the CBD group. Exploratory wholebrain results replicated previous findings of hyperperfusion in the hippocampus, striatum and midbrain in CHR patients, and provided novel evidence of increased rCBF in inferior-temporal and lateral-occipital regions in patients under CBD compared to placebo. CONCLUSIONS: These findings suggest that hippocampal blood flow is elevated in the CHR state and may be partially normalized by a single dose of CBD. CBD therefore merits further investigation as a potential novel treatment for this population.

A randomised double-blind placebo-controlled trial of minocycline and/or omega-3 fatty acids added to treatment as usual for at risk Mental States: The NAYAB study.

BACKGROUND: Inflammatory mechanisms are thought to contribute to the onset of psychosis in persons with an at-risk mental state (ARMS). We investigated whether the anti-inflammatory properties of minocycline and omega-3 polyunsaturated fatty acids (omega-3), alone or synergistically, would prevent transition to psychosis in ARMS in a randomised, double-blind, placebo-controlled trial in Pakistan. METHODS: 10,173 help-seeking individuals aged 16-35 years were screened using the Prodromal Questionaire-16. Individuals scoring 6 and over were interviewed using the Comprehensive Assessment of At-Risk Mental States (CAARMS) to confirm ARMS. Participants (n = 326) were randomised to minocycline, omega-3, combined minocycline and omega-3 or to double placebo for 6 months. The primary outcome was transition to psychosis at 12 months. FINDINGS: Forty-five (13.8 %) participants transitioned to psychosis. The risk of transition was greater in those randomised to omega-3 alone or in combination with minocycline (17.3.%), compared to 10.4 % in those not exposed to omega-3; a risk-ratio (RR) of 1.67, 95 % CI [0.95, 2.92] p = 0.07. The RR for transitions on minocycline vs. no minocycline was 0.86, 95 % CI [0.50, 1.49] p > 0.10. In participants who did not become psychotic, CAARMS and depression symptom scores were reduced at six and twelve months (mean CAARMS difference = 1.43; 95 % CI [0.33, 1.76] p < 0.01 in those exposed to omega-3. Minocycline did not affect CAARMS or depression scores. INTERPRETATION: In keeping with other studies, omega-3 appears to have beneficial effects on ARMS and mood symptom severity but it increased transition to psychosis, which may reflect metabolic or developmental consequences of chronic poor nutrition in the population. Transition to psychosis was too rare to reveal a preventative effect of minocycline but minocycline did not improve symptom severity. ARMS symptom severity and transition to psychosis appear to have distinct pathogeneses which are differentially modulated by omega-3 supplementation. FUNDING: The study was funded by the Stanley Research Medical Institute.

Diagnostic accuracy of non-invasive tests to screen for at-risk MASH-An individual participant data meta-analysis.

BACKGROUND & AIMS: There is a need to reduce the screen failure rate (SFR) in metabolic dysfunction-associated steatohepatitis (MASH) clinical trials (MASH+F2-3; MASH+F4) and identify people with high-risk MASH (MASH+F2-4) in clinical practice. We aimed to evaluate non-invasive tests (NITs) screening approaches for these target conditions. METHODS: This was an individual participant data meta-analysis for the performance of NITs against liver biopsy for MASH+F2-4, MASH+F2-3 and MASH+F4. Index tests were the FibroScan-AST (FAST) score, liver stiffness measured using vibration-controlled transient elastography (LSM-VCTE), the fibrosis-4 score (FIB-4) and the NAFLD fibrosis score (NFS). Area under the receiver operating characteristics curve (AUROC) and thresholds including those that achieved 34% SFR were reported. RESULTS: We included 2281 unique cases. The prevalence of MASH+F2-4, MASH+F2-3 and MASH+F4 was 31%, 24% and 7%, respectively. Area under the receiver operating characteristics curves for MASH+F2-4 were .78, .75, .68 and .57 for FAST, LSM-VCTE, FIB-4 and NFS. Area under the receiver operating characteristics curves for MASH+F2-3 were .73, .67, .60, .58 for FAST, LSM-VCTE, FIB-4 and NFS. Area under the receiver operating characteristics curves for MASH+F4 were .79, .84, .81, .76 for FAST, LSM-VCTE, FIB-4 and NFS. The sequential combination of FIB-4 and LSM-VCTE for the detection of MASH+F2-3 with threshold of .7 and 3.48, and 5.9 and 20 kPa achieved SFR of 67% and sensitivity of 60%, detecting 15 true positive cases from a theoretical group of 100 participants at the prevalence of 24%. CONCLUSIONS: Sequential combinations of NITs do not compromise diagnostic performance and may reduce resource utilisation through the need of fewer LSM-VCTE examinations.

Cost-effectiveness study of FIB-4 followed by transient elastography screening strategy for advanced hepatic fibrosis in a NAFLD at-risk population.

BACKGROUND & AIMS: The cost-effectiveness to screen hepatic fibrosis in at-risk population as recommended by several professional societies has been limited. This study aimed to investigate the cost-effectiveness of this screening strategy in the expanded at-risk population recently proposed by several societies. METHODS: A combined model of the decision tree and Markov models was developed to compare expected costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) between screening and no screening groups. The model included liver disease-related health states and cardiovascular disease (CVD) states as a base-case analysis. Screening strategy consisted of fibrosis-4 index (FIB-4) followed by vibration-controlled transient elastography (VCTE) and intensive lifestyle intervention (ILI) as a treatment for diagnosed patients. RESULTS: Cost-effectiveness analysis showed that screening the at-risk population entailed $298 incremental costs and an additional 0.0199 QALY per patient compared to no screening (ICER $14 949/QALY). Screening was cost-effective based on the implicit ICER threshold of $25 000/QALY in Korea. When the effects of ILI on CVD and extrahepatic malignancy were incorporated into the cost-effectiveness model, the ICER decreased by 0.85 times from the base-case analysis (ICER $12 749/QALY). In contrast, when only the effects of liver disease were considered in the model, excluding cardiovascular disease effects, ICER increased from the baseline case analysis to $16 305. Even when replacing with medical costs in Japan and U.S., it remained cost-effective with the estimate below the countries' ICER threshold. CONCLUSIONS: Our study provides compelling evidence supporting the cost-effectiveness of FIB-4-based screening the at-risk population for advanced hepatic fibrosis.

Altered extracellular matrix-related pathways accelerate the transition from normal to prefibroid myometrium in Black women.

BACKGROUND: Black women experience a disproportionate impact of uterine fibroids compared to White women, including earlier diagnosis, higher frequency, and more severe symptoms. The etiology underlying this racial disparity remains elusive. OBJECTIVE: The aim of this study was to evaluate the molecular differences in normal myometrium (fibroid-free uteri) and at-risk myometrium (fibroid-containing uteri) tissues in Black and White women. STUDY DESIGN: We conducted whole-genome RNA-seq on normal and at-risk myometrium tissues obtained from both self-identified Black and White women (not Hispanic or Latino) to determine global gene expression profiles and to conduct enriched pathway analyses (n=3 per group). We initially assessed the differences within the same type of tissue (normal or at-risk myometrium) between races. Subsequently, we analyzed the transcriptome of normal myometrium compared to at-risk myometrium in each race and determined the differences between them. We validated our findings through real-time PCR (sample size range=5-12), western blot (sample size range=5-6), and immunohistochemistry techniques (sample size range=9-16). RESULTS: The transcriptomic analysis revealed distinct profiles between Black and White women in normal and at-risk myometrium tissues. Interestingly, genes and pathways related to extracellular matrix and mechanosensing were more enriched in normal myometrium from Black than White women. Transcription factor enrichment analysis detected greater activity of the serum response transcription factor positional motif in normal myometrium from Black compared to White women. Furthermore, we observed increased expression levels of myocardin-related transcription factor-serum response factor and the serum response factor in the same comparison. In addition, we noted increased expression of both mRNA and protein levels of vinculin, a target gene of the serum response factor, in normal myometrium tissues from Black women as compared to White women. Importantly, the transcriptomic profile of normal to at-risk myometrium conversion differs between Black and White women. Specifically, we observed that extracellular matrix-related pathways are involved in the transition from normal to at-risk myometrium and that these processes are exacerbated in Black women. We found increased levels of Tenascin C, type I collagen alpha 1 chain, fibronectin, and phospho-p38 MAPK (Thr180/Tyr182, active) protein levels in at-risk over normal myometrium tissues from Black women, whereas such differences were not observed in samples from White women. CONCLUSION: These findings indicate that the racial disparities in uterine fibroids may be attributed to heightened production of extracellular matrix in the myometrium in Black women, even before the tumors appear. Future research is needed to understand early life determinants of the observed racial differences.

Influenza vaccination patterns among at-risk patients during the Covid-19 pandemic-a retrospective cross-sectional study based on claims data.

PURPOSE: The Covid-19 pandemic may have encouraged at-risk patients to get vaccinated against influenza for the first time. As previous vaccinations are known predictors for further vaccinations, knowledge about individual vaccination patterns, especially in first time vaccinated patients, is of great interest. The aim of this study was to determine influenza vaccination uptake rate (VUR), individual vaccination patterns and factors associated with vaccination uptake among at-risk patients. METHODS: The study design was retrospective cross-sectional. Based on claims data, VUR was determined for four influenza seasons (2018/2019-2021/2022). In a cohort subgroup, with data available for all seasons, VUR, vaccination patterns and factors associated with uptake were determined. At-risk patients were people aged ≥ 65 and adult patients with chronic diseases. RESULTS: We included n = 238,461 patients in the cross-sectional analysis. Overall VUR ranged between 21.8% (2018/2019) and 29.1% (2020/2021). Cohort subgroup consisted of n = 138,526 patients. Within the cohort, 56% were never vaccinated and 11% were vaccinated in all seasons. 14.3% of previously unvaccinated patients were vaccinated for the first time in the first pandemic season (2020/2021 season). The strongest predictor for vaccination was history of vaccinations in all previous seasons (OR 56.20, 95%CI 53.62-58.90, p < 0.001). CONCLUSION: Influenza VUR increased during the Covid-19 pandemic, but only a minority of previously eligible but unvaccinated at-risk patients were vaccinated for the first time in the first pandemic season. Previous vaccinations are predictors for subsequent vaccinations and health care professionals should actively address at-risk patients' vaccination history in order to recommend vaccination in future seasons.

Dose to organs at risk for total body irradiation: Single-institution data using the modulated arc total body irradiation technique.

BACKGROUND: Organs at risk (OAR) dose reporting for total body irradiation (TBI) patients is limited, and standardly reported only as mean doses to the lungs and kidneys. Consequently, dose received and effects on other OAR remain unexplored. To remedy this gap, this study reports dose data on an extensive list of OAR for patients treated at a single institution using the modulated arc total body irradiation (MATBI) technique. METHOD: An audit was undertaken of all patients treated with MATBI between January 2015 and March 2021 who had completed their course of treatment. OAR were contoured on MATBI patient treatment plans, with 12 Gy in six fraction prescription. OAR dose statistics and dose volume histogram data are reported for the whole body, lungs, kidneys, bones, brain, lens, heart, liver and bowel bag. RESULTS: The OAR dose data for 29 patients are reported. Mean dose results are body 11.77 Gy, lungs 9.86 Gy, kidneys 11.84 Gy, bones 12.03 Gy, brain 12.12 Gy, right lens 12.31 Gy, left lens 12.64 Gy, heart 11.07 Gy, liver 11.81 Gy and bowel bag 12.06 Gy. Dose statistics at 1-Gy intervals of V6-V13 for lungs and V10-V13 for kidneys are also included. CONCLUSION: This is the first time an extensive list of OAR data has been reported for any TBI technique. Due to the paucity of reporting, this information could be used by centres implementing the MATBI technique, in addition to aiding comparison between TBI techniques, with the potential for greater understanding of the relationship between dose volume data and toxicity.

Stillbirth risk by fetal size among 126.5 million births in 15 countries from 2000 to 2020: A fetuses-at-risk approach.

OBJECTIVE: To compare stillbirth rates and risks for small for gestational age (SGA), large for gestational age (LGA) and appropriate for gestational age (AGA) pregnancies at 24-44 completed weeks of gestation using a birth-based and fetuses-at-risk approachs. DESIGN: Population-based, multi-country study. SETTING: National data systems in 15 high- and middle-income countries. POPULATION: Live births and stillbirths. METHODS: A total of 151 country-years of data, including 126 543 070 births across 15 countries from 2000 to 2020, were compiled. Births were categorised into SGA, AGA and LGA using INTERGROWTH-21st standards. Gestation-specific stillbirth rates, with total births as the denominator, and gestation-specific stillbirth risks, with fetuses still in utero as the denominator, were calculated from 24 to 44 weeks of gestation. MAIN OUTCOME MEASURES: Gestation-specific stillbirth rates and risks according to size at birth. RESULTS: The overall stillbirth rate was 4.22 per 1000 total births (95% CI 4.22-4.23) across all gestations. Applying the birth-based approach, the stillbirth rates were highest at 24 weeks of gestation, with 621.6 per 1000 total births (95% CI 620.9-622.2) for SGA pregnancies, 298.4 per 1000 total births (95% CI 298.1-298.7) for AGA pregnancies and 338.5 per 1000 total births (95% CI 337.9-339.0) for LGA pregnancies. Applying the fetuses-at-risk approach, the gestation-specific stillbirth risk was highest for SGA pregnancies (1.3-1.4 per 1000 fetuses at risk) prior to 29 weeks of gestation. The risk remained stable between 30 and 34 weeks of gestation, and then increased gradually from 35 weeks of gestation to the highest rate of 8.4 per 1000 fetuses at risk (95% CI 8.3-8.4) at ≥42 weeks of gestation. The stillbirth risk ratio (RR) was consistently high for SGA compared with AGA pregnancies, with the highest RR observed at ≥42 weeks of gestation (RR 9.2, 95% CI 15.2-13.2), and with the lowest RR observed at 24 weeks of gestation (RR 3.1, 95% CI 1.9-4.3). The stillbirth RR was also consistently high for SGA compared with AGA pregnancies across all countries, with national variability ranging from RR 0.70 (95% CI 0.43-0.97) in Mexico to RR 8.6 (95% CI 8.1-9.1) in Uruguay. No increased risk for LGA pregnancies was observed. CONCLUSIONS: Small for gestational age (SGA) was strongly associated with stillbirth risk in this study based on high-quality data from high- and middle-income countries. The highest RRs were seen in preterm gestations, with two-thirds of the stillbirths born as preterm births. To advance our understanding of stillbirth, further analyses should be conducted using high-quality data sets from low-income settings, particularly those with relatively high rates of SGA.

Performance of MAST, FAST, and MEFIB in predicting metabolic dysfunction-associated steatohepatitis.

BACKGROUND AND AIM: To identify individuals with metabolic dysfunction-associated steatohepatitis (MASH) or "at-risk" MASH among patients with metabolic dysfunction-associated steatotic liver disease (MASLD), three noninvasive models are available with satisfactory efficiency, which include magnetic resonance imaging [MRI]- AST (MAST), FibroScan-AST (FAST score), and magnetic resonance elastography [MRE] plus FIB-4 (MEFIB). We aimed to evaluate the most accurate approach for diagnosing MASH or "at-risk" MASH. METHODS: We included 108 biopsy-proven MASLD patients who underwent simultaneous assessment of MRE, MRI proton density fat fraction (MRI-PDFF), and FibroScan scans. Compared with the histological diagnosis, we analyzed the AUC of each model and assessed the accuracy. RESULTS: Our study cohort consisted of 64.8% of MASH and 25.9% of "at-risk" MASH. When analyzing the performance of each model for the diagnostic accuracy of MASH, we found that the AUC [95% CI] of MAST was comparable to FAST (0.803 [0.719-0.886] vs 0.799 [0.707-0.891], P = 0.930) and better than MEFIB (0.671 [0.571-0.772], P = 0.005). Similar findings were observed in the "at-risk" MASH patients. The AUCs [95% CI] for MAST, FAST, and MEFIB were 0.810 [0.719-0.900], 0.782 [0.689-0.874], and 0.729 [0.619-0.838], respectively. The models of MAST and FAST had comparable AUCs (P = 0.347), which were statistically significantly higher than that of MEFIB (P = 0.041). Additionally, the cutoffs for diagnosis of MASH were lower than "at-risk" MASH. CONCLUSION: MAST and FAST performed better than MEFIB in diagnosing "at-risk" MASH and MASH using lower cutoff values. Our findings provided evidence for selecting the most accurate noninvasive model to identify patients with MASH or at-risk MASH.

Mentalizing impairments and hypermentalizing bias in individuals with first-episode schizophrenia-spectrum disorder and at-risk mental state: the differential roles of neurocognition and social anxiety.

Mentalizing, or theory of mind (ToM), impairments and self-referential hypermentalizing bias are well-evident in schizophrenia. However, findings compared to individuals with at-risk mental states (ARMS) are inconsistent, and investigations into the relationship between social cognitive impairments and social anxiety in the two populations are scarce. This study aimed to examine and compare these deficits in first-episode schizophrenia-spectrum disorder (FES) and ARMS, and to explore potential specific associations with neurocognition and symptomatology. Forty patients with FES, 40 individuals with ARMS, and 40 healthy controls (HC) completed clinical assessments, a battery of neurocognitive tasks, and three social cognitive tasks. The comic strip and hinting tasks were used to measure non-verbal and verbal mentalizing abilities, and the gaze perception task was employed to assess self-referential hypermentalizing bias. FES and ARMS showed comparable mentalizing impairments and self-referential hypermentalizing bias compared to HC. However, only ambiguous self-referential gaze perception (SRGP) bias remained significantly different between three groups after controlling for covariates. Findings suggested that self-referential hypermentalizing bias could be a specific deficit and may be considered a potential behavioral indicator in early-stage and prodromal psychosis. Moreover, working memory and social anxiety were related to the social cognitive impairments in ARMS, whereas higher-order executive functions and positive symptoms were associated with the impairments in FES. The current study indicates the presence of stage-specific mechanisms of mentalizing impairments and self-referential hypermentalizing bias, providing insights into the importance of personalized interventions to improve specific neurocognitive domains, social cognition, and clinical outcomes for FES and ARMS.

Resting state hyperconnectivity of the default mode network in schizophrenia and clinical high-risk state for psychosis.

Disrupted functional connectivity (FC) of the default mode network (DMN) may have a pathophysiological role in schizophrenia. However, functional magnetic resonance imaging (fMRI) of the DMN in schizophrenia patients has shown inconsistent results. It also remains unclear whether individuals with at-risk mental state (ARMS) have an altered DMN connectivity and whether it is related to clinical characteristics. This fMRI study examined resting-state FCs of the DMN and its relevance to clinical/cognitive variables in 41 schizophrenia patients, 31 ARMS individuals, and 65 healthy controls. Compared with controls, schizophrenia patients had significantly increased FCs within the DMN and between the DMN and diverse cortical areas, whereas ARMS patients had increased FCs only between the DMN and occipital cortex. FC of the lateral parietal cortex with superior temporal gyrus was positively correlated with negative symptoms in schizophrenia, whereas FC of that with interparietal sulcus was negatively correlated with general cognitive impairment in ARMS. Our findings suggest that increased FCs between the DMN and visual network commonly seen in schizophrenia and ARMS subjects may reflect a network-level disturbance representing a general vulnerability to psychosis. In addition, FC changes related to the lateral parietal cortex may underpin clinical characteristics of ARMS and schizophrenia subjects.

Exploring diagnostic events and first referrals in cancer patient pathways in primary care. A questionnaire survey.

BACKGROUND: Cancer diagnostic pathways in general practice are often nonlinear, and several events can delay timely diagnosis. OBJECTIVES: To explore cancer diagnostic processes in general practice, examining how patients' symptom presentations, sex, and age are associated with the occurrence of predefined potentially delaying events and the first referrals. METHOD: General practices in 3 Danish Regions were invited to participate in a questionnaire survey, addressing patient's symptom presentation, diagnostic process events, and first referral. The general practitioners (GPs) received a list of their incident cancer patients from the preceding 2 years. RESULTS: In total 187 general practices participated, including 5,908 patients with the cancer diagnostic pathways initiated in general practice. Presenting with nonspecific symptoms was associated with potentially delaying events, even when the patient also had specific symptoms. Almost half of the patients were referred to a cancer patient pathway (CPP) first, men more often than women, and 10% were referred for acute hospitalization. In 23% of the diagnostic processes, GPs initially treated or referred patients on suspicion of another disease rather than cancer and waited due to normal examinations in 1 out of 20 patients. Excluding sex-specific cancers, these 2 events were more prevalent in women. Men less often complied to the follow-up agreement. Younger patients were less often first referred to a CPP and together with older patients more often first acutely hospitalized. CONCLUSION: In cancer diagnostic processes in general practice, first referrals and the occurrence of potentially delaying events are associated with the patient's age, sex, and specificity of symptoms.

The full spectrum of clinical stages of psychosis at prison entry: prevalence and concurrent validity of symptom screening.

PURPOSE: Despite the high rates of psychotic disorders amongst people in prison, current prison mental health screening approaches have not included assessment of the full psychosis spectrum to capture those at-risk of an emerging psychosis as well as those with established illness nor assessed the concurrent validity of psychosis symptom screening. METHODS: Using a clinical staging approach to establish the prevalence of Ultra High Risk (UHR), first episode of psychosis (FEP) and established psychosis (EP) groups, 291 adults entering custody in two prison reception centres in NSW completed a two-stage (screening and validation) interview process. The Comprehensive Assessment of At-Risk Mental States (CAARMS) was used to determine the clinical stages of psychosis and concurrent validity of symptom screening in identifying individuals on the psychosis spectrum was formally assessed. RESULTS: Amongst men and women entering prison, almost one quarter (24.1%) met UHR criteria, 5.1% met the FEP threshold and 10.6% had an established psychosis. Those on the psychosis spectrum reported greater disadvantage across sociodemographic and justice factors. The presence of perceptual disturbance and paranoid beliefs emerged as the two best screening items for identifying those with an underlying psychosis spectrum illness. CONCLUSION: The prevalence of psychosis spectrum illness, including the UHR state, amongst those entering prison is high. Current prison mental health approaches should include screening for the presence of perceptual disturbances and paranoid beliefs to improve the detection of psychosis spectrum illness.

Screening for psychosis risk in primary mental health care services - Implementation, prevalence and recovery trajectories.

OBJECTIVES: Early interventions improve outcomes for people at high risk of psychosis and are likely to be cost saving. This group tends to seek help for emotional problems - depression and anxiety - via primary care services, where early detection methods are poor. We sought to determine prevalence rates of high risk for psychosis in UK primary care mental health services and clinical outcomes following routinely delivered psychological therapies. METHODS: We used a brief screen designed for settings with low base rates and significant time constraints to determine prevalence of high risk for psychosis in UK 'Talking Therapies' services. We examined socio-demographic characteristics, presenting problems and recovery trajectories for this group, compared with people not at risk of psychosis. RESULTS: A 2-item screen selected for specificity yielded a prevalence rate of 3% in primary care mental health services. People at elevated risk of psychosis were younger and more likely to report at least one long-term physical condition. This group presented with higher levels of depression, anxiety and trauma symptoms at assessment and were less likely to have recovered at the end of treatment, compared to people not at risk. CONCLUSIONS: Very brief screening tools can be implemented in busy health care settings. The 3% of referrals to UK primary care psychological therapies services at elevated risk of psychosis typically present with more severe symptoms and greater levels of comorbidity and may require augmented interventions to recover fully.

Early localization of tissue at risk for delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: blood distribution on initial imaging vs early CT perfusion.

OBJECTIVE: Delayed cerebral ischemia (DCI) is a potentially reversible adverse event after aneurysmal subarachnoid hemorrhage (aSAH), when early detected and treated. Computer tomography perfusion (CTP) is used to identify the tissue at risk for DCI. In this study, the predictive power of early CTP was compared with that of blood distribution on initial CT for localization of tissue at risk for DCI. METHODS: A consecutive patient cohort with aSAH treated between 2012 and 2020 was retrospectively analyzed. Blood distribution on CT was semi-quantitatively assessed with the Hijdra-score. The vessel territory with the most surrounding blood and the one with perfusion deficits on CTP performed on day 3 after ictus were considered to be at risk for DCI, respectively. RESULTS: A total of 324 patients were included. Delayed infarction occurred in 17% (56/324) of patients. Early perfusion deficits were detected in 82% (46/56) of patients, 85% (39/46) of them developed infarction within the predicted vessel territory at risk. In 46% (25/56) a vessel territory at risk was reliably determined by the blood distribution. For the prediction of DCI, blood amount/distribution was inferior to CTP. Concerning the identification of "tissue at risk" for DCI, a combination of both methods resulted in an increase of sensitivity to 64%, positive predictive value to 58%, and negative predictive value to 92%. CONCLUSIONS: Regarding the DCI-prediction, early CTP was superior to blood amount/distribution, while a consideration of subarachnoid blood distribution may help identify the vessel territories at risk for DCI in patients without early perfusion deficits.

Nutrition intervention goals from the perspectives of patients at risk of malnutrition: A qualitative study.

BACKGROUND: Nutrition counselling is characterised by a collaborative approach where the patient and the dietitian establish goals that promote health and self-management. Little is known about goal-setting in nutrition interventions of patients at risk of malnutrition. The present study aims to describe the perspectives and needs of patients at risk of malnutrition regarding goals of nutrition interventions. METHODS: Semi-structured interviews were conducted with 15 patients from three primary care centres and one hospital in mid-Sweden selected through purposive sampling. Interview transcripts were analysed using reflexive thematic analysis following the six-phase guidelines of Braun and Clarke to identify patterns of shared meaning and themes in the data. RESULTS: The findings highlight that the participants rarely reflected on their personal goals of the nutrition intervention. Instead, they strived to maintain strength and energy, with the nutrition counselling being seen as supportive in managing nutrition impact symptoms. They described discrepancies between their perspectives and the dietitian's regarding weight goals and the diet prescribed to gain weight. CONCLUSIONS: The study findings suggest that elucidating patients' goals is key to counteracting the discrepancies between the dietitians' clinically oriented goals and patients' perspectives. Goal-setting is part of the dietitian's structured working process, whereas the patient's lifeworld is complex and unstructured. To provide person-centred nutrition care, new strategies and tools are needed to facilitate collaborative goal-setting. These approaches will bridge the gap between clinical goals and patients' individual needs, promoting better alignment and improved outcomes.

Association between being at-risk of malnutrition and discontinued home medical care among older patients: a 1-year follow-up study.

BACKGROUND: Both malnutrition and at-risk of malnutrition are prevalent among older patients receiving home medical care. Discontinuation of home medical care usually occurs when an older patient is admitted to a hospital or nursing home or dies. This study aimed to assess prospective associations between nutritional status and discontinuation of home medical care in older patients. METHODS: Three hundred and thirty-three Japanese older patients receiving home-visit nursing care services were included in this study. Their nutritional status was assessed using the Mini Nutritional Assessment®-Short Form, and patients were classified into three groups (well-nourished, at-risk of malnutrition and malnourished). Outcomes were confirmed at the 1-year follow-up survey. Hazard ratios (HRs) and 95% confidence intervals (CIs) for discontinuation of home medical care based on nutritional status were calculated using a Cox proportional hazard model. Covariates included age, sex, living status, economic status, activities of daily living, comorbidities and dysphagia status. RESULTS: In total, 297 patients (median age: 84 years) were analysed. At baseline, 48.5% of the patients were at-risk of malnutrition and 18.9% were malnourished. During the observation period of 1 year, 27.6% patients discontinued their home medical care. In the adjusted model, the HR for discontinuation of home medical care among those at-risk of malnutrition was 2.44 (95% CI: 1.34-4.45) times than that of the well-nourished group, although the malnourished group was not significantly associated with discontinuation of home medical care (HR: 1.69, 95% CI: 0.77-3.72; referent: well-nourished). CONCLUSIONS: At-risk of malnutrition was associated with discontinuation of home medical care among older patients.