Follow-up of curatively treated cancer in primary care:a qualitative study of the views of Dutch GPs

BACKGROUND: Follow-up for cancer typically occurs in secondary care, and improved survival has increased demands on these services. Other care models may alleviate this burden, such as moving (parts of) follow-up care for curatively treated patients from secondary to primary care (care substitution). AIM: To explore the opinions of GPs regarding the potential benefits, barriers, and requirements of care substitution for breast and colorectal cancer. DESIGN AND SETTING: A qualitative study of the opinions of purposively sampled GPs in Dutch primary care. METHOD: Focus group sessions and individual semi-structured interviews were recorded and transcribed verbatim. Data were analysed by two independent researchers using thematic analysis. RESULTS: Two focus groups (n = 14) were conducted followed by nine individual interviews. Three main themes were identified: perceived benefits, perceived barriers, and perceived requirements. Perceived benefits included better accessibility and continuity of care, and care closer to patients' homes. Uncertainty about cancer-related competences and practical objections were perceived as barriers. Requirements included close specialist collaboration, support from patients for this change, and stepwise implementation to avoid loss of existing care quality. CONCLUSION: Most GPs reported that they were not in favour of complete care substitution, but that primary care could have greater formal involvement in oncological follow-up if there is close collaboration with secondary care (that is, shared care), support from patients, sufficient resource allocation, stepwise implementation with clear guidelines, and monitoring of quality. Clear and broadly supported protocols need to be developed and tested before implementing follow-up in primary care

The Progress and Pitfalls of Pharmacogenetics-Based Precision Medicine in Schizophrenia Spectrum Disorders:A Systematic Review and Meta-Analysis

The inadequate efficacy and adverse effects of antipsychotics severely affect the recovery of patients with schizophrenia spectrum disorders (SSD). We report the evidence for associations between pharmacogenetic (PGx) variants and antipsychotics outcomes, including antipsychotic response, antipsychotic-induced weight/BMI gain, metabolic syndrome, antipsychotic-related prolactin levels, antipsychotic-induced tardive dyskinesia (TD), clozapine-induced agranulocytosis (CLA), and drug concentration level (pharmacokinetics) in SSD patients. Through an in-depth systematic search in 2010–2022, we identified 501 records. We included 29 meta-analyses constituting pooled data from 298 original studies over 69 PGx variants across 39 genes, 4 metabolizing phenotypes of CYP2D9, and 3 of CYP2C19. We observed weak unadjusted nominal significant (p &lt; 0.05) additive effects of PGx variants of DRD1, DRD2, DRD3, HTR1A, HTR2A, HTR3A, and COMT (10 variants) on antipsychotic response; DRD2, HTR2C, BDNF, ADRA2A, ADRB3, GNB3, INSIG2, LEP, MC4R, and SNAP25 (14 variants) on weight gain; HTR2C (one variant) on metabolic syndrome; DRD2 (one variant) on prolactin levels; COMT and BDNF (two variants) on TD; HLA-DRB1 (one variant) on CLA; CYP2D6 (four phenotypes) and CYP2C19 (two phenotypes) on antipsychotics plasma levels. In the future, well-designed longitudinal naturalistic multi-center PGx studies are needed to validate the effectiveness of PGx variants in antipsychotic outcomes before establishing any reproducible PGx passport in clinical practice.</p

Polygenic risk score for schizophrenia was not associated with glycemic level (HbA1c) in patients with non-affective psychosis:Genetic Risk and Outcome of Psychosis (GROUP) cohort study

Introduction: Type 2 diabetes (T2D) is a common comorbidity in patients with schizophrenia (SCZ). The underlying pathophysiologic mechanisms are yet to be fully elucidated, although it can be argued that shared genes, environmental factors or their interaction effect are involved. This study investigated the association between polygenic risk score of SCZ (PRSSCZ) and glycated haemoglobin (HbA1c) while adjusting for polygenic risk score of T2D (PRST2D), and clinical and demographic covariables. Methods: Genotype, clinical and demographic data of 1129 patients with non-affective psychosis were extracted from Genetic Risk and Outcome of Psychosis (GROUP) cohort study. The glycated haemoglobin (HbA1c) was the outcome. PRS was calculated using standard methods. Univariable and multivariable linear regression analyses were applied to estimate associations. Additionally, sensitivity analysis based on multiple imputation was done. After correction for multiple testing, a two-sided p-value ≤.003 was considered to discover evidence for an association. Results: Of 1129 patients, 75.8% were male with median age of 29 years. The mean (standard deviation) HbA1c level was 35.1 (5.9) mmol/mol. There was no evidence for an association between high HbA1c level and increased PRSSCZ (adjusted regression coefficient (aβ) = 0.69, standard error (SE) = 0.77, p-value =.37). On the other hand, there was evidence for an association between high HbA1c level and increased PRST2D (aβ = 0.93, SE = 0.32, p-value =.004), body mass index (aβ = 0.20, SE = 0.08, p-value =.01), diastolic blood pressure (aβ = 0.08, SE = 0.04, p-value =.03), late age of first psychosis onset (aβ = 0.19, SE = 0.05, p-value =.0004) and male gender (aβ = 1.58, SE = 0.81, p-value =.05). After multiple testing correction, there was evidence for an association between high HbA1c level and late age of first psychosis onset. Evidence for interaction effect between PRSscz and antipsychotics was not observed. The multiple imputation-based sensitivity analysis provided consistent results with complete case analysis. Conclusions: Glycemic dysregulation in patients with SCZ was not associated with PRSSCZ. This suggests that the mechanisms of hyperglycemia or diabetes are at least partly independent from genetic predisposition to SCZ. Our findings show that the change in HbA1c level can be caused by at least in part due to PRST2D, late age of illness onset, male gender, and increased body mass index and diastolic blood pressure

Abnormal connectivity between attentional, language and auditory networks in schizophrenia

Brain circuits involved in language processing have been suggested to be compromised in patients with schizophrenia. This does not only include regions subserving language production and perception, but also auditory processing and attention. We investigated resting state network connectivity of auditory, language and attention networks of patients with schizophrenia and hypothesized that patients would show reduced connectivity. Patients with schizophrenia (n=45) and healthy controls (n=30) underwent a resting state fMRI scan. Independent components analysis was used to identify networks of the auditory cortex, left inferior frontal language regions and the anterior cingulate region, associated with attention. The time courses of the components where correlated with each other, the correlations were transformed by a Fisher's Z transformation, and compared between groups. In patients with schizophrenia, we observed decreased connectivity between the auditory and language networks. Conversely, patients showed increased connectivity between the attention and language network compared to controls. There was no relationship with severity of symptoms such as auditory hallucinations. The decreased connectivity between auditory and language processing areas observed in schizophrenia patients is consistent with earlier research and may underlie language processing difficulties. Altered anterior cingulate connectivity in patients may be a correlate of habitual suppression of unintended speech, or of excessive attention to internally generated speech. This altered connectivity pattern appears to be present independent of symptom severity, and may be suggestive of a trait, rather than a state characteristic. (C) 2011 Elsevier B.V. All rights reserved

Do routine outcome monitoring results translate to clinical practice? A cross-sectional study in patients with a psychotic disorder

Background: The use of Routine Outcome Monitoring (ROM) in mental health care has increased widely during the past decade. Little is known, however, on the implementation and applicability of ROM outcome in daily clinical practice. In the Netherlands, an extensive ROM-protocol for patients with psychotic disorders has been implemented over the last years (ROM-Phamous). The current study investigated to what extent ROM results translate to daily clinical practice. Therefore, we investigated whether clinical problems as identified with ROM were detected and used in the treatment of patients with psychotic disorders. Methods: Out of the ROM database of 2010 (n = 1040), a random sample of 100 patients diagnosed with a psychotic disorder was drawn. ROM-data used in this study included a physical examination, laboratory tests, interviews and self-report questionnaires. Based on these data, the prevalence of positive and negative symptoms, psychosocial problems and cardiovascular risk factors was determined. Next, we investigated whether these problems, as identified with ROM, were reflected in the treatment plans of patients, as an indication of the use of ROM in clinical practice. Results: The sample consisted of 63 males and 37 females. The mean age was 44 and the mean duration of illness was 17.7 years. The prevalence of positive and negative symptoms, psychosocial problems and cardiovascular risk factors ranged from 11 to 86 %. In the majority of cases, problems as identified with ROM were not reflected in the treatment plans of patients. Conclusions: We found a substantial discrepancy between the ROM measurements and the treatment plans, i.e. low rates of detection of symptoms, psychosocial problems and cardiovascular risk factors in the treatment plans, even though these problems were identified with ROM. The opposite occurred as well, where problems were reflected in the treatment plans but not identified with ROM. Thus, ROM and daily clinical practice appear to be two separate processes, whereas ideally they should be integrated. Strong efforts should be made to integrate ROM and consequent treatment activities. Such integration may help to provide patients with adequate and customized care and simultaneously minimize under-and over-treatment

Pharmacological treatment for psychotic depression

Background Evidence is limited regarding the most effective pharmacological treatment for psychotic depression: monotherapy with an antidepressant, monotherapy with an antipsychotic, another treatment (e.g. mifepristone), or combination of an antidepressant plus an antipsychotic. This is an update of a review first published in 2005 and last updated in 2015. Objectives 1. To compare the clinical efficacy of pharmacological treatments for patients with an acute psychotic depression: antidepressant monotherapy, antipsychotic monotherapy, mifepristone monotherapy, and the combination of an antidepressant plus an antipsychotic versus placebo and/or each other. 2. To assess whether differences in response to treatment in the current episode are related to non-response to prior treatment. Search methods A search of the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR); Ovid MEDLINE (1950-); Embase (1974-); and PsycINFO (1960-) was conducted on 21 February 2020. Reference lists of all included studies and related reviews were screened and key study authors contacted. Selection criteria All randomised controlled trials (RCTs) that included participants with acute major depression with psychotic features, as well as RCTs consisting of participants with acute major depression with or without psychotic features, that reported separately on the subgroup of participants with psychotic features. Data collection and analysis Two review authors independently extracted data and assessed risk of bias in the included studies, according to criteria from the Cochrane Handbook for Systematic Reviews of Interventions. Data were entered into RevMan 5.1. We used intention-to-treat data. Primary outcomes were clinical response for efficacy and overall dropout rate for harm/tolerance. Secondary outcome were remission of depression, change from baseline severity score, quality of life, and dropout rate due to adverse effects. For dichotomous efficacy outcomes (i.e. response and overall dropout), risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. Regarding the primary outcome of harm, only overall dropout rates were available for all studies. If the study did not report any of the response criteria as defined above, remission as defined here could be used as an alternative. For continuously distributed outcomes, it was not possible to extract data from the RCTs. Main results The search identified 3947 abstracts, but only 12 RCTs with a total of 929 participants could be included in the review. Because of clinical heterogeneity, few meta-analyses were possible. The main outcome was reduction in severity (response) of depression, not of psychosis. For depression response, we found no evidence of a difference between antidepressant and placebo (RR 8.40, 95% CI 0.50 to 142.27; participants = 27, studies = 1; very low-certainty evidence) or between antipsychotic and placebo (RR 1.13, 95% CI 0.74 to 1.73; participants = 201, studies = 2; very low-certainty evidence). Furthermore, we found no evidence of a difference in overall dropouts with antidepressant (RR 1.24, 95% CI 0.34 to 4.51; participants = 27, studies = 1; very low-certainty evidence) or antipsychotic monotherapy (RR 0.79, 95% CI 0.57 to 1.08; participants = 201, studies = 2; very low-certainty evidence). No evidence suggests a difference in depression response (RR 2.09, 95% CI 0.64 to 6.82; participants = 36, studies = 1; very low-certainty evidence) or overall dropouts (RR 1.79, 95% CI 0.18 to 18.02; participants = 36, studies = 1; very low-certainty evidence) between antidepressant and antipsychotic. For depression response, low- to very low-certainty evidence suggests that the combination of an antidepressant plus an antipsychotic may be more effective than antipsychotic monotherapy (RR 1.83, 95% CI 1.40 to 2.38; participants = 447, studies = 4), more effective than antidepressant monotherapy (RR 1.42, 95% CI 1.11 to 1.80; participants = 245, studies = 5), and more effective than placebo (RR 1.86, 95% CI 1.23 to 2.82; participants = 148, studies = 2). Very low-certainty evidence suggests no difference in overall dropouts between the combination of an antidepressant plus an antipsychotic versus antipsychotic monotherapy (RR 0.79, 95% CI 0.63 to 1.01; participants = 447, studies = 4), antidepressant monotherapy (RR 0.91, 95% CI 0.55 to 1.50; participants = 245, studies = 5), or placebo alone (RR 0.75, 95% CI 0.48 to 1.18; participants = 148, studies = 2). No study measured change in depression severity from baseline, quality of life, or dropouts due to adverse events. We found no RCTs with mifepristone that fulfilled our inclusion criteria. Risk of bias is considerable: we noted differences between studies with regards to diagnosis, uncertainties around randomisation and allocation concealment, treatment interventions (pharmacological differences between various antidepressants and antipsychotics), and outcome criteria. Authors' conclusions Psychotic depression is heavily under-studied, limiting confidence in the conclusions drawn. Some evidence indicates that combination therapy with an antidepressant plus an antipsychotic is more effective than either treatment alone or placebo. Evidence is limited for treatment with an antidepressant alone or with an antipsychotic alone. Evidence for efficacy of mifepristone is lacking

Glutamate in dorsolateral prefrontal cortex and auditory verbal hallucinations in patients with schizophrenia:A (1)H MRS study

Purpose: Glutamatergic models of psychosis propose that dysfunction of N-methyl-D-aspartate (NMDA) receptors, and associated excess of glutamate, may underlie psychotic experiences in people with schizophrenia. However, little is known about the specific relation between glutamate and auditory verbal hallucinations (AVH) in patients with psychosis. In this study, levels of glutamate + glutamine (Glx) in the left lateral prefrontal lobe were determined using proton magnetic resonance spectroscopy (H-1 MRS) to calculate their association with AVH. Methods: Sixty-seven patients with schizophrenia and thirty healthy control participants (HC) underwent magnetic resonance spectroscopy (MRS) to estimate levels of Glx in the white matter of the left prefrontal lobe. The spectrum was estimated from an 8 mm(3) voxel placed in the left lateral prefrontal region, belonging to both the cingulum and forceps minor. Patients with lifetime AVH (AVH group; n = 45) and patients without lifetime AVH were compared (NoAVH group; n = 22) to control participants. Results: Levels of Glx were significantly different between the groups (F(2,94) = 5.27, p = 0.007). Planned comparisons showed that higher Glx levels were found in control participants than in the total patient group (p = 0.010). However, patients with lifetime AVH had higher levels of Glx compared to patients without lifetime AVH (p = 0.019). Creatin levels were similar in all three groups. We found no association between Gix and the severity of symptoms (item P3 of the PANSS or PANSS positive subscale). Conclusion: The higher Glx levels in patients with lifetime AVH as compared to patients without lifetime AVH suggest a mediating role for Glx in AVH. Our results are consistent with a previous study that found similar decreased levels of Glx in patients with schizophrenia, and increased levels in an AVH group as compared to a NoAVH group. The role of the glutamatergic system deserves further investigation, for example in different brain regions and in relation to clinical variables