CYP2D6 genotypes in revolving door patients with bipolar disorders: A case series.
Ontology highlight
ABSTRACT:
SUBMITTER: Seripa D
PROVIDER: S-EPMC6155952 | biostudies-literature | 2018 Sep
REPOSITORIES: biostudies-literature
Publications
CYP2D6 genotypes in revolving door patients with bipolar disorders: A case series.
Seripa Davide D Lozupone Madia M Miscio Giuseppe G Stella Eleonora E La Montagna Maddalena M Gravina Carolina C Urbano Maria M di Mauro Lazzaro L Daniele Antonio A Greco Antonio A Logroscino Giancarlo G Panza Francesco F Bellomo Antonello A
Medicine 20180901 37
<h4>Rationale</h4>In psychiatric disorders, interindividual differences in cytochrome P450 (CYP)2D6 (CYP2D6) enzymatic activity could be responsible of adverse drug reactions (ADRs) and therapeutic failures (TFs) for CYP2D6-metabolized drugs, contributing to the periodical hospital readmissions of the revolving door (RD) condition.<h4>Patient concerns</h4>We investigated CYP2D6 genotypes in a controlled series of 5 consecutive RD patients with Bipolar Disorder (BD).<h4>Diagnoses</h4>Psychiatric ...[more]
Similar Datasets
Project description:Background'Revolving door' patients in general practice are repeatedly removed from general practitioners' (GP) lists. This paper reports a qualitative portion of the first mixed methods study of these marginalised patients.MethodsWe conducted qualitative semi-structured interviews with six practitioner services staff and six GPs in Scotland, utilizing Charmazian grounded theory to characterise 'revolving door' patients and their impact from professionals' perspectives.Results'Revolving door' patients were reported as having three necessary characteristics; they had unreasonable expectations, exhibited inappropriate behaviours and had unmet health needs. A range of boundary breaches were reported too when 'revolving door' patients interacted with NHS staff.ConclusionsWe utilise the 'sensitising concepts' of legitimacy by drawing on literature about 'good and bad' patients and 'dirty work designations.' We relate these to the core work of general practice and explore the role that medical and moral schemas have in how health service professionals understand and work with 'revolving door' patients. We suggest this may have wider relevance for the problem doctor patient relationship literature.
| S-EPMC3930014 | biostudies-literature
Project description:BackgroundWe describe the health of "revolving door" patients in general practice in Scotland, estimate changes in their number over the timescale of the study, and explore reasons for changes, particularly related to NHS and government policy.MethodsA mixed methods predominantly qualitative study, using a grounded theory approach, set in Scottish general practice. Semi-structured interviews were conducted with professional key informants, 6 Practitioner Services staff who administer the GP registration system and 6 GPs with managerial or clinical experience of working with "revolving door" patients. Descriptive statistical analysis and qualitative analysis of patient removal episodes linked with routine hospital admissions, outpatient appointments, drug misuse treatment episodes and deaths were carried out with cohorts of "revolving door" patients identified from 1999 to 2005 in Scotland.ResultsA "revolving door" patient is removed 4 or more times from GP lists in 7 years. Patients had complex health issues including substance misuse, psychiatric and physical health problems and were at high risk of dying. There was a dramatic reduction in the number of "revolving door" patients during the course of the study.Conclusions"Revolving door" patients in general practice had significant health problems. Their numbers have reduced dramatically since 2004 and this probably resulted from improved drug treatment services, pressure from professional bodies to reduce patient removals and the positive ethical regulatory and financial climate of the 2004 GMS GP contract. This is a positive development for the NHS.
| S-EPMC3528483 | biostudies-literature
Project description:Little is known about the extent of mental, neurological and substance-use (MNS) disorders re-hospitalization in South Africa. We examined the extent of one-year MNS re-hospitalization (MNS-R) in a rural South African primary health care facility (PHCF).We conducted a retrospective analysis of hospital administrative data from 10,525 adults discharged from a rural PHCF in KwaZulu-Natal Province, South Africa. Chi-squared tests were utilized to describe MNS-R within one year of an index hospital admission in individuals with MNS, with a sub-analysis also being conducted to describe schizophrenia re-hospitalization (S-R).The prevalence of MNS and schizophrenia recorded at an index hospitalization was 5% and 1%, respectively. A total of 44/67 (66%) individuals with a diagnosis of MNS at the index hospitalization were classified as having MNS-R during oneyear follow-up period. Half of those diagnosed with schizophrenia at the index hospitalization (6/12 patients) were classified as having S-R during one-year follow-up period. There was a significant association between re-hospitalization outcomes (MNS-R and S-R) and MNS (p<0.01) or schizophrenia diagnosis (p<0.01) at index baseline hospitalization.The extent of MNS-R and S-R remains relatively high in rural South Africa, and needs further health systems strengthening to prevent revolving door occurrences.
| S-EPMC5111991 | biostudies-other
Project description:ObjectiveDespite the recurring nature of the disease process in many psychiatric patients, individual careers and time to readmission rarely have been analysed by statistical models that incorporate sequence and velocity of recurrent hospitalisations. This study aims at comparing four statistical models specifically designed for recurrent event history analysis and evaluating the potential impact of predictor variables from different sources (patient, treatment process, social environment).MethodThe so called Andersen-Gil counting process model, two variants of the conditional models of Prentice, Williams, and Peterson (gap time model, conditional probability model), and the so called frailty model were applied to a dataset of 17’145 [corrected] patients observed during a 12 years period starting from 1996 and leading to 37’697 psychiatric hospitalisations Potential prognostic factors stem from a standardized patient documentation form.ResultsEstimated regression coefficients over different models were highly similar, but the frailty model best represented the sequentiality of individual treatment careers and differing velocities of disease progression. It also avoided otherwise likely misinterpretations of the impact of gender, partnership, historical time and length of stay. A widespread notion of psychiatric diseases as inevitably chronic and worsening could be rejected. Time in community was found to increase over historical time for all patients. Most important protective factors beyond diagnosis were employment, partnership, and sheltered living situation. Risky conditions were urban living and a concurrent substance use disorder.ConclusionPrognostic factors for course of diseases should be determined only by statistical models capable of adequately incorporating the recurrent nature of psychiatric illnesses.
| S-EPMC3792950 | biostudies-literature
Project description:Objective: Anorexia nervosa (AN) is a severe psychiatric illness with multifactorial etiology and unsatisfactory treatment outcomes. Hospitalization is required for a substantial number of patients, and readmission (RA) commonly occurs. Some individuals need multiple hospitalizations sometimes over a short amount of time, thus, delineating the "revolving door" (RD) phenomenon. However, very little is known about readmissions and their frequency in AN. Therefore, we aimed to longitudinally investigate readmissions in AN in order to: (a) characterize patients with AN who need readmission (i.e., RA-AN), sometimes rapidly (RD-AN); (b) ascertain differences between RA-AN and non-RA-AN groups during baseline hospitalization; (c) investigate as to whether clinical or psychometric parameters worsened on RA; and (d) analyze predictors of time-to-readmission in AN. Methods: A total of 170 inpatients with AN were enrolled at their baseline hospitalization; all their subsequent rehospitalizations were recorded with a longitudinal design by which each patient has been observed for 3 years. Patients were classified as RD-AN if requiring a readmission <12 months since last discharge. Clinical characteristics were measured upon admission and discharge for each hospitalization, and at all time points, patients completed questionnaires assessing eating and general psychopathology, and body shape concerns. Results: Sixty-seven patients (39.4%) needed at least one readmission and 62 (92.5% of RA-AN) reported RD. Compared with non-RA-AN, those with RA-AN were younger, reported a shorter duration of illness, and were more frequently diagnosed with AN-BP. Also, greater severity of anxious and depressive symptoms and body shape concerns emerged in the RA-AN group. The outcome of baseline hospitalization did not differ between groups, and only depressive symptoms worsened at readmission. Shorter duration of AN and low weight gain during baseline hospitalization predicted early readmission but did not survive statistical control. In contrast, high scores on drive for thinness upon baseline hospital entry robustly predicted a shorter time to readmission even after statistical control. Discussion: Individuals with AN who require readmission do so over a short period notwithstanding a positive treatment outcome during their baseline hospitalization. Shorter time-to-readmission can be predicted mostly in case of marked drive for thinness and poor weight gain at baseline hospital admission.
| S-EPMC8342847 | biostudies-literature
Project description: Not available
| S-EPMC8884477 | biostudies-literature
Project description:Tamoxifen is a pro-drug widely used in breast cancer patients to prevent tumor recurrence. Prior work has revealed a role of cytochrome and sulfotransferase enzymes in tamoxifen metabolism. In this descriptive study, correlations were examined between concentrations of tamoxifen metabolites and genotypes for CYP2D6, CYP3A4, CYP3A5, SULT1A1, SULT1A2 and SULT1E1 in 135 patients with estrogen receptor-positive breast cancer. Patients were genotyped using the Roche-AmpliChip® CYP450 Test, and Real-Time and conventional PCR-RFLP. Plasma tamoxifen, 4-hydroxy-tamoxifen, N-desmethyl-tamoxifen, endoxifen and tamoxifen-N-oxide were isolated and quantified using a high-pressure liquid chromatography-tandem mass spectrometry system. Significantly higher endoxifen levels were detected in patients with the wt/wt CYP2D6 compared to the v/v CYP2D6 genotype (p<0.001). No differences were detected in the remaining tamoxifen metabolites among CYP2D6 genotypes. Patients featuring the SULT1A2*2 and SULT1A2*3 alleles showed significantly higher plasma levels of 4-hydroxy-tamoxifen and endoxifen (p = 0.025 and p = 0.006, respectively), as likely substrates of the SULT1A2 enzyme. Our observations indicate that besides the CYP2D6 genotype leading to tamoxifen conversion to potent hydroxylated metabolites in a manner consistent with a gene-dose effect, SULT1A2 also seems to play a role in maintaining optimal levels of both 4-hydroxy-tamoxifen and endoxifen.
| S-EPMC3726442 | biostudies-literature
Project description:Pathogenic MAGEL2 variants result in the phenotypes of Chitayat-Hall syndrome (CHS), Schaaf-Yang syndrome (SYS) and Prader-Willi syndrome (PWS). We present five patients with mutations in MAGEL2, including the first patient reported with a missense variant, adding to the limited literature. Further, we performed a systematic review of the CHS and SYS literature, assess the overlap between CHS, SYS and PWS, and analyze genotype-phenotype correlations among them. We conclude that there is neither a clinical nor etiological difference between CHS and SYS, and propose that the two syndromes simply be referred to as MAGEL2-related disorders.
| S-EPMC6864226 | biostudies-literature
Project description:BackgroundIn recent years, the incidence rate of vivax malaria recurrence still had 3.1% in Yunnan Province population after eradication therapy using primaquine (PQ). In order to understand the specific failure reasons for preventing vivax malaria relapses, a preliminary exploration on the CYP2D6 enzyme activity was carried out in the vivax malaria patients in Yunnan Province population by analysing mutational polymorphism in the coding region of CYP2D6 gene.MethodsBlood samples were collected from vivax malaria patients with suspected relapse (SR) and non-relapsed (NR) malaria in Yunnan Province. The DNA fragments containing 9 exons regions of human CYP2D6 gene were amplified by performing PCR and sequenced. The sequencing results were aligned by using DNAStar 11.0 to obtain the coding DNA sequence (CDS) of CYP2D6 gene. DnaSP 6.11.01 software was used to identify mutant polymorphisms and haplotypes of the CDS chain. The waterfall function of GenVisR package in R was utilized to visualize the mutational landscape. The alleles of CYP2D6 gene were identified according to the criteria prescribed by Human Cytochrome P450 (CYP) Allele Nomenclature Committee Database and the CYP2D6 enzyme activity was predicted based on diploid genotype.ResultsA total of 320 maternal CDS chains, including 63 from SR group and 257 from NR group, were obtained. Twelve mutant loci, including c.31 (rs769259), c.100 (rs1065852), c.271 (rs28371703), c.281 (rs28371704), c.294 (rs28371705), c.297 (rs200269944), c.336 (rs1081003), c.408 (rs1058164), c.505 (rs5030865), c.801 (rs28371718), c.886 (rs16947), and c.1,457 (rs1135840) were observed on the 640 CDS chains (including 320 maternal and 320 paternal chains). The high-frequency mutation at rs1135840 (0.703) and low-frequency mutation, such as rs28371703, were detected only in the SR group. The frequency of mutant rs1058164 and rs1135840 were significantly increased in the SR group ([Formula: see text]= 4.468, 5.889, P < 0.05), as opposed to the NR group. Of the 23 haplotypes (from Hap_1 to Hap_23), the nomenclatures of 11 allelic forms could be found: Hap_3 was non-mutant, Hap_2 accounted for the highest frequency (36.9%, 236/640), and Hap_9 had the most complex sequence structure, containing 7 loci mutations. Allele *10 was the most frequent among these genotypes (0.423). Among the allele *10 standard named genotypes, *1/*10, *1/*1 and *2/*10 were significantly more frequent in the NR group ([Formula: see text]= 3.911, P < 0.05) and all showed uncompromised enzyme activity; the impaired genotype *10/*39 was more frequent in the SR group ([Formula: see text]= 10.050, P < 0.05), and genotype *4/*4was detected only in the SR group.ConclusionIn the patients receiving PQ dosage in Yunnan Province population, both rs1135840 single nucleotide polymorphism and *10 allele form was common in the CYP2D6 gene. Low-frequency mutation sites, such as rs28371703, were only presented in patients with vivax malaria relapse.
| S-EPMC8620920 | biostudies-literature
Project description:Behavioural Activation (BA) is associated with a substantial evidence base for treatment of acute unipolar depression, and has promise as an easily disseminable psychological intervention for bipolar depression. Using a randomised multiple baseline case series design we examined the feasibility and acceptability of an adapted version of BA in a U.K. outpatient sample of 12 adults with acute bipolar depression. Participants were allocated at random to a 3-8 week wait period before being offered up to 20 sessions of BA. They completed outcome measures at intake, pre- and post-treatment and weekly symptom measures across the study period. Retention in therapy was high (11/12 participants completed the target minimum number of sessions), and all participants returning acceptability measures reported high levels of satisfaction with the intervention. No therapy-related serious adverse events were reported, nor were there exacerbations in manic symptoms that were judged to be a result of the intervention. The pattern of change on outcome measures is consistent with the potential for clinical benefit; six of the nine participants with a stable baseline showed clinically significant improvement on the primary outcome measure. The findings suggest adapted BA for bipolar depression is a feasible and acceptable approach that merits further investigation.
| S-EPMC9599144 | biostudies-literature