IFN-λ4 is associated with increased risk and earlier occurrence of gastrointestinal, respiratory and malarial infections in Malian children

ABSTRACTGenetic polymorphisms within the IFNL3/IFNL4 genomic region, which encodes type III interferons, have been strongly associated with impaired clearance of hepatitis C virus (HCV) infection. We hypothesized that type III interferons might be important for the immune response to other pathogens as well. In a cohort of 914 Malian children, we analyzed episodes of malaria, gastrointestinal and respiratory infections using information for 30,626 clinic visits from birth through up to 5 years of follow-up. Genetic polymorphisms IFNL4-rs368234815 and IFNL3-rs4803217 that functionally affect type III interferons were genotyped with TaqMan assays. For both genetic variants and each infection, we evaluated time-to-first episode and calculated odds ratios (ORs) for the risk of an infection episode during follow-up, controlling for relevant covariates. Compared to children with the rs368234815-TT/TT genotype (IFN-λ4-Null), each copy of the rs368234815-dG allele was associated with an earlier first episode of a gastrointestinal infection (p=0.003) and respiratory infection (p=0.045). The risk of experiencing an infection episode during the follow-up was also significantly increased with each copy of the rs368234815-dG allele – for gastrointestinal infections (OR=1.53, 95%CI (1.13-2.07), p=0.005) and malaria (OR=1.30, 95%CI (1.02-1.65), p=0.033). IFNL4-rs368234815 and IFNL3-rs4803217 were in moderate linkage disequilibrium in this population (r2=0.78), and all the associations for rs4803217 were weaker and lost significance after adjusting for rs368234815, implicating IFN-λ4 and not IFN-λ3 as the primary cause of these associations. We conclude that the ability to produce IFN-λ4 may have broad health-related implications by negatively affecting the immune response and clinical outcomes of several common infections.

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IFN-λ4 is associated with increased risk and earlier occurrence of several common infections in African children

Genes and Immunity ◽

10.1038/s41435-021-00127-7 ◽

2021 ◽

Author(s):

Ludmila Prokunina-Olsson ◽

Robert D. Morrison ◽

Adeola Obajemu ◽

Almahamoudou Mahamar ◽

Sungduk Kim ◽

...

Keyword(s):

Respiratory Infections ◽

Genomic Region ◽

First Episode ◽

Genetic Associations ◽

Gastrointestinal Infections ◽

Type Iii ◽

Functional Variants ◽

Younger Age ◽

Increased Risk ◽

Pediatric Infections

AbstractGenetic polymorphisms within the IFNL3/IFNL4 genomic region, which encodes type III interferons, have been strongly associated with clearance of hepatitis C virus. We hypothesized that type III interferons might be important for the immune response to other pathogens as well. In a cohort of 914 Malian children, we genotyped functional variants IFNL4-rs368234815, IFNL4-rs117648444, and IFNL3-rs4803217 and analyzed episodes of malaria, gastrointestinal, and respiratory infections recorded at 30,626 clinic visits from birth up to 5 years of age. Compared to children with the rs368234815-TT/TT genotype (IFN-λ4-Null), rs368234815-dG allele was most strongly associated with an earlier time-to-first episode of gastrointestinal infections (p = 0.003). The risk of experiencing an infection episode during the follow-up was also significantly increased with rs368234815-dG allele, with OR = 1.53, 95%CI (1.13–2.07), p = 0.005 for gastrointestinal infections and OR = 1.30, 95%CI (1.02–1.65), p = 0.033 for malaria. All the associations for the moderately linked rs4803217 (r2 = 0.78 in this set) were weaker and lost significance after adjusting for rs368234815. We also analyzed all outcomes in relation to IFN-λ4-P70S groups. Our results implicate IFN-λ4 and not IFN-λ3 as the primary functional cause of genetic associations with increased overall risk and younger age at first clinical episodes but not with recurrence or intensity of several common pediatric infections.

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Patterns and predictors of hospitalisation in first-episode psychosis

The British Journal of Psychiatry ◽

10.1192/bjp.178.6.518 ◽

2001 ◽

Vol 178 (6) ◽

pp. 518-523 ◽

Cited By ~ 47

Author(s):

Attila Sipos ◽

Glynn Harrison ◽

David Gunnell ◽

Shazad Amin ◽

Swaran P. Singh

Keyword(s):

Negative Symptoms ◽

First Episode Psychosis ◽

Psychiatric Services ◽

First Episode ◽

Psychotic Episode ◽

Duration Of Untreated Illness ◽

Specialist Services ◽

Increased Risk ◽

Episode Psychosis

BackgroundLittle is known about predictors of hospitalisation in patients with first-episode psychosis.AimsTo identify the pattern and predictors of hospitalisation of patients with a first psychotic episode making their first contact with specialist services.MethodThree-year follow-up of a cohort of 166 patients with a first episode of psychosis making contact with psychiatric services in Nottingham between June 1992 and May 1994.ResultsEighty-eight (53.0%) patients were admitted within 1 week of presentation; 32 (19.3%) were never admitted during the 3 years of follow-up. Manic symptoms at presentation were associated with an increased risk of rapid admission and an increased overall risk of admission; negative symptoms and a longer duration of untreated illness had an increased risk of late admission.ConclusionsCommunity-oriented psychiatric services might only delay, rather than prevent, admission of patients with predominantly negative symptoms and a longer duration of untreated illness. First-episode studies based upon first admissions are likely to be subject to selection biases, which may limit their representativeness.

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The Impact of Cannabis in the Early Stages of Schizophrenia: A 3-Year Longitudinal Study on Cannabis Influence on Relapse Rates

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.2137 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S196-S197

Author(s):

M. Gomez Revuelta ◽

M. Juncal Ruiz ◽

O. Porta Olivares ◽

V. Gajardo Galan ◽

G. Pardo de Santayana Jenaro ◽

...

Keyword(s):

Intervention Program ◽

Response To Treatment ◽

Rank Test ◽

First Episode ◽

Term Outcome ◽

Long Term Outcome ◽

Early Stages ◽

Increased Risk ◽

The Impact

IntroductionThe first five years after the onset of a first episode of psychosis (FEP) are crucial for long term outcome. In this period, the risk of relapse is particularly high. Consequences of relapse include an increased risk of neurotoxicity, chronicity, hospitalization, decreased response to treatment, increased economic burden and functional impairment.ObjectivesTo discern the influence of cannabis on relapse as it may contribute to adopt specific measures in patients during early stages of the illness.Material and methodsPAFIP is an early intervention program for patients with a FEP. Between January 2005 and January 2011, 163 patients were recruited for this study. They were followed-up during 3 years at intervals of three months. The sample was divided into three groups: (1) those non-cannabis users neither before the FEP nor during follow-up (nn), (2) consumers before the FEP and during follow-up (ss) and (3) consumers before the FEP that gave up consumption during follow-up (sn).ResultsNo statistically significant differences between the three groups were observed but a trend (P = 0.057) towards a more enduring survival in Group 3 (sn). (Kaplan–Meier curve and detailed Log Rank Test results will be included in the final poster).ConclusionsCannabis has a detrimental effect on schizophrenia. The interruption of its use could contribute to improve the outcome of the disease, as the results of our study suggest.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Management and outcomes of pneumothorax in adult patients with Langerhans cell Histiocytosis

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-019-1203-5 ◽

2019 ◽

Vol 14 (1) ◽

Cited By ~ 1

Author(s):

Pierre Le Guen ◽

Sylvie Chevret ◽

Emmanuelle Bugnet ◽

Constance de Margerie-Mellon ◽

Gwenaël Lorillon ◽

...

Keyword(s):

Lung Function ◽

Thoracic Surgery ◽

Langerhans Cell Histiocytosis ◽

Recurrent Events ◽

Langerhans Cell ◽

First Episode ◽

Factors Associated ◽

Increased Risk ◽

Ipsilateral Recurrence

Abstract Background Pneumothorax may recur during pulmonary Langerhans cell histiocytosis (PLCH) patients’ follow-up and its management is not standardised. The factors associated with pneumothorax recurrence are unknown. Methods In this retrospective study, PLCH patients who experienced a pneumothorax and were followed for at least 6 months after the first episode were eligible. The objectives were to describe the treatment of the initial episode and pneumothorax recurrences during follow-up. We also searched for factors associated with pneumothorax recurrence and evaluated the effect on lung function outcome. Time to recurrence was estimated by the Kaplan Meier method and the cumulative hazard of recurrence handling all recurrent events was estimated. Univariate Cox models and Andersen-Gill counting process were used for statistical analyses. Results Fourty-three patients (median age 26.5 years [interquartile range (IQR), 22.9–35.4]; 26 men, 39 current smokers) were included and followed for median time of 49 months. Chest tube drainage was the main management of the initial pneumothorax, which resolved in 70% of cases. Pneumothorax recurred in 23 (53%) patients, and overall 96 pneumothoraces were observed during the study period. In the subgroup of patients who experienced pneumothorax recurrence, the median number of episodes per patient was 3 [IQR, 2–4]. All but one recurrence occurred within 2 years after the first episode. Thoracic surgery neither delayed the time of occurrence of the first ipsilateral recurrence nor reduced the overall number of recurrences during the study period, although the rate of recurrence was lower after thoracotomy than following video-assisted thoracic surgery (p = 0.03). At the time of the first pneumothorax, the presence of air trapping on lung function testing was associated with increased risk of recurrence (hazard ratio = 5.08; 95% confidence interval [1.18, 21.8]; p = 0.03). Pneumothorax recurrence did not predict subsequent lung function decline (p = 0.058). Conclusions Our results show that pneumothorax recurrences occur during an “active” phase of PLCH. In this observational study, the time of occurrence of the first ipsilateral recurrence and the overall number of pneumothorax recurrences were similar after conservative and thoracic surgical treatments. Further studies are needed to determine the best management to reduce the risk of pneumothorax recurrence in PLCH patients.

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The impact of Cannabis in Schizophrenia: Pafip Three-year Longitudinal Study on Outcome and Functionality After a First Episode of Psychosis

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.1962 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S136-S137

Author(s):

M. Gomez Revuelta ◽

M. Juncal Ruiz ◽

O. Porta Olivares ◽

M. Fernández Rodríguez ◽

D. Abejas Díez ◽

...

Keyword(s):

Intervention Program ◽

Age Of Onset ◽

Cannabis Use ◽

First Episode ◽

Long Term Outcome ◽

Clinical Prognosis ◽

Increased Risk ◽

The Impact

IntroductionThe association between cannabis and psychosis makes crucial the intervention on cannabis use disorder at first episodes of psychosis (FEP), especially among young population. In this group of patients, the harmful potential of cannabis is more evident by its influence on neurodevelopment. However, the nature of the association cannabis-psychosis is not clearly described. It seems to represent a mediating factor for an increased risk of psychosis in healthy and high-risk populations, determining an earlier age of onset and worsening long term outcome.ObjectivesTo assess the impact of cannabis in terms of functional and clinical prognosis in patients recruited after a FEP.Material and methodsPAFIP is an early intervention program for early stages of psychosis. One hundred and sixty-three were included, followed-up at regular intervals of six months for three years with administration of clinical and functional scales (BPRS, SAPS, SANS, CDRS, GAF and Drake). Patients were divided into three groups: (1) those non-users neither before the onset nor during follow-up (nn) PEP, (2) consumers before the FEP and during follow-up (ss) and (3) consumers before the FEP that gave up consumption during follow-up (sn).ResultsNo statistically significant differences were observed in terms of functionality at three-year follow-up endpoint but a trend to a better-preserved functionality in the sn group. The sn group presented lower scores in scales for positive symptoms with respect to the comparison groups.ConclusionsThe interruption in cannabis use may have a beneficial effect on short-term clinical prognosis and functionality on long term.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Substance misuse in first-episode psychosis: 15-month prospective follow-up study

The British Journal of Psychiatry ◽

10.1192/bjp.bp.105.017236 ◽

2006 ◽

Vol 189 (3) ◽

pp. 229-234 ◽

Cited By ~ 102

Author(s):

D. Wade ◽

S. Harrigan ◽

J. Edwards ◽

P. M. Burgess ◽

G. Whelan ◽

...

Keyword(s):

Substance Misuse ◽

First Episode Psychosis ◽

Patient Admission ◽

First Episode ◽

Positive Symptoms ◽

Follow Up Study ◽

Increased Risk ◽

Episode Psychosis ◽

Time To Relapse

BackgroundWell-designed prospective studies of substance misuse in first-episode psychosis can improve our understanding of the risks associated with comorbid substance misuse and psychosis.AimsTo examine the potential effects of substance misuse on in-patient admission and remission and relapse of positive symptoms in first-episode psychosis.MethodThe study was a prospective 15-month follow-up investigation of 103 patients with first-episode psychosis recruited from three mental health services.ResultsSubstance misuse was independently associated with increased risk of in-patient admission, relapse of positive symptoms and shorter time to relapse of positive symptoms after controlling for potential confounding factors. Substance misuse was not associated with remission or time to remission of positive symptoms. Heavy substance misuse was associated with increased risk of in-patient admission, relapse and shorter time to relapse.ConclusionsSubstance misuse is an independent risk factor for a problematic recovery from first-episode psychosis.

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AB0242 SURVIVAL ANALYSIS IN THE DEVELOPMENT OF SERIOUS INFECTIONS AND SERIOUS RESPIRATORY INFECTIONS IN AR PATIENTS INCLUDED IN A VACCINATION PROGRAM

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5061 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1421-1422

Author(s):

L. Domínguez ◽

P. Rodriguez Cundin ◽

V. Calvo-Río ◽

N. Vegas-Revenga ◽

V. Portilla ◽

...

Keyword(s):

Survival Analysis ◽

Soft Tissues ◽

Hospital Admissions ◽

Respiratory Infections ◽

Vaccination Program ◽

Research Support ◽

Increased Risk ◽

Serious Infections ◽

Tract Infections

Background:Rheumatoid arthritis is an autoimmune disorder in which patients have an increased risk of developement of serious infections. This risk may be augmented due to RA itself and to immunosuppressive drugs, specially biologic therapy. Vaccination programs may change this condition.Objectives:Our aim in this study was to evaluate the incidence of serious infections in a vaccinate RA patients cohort.Methods:Prospective study of 401 patients diagnosed with RA who were invited to participate in the vaccination program of the Preventive Medicine department of our hospital from October 2011 to October 2016. The follow up was made until June 2017 with a minimun follow-up period of 8 months and maximun of 5.5 years. Serious infections were defined as those that required hospitalization or at least one dose of intravenous antibiotic treatement at emergency room. Information was retrieved from dthe hospital records.Only 7 patients refused vaccination (2%). Information was not obtained in 4 of the remaining 394 patients. Therefore, these 4 patients were not incuded in the assessment.Survival análisis was assessed by Kaplan-Meier method.Results:We finally studied 390 patients (307♀/83♂) mean age±SD 61,28 ± 12,9 years that participate in the vaccination program and followed-up. The main features at the time of vaccination were: median disease duration (4years), positive rheumatoid factor (56,7%), subcutaneous nodules (4.9%), erosive arthritis (36.9%), pulmonary fibrosis (3.8%), secondary Sjögren syndrome (5.1%), other extraartocular manifestations (14.6%) and rheumatoid vasculitis (5.6%) Most patients had received imunosuppressive drugs before the vaccination program. The most frequently used were systemic corticosteroids (n=228), methotrexate (n=362) and biologic agents (40.3%).During the follow-up, 42 patients (10.7%) had required hospital admissions due to infections, 17 of them were severe respiratory infections (4.35%). The remaining 25 admissions were in the setting of urinary tract infections (n=12), intraabdominal infections (7), skin and soft tissues (12) and articular (1). Also 12 of these patients had a zoster herpes.Afeter a median follow-up of 1061,89 ± 417 days, the incidence of serious infection, with a CI (95%), was 4.00 (2.95-5.41) for 100 patients yearly. Concerning to admissions due to serious respiratory infections, with a CI (95%), was 1.55 (0.9-2.47) for 100 patients yearly.Images 1 and 2.Image 1.Survival analysis on serious infectionsImage 1.Survival analysis on serious respiratory infectionsConclusion:In this stydy we can concluded that our RA vaccinated patients present a dicrease of the incidence of serious infeccions, similar to other published cohorts. The incidence of serious respiratory infections shows a dicrease even lower to other published cohorts. The vaccination program seems to be effective to prevent hospital admissions due to infections.Disclosure of Interests:Lucia Domínguez: None declared, Paz Rodriguez Cundin: None declared, Vanesa Calvo-Río Grant/research support from: MSD and Roche, Speakers bureau: AbbVie, Lilly, Celgene, Grünenthal, UCB Pharma, Nuria Vegas-Revenga Grant/research support from: AbbVie, Roche, Pfizer, Lilly, Gebro Pharma, MSD, Novartis, Bristol-Myers, Janssen, and Celgene, Virginia Portilla: None declared, Francisco Manuel Antolin-Juarez: None declared, Maria Henar Rebollo Rodriguez: None declared, Alfonso Corrales Speakers bureau: Abbvie, Natalia Palmou-Fontana: None declared, D. Prieto-Peña: None declared, Monica Calderón-Goercke: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Ricardo Blanco Grant/research support from: AbbVie, MSD, and Roche, Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, and MSD

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Post-Thrombotic Syndrome and Quality-of-Life after Venous Thromboembolism in Young and Middle-Aged Women

Blood ◽

10.1182/blood.v126.23.2309.2309 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2309-2309 ◽

Cited By ~ 1

Author(s):

Maria Ljungqvist ◽

Margareta Holmstrom ◽

Helle Kieler ◽

Gerd Larfars

Keyword(s):

Quality Of Life ◽

Venous Thromboembolism ◽

First Episode ◽

Common Complication ◽

Middle Aged ◽

Post Thrombotic Syndrome ◽

Increased Risk ◽

History Of

Abstract Introduction: Post-thrombotic syndrome (PTS) is the most common complication after a venous thromboembolism (VTE). PTS is a chronic condition affecting health-related quality-of-life (QoL). In this study we aimed to determine the risk of PTS and how it affects QoL after a first episode of VTE in young and middle-aged women. Methods: We conducted a cohort study, including 1438 women with a first episode of VTE. Patients were recruited from 'Thrombo Embolism Hormonal Study' (TEHS), a Swedish nation-wide case-control study on risk factors for VTE in women 18-65 years of age. Consecutive patients with a first episode of deep vein thrombosis (DVT) in the lower leg or pulmonary embolism (PE) were included between 2002 and 2009. In 2011 all women still living in Sweden were followed up through a questionnaire. PTS was measured using self-reported Villalta score and Veins-QoL was used to measure QoL. Results: After a median follow-up time of 6 years 1049 patients accepted participation in the follow-up study. The reported prevalence of PTS was 20 % for all patients, 28 % among women with a previous episode of a proximal DVT, 19 % among women with a previous distal DVT and 12 % among women with PE. Women with a history of leg symptoms before the first VTE-event had a higher risk of PTS (OR 3.5 (95% CI 2.5 - 4.8), with a prevalence of 32% compared to 12% in women with no history of leg symptoms. Obese women were at increased risk of PTS (OR 1.9, 95% CI 1.4 - 2.7) compared to non-obese. Similar women with proximal DVT (OR 1.6, 95% CI 1.1 - 2.3) and ipsilateral recurrence (OR 3.8, 95% CI 1.9 - 7.7) had increased risk of PTS. Patients with PTS scored lower on Veins-QoL (44 vs. 52, p < 0.01). Conclusions: PTS is a common complication of VTE. Women with a history of leg-symptoms before time of VTE-diagnosis have more than 3-fold increased risk of PTS. Occurrence of PTS significantly reduces QoL. Disclosures No relevant conflicts of interest to declare.

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A critical analysis of recent data on the long-term outcome of antipsychotic treatment

Psychological Medicine ◽

10.1017/s0033291718003811 ◽

2018 ◽

Vol 49 (5) ◽

pp. 750-753 ◽

Cited By ~ 5

Author(s):

Joanna Moncrieff ◽

Sandra Steingard

Keyword(s):

Negative Symptoms ◽

First Episode ◽

Antipsychotic Treatment ◽

Term Outcome ◽

Long Term Outcome ◽

Level Of Functioning ◽

Risk Of Death ◽

Increased Risk

AbstractNew studies of long-term outcomes claim to show that taking antipsychotics on a continuous and indefinite basis is the best approach for people diagnosed with a first episode of psychosis or schizophrenia. A 10-year follow-up of a trial of quetiapine maintenance, for example, found a higher proportion of people with a poor composite outcome in the group initially randomised to placebo. However, most people classified as showing poor outcome were rated as having a mild score on a single psychotic symptom; there were no differences in overall symptoms, positive or negative symptoms or level of functioning. Moreover, 16% of participants did not have a follow-up interview and data from the end of the original trial were used instead. A study using a Finnish database suggested that mortality and readmission were higher in people who did not start long-term antipsychotic treatment or who discontinued it as compared with long-term continuous users. However, the analysis did not control for important confounders and is likely to reflect the fact that people who do not comply with treatment are at higher risk of death due to underlying health risks and behaviours. The analysis showed a slightly higher risk of readmission among non-users of antipsychotics compared with long-term users and a more substantial increased risk among people who discontinued treatment. However, follow-up ceased at the first readmission and therefore eventual, long-term outcome was not assessed. Speed of reduction and whether it was done with or without clinical support were also not distinguished.

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Thrombophilia and risk of VTE recurrence according to the age at the time of first VTE manifestation

VASA ◽

10.1024/0301-1526/a000447 ◽

2015 ◽

Vol 44 (4) ◽

pp. 313-323 ◽

Cited By ~ 6

Author(s):

Lea Weingarz ◽

Marc Schindewolf ◽

Jan Schwonberg ◽

Carola Hecking ◽

Zsuzsanna Wolf ◽

...

Keyword(s):

Factor V Leiden ◽

Cox Proportional Hazards ◽

First Episode ◽

Factor V ◽

Factor V Leiden Mutation ◽

Younger Patients ◽

Risk Of Recurrence ◽

G20210a Mutation ◽

Increased Risk ◽

The Impact

Abstract. Background: Whether screening for thrombophilia is useful for patients after a first episode of venous thromboembolism (VTE) is a controversial issue. However, the impact of thrombophilia on the risk of recurrence may vary depending on the patient’s age at the time of the first VTE. Patients and methods: Of 1221 VTE patients (42 % males) registered in the MAISTHRO (MAin-ISar-THROmbosis) registry, 261 experienced VTE recurrence during a 5-year follow-up after the discontinuation of anticoagulant therapy. Results: Thrombophilia was more common among patients with VTE recurrence than those without (58.6 % vs. 50.3 %; p = 0.017). Stratifying patients by the age at the time of their initial VTE, Cox proportional hazards analyses adjusted for age, sex and the presence or absence of established risk factors revealed a heterozygous prothrombin (PT) G20210A mutation (hazard ratio (HR) 2.65; 95 %-confidence interval (CI) 1.71 - 4.12; p < 0.001), homozygosity/double heterozygosity for the factor V Leiden and/or PT mutation (HR 2.35; 95 %-CI 1.09 - 5.07, p = 0.030), and an antithrombin deficiency (HR 2.12; 95 %-CI 1.12 - 4.10; p = 0.021) to predict recurrent VTE in patients aged 40 years or older, whereas lupus anticoagulants (HR 3.05; 95%-CI 1.40 - 6.66; p = 0.005) increased the risk of recurrence in younger patients. Subgroup analyses revealed an increased risk of recurrence for a heterozygous factor V Leiden mutation only in young females without hormonal treatment whereas the predictive value of a heterozygous PT mutation was restricted to males over the age of 40 years. Conclusions: Our data do not support a preference of younger patients for thrombophilia testing after a first venous thromboembolic event.

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