ANCA in patients with systemic lupus erythematosus. A cross sectional study in Brazilian patients and review of literature.

BACKGROUND: Antineutrophil cytoplasmatic antibodies (ANCA) have been detected in patients with systemic lupus erythematosus (SLE). In this study, we investigated the presence of ANCA in a sample of Brazilian SLE patients and its possible associations with clinical and serological outcomes. Additionally, we reviewed the literature of on ANCA in SLE. RESULTS: The presence of ANCA was detected in 130 patients using indirect immunofluorescence (IIF). The test was positive in 29.9% of the cases (17.6% pANCA and 11.5% cANCA). Male sex and peripheral vasculitis were more prevalent in the ANCA-positive sample. cANCA was associated with lupus anticoagulant and pANCA had a positive association with peripheral vasculitis and a negative association with anti- SSB/La antibodies. In the 22 studies included in the literature review, a wide range of ANCA positivity was found (13% to 81.1% by IIF and 0 to 22.2% by ELISA). ANCA was associated with renal damage in the Asian population. Although other associations have been found in isolated studies, they were not consistently reported. CONCLUSIONS: The ANCA prevalence found in this Brazilian sample was within the range reported in the literature and these autoantibodies were more frequent in males and in patients with vasculitis. The literature showed controversial results on the association between ANCA and SLE disease activity or clinical characteristics.

Mannose Binding Lectin and C3 Serum Levels in Coronary Artery Disease: A Cross-Sectional Study.

BACKGROUND: The process of tissue injury in coronary artery disease (CAD) has been associated with activation of the complement system, partly due to the action of mannose-binding lectin (MBL) and C3, which are expressed in atherosclerotic lesions. OBJECTIVE: The aim of this study was to evaluate the serum levels of MBL and C3 in patients with CAD and to compare them with healthy controls. Additionally, we aim to assess the correlation between MBL and C3 levels and cardiometabolic parameters. METHODS: MBL and C3 serum concentration were determined by ELISA and immunoturbidimetry, respectively, in up to 119 patients undergoing coronary angiography for CAD evaluation, comprising 48 individuals diagnosed with acute myocardial infarction (MI) and 71 without MI. A total of 93 paired healthy controls were included in the study. RESULTS: Individuals with CAD had MBL serum concentration higher than controls (p = .002), regardless of the presence of MI (p = .006). In addition, high concentration of MBL (>2000 ng/mL) was more frequent in patients with CAD (p = .007; OR = 2.6; 95% CI = 1.3-5.1). C3 levels were not significantly associated with any of the patient groups but were positively correlated with cardiometabolic parameters such as body mass index (BMI) and triglycerides levels. CONCLUSIONS: Higher concentrations of MBL were found to be associated with CAD, whereas C3 levels were found to be associated with cardiovascular risk factors.

Alexithymia in systemic lupus erythematosus: A cross sectional study in a Brazilian sample.

BACKGROUND: Alexithymia is considered as a reduced capacity to be aware of, to clearly recognize, and to define one's feelings with a limited fantasy and a concrete, externally oriented cognitive style. Some studies have stated that alexithymia is more common in systemic lupus erythematosus patients (SLE) than in general population but there is a paucity of studies in such context. AIM: To study the prevalence of alexithymia in a sample of SLE patients looking for associated epidemiological and clinical findings and its relationship to quality of life. METHODS: Cross-sectional study in 93 SLE patients collecting clinical, epidemiological, and serological data, data on quality of life by 12 item short health survey (SF-12), and alexithymia by Toronto scale (TAS-26). Disease's cumulative damage was measured by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage index. RESULTS: In this sample (90.3% females and median age of 46 years), 55.9% had alexithymia; 22/92 (23.9%) did not and 19/93 (20.4%) had inconclusive results. Alexithymia presence had a positive association with age (p = 0.01) and a negative association with presence of glomerulonephritis (25% vs 59%; p = 0.005) and glucocorticoid use (19.2% vs 59.0%; p = 0.0007). A negative correlation of TAS-26 was observed with mental domain of (r = -0.46; p < 0.0001) and physical domain (r = -0.32; p = 0.004) of SF-12, but not with cumulative damage index. CONCLUSION: We found a high prevalence of alexithymia in this sample of SLE patients that negatively associated with quality of life, but not with cumulative damage index.

Cognitive dysfunction in patients with systemic lupus erythematosus. A cross-sectional study in a Brazilian sample.

BACKGROUND: Cognitive dysfunction (CD) is frequently found in patients with systemic lupus erythematosus (SLE) and contributes to impairment in the patient's quality of life. AIM: To study CD in a sample of patients and the possible associations with cumulative damage, disease activity, clinical/serological profile, and cumulative glucocorticoid dose. METHODS: Included in this study are 103 patients with SLE and 95 controls for cognitive performance through MoCA (Montreal Cognitive Assessment) and MMSE (Mini-Mental State Examination). Disease activity was measured by SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) and cumulative organ damage by SLICC/ACR/DI (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index). CES-D (Center for Epidemiological Studies-Depression) scale was used to evaluate depression. Data on clinical and serological profile, treatment, and cumulative glucocorticoid dose were also collected. RESULTS: Patients with SLE had worse performance in the MoCA (p = 0.009) and MMSE (p = 0.01) than controls. The MoCA results showed that visuospatial and abstraction domains (p = 0.03 and p = 0.002, respectively) were impaired, and the MMSE results showed that language and spatial orientation were reduced (p = 0.002 and p = 0.01, respectively) when compared to controls. Both questionnaires (MoCA with r = -0.29 and MMSE r = -0.21) correlated negatively with SLICC/ACR/DI and the MoCA with SLEDAI (r = -0.22). No associations were found with cumulative glucocorticoid dose, degree of depression, and clinical or serological profile. CONCLUSIONS: According to the MoCA, visuospatial cognition and abstraction were impaired, and according to the MMSE, spatial orientation and language were impaired in patients with SLE. The CD was correlated with cumulative damage and disease activity. These findings demonstrate that both disease-activity and disease-injury associated CD is found broadly in SLE patients in a Brazilian population, supporting the prior reports of CD in other regional SLE populations.

Concerns Regarding Gynecological Aspects of Brazilian Girls and Women With Down Syndrome: A Cross-Sectional Study of Caregivers' Opinions.

PURPOSE: Girls and women with Down syndrome (DS) and their caregivers may have more difficulties in dealing with puberty, menstruation, and sexuality than those without DS. Our aim was to understand the concerns of these caregivers about gynecological aspects, including menstruation, contraception, and sexual practice. METHODS: We performed a cross-sectional study that included caregivers of females with DS aged 9 years or older and both in pre- and post-menarche. The caregivers answered a questionnaire about their concerns regarding puberty, menstruation, sexuality, and contraception methods. RESULTS: We enrolled 100 caregivers of females with DS. Caregivers' major concern was menstrual bleeding. Most caregivers (57%) would not prohibit romantic relationships, including sexual relationships. Of the care recipients, 78 had reached menarche and their most common complaints were pain and behavioral changes. Regarding sexual behavior, 2% had already had sexual intercourse. Contraception was used by 14 of the 78 (17.9%) post-menarche females with weight gain as the most common side effect (43%). CONCLUSIONS: In our sample, females with DS had sexual development comparable to those without the syndrome. As these females become increasingly independent, it is necessary to guide caregivers and primary care physicians, especially gynecologists, about the difficulties related to the menstrual period.

C5a Serum Levels in Patients with Endometriosis: A Cross-Sectional Study.

Endometriosis (EM) is a gynecological disorder that presents significant immune dysregulation in its pathophysiology. Recent studies indicate that the Complement System may play a significant role in the immune processes involved in peritoneal clearance and inflammation in EM patients. C5a is a potent anaphylatoxin molecule of complement associated with the development of inflammatory disorders, however its possible impact on EM development requires further investigation. The aim of this study was to determine the concentration of serum C5a in women with EM and to investigate its possible association with severity, symptoms, age and the timing of infertility. Ninety-four patients with EM (from stage I to IV) and 50 healthy controls were assessed for C5a serum levels. Clinical and demographic data were included in the analysis. C5a serum levels were higher in patients with EM than in controls (39.5 ng/mL vs. 26.0 ng/mL; p < .0001), but not different between the EM stages. No association was observed between C5a serum concentration and the presence of symptoms, age, symptom time or infertility time. The C5a serum levels were higher in patients with EM than in controls but not associated with the severity or clinical findings.

Intestinal histological findings in patients with spondyloarthritis: a study of the relationship with disease activity.

The role of intestinal microbioma and subclinical bowel inflammation in the etiology of sponsyloarthritis (SpA) has gained a lot of attention recently. Almost 65% of SpA patients will have asymptomatic bowel inflammation if assessed by ileocolonoscopy. The connection between intestinal inflammation and SpA originated the gut-joint axis hypothesis in which monocytes and T cells found in the joint would have origin in the gut.

Seropositivity for syphilis among Brazilian blood donors. A retrospective study 2015-2020.

INTRODUCTION: Syphilis is a transfusion-transmitted infection and the disease re-emerged in many countries, including Brazil, as a public health risk. OBJECTIVE: Evaluate the prevalence of positive serology in blood donations rejected by Hemobanco (Curitiba- PR) from January 2015 to December 2020, with special focus in syphilis. METHODOLOGY: In the studied period, we analyzed the number of blood donations discarded annually for each serological test performed on blood donors' samples, according to gender and donors age. RESULTS: Within the studied period, 134,741 blood donation were analyzed. 54.5 % of sample were male. Otherwise, it was observed a significant increase in the number of donations by females (P < 0.0001). There was an increase of 437 % in the prevalence of syphilis positive serology made by donors with ≥ 60 years. Besides that, it was noticed a significant increase in donations by aged people throughout these six years (P < 0.0001). The percentage of total blood donation deferred had a significant reduction, although it was observed an increase in the rate of discarded blood bags due to positive serology in the first 4 studied years. It was observed an increase of 20 % in positive syphilis serology. CONCLUSION: The greatest cause of discard of blood donations changed during the analyzed 5-years; there was an increase in seropositivity donations from donors with ≥ 60 years old. In 2015, Hepatitis B (0.8 %) was the most prevalent and in 2020, syphilis became more prevalent (0.82 %). The medical community should be aware of the rising number of cases of syphilis infection. There is an urgent need to implement actions against the dissemination of this disease.

Impact of assisted reproduction treatment on sexual function of patients diagnosed with infertility.

PURPOSE: This study aims to update and systematize the existing evidence on the prevalence of sexual dysfunction and depression in infertile couple Renatos undergoing assisted reproduction treatments. METHODS: A bibliographic search regarding sexual dysfunction in infertile couples was performed on PubMed and LILACS, with no restrictions on the date of publication of the article. The Newcastle-Ottawa Scale (NOS) was used to evaluate studies quality. Data collection process was conducted using a form previously planned and tested, extracting the goal information in a descriptive way. RESULTS: From 111 records, only eight prospective studies were included in the synthesis. Although most of the selected studies assessed only women, three studies assessed the couple. All of them used questionnaires that showed that infertile couples experienced a higher number of sexual dysfunctions during the infertility treatment process, especially women. Regarding depression, going through the infertility process and its treatment leads to significant emotional damage to the patient or couple. CONCLUSION: Of the eight studies analyzed, six reached the conclusion that infertility is related to higher rates of sexual dysfunction. Seven studies also concluded that anxiety and depression are more prevalent in infertile patients. The treatment of sexual dysfunction is multidisciplinary, with the team being a general practitioner, gynecologist, psychologist and specialized nurse. If an organic disorder is detected, there may be a need to include specialists such as urology, gastroenterology and anesthesia. Psychological approaches often include some combination of sex education, identification of emotional and cultural factors, and eventually, couples therapy.

Upper gastrointestinal complaints in celiac patients at diagnosis. Association with endoscopic and histopathological findings.

This study investigated the prevalence of upper gastrointestinal symptoms in Brazilian patients at the time of diagnosis with celiac disease (CD), associating them with endoscopic and histopathological findings. A retrospective study was performed including adult patients diagnosed with CD from January 2013 to December 2019.

Gynecological Care for Women With Intellectual Disabilities: A Brazilian Study.

We aimed to identify the main challenges in the gynecological care and management of patients with intellectual disability by gynecologists. Gynecologists answered to online questionnaires about situations in which the professional reports their confidence in caring for patients with intellectual disability. Were studied 143 responses, 75% women. Among them, 53.8% felt apprehensive to conduct a routine gynecological screening, 60% were confident in advising about contraceptive services and examining the genitals. The greatest difficulty was indicating drugs to suppress menstruation and managing patients with severe intellectual disability. The female doctors were more prepared in the care of disability patients and recent certified gynecologists were more insecure. The main difficulty was time for examinations (39.2%) and the main solution was to improve medical training (64.2%). The main challenges of the gynecologist included the amount of time needed to provide clinical services, the lack of knowledge and skill; and ethical concerns.

Systemic lupus erythematosus in children and adults: A retrospective study in Brazilian patients.

BACKGROUND: Systemic lupus erythematosus (SLE) may have a different serological and clinical profile according to age of disease onset. AIM: To compare clinical presentation and serological data from patients with SLE onset in childhood (cSLE) with disease onset in adulthood (aSLE) in a sample of Brazilian patients. METHODS: Retrospective study of 614 SLE patients from a single Rheumatology Unit from Brazil: 77 (12.5%) cSLE and 537 (87.4%) aSLE. Clinical and serological data were obtained from the charts. Comparisons of cSLE with aSLE in general and according to patient's gender were made. RESULTS: The comparison of whole sample showed that children had more malar rash (p = 0.04), seizures (p < 0.0001), psychosis (p = 0.02), glomerulonephritis (p = 0.001), anti-dsDNA (p = 0.008), anticardiolipin IgM (p = 0.04) but less discoid lesions (p = 0.01), anti-Ro (p < 0.0001) and anti-La antibodies (p = 0.007). When only the male sample was compared, no differences in glomerulonephritis and anti-dsDNA frequencies were found. CONCLUSION: Children had a higher frequency of severe manifestations (glomerulonephritis and central nervous system) than adults. The difference in glomerulonephritis occurrence disappeared when only males were compared.

Fibromyalgia and sexual performance: a cross-sectional study in 726 Brazilian patients.

Fibromyalgia (FM) causes generalized musculoskeletal pain and sexual life may also be impaired in these patients. We aimed to study sexual performance in FM patients comparing them with healthy controls and verify if there is association of epidemiological variables, degree of musculoskeletal pain and associated diseases with sexual performance in this group of patients. This is a cross-sectional study based in an internet survey. FM and controls filled a questionnaire on epidemiological data, associated diseases, and musculoskeletal pain. Also answered the validate questionnaires Female Sexual Function Index (FSFI) and the Sexual Quotient-Females (SQ-F) to evaluate the sexual performance. The survey was answered for 1584 individuals: 726 FM patients and 858 paired controls. Sexual performance evaluated by FSFI and by SQ-F was worse in the FM group than controls in all studied domains (all with p < 0.0001). According to SQ-F, 63% of them had a regular to null performance; according to FSFI, 83% had sexual dysfunction. Sexual performance was worse in those on menopause (< 0.0001). A modest correlation of age (rho - 0.09 for SQ-F and - 0.10 for FSFI) and degree of musculoskeletal pain (rho = - 0.21 for SQ-F and - 0.23 for FSFI) with sexual performance indexes were found. Psychiatric illness was also associated with lower SQ-F (p = 0.001). There is a high prevalence of sexual dysfunction in FM that associates with the presence of menopause, psychiatric comorbidities, older age, and high degree of musculoskeletal pain.

Sleep Disturbance in Scleroderma.

INTRODUCTION: Sleep quality may be impaired in systemic scleroderma (SSc) patients and contribute to loss of life quality. AIM: The aims of this study were to study the prevalence of sleep disturbance in SSc patients and its possible association with epidemiological, clinical and laboratory data, treatment used, and depression, and to verify the association of sleep disturbance and quality of life in this group of patients. METHODS: This is a cross-sectional study including 60 SSc patients. Epidemiological, clinical, laboratory, and treatment data were extracted from the medical records. To evaluate sleep quality, the PSQI (Pittsburgh Sleep Quality Index) was used; to evaluate depression, the CES-D (Center for Epidemiological Scale-Depression) was used; and to evaluate quality of life, SF-12 (12-Item Short-Form Health Survey) was used. Disease severity was evaluated by the Medsger index and the degree of cutaneous involvement by the modified Rodnan index. RESULTS: The prevalence of patients with sleep disturbance was 73.3%. Sleep disturbance was associated with esophageal involvement (p = 0.03), Medsger index with higher disease severity (p = 0.01), and more depressive mood (p = 0.002). Patients with poor quality of sleep had worse quality of life by the SF-12 in mental (p = 0.001) and physical domains (p = 0.0008). No associations were found with epidemiological, serological, and treatment variables (all P's = nonsignificant). CONCLUSIONS: There is a high prevalence of sleep disturbance in patients with SSc that is associated with esophageal involvement, severity of disease, depression, and worse quality of life.

Dry eye and percentage of body fat: a cross-sectional prospective study.

BACKGROUND: Dry eyes are common in the general population. Some studies associate high prevalence of dry eyes with lipid metabolic changes and body fat composition. AIM: To study the association of dry eye with percentage of body fat. METHODS: One hundred and thirty five individuals (44 males and 91 females; median age of 42 years) were studied in a cross-sectional prospective study. Schirmer test and TBUT (tear breakup time) test were used to access dry eye. Body composition (percentage of lean and fat mass) were calculated using anthropometric measurements that included height, weight, abdominal, waist and neck circumference. RESULTS: About 44.4% of the sample had abnormal Schirmer test, and 70.3% had abnormal TBUT. Schirmer tests values were associated with age (p = 0.0006) female gender (p = 0.04) and percentage of body fat (p = 0.02). Abnormal TBUT test associated only with age (p = 0.0005). CONCLUSIONS: Percentage of body fat is associated with abnormal Schirmer but not TBUT test.

Management of contraceptives and menstrual complaints in patients with Down syndrome.

Enhanced health care for patients with Down syndrome (DS) results in improved overall quality of life and longer life expectancy. The main gynecologic complaints of patients with DS and their caregivers relate to menstrual cycles, hygiene and reproductive issues. Certain aspects, such as age of menarche, menstrual cycles, internal genitalia, and hormone profile are similar to those observed in the general population. However, individuals with DS may have a higher incidence of other disorders related to menstruation, such as hypothyroidism, epilepsy and use of anticonvulsants. Contraceptive measures for individuals with DS can be used for both contraception and control of menstrual symptoms. The physician must be to make an individualized recommendation aimed at offering the most efficient and least invasive method with the fewest side effects. Among medical options are oral contraceptives, quarterly injectable medroxyprogesterone acetate, oral progesterone, a levonorgestrel-releasing intrauterine system, transdermal patch and vaginal rings. Surgical methods, including hysterectomy, endometrial ablation, or tubal ligation, are rarely considered because they raise ethical and legal questions. This article reviews the literature and basic guidelines to assist physicians who attend adolescent girls and women with DS to provide guidance on the appropriate management of the main gynecologic complaints of this population.

Rheumatoid arthritis and cognition dysfunction: lack of association with cumulative glucocorticoid use.

Aim: To study if cumulative glucocorticoid use could be related to cognitive impairment in rheumatoid arthritis (RA) patients.Methods: A sample of 60 RA patients and 64 controls were studied for the Mini Mental State Examination (MMSE) and depression scale (using CES-D or Center for Epidemiological Studies Depression scale). RA patients also filled a visual analogic scale (VAS) of pain and had disease activity evaluated by DAS-28 ESR (disease activity score using erythrocyte sedimentation rate). Clinical and treatment data, including cumulative dose of glucocorticoid, were collected from the charts.Results: Patients with RA had more cognitive impairment and depression than controls (p = .002 and .03, respectively). A weak and negative association of MMSE with VAS of pain was found (rho= -0.16; 95%CI = 0.49-0.004; p = .04) but not with depression and cumulative glucocorticoid doses (p = .22 and p = .52, respectively).Conclusion: Although RA patients have more cognitive impairment than controls, no correlation of this problem with cumulative glucocorticoid doses was found.

ASCA (Anti-Saccharomyces cerevisiae Antibody) in Patients With Scleroderma.

OBJECTIVES: The majority of scleroderma (SSc) patients present gastrointestinal involvement. Motility is usually compromised but few studies address permeability changes in the intestinal wall. ASCA (anti-Saccharomyces cerevisiae antibodies) positivity is associated with increased intestinal permeability. In this study we aimed to investigate ASCA positivity in SSc patients and its association with clinical, serological and epidemiological data. METHODS: Seventy-four SSc patients and 57 healthy controls were studied for ASCA (IgG and IgA) positivity by ELISA. ASCA positivity was associated with demographic, clinical severity index (by Medsger score) and serological data in SSc patients. RESULTS: ASCA-IgG was positive in 32/74 (43.2%) patients of the SSc group and 1/57 (1.7%) of controls (p < 0.0001); ASCA-IgA was positive in 12/74 (16.2%) of the SSc group and 3/57 (5.2%) of controls (p = 0.05). In univariate analysis, ASCA-IgG presence was associated positively with African ethnic background (p < 0.001) and negatively associated with anticentromere antibodies (p = 0.013); ASCA-IgA had a negative association with Medsger score (p = 0.05). In multivariate analysis ASCA-IgG associated independently only with African ethnic background. CONCLUSION: Positivity for ASCA-IgG and ASCA-IgA is higher among scleroderma patients than controls. African descendants have more positivity for ASCA-IgG. ASCA-IgA is less frequent in patients with a more severe disease.

Plasma levels of pentraxin 3 in patients with spondyloarthritis.

CONTEXT: Determining the disease's inflammatory activity in spondyloarthritis (SpA) is difficult although very important as it is this that drives treatment. OBJECTIVE: To investigate if plasma pentraxin-3 (PTX3) could act as an inflammatory marker in SpA. METHODS: Eighty one SpA patients (11 with psoriatic arthritis (PsoA) and 70 with ankylosing spondylitis (AS)) and 90 gender and age paired controls were studied for plasma PTX3 levels by ELISA. Patients had determinations of disease activity through C reactive protein (CRP), erythrocyte sedimentation rate (ESR), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP. Epidemiological, clinical and treatment data were collected through chart review. RESULTS: SpA patients had lower concentrations of plasma PTX3 than controls (median of 0.95 ng/mL vs 1.64 ng/mL; p < 0.0001). Correlation of PTX3 levels and BASDAI, ASDAS-CPR, CRP levels and ESR could not be found. No differences in PTX3 levels were detected between PSoA and AS patients (p = 0.42). Uveitis, presence of HLA B27, tobacco exposure, age and disease duration did not influence PTX3 levels. CONCLUSIONS: PTX3 plasma levels do not reflect disease activity in SpA. However, it probably participates in the ethiopathogenetic process, as it is consumed in these patients.

Rheumatic Disease Autoantibodies in Patients with Autoimmune Thyroid Diseases.

BACKGROUND: Patients with autoimmune thyroid diseases (ATD) such as Graves' disease (GD) and Hashimoto thyroiditis (HT) may have non-organ specific autoantibodies such as antinuclear antibodies (ANA) and rheumatoid factor (RF). AIM: To study the prevalence of rheumatic autoantibodies in a group of ATD patients without known rheumatic diseases and to evaluate its association with the patients' epidemiological and treatment profiles. To follow positive non-organ specific autoantibody-positive ATD individuals to investigate whether they will develop a rheumatic disorder. METHODS: A sample of 154 ATD patients (70 HT and 84 GD; mean age 45.3 ± 14.2) had determination of ANA by immunofluorescence, using hep-2 cells as substrate, extractable nuclear antigen profile by ELISA kits and RF by latex agglutination. Epidemiological and treatment profiles were obtained through chart review. These patients were followed for the mean period of 5 years, between 2010 and 2015. RESULTS: Positive ANA was found in 17.5% (27/154) of the patients: anti-Ro/SS-A in 4/154 (2.5%); anti-RNP in 4/154 (2.5%), and anti-La/SS-B in 3/154 (1.9%). None had anti-Sm antibodies. RF was detected in 12/154 (7.7%) of ATD patients and was more common in older individuals (p = 0.007). There was a positive association between the presence of RF and ANA (p = 0.03; OR 3.89; 95% CI 1.1-13.3). None of the patients with positive autoantibodies developed clinical rheumatic diseases during the period of observation. CONCLUSION: We found rheumatic autoantibodies in 17.5% of ATD patients without rheumatic diseases. None of them were associated with the appearance of clinical rheumatic disorder during the period of 5 years.