The contribution of first-episode illness characteristics and cumulative antipsychotic usage to progressive structural brain changes over a long-term follow-up in schizophrenia.

Exposure to antipsychotics as well as certain first-episode illness characteristics have been associated with greater gray matter (GM) deficits in the early phase of schizophrenia. Whether the first-episode illness characteristics affect the long-term progression of the structural brain changes remain unexplored. We therefore assessed the role of first-episode illness characteristics and life-time antipsychotic use in relation to long-term structural brain GM changes in schizophrenia. Individuals with schizophrenia (SZ, n = 29) and non-psychotic controls (n = 61) from the Northern Finland Birth Cohort 1966 underwent structural MRI at the ages of 34 (baseline) and 43 (follow-up) years. At follow-up, the average duration of illness was 19.8 years. Voxel-based morphometry was used to assess the effects of predictors on longitudinal GM changes in schizophrenia-relevant brain areas. Younger age of onset (AoO), higher cumulative antipsychotic dose and severity of symptoms were associated with greater GM deficits in the SZ group at follow-up. None of the first-episode illness characteristics were associated with longitudinal GM changes during 9-year follow-up period. We conclude that a younger AoO and high life-time antipsychotic use may contribute to progression of structural brain changes in schizophrenia. Apart from AoO, other first-episode illness characteristics may not contribute to longitudinal GM changes in midlife.

Long-Term Follow-Up After Maxillary Sinus Balloon Sinuplasty and ESS.

OBJECTIVES: The aim of this controlled follow-up study was to compare the need for revision surgery, long-term efficacy, and satisfaction in chronic rhinosinusitis patients who had undergone maxillary sinus operation with either balloon sinuplasty or traditional endoscopic sinus surgery (ESS) technique. METHODS: Thirty-nine ESS patients and 36 balloon patients of our previously described cohort, who had been primarily operated in 2008 to 2010, were contacted by phone. Symptoms, satisfaction, and need for revision surgery were asked. In addition, we collected data of patients who had undergone primary maxillary sinus balloon sinuplasty in the Helsinki University Hospital during the years 2005 to 2019. As a control group, we collected data of patients who had undergone primary maxillary sinus ESS at 3 Finnish University Hospitals, and 1 Central Hospital in years 2005, 2008, and 2011. RESULTS: Altogether, 77 balloon patients and 82 ESS patients were included. The mean follow-up time was 5.3 years in balloon group and 9.8 years in ESS group. Revision surgery was performed on 17 balloon patients and 6 ESS patients. In the survival analysis, the balloon sinuplasty associated significantly with a higher risk of revision surgery compared to ESS. According to the phone interviews, 82% of ESS patients and 75% of balloon patients were very satisfied with the primary operation. CONCLUSION: Although the patient groups expressed equal satisfaction and change in symptoms after the operations, the need for revision surgery was higher after balloon sinuplasty than after ESS. This should be emphasized when counselling patients regarding surgical options.

Early Adversity and Emotion Processing From Faces: A Meta-analysis on Behavioral and Neurophysiological Responses.

BACKGROUND: Although the link between early adversity (EA) and later-life psychiatric disorders is well established, it has yet to be elucidated whether EA is related to distortions in the processing of different facial expressions. We conducted a meta-analysis to investigate whether exposure to EA relates to distortions in responses to different facial emotions at three levels: 1) event-related potentials of the P100 and N170, 2) amygdala functional magnetic resonance imaging responses, and 3) accuracy rate or reaction time in behavioral data. METHODS: The systematic literature search (PubMed and Web of Science) up to April 2020 resulted in 29 behavioral studies (n = 8555), 32 functional magnetic resonance imaging studies (n = 2771), and 3 electroencephalography studies (n = 197) for random-effect meta-analyses. RESULTS: EA was related to heightened bilateral amygdala reactivity to sad faces (but not other facial emotions). Exposure to EA was related to faster reaction time but a normal accuracy rate in response to angry and sad faces. In response to fearful and happy faces, EA was related to a lower accuracy rate only in individuals with recent EA exposure. This effect was more pronounced in individuals with exposure to EA before (vs. after) the age of 3 years. These findings were independent of psychiatric diagnoses. Because of the low number of eligible electroencephalography studies, no conclusions could be reached regarding the effect of EA on the event-related potentials. CONCLUSIONS: EA relates to alterations in behavioral and neurophysiological processing of facial emotions. Our study stresses the importance of assessing age at exposure and time since EA because these factors mediate some EA-related perturbations.

Return to the labour market in schizophrenia and other psychoses: a register-based Northern Finland Birth Cohort 1966 study.

PURPOSE: The prospects and predictors of returning to the labour market after long-term work disability in psychoses are unclear. Our aim was to study the proportion and characteristics of persons with schizophrenia and other psychoses who return to the labour market after receiving a disability pension. METHODS: In this 50-year follow-up study in the Northern Finland Birth Cohort 1966 (NFBC1966), national registers on demographics, care, and disability pensions were used to detect and characterize individuals who had been on a disability pension for psychiatric reasons. We compared individuals with schizophrenia (SZ, n = 223) or other psychoses (OP, n = 200) to those with non-psychotic psychiatric disorders (NP, n = 1815) regarding demographics and end of pension by cross-tabulations and logistic regression. RESULTS: Of the 170 (74%) persons with SZ who had been on disability pension for a psychiatric reason, 15 (9%) returned to the labour market. Corresponding percentages were 19% for OP and 28% for NP. In SZ, being married, a later onset age of psychosis, and better school performance, and in OP and NP, having children predicted returning to the labour market. In all groups, a shorter length of the latest disability pension associated with returning to the labour market. CONCLUSION: Although rare, it is possible to return to the labour market after a disability pension due to psychosis. Factors predicting a return to the labour market could be taken into account when planning rehabilitation.

Accessory maxillary ostium repair using middle turbinate flap: a case series of 116 patients with chronic rhinosinusitis.

BACKGROUND: The ostiomeatal complex (OMC), comprising a small natural maxillary sinus ostium and narrow infundibulum, transmits the air diffusion into the antrum and mucociliary transport from the antrum, and is considered a key area in chronic rhinosinusitis (CRS). Thin membranous anterior and posterior fontanelle areas below the OMC can rupture forming a perforation, accessory maxillary ostium (AMO), that increases antral airflow changing the anatomy and function of the sinus. The purpose of this study was to report the first case series of CRS patients who had undergone repair of fontanelle defects aiming to reconstruct normal structures. METHODS: Between 2011 and 2017, a total of 157 perforations were diagnosed and repaired in 121 of 525 consecutive endoscopic sinus operations performed by the author. Defects were 3 mm to 4 mm in size (range, 1 mm to 7 mm). A flap cut from the undersurface of the middle turbinate was used. In total, 101 patients received concurrent balloon catheter dilation (BCD), while 15 patients had only an AMO repair. The mean endoscopic follow-up time was 16 weeks (range, 1 to 188 weeks). RESULTS: Overall, 101 perforations were closed, 21 open, and 17 partially open. A history of earlier endoscopic sinus surgery (ESS) or BCD surgery, presence of nasal polyposis or whether the repair was made without simultaneous BCD did not influence the closure rate. Postoperative febrile sinusitis occurred in 26 patients. CONCLUSION: Repair of AMO is in theory a beneficial and technically feasible office procedure with only transient side effects. Three out of 4 perforations were closed after repair.

Comparison of intra-operative characteristics and early post-operative outcomes between endoscopic sinus surgery and balloon sinuplasty.

CONCLUSION: In terms of operation time, anesthesia method, and low complication rate, ESS and balloon sinuplasty seemed comparable. The advantages of balloon sinuplasty were shown to be shortness of sick leave, possibility to be performed as an in-office procedure, and lower adhesion formation. BACKGROUND: Endoscopic sinus surgery (ESS) has been considered as a treatment of choice for persistent chronic rhinosinusitis (CRS). During the last decade balloon sinuplasty has been introduced as an alternative technique to dilate the ostium. Although balloon sinuplasty is considered relatively safe and efficient, comparative evidence of its putative intra-operative and post-operative advantages remain limited. OBJECTIVES: The aim of this retrospective controlled study was to evaluate intra-operative factors and early post-operative outcomes among CRS patients who had undergone maxillary sinus operation with either balloon sinuplasty or ESS technique. MATERIALS AND METHODS: Data were collected from 208 patients with CRS treated either with ESS or balloon sinuplasty during the years 2008-2010. Intra- and peri-operative factors were collected from patient records of the patients who met the inclusion criteria (n = 39 in ESS group and n = 36 in balloon sinuplasty group). RESULTS: There was no significant difference in operation time and anesthesia method between the two groups. No complications occurred with either technique. All ESS procedures and 67% of the balloon sinuplasty procedures were done in the hospital setting, whereas 33% of the balloon sinuplasty procedures were done in the office setting. The duration of sick leave and the number of patients with adhesions were significantly higher in the ESS group compared to the balloon sinuplasty group.

Prognosis of schizophrenia spectrum disorder may not be predetermined during early development--the Northern Finland Birth Cohort 1966.

BACKGROUND: Little is known about whether factors during the first years of life predict later outcomes in schizophrenia spectrum disorder (SSD). As part of the Northern Finland Birth Cohort 1966, we examined if prospectively collected early parenthood-related and developmental factors predict employment and hospitalization in individuals with and without SSD. METHODS: Overall, 161 individuals with SSD and 10,116 without SSD were included in the study. Outcomes were analysed at age of 44-45years, defining "employment" as being employed for at least 25% of working days and "hospitalization" as having psychiatric hospitalization at least once during the last two years of follow-up. Maternal age, wantedness of pregnancy, grand multiparity, parental psychoses, birth weight, birth height, age of standing up and standing and walking without support were analysed as predictors. RESULTS: Of the individuals with SSD, only 11.2% were employed, although 77.6% remained not hospitalized. In individuals with SSD, only young maternal age was associated with lower probability (OR 0.25, CI 0.08-0.77) of being non-hospitalized after controlling for sex and onset age of illness. Among persons without SSD, almost all parenthood-related and developmental factors were related to employment, while grand multiparity and parental psychosis were related to hospitalization after controlling for sex. CONCLUSIONS: Only one of the early parenthood-related and developmental factors analysed in this study predicted outcome in individuals with SSD, while among those without SSD almost all factors were related to employment. Thus, prognosis of SSD does not seem to be predetermined much by early development.

Long-term follow-up after ESS and balloon sinuplasty: Comparison of symptom reduction and patient satisfaction.

CONCLUSION: This is the first controlled study of balloon sinuplasty's long-term efficacy with the follow-up time over 5 years. The results are in accordance with a previous 2-year-follow-up study. Both techniques retained the efficacy and patient satisfaction on average 6 years after the surgery. BACKGROUND: Endoscopic sinus surgery (ESS) and balloon sinuplasty are considered as a treatment for chronic rhinosinusitis (CRS) after a failure of conservative therapy. High cost and lack of long-term follow-up studies restrain the use of balloon sinuplasty. OBJECTIVE: The aim of this study was to compare long-term efficacy and satisfaction in CRS patients who had undergone maxillary sinus operation with either balloon sinuplasty or ESS technique. Previous or additional sinonasal operations were exclusion criteria. MATERIALS AND METHODS: Study patients were recruited from 208 CRS-patients who underwent either ESS or balloon sinuplasty. Patients with nasal polyposis (gradus ≥ 2), previous sinonasal surgery, unilateral disease, or immune deficiency were excluded. Altogether 45 patients in the ESS group and 40 patients in the balloon group were included. Of these, 30 and 28, respectively, answered to a phone interview held on average 6 years after primary surgery. Symptom reduction and long-term satisfaction were evaluated by using symptom scores of 19 parameters altogether. RESULTS: Both groups experienced improvement in symptoms and were equally satisfied with the operation. The number of patient-reported acute exacerbations was higher among the balloon dilated patients. Also, the reduction of thick nasal discharge was less evident in the balloon sinuplasty group. Four patients in the balloon sinuplasty group underwent revision surgery. There were no revisions in the ESS group.

Factors affecting revision rate of chronic rhinosinusitis.

OBJECTIVE: Chronic rhinosinusitis (CRS) is a variable multifactorial disease. It can be divided into forms with nasal polyps (CRSwNP) and without (CRSsNP). Sinus and/or nasal polypectomy surgery are considered if maximal conservative treatment is insufficient. The predictive factors of the need of revision surgery comprise mostly the CRSwNP phenotype and are not fully understood. STUDY DESIGN: The aim of this follow-up study was to evaluate the factors associated with the revision surgery rate in CRS patients with variable extent of disease. METHODS: Data of CRS patients (N = 178) undergoing sinus surgery and/or nasal polypectomy in 2001 to 2010 were used. Patient characteristics and follow-up data were collected from patient records and questionnaires. Associations were analyzed by Fisher's exact, Mann Whitney U, and the Kaplan-Meier method with log-rank test. Unadjusted Cox's proportional hazard models were used for 12 variables and were fitted for the need for revision sinus surgery and/or nasal polypectomy during follow-up of in average 9 years. RESULTS: The proportion of CRS patients who had undergone revision in 5 years was 9.6%. After adjustment, the following factors associated significantly with the need for recurrent CRS surgery: allergic rhinitis, corticosteroid treatment, previous surgery of CRS, and recurrent NP. CONCLUSION: Increased risk of progressive CRS phenotypes with the need for revision surgery would putatively be recognized by relatively simple clinical questions. Further studies with increased sample size are needed to evaluate whether these predictive factors would be relevant for developing better detection and management of progressive CRS. LEVEL OF EVIDENCE: 2b.

Use of psychiatric medications in schizophrenia and other psychoses in a general population sample.

The information on the use of psychiatric medications in general population-based samples is limited. Our aim was to analyse the use of psychiatric medications and factors associated with antipsychotic use in psychoses in a general population sample. Fifty-five persons with schizophrenia, 21 with bipolar psychosis or psychotic depression and 20 with other psychoses from the Northern Finland Birth Cohort 1966 were examined at about 43 years of age. The frequency of use and dosage of psychiatric medication and the factors associated with the use of antipsychotics were analysed. Antipsychotics were used by 85% of schizophrenia, 65% of bipolar psychosis or psychotic depression and 62% of other psychoses cases; antidepressants were used by 22%, 60% and 33%; and benzodiazepines by 42%, 35% and 10%, respectively. In all the diagnostic groups, higher symptom scores and a higher number of hospital days were associated with the use of antipsychotics. In schizophrenia and other psychoses, poorer social and occupational functioning, and in other psychoses, female gender and lower education were also associated with the use of antipsychotics. Our results may partly indicate that, especially in schizophrenia, the effectiveness of antipsychotics is not as good as expected.

Twenty Years of Schizophrenia Research in the Northern Finland Birth Cohort 1966: A Systematic Review.

Birth cohort designs are useful in studying adult disease trajectories and outcomes, such as schizophrenia. We review the schizophrenia research performed in the Northern Finland Birth Cohort 1966 (NFBC 1966), which includes 10,934 individuals living in Finland at 16 years of age who have been monitored since each mother's mid-pregnancy. By the age of 44, 150 (1.4%) had developed schizophrenia. There are 77 original papers on schizophrenia published from the NFBC 1966. The early studies have found various risk factors for schizophrenia, especially related to pregnancy and perinatal phase. Psychiatric and somatic outcomes were heterogeneous, but relatively poor. Mortality in schizophrenia is high, especially due to suicides. Several early predictors of outcomes have also been found. Individuals with schizophrenia have alterations in brain morphometry and neurocognition, and our latest studies have found that the use of high lifetime doses of antipsychotics associated with these changes. The schizophrenia research in the NFBC 1966 has been especially active for 20 years, the prospective study design and long follow-up enabling several clinically and epidemiologically important findings. When compared to other birth cohorts, the research in the NFBC 1966 has offered also unique findings on course and outcome of schizophrenia.

Duration of untreated psychosis as predictor of long-term outcome in schizophrenia: systematic review and meta-analysis.

BACKGROUND: Duration of untreated psychosis (DUP) is one of the few potentially modifiable predictors of outcomes of schizophrenia. Long DUP as a predictor of poor short-term outcome has been addressed in previous meta-analyses, but the long-term effects of DUP remain unclear. AIMS: To analyse the associations between DUP and long-term outcomes of schizophrenia. METHOD: A systematic literature search was performed using seven electronic databases and manual searches. Random effects weighted meta-analysis with correlation coefficients was used to pool the results. RESULTS: We identified 3493 unique publications, from which 33 samples met our predefined selection criteria. Long DUP correlated statistically significantly with poor general symptomatic outcome, more severe positive and negative symptoms, lesser likelihood of remission and poor social functioning and global outcome (correlations 0.13-0.18). Long DUP was not associated with employment, quality of life or hospital treatment. CONCLUSIONS: The small but mostly consistent correlation between long DUP and poor outcome indicates that early intervention in psychosis may have at least subtle positive effects on the long-term course of illness.

Association between the duration of untreated psychosis and short- and long-term outcome in schizophrenia within the Northern Finland 1966 Birth Cohort.

BACKGROUND: Long duration of untreated psychosis (DUP) may relate to poor outcome in schizophrenia. However, the associations between DUP and outcomes, particularly in later course of illness, remain unclear. Our aim was to explore the associations between DUP and short- and long-term outcomes in schizophrenia. METHODS: Data was collected for subjects with schizophrenia (n=89) in the population-based Northern Finland 1966 Birth Cohort. DUP was obtained from medical records, and its associations with short- (under 2years) and long-term clinical and social outcomes were assessed extending to 20years after the onset of the illness. RESULTS: Longer DUP predicted longer length of first hospitalisation and increased the risk of rehospitalisation during the first two years. Longer DUP associated with decreased probability of disability pension, smaller amount of time spent in hospital, and higher proportion of time at work during the first 10years of the follow-up. CONCLUSIONS: Regarding early outcome, long DUP may be a modest marker and proxy measure of a more severe clinical phenotype. The divergent results of earlier studies and the association between long DUP and better long-term outcome in our study, indicate that the length of DUP does not necessarily predict poor outcome in long-term follow-up. This may also be due to methodical difficulties, e.g. insufficient power and residual confounding linked to long follow-up studies.

Endoscopic sinus surgery might reduce exacerbations and symptoms more than balloon sinuplasty.

BACKGROUND: Endoscopic sinus surgery (ESS) is considered after medical therapy failure of chronic rhinosinusitis (CRS). The balloon sinuplasty dilates the natural ostium without moving mucosa or bone. It still lacks evidence from randomized controlled trials. The aim of this retrospective controlled study was to compare the symptom outcomes after maxillary sinus surgery with either the ESS or the balloon sinuplasty technique. No previous or additional sinonasal operations were accepted. METHODS: Two hundred eight patients with CRS without nasal polyps underwent either balloon sinuplasty or ESS. The patients who met with the inclusion criteria (n = 45 in ESS group and n = 40 in balloon group) replied to a questionnaire of history factors, exacerbations, and a visual analog scale (VAS) scoring of the change in symptoms, on average 28 ± 6 (mean ± SD) months postoperatively. RESULTS: The groups were identical in the response rate (64%), patient characteristics, and the improvement in all of the asked symptoms. Patients with CRS-related comorbidity and/or present occupational exposure had a statistically significantly better symptom reduction after ESS than after balloon sinusotomy. Moreover, the balloon sinusotomy group reported a statistically significant higher number of maxillary sinus punctures and antibiotic courses during the last 12 months. CONCLUSION: ESS might be superior to balloon sinuplasty, especially in patients with risk factors. There is a need to perform more controlled studies on the treatment choices of CRS.

Association between duration of untreated psychosis and brain morphology in schizophrenia within the Northern Finland 1966 Birth Cohort.

BACKGROUND: Duration of untreated psychosis (DUP) has been linked with poor prognosis and changes in the brain structure in schizophrenia at least at the beginning of the disease, but it is still unknown whether DUP relates to brain morphometry in the longer term. Our aim was to analyze the relation between DUP and the brain structure in schizophrenia in the general population, after several years of illness. METHODS: Brains of subjects with psychosis from the Northern Finland 1966 Birth Cohort (NFBC 1966) were scanned with MRI during 1999-2001 after an 11-year follow-up. DUP was assessed from medical records and regressed against global and local tissue density measurements. The brain morphometric and the DUP information were available for 46 subjects with DSM-III-R schizophrenia. RESULTS: The DUP did not correlate with volumes of the total gray or white matter or the cerebrospinal fluid. The length of DUP associated positively with reduced densities of the right limbic area and the right hippocampus. CONCLUSIONS: Long DUP was slightly associated with reductions of gray matter densities in the limbic area and especially the hippocampus after several years follow-up, supporting the hypothesis that, compared to short DUP, long DUP might be a marker of different disease trajectories including subtle morphometric changes.

Acute sinusitis: Finnish clinical practice guidelines.

These clinical practice guidelines aim at providing assistance mainly to primary health care physicians for the diagnosis and management of acute sinusitis. Despite the huge impact of upper respiratory infections, criteria for diagnoses are often vague, and physicians are often uncertain of their diagnoses. This is not surprising, as the sole definition of acute sinusitis is somewhat confusing, not to mention the existing discrepancies between treatments, even among specialists. The Finnish Society of Otorhinolaryngology has set up a committee to evaluate existing data on acute sinusitis and to formulate these guidelines. The committee comprised Finnish experts in adult and paediatric otorhinolaryngology, clinical microbiology, radiology, paediatrics, and epidemiology. Recommendations given are based on the principles of evidence-based medicine, with the level of evidence presented.

Local anesthesia with EMLA cream for maxillary sinus puncture.

Maxillary sinus puncture is traditionally carried out through the lateral wall of the inferior nasal meatus under local anesthesia. One problem with it is that the insertion of a cotton-tipped applicator soaked in local anesthetic is painful. Patients also dislike waiting for the anesthetic effect with the metallic applicators in the nose. In this study, we present a new, well-tolerated method of topical anesthesia for maxillary sinus puncture via the inferior meatus of the nose. Twenty adult patients with maxillary sinus infection who were undergoing bilateral maxillary sinus puncture were studied. One side of each patient's nose was anesthetized with a cotton-tipped applicator moistened with a lidocaine-adrenaline solution (LA), and the other side was anesthetized with EMLA cream instilled with a suction needle and syringe; the sides were chosen randomly. The mean "application of anesthesia" pain score on a 100-mm visual analog scale was 39.2 for the LA side and 9.1 for the EMLA side (p < .01). The anesthesia required for puncture was reached more quickly on the EMLA side than on the LA side (p = .02). The mean puncture pain score was 25.1 with LA and 8.6 with EMLA (p = .01). Fourteen patients out of the 20 (70%) found EMLA more tolerable, 3 patients (15%) found no difference, and 3 patients (15%) preferred LA (p < .01). We conclude that EMLA is better-tolerated and quicker-acting than LA for local anesthesia in maxillary sinus puncture.