Emerging Therapies in Hypothyroidism.

Levothyroxine (LT4) is effective for most patients with hypothyroidism. However, a minority of the patients remain symptomatic despite the normalization of serum thyrotropin levels. Randomized clinical trials including all types of patients with hypothyroidism revealed that combination levothyroxine and liothyronine (LT4+LT3) therapy is safe and is the preferred choice of patients versus LT4 alone. Many patients who do not fully benefit from LT4 experience improved quality of life and cognition after switching to LT4+LT3. For these patients, new slow-release LT3 formulations that provide stable serum T3 levels are being tested. In addition, progress in regenerative technology has led to the development of human thyroid organoids that restore euthyroidism after being transplanted into hypothyroid mice. Finally, there is a new understanding that, under certain conditions, T3 signaling may be compromised in a tissue-specific fashion while systemic thyroid function is preserved. This is seen, for example, in patients with metabolic (dysfunction)-associated fatty liver disease, for whom liver-selective T3-like molecules have been utilized successfully in clinical trials.

Factors influencing the tendency of residual symptoms in patients with depressive disorders: a longitudinal study.

BACKGROUND: Residual symptoms of depressive disorders are serious health problems. However, the progression process is hardly predictable due to high heterogeneity of the disease. This study aims to: (1) classify the patterns of changes in residual symptoms based on homogeneous data, and (2) identify potential predictors for these patterns. METHODS: In this study, we conducted a data-driven Latent Class Growth Analysis (LCGA) to identify distinct tendencies of changes in residual symptoms, which were longitudinally quantified using the QIDS-SR16 at baseline and 1/3/6 months post-baseline for depressed patients. The association between baseline characteristics (e.g. clinical features and cognitive functions) and different progression tendencies were also identified. RESULTS: The tendency of changes in residual symptoms was categorized into four classes: "light residual symptom decline (15.4%)", "residual symptom disappears (39.3%)", "steady residual symptom (6.3%)" and "severe residual symptom decline (39.0%)". We observed that the second class displayed more favorable recuperation outcomes than the rest of patients. The severity, recurrence, polypharmacy, and medication adherence of symptoms are intricately linked to the duration of residual symptoms' persistence. Additionally, clinical characteristics including sleep disturbances, depressive moods, alterations in appetite or weight, and difficulties with concentration have been identified as significant factors in the recovery process. CONCLUSIONS: Our research findings indicate that certain clinical characteristics in patients with depressive disorders are associated with poor recovery from residual symptoms following acute treatment. This revelation holds significant value in the targeted attention to specific patients and the development of early intervention strategies for residual symptoms accordingly.

The moderated-mediation role of risk perception and intolerance of uncertainty in the association between residual symptoms and psychological distress: a cross-sectional study after COVID-19 policy lifted in China.

BACKGROUND: A considerable number of individuals infected with COVID-19 experience residual symptoms after the acute phase. However, the correlation between residual symptoms and psychological distress and underlying mechanisms are scarcely studied. We aim to explore the association between residual symptoms of COVID-19 and psychological distress, specifically depression, anxiety, and fear of COVID-19, and examine the role of risk perception and intolerance of uncertainty in the association. METHODS: A cross-sectional survey was conducted by online questionnaire-based approach in mid-January 2023. Self-reported demographic characteristics, COVID-19-related information, and residual symptoms were collected. Depression, anxiety, fear, risk perception and intolerance of uncertainty were evaluated using the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Fear of COVID-19 Scale (FCV-19S), COVID-19 Risk Perception Scale and Intolerance of Uncertainty Scale-12 (IUS-12), respectively. Linear regression analyses were conducted to explore the associations. A moderated mediation model was then constructed to examine the role of risk perception of COVID-19 and intolerance of uncertainty in the association between residual symptoms and psychological distress. RESULTS: 1735 participants effectively completed the survey. 34.9% of the patients experienced residual symptoms after acute phase of COVID-19. Psychological distress was markedly increased by COVID-19 infection, while residual symptoms had a significant impact on psychological distress (Ps < 0.001), including depression (ß = 0.23), anxiety (ß = 0.21), and fear of COVID-19 (ß = 0.14). Risk perception served as a mediator between residual symptoms and all forms of psychological distress, while intolerance of uncertainty moderated the effect of risk perception on depression and anxiety. CONCLUSION: A considerable proportion of patients experience residual symptoms after acute phase of COVID-19, which have a significant impact on psychological distress. Risk perception and intolerance of uncertainty play a moderated-mediation role in the association between residual symptoms and depression/anxiety. It highly suggests that effective treatment for residual symptoms, maintaining appropriate risk perception and improving intolerance of uncertainty are critical strategies to alleviate COVID-19 infection-associated psychological distress.

Epidemiology of post-COVID conditions beyond 3 years and factors associated with their persistence longer than 2 years: A cross-sectional study.

OBJECTIVE: This study aimed to investigate the epidemiology of post-coronavirus disease 2019 (COVID-19) conditions (PCCs) beyond 3 years and identify factors associated with their persistence longer than 2 years. STUDY DESIGN: Cross-sectional questionnaire-based survey. METHODS: We surveyed patients who had recovered from COVID-19 and visited our institution from February 2020 to November 2021. Demographic and clinical data and information on the presence and duration of PCCs were obtained. We identified factors associated with the persistence of PCCs longer than 2 years using multivariate linear regression analyses. RESULTS: Among 935 patients surveyed, 407 completed the survey. Among them, 360 patients had mild disease in the acute phase. The proportions of participants with at least one symptom at 1, 2, and 3 years after symptom onset or COVID-19 diagnosis were 33.2%, 29.8%, and 5.7%, respectively. The numbers of participants with and without any residual symptoms 2 years after the onset of COVID-19 were 87 and 193, respectively. After multivariate adjustment, persistence of PCCs longer than 2 years was associated with lower body mass index, presence of any underlying medical conditions, and number of symptoms lasting for more than 1 month ≥ 5. CONCLUSIONS: The prevalence of PCCs decreased 2 years after symptom onset or COVID-19 diagnosis. We also identified factors associated with PCC persistence longer than 2 years, which could help primary care physicians and patients with PCCs predict the duration of PCCs and better understand their natural history, thus reducing patients' anxiety about their duration.

Prognostic factors for residual symptoms following percutaneous endoscopic lumbar discectomy.

To explore the risk factors for residual symptoms following percutaneous endoscopic lumbar discectomy (PELD). A retrospective case-controlled study. From January 2015 to December 2020, consecutive patients who underwent PELD for lumbar disc herniation (LDH) in our department were retrospectively studied. All the patients were followed-up at least two years. Residual symptoms were analyzed for association with baseline data, clinical feature, physical examination, and radiographic characteristics, which were used to detected the risk factors. A total of 339 patients were included in this study, with a mean follow-up of 28.7 ± 3.6 months. Of the enrolled patients, 90 (26.5%) patients experienced residual low back pain (LBP), and 76 (22.4%) patients experienced leg numbness (LN). Multivariate logistic regression analysis revealed that intervertebral disc calcification on CT scans (odd ratio, 0.480; 95% confidence interval: 0.247 ~ 0.932; P < 0.05) was independent risk factor for postoperative residual LBP with odd ratio and longer symptom duration was risk factor for postoperative residual LN (odd ratio, 2.231; 95% confidence interval:1.066 ~ 4.671; P < 0.05). Residual symptoms following transforaminal endoscopic surgery are quite prevalent. Intervertebral disc calcification is a protective factor for residual low back pain, and a longer symptom duration is a risk factor for residual leg numbness.

Positive intrathecal anti-Borrelia antibody synthesis: what are the implications for clinical practice? Clinical features and outcomes of 138 patients in a French multicenter cohort study.

We aimed to describe the clinical characteristics, management, and residual symptoms (RS) in patients with definite and possible Lyme neuroborreliosis (LNB). We conducted a retrospective French multicenter cohort study (2010-2020). Cases of LNB were defined as clinical manifestations attributed to LNB and a positive Borrelia-specific intrathecal antibody index (AI) ("possible" LNB) and with pleocytosis ("definite" LNB). Risk factors of RS were determined using a logistic regression model. We included 138 adult patients with a positive AI. Mean age was 59.5 years (± 14.7). The median duration of symptoms before diagnosis was 1.0 [0.5-4.0] months. The most frequent manifestation was radicular pain (n = 79, 57%). Complete cerebrospinal fluid (CSF) leukocyte analysis was available in 131 patients, of whom 72 (55%) had pleocytosis. Patients with definite LNB had a shorter duration of symptoms (median 1.0 [0.5-2.6] vs. 3.0 [0.6-7.0] months, p < 0.01) and more radicular pain (74% vs 44%, p < 0.01) than patients with possible LNB. At the last visit (median duration of follow-up: 70 [30-175] days), 74/124 patients (59.7%) reported RS, mostly radicular pain (n = 31, 25%). In multivariate analysis, definite LNB (OR = 0.21 [0.05-0.931], p = 0.039) and duration of symptoms less than 3 months (OR = 0.04 [0.01-0.37], p = 0.005) were protective factors against RS at last follow-up. Our study highlights the challenges of LNB management, especially for patients with a positive AI without pleocytosis, questioning whether LB is still ongoing or not. Early diagnosis and treatment are important to improve outcomes and to lower potential RS.

Dysfunctional self-reported interoception predicts residual symptom burden of fatigue in major depressive disorder: an observational study.

BACKGROUND: Fatigue is a core symptom of major depressive disorder (MDD) and is frequently refractory to antidepressant treatment, leading to unfavorable clinical/psychosocial outcomes. Dysfunctional self-reported interoception (i.e., maladaptive focus on the body's physiological condition) is prevalent in MDD and could contribute to residual symptom burden of fatigue. Therefore, we explored (a.) cross-sectional correlations between both dimensions and investigated (b.) prospective associations between interoceptive impairments at admission and symptom severity of fatigue at the end of hospitalization. METHODS: This observational, exploratory study included 87 patients suffering from MDD who completed self-rating scales, the Multidimensional Assessment of Interoceptive Awareness, Version 2 (MAIA-2), and the Multidimensional Fatigue Inventory (MFI-20), at the beginning and end of hospitalization. Bivariate correlations (r) and hierarchical regression analyses were performed. RESULTS: The cross-sectional analysis showed moderate to large negative correlations between the MAIA-2 and MFI-20 dimensions except for the Not-Distracting scale. Symptoms of general, physical, and mental fatigue at the end of hospitalization were predicted by reduced body Trusting (ß = -.31, p = .01; ß = -.28, p = .02; ß = -.31, p = .00, respectively). Increased Body Listening (ß = .37, p = .00), Not-Worrying (ß = .26, p = .02), and diminished Attention Regulation (ß = -.32, p = .01) predicted higher mental fatigue. CONCLUSIONS: Diminished body confidence at baseline identified patients at risk for post-treatment fatigue and could therefore serve as a target for improving antidepressant therapy. Body-centered, integrative approaches could address treatment-resistant fatigue in MDD. However, clinicians may also consider the potential adverse effect of increased Body Listening and Not-Worrying on mental fatigue in psychotherapeutic and counselling approaches. Due to the exploratory nature of this study, the results are preliminary and need to be replicated in pre-registered trials with larger sample sizes.

Are We Restoring Thyroid Hormone Signaling in Levothyroxine-Treated Patients With Residual Symptoms of Hypothyroidism?

INTRODUCTION: Levothyroxine (LT4) at doses that maintain the serum thyroid-stimulating hormone levels within the normal range constitutes the standard of care for the treatment of hypothyroidism. After a few months, this eliminates the signs and symptoms of overt hypothyroidism in the majority of patients, owing to the endogenous activation of thyroxine to triiodothyronine, the biologically active thyroid hormone. Still, a small percentage of the patients (10%-20%) exhibit residual symptoms, despite having normal serum thyroid-stimulating hormone levels. These symptoms include cognitive, mood, and metabolic deficits, with a significant impairment in psychological well-being and quality of life. OBJECTIVE: To provide a summary of progress in the approach of patients with hypothyroidism that exhibit residual symptoms despite treatment. METHODS: We reviewed the current literature and here we focused on the mechanisms leading to a deficiency of T3 in some LT4-treated patients, the role of residual thyroid tissue and the rationale for combination therapy with LT4 + liothyronine (LT3). RESULTS: A score of clinical trials comparing therapy with LT4 versus LT4 + LT3 concluded that both are safe and equally effective (neither is superior); however, these trials failed to recruit a sufficiently large number of patients with residual symptoms. New clinical trials that considered LT4-treated symptomatic patients revealed that such patients benefit from and prefer therapy containing LT4 + LT3; desiccated thyroid extract has also been used with similar results. A practical approach to patients with residual symptoms and on initiation of combination therapy with LT4 + LT3 is provided. CONCLUSION: A recent joint statement of the American, British, and European Thyroid Associations recommends that a trial with combination therapy be offered to patients with hypothyroidism that do not fully benefit from therapy with LT4.

Assessment of residual dizziness after successful canalith repositioning maneuvre in benign paroxysmal positional vertigo patients: a questionnaire-based study.

OBJECTIVE: The purpose of this study was to assess residual dizziness (RD) after successful canalith repositioning maneuvre (CRM) treatment in patients with benign paroxysmal positional vertigo (BPPV) using Dizziness Handicap Inventory (DHI) questionnaire and Visual Analog Scale (VAS). METHODS: One hundred sixty BPPV patients after successful CRM treatment were recruited. All patients were divided into the residual dizziness (RD) group and without RD group. The DHI questionnaire and VAS before CRM and follow-up were asked to complete. For analysis of the improvement in symptom, we defined ∆DHI and ∆VAS as the difference between the baseline score and the follow-up score. RESULTS: High incidence of RD was observed in the older patients (p < 0.001). The incidence of hypertension in the RD group was also significantly higher than that of the without RD group (p = 0.022). The ∆DHI-P, ∆DHI-E, ∆DHI-F, ∆DHI-T, and ∆VAS scores in the without RD group were significantly higher than that of the RD group (p < 0.001). When the cutoff point of the ∆DHI total scores was 17, the sensitivity was 64.86% and the specificity was 73.26% for diagnosing RD. When the cutoff point of the ∆VAS scores was 2.5, the sensitivity was 77.03% and the specificity was 81.40% for diagnosing RD. CONCLUSIONS: RD is prone to occur in the older patients and ∆VAS exhibits higher sensitivity and specificity in assessing RD.

Epidemiology of post-COVID conditions beyond 1 year: a cross-sectional study.

OBJECTIVE: The aim of this study was to investigate the epidemiology of post-COVID conditions beyond 12 months and identify factors associated with the persistence of each condition. STUDY DESIGN: This was a cross-sectional questionnaire-based survey. METHODS: We conducted the survey among patients who had recovered from COVID-19 and visited our institute between February 2020 and November 2021. Demographic and clinical data and data regarding the presence and duration of post-COVID conditions were obtained. We identified factors associated with the persistence of post-COVID conditions using multivariable linear regression analyses. RESULTS: Of 1148 surveyed patients, 502 completed the survey (response rate, 43.7%). Of these, 393 patients (86.4%) had mild disease in the acute phase. The proportion of participants with at least one symptom at 6, 12, 18, and 24 months after symptom onset or COVID-19 diagnosis was 32.3% (124/384), 30.5% (71/233), 25.8% (24/93), and 33.3% (2/6), respectively. The observed associations were as follows: fatigue persistence with moderate or severe COVID-19 (ß = 0.53, 95% confidence interval [CI] = 0.06-0.99); shortness of breath with moderate or severe COVID-19 (ß = 1.39, 95% CI = 0.91-1.87); cough with moderate or severe COVID-19 (ß = 0.84, 95% CI = 0.40-1.29); dysosmia with being female (ß = -0.57, 95% CI = -0.97 to -0.18) and absence of underlying medical conditions (ß = -0.43, 95% CI = -0.82 to -0.05); hair loss with being female (ß = -0.61, 95% CI = -1.00 to -0.22), absence of underlying medical conditions (ß = -0.42, 95% CI = -0.80 to 0.04), and moderate or severe COVID-19 (ß = 0.97, 95% CI = 0.41-1.54); depressed mood with younger age (ß = -0.02, 95% CI = -0.04 to -0.004); and loss of concentration with being female (ß = -0.51, 95% CI = -0.94 to -0.09). CONCLUSIONS: More than one-fourth of patients after recovery from COVID-19, most of whom had had mild disease in the acute phase, had at least one symptom at 6, 12, 18, and 24 months after onset of COVID-19, indicating that not a few patients with COVID-19 suffer from long-term residual symptoms, even in mild cases.

[Clinical characteristics and follow-up analysis of 12 patients of acute phosphine poisoning].

Objective: To investigate the clinical characteristics of patients with acute phosphine poisoning, and to follow up and evaluate the prognosis of patients. Methods: In May 2022, 12 patients with phosphine poisoning by respiratory inhalation in Beijing Chao-Yang Hospital of Capital Medical University were analyzed. The patients were treated with symptomatic support therapy. Three months later, patients were re-evaluated the symptoms of poisoning, pulmonary function and magnetic resonance imaging (MRI) of the brain to understand the prognosis of the phosphine poisoning. Results: The main symptoms of 12 patients were respiratory and central nervous system symptoms with hypoxia. The symptoms of poisoning improved after treatment. Follow-up found that the patients had different degrees of residual symptoms. Pulmonary function showed increased airway resistance. Airway challenge test was positive in some patients. MRI of the head of some patients showed small ischemic focus in bilateral frontal lobes. Conclusion: Acute phosphine poisoning may cause persistent damage to the respiratory system and central system, and residual symptoms after 3 months.

Residual posttraumatic stress disorder symptoms after provision of brief behavioral intervention in low- and middle-income countries: An individual-patient data meta-analysis.

BACKGROUND: To address shortages of mental health specialists in low- and middle-income countries, task-shifting approaches have been employed to train nonspecialists to deliver evidence-based scalable psychosocial interventions. Problem Management Plus (PM+) is a brief transdiagnostic nontrauma focused intervention for people affected by adversity. This study reports on the capacity of PM+ to address specific symptoms of posttraumatic stress disorder (PTSD). METHODS: Individual patient data from three randomised controlled trials were combined and analysed to observe the impacts of PM+ (n = 738) or enhanced treatment as usual (ETAU) (n = 742) interventions on specific PTSD symptoms at posttreatment and 3-month follow-up. The PTSD-Checklist for DSM-5 (PCL-5) was used to index PTSD symptoms, and presence of each symptom was defined as moderate severity (score ≥ 2 on individual items). RESULTS: The average PCL-5 score at baseline was 26.1 (SD: 16.8) with 463 (31.3%) scoring above 33, indicative of a diagnosis of PTSD. Following intervention, 12.5% and 5.8% of participants retained a score greater than 33 at postassessment and follow-up, respectively. There was greater symptom reduction for PM+ than for ETAU for most symptoms. Hyperarousal symptoms were the most common residual symptoms after PM+, with more than 30% of participants reporting persistent sleep disturbance, concentration difficulties, and anger. CONCLUSION: PM+ led to greater reduction in symptoms relating to re-experiencing and avoidance. The evidence indicates that strategies focusing on hyperarousal symptoms including sleep, concentration, and anger difficulties, could be strengthened in this brief intervention.

Classification and prognostic factors of residual symptoms after minimally invasive lumbar decompression surgery using a cluster analysis: a 5-year follow-up cohort study.

PURPOSE: Residual symptoms indicating incomplete remission of lower leg numbness or low back pain may occur after spine surgery. The purpose was to elucidate the pattern of residual symptoms 5 years after minimally invasive lumbar decompression surgery using a cluster analysis. METHODS: The study comprised 193 patients with lumbar spinal stenosis (LSS) (108 men, 85 women) ranging in age from 40 to 86 years (mean, 67.9 years). Each patient underwent 5-year follow-up. The Japanese Orthopedic Association score and visual analog scale scores for low back pain, leg pain, and leg numbness at 5 years were entered into the cluster analysis to characterize postoperative residual symptoms. Other clinical data were analyzed to detect the factors significantly related to each cluster. RESULTS: The analysis yielded four clusters representing different patterns of residual symptoms. Patients in cluster 1 (57.0%) were substantially improved and had few residual symptoms of LSS. Patients in cluster 2 (11.4%) were poorly improved and had major residual symptoms. Patients in cluster 3 (17.6%) were greatly improved but had mild residual low back pain. Patients in cluster 4 (14.0%) were improved but had severe residual leg numbness. Prognostic factors of cluster 2 were a short maximum walking distance, motor weakness, resting lower leg numbness, cofounding scoliosis, and high sagittal vertical axis. CONCLUSIONS: This is the first study to identify specific patterns of residual symptoms of LSS after decompression surgery. Our results will contribute to acquisition of preoperative informed consent and identification of patients with the best chance of postoperative improvement.

Association between residual symptoms and social functioning in patients with depression.

OBJECTIVE: There is a lack of data about residual symptoms in Chinese patients with depression. The aim of this study was to evaluate the association of residual symptoms with social functional impairment in these patients. METHODS: This was a multicenter cross-sectional study conducted in 11 hospitals in eight cities of China from September 2014 to April 2015. Residual symptoms and social functioning were assessed using the SDS, QIDS-SR16, Q-LES-Q-SF, and PHQ-15 scales. Logistic regression analysis was used to determine the factors associated with social functional impairment. RESULTS: Among the 1503 patients, 915 (60.9%) had no functional impairment (SDS ≤6) and 588 (39.1%) showed functional impairment (SDS >6). Those with impairment had higher PHQ-15 scores (7.4 ± 4.8 vs. 4.0 ± 3.4, P < 0.0001), lower Q-LES-Q-SF scores (all items P < 0.0001), higher SDS scores (13.9 ± 5.7 vs. 2.8 ± 2.2, P < 0.0001), and higher scores for all QIDS dimensions (all P < .0001). The factors related to functional impairment included QIDS dimension 7 (loss of interest) (OR = 2.137, 95%CI 1.600-2.853, P < 0.0001), QIDS dimension 9 (mental anxiety) (OR = 1.627, 95%CI 1.215-2.180, P = 0.0011), QIDS dimension 3 (appetite) (OR = 1.502, 95%CI 1.141-1.977, P = 0.0037), QIDS dimension 8 (energy) (OR = 1.468, 95%CI 1.092-1.973, P = 0.0110), age (OR = 0.982, 95%CI 0.971-0.993, P = 0.0013), disease course (OR = -1.004, 95%CI 1.002-1.006, P = 0.0004), and QIDS dimension 1 (sleep disorders) (OR = 1.622, 95%CI 1.068-2.463, P = 0.0232). CONCLUSION: Compared with patients with normal social function, cases with impaired social function have more physical symptoms, more residual symptoms of depression, and less satisfaction with the quality of life. Residual symptoms are associated with social functional impairment in patients with depression.

Health problems among breast cancer survivors after completing conventional treatments: A cross-sectional study.

This cross-sectional design study aimed to explore health problems among breast cancer survivors after completing conventional treatments. Purposive sampling was adopted to recruit 160 breast cancer survivors from a regional tertiary care hospital and hospital with a specialist cancer center in southern Thailand. STROBE checklist of items for cross-sectional studies is applied to report the study. Five most frequent, severe, and distressing symptoms faced in the first 3 years after cancer treatment were reported as numbness to the affected side, difficulty sleeping, fatigue, pain, and skin changes. Almost half of the participants reported symptoms indicating a definite diagnosis of anxiety, and nearly 70% of them rated themselves as borderline depressed or depressed. Approximately 50% of participants reported no change in their relationships with significant people, and about 60% of them reported a high-level fear of recurrence. Symptom frequency, severity, and distress were positively associated with anxiety, depression, and menopausal symptoms, while relationship changes were negatively associated with menopausal symptoms, anxiety, and depression. Support and information for these women are required after active treatment has ceased to deal with ongoing symptoms.

Residual eating disorder symptoms and clinical features in remitted and recovered eating disorder patients: A systematic review with meta-analysis.

OBJECTIVE: In psychiatry, the presence of residual symptoms after treatment is linked to the definitions of remission and recovery. To identify the presence of residual eating disorder (ED) symptoms and associated non-ED clinical features in remitted and recovered EDs, the current systematic review with meta-analysis was performed. METHOD: A systematic review was conducted on residual ED symptoms and non-ED clinical features including comorbid psychopathology, neurophysiological functioning, cognitive functioning, and quality of life in ED patients considered remitted or recovered. To examine residual ED symptoms, meta-analyses were performed while considering age, study quality, remission, and recovery criteria strictness as moderators. Sensitivity, publication bias, and heterogeneity analyses were also conducted. RESULTS: The 64 studies selected for the systematic review underscored the presence of residual ED symptoms in anorexia nervosa (AN) and bulimia nervosa (BN), and impairments and deficits in the additional features examined. From the 64 studies, 31 were selected regarding residual ED symptoms in AN for meta-analysis. Large effect sizes indicated that remitted/recovered AN patients reported significantly lower body mass index (Hedges' g = -0.62[-0.77, -0.46]) and significantly greater symptomatology in terms of ED examination-questionnaire (Hedges'g = 0.86 [0.48,1.23]) and ED inventory (Hedges' g = 0.94[0.64,1.24]) than healthy controls, independently of remission and recovery criteria strictness, age, and study quality. DISCUSSION: The presence of residual ED symptoms in AN is quantitatively supported, whereas the presence of residual ED symptoms in BN should be further investigated. Data on binge-eating disorder are missing. Future research should use consistent, multicomponent, and standardized comparable indicators of recovery.

OBJETIVO: En psiquiatría, la presencia de síntomas residuales después de tratamiento está ligado a las definiciones de remisión y recuperación. Para identificar la presencia de síntomas residuales del trastorno de la conducta alimentaria (TCA) y características clínicas no de TCA asociadas en pacientes remitidos y recuperados de TCAs, se realizó la presente revisión sistemática con meta-análisis. MÉTODO: Se realizó una revisión sistemática en síntomas residuales de TCA y en características clínicas no de TCA incluyendo psicopatología comórbida, funcionamiento neurofisiológico, funcionamiento cognitivo, y calidad de vida en pacientes con TCA considerados remitidos o recuperados. Para examinar los síntomas residuales de TCA se realizaron meta-análisis considerando edad, calidad del estudio, criterios de remisión y recuperación estrictos como moderadores. También se realizaron análisis de sensibilidad, sesgo de publicación y heterogenicidad. RESULTADOS: Los 64 estudios seleccionados para la revisión sistemática destacaron la presencia de síntomas residuales de TCA en anorexia nervosa (AN) y bulimia nervosa (BN), y alteraciones y déficits en las características adicionales examinadas. De los 64 estudios, 31 fueron seleccionados para meta-análisis por los síntomas residuales de TCA en AN. Las medidas de efecto mayor indicaron que los pacientes remitidos/recuperados de AN reportaron índices de masa corporal significativamente menores (Hedges' g = -0.62[-0.77,-0.46]) y significativamente mayor sintomatología en términos del Cuestionario de Evaluación de TCA (Eating Disorder Examination-Questionnaire) (Hedges' g = 0.86 19 [0.48,1.23]) y el Inventario de TCA (Eating Disorder Inventory) (Hedges' g= 0.94[0.64,1.24]) que los controles sanos, independientemente de lo estricto de los criterios de remisión y recuperación, edad y calidad del estudio. DISCUSIÓN: La presencia de síntomas residuales de TCA en AN es apoyada cuantitativamente, mientras que la presencia de síntomas residuales de TCA en BN necesita ser investigada a mayor profundidad. Los datos en trastorno de atracones están ausentes. Las investigaciones futuras deberían utilizar indicadores de recuperación consistentes, de múltiples componentes y estandarizados.

Effectiveness of Internet-Delivered Computerized Cognitive Behavioral Therapy for Patients With Insomnia Who Remain Symptomatic Following Pharmacotherapy: Randomized Controlled Exploratory Trial.

BACKGROUND: In reality, pharmacotherapy still remains the most common treatment for insomnia. OBJECTIVE: This study aimed to examine the effectiveness of our internet-delivered computerized cognitive behavioral therapy (ICBT) program as an adjunct to usual care (UC) compared with UC alone in patients with insomnia who remain symptomatic following hypnotics. METHODS: We recruited 23 patients with insomnia who remained symptomatic following pharmacologic treatment including benzodiazepines, and we conducted an exploratory randomized controlled trial. The primary outcome was the Pittsburgh Sleep Quality Index (PSQI) at week 6 of the treatment. Secondary outcomes were sleep onset latency, total sleep time, sleep efficiency, number of awakenings, refreshment and soundness of sleep, anxiety by Hospital Anxiety and Depression Scale, depression measured by the Center for Epidemiologic Studies Depression Scale, and quality of life (QOL) measured by the EuroQol-5D. All parameters were measured at weeks 0 (baseline), 6 (postintervention), and 12 (follow-up). RESULTS: The adjusted mean reduction (-6.11) in PSQI at week 6 from baseline in the ICBT plus UC group was significantly (P<.001) larger than the adjusted mean reduction (0.40) in the UC alone group. Significant differences were also found in favor of ICBT plus UC for PSQI, sleep onset latency, sleep efficiency, number of awakenings, and depression at all assessment points. Refreshment, soundness of sleep, anxiety, and QOL improved by week 6 in ICBT plus UC compared with UC alone. There were no reports of adverse events in either group during the study. CONCLUSIONS: These results indicated that our 6-week ICBT program is an effective treatment adjunct to UC for improving insomnia and related symptoms even after unsuccessful pharmacotherapy. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry: UMIN000021509; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000023545 (Archived by WebCite at http://www.webcitation. org/75tCmwnYt).

Modifiable and non-modifiable factors associated with functional impairment during the inter-episodic periods of bipolar disorder.

The chronic, long-term evolution of bipolar disorder (BD) requires a careful clinical characterization with prognostic implications in terms of symptom and functional control. The OPTHYMUM multicenter study was conducted in France with the objective of evaluating residual symptoms on overall functioning of BD patients during inter-episodic period. The aims of the present study were to identify the potentially modifiable (e.g., treatable) and non-modifiable variables associated with functional impairment during the inter-episodic periods of BD. Sample was divided into two groups according to level of functioning (adequate vs. impaired), based on the FAST scale total score. FAST cut-off for functional impairment is a score >11. The two subgroups were compared as per sociodemographic and clinical variables with standard univariate analyses, and a logistic regression model was created. The model as a whole contained independent non-modifiable factors (age, gender, BD type, illness duration) and modifiable factors (illness severity, predominant polarity, depressive and manic residual symptoms, comorbidities). The final model was statistically significant (χ 2 = 53.89, df = 5, p < 0.001). Modifiable factors most strongly associated with functional impairment were manic predominant polarity (OR = 1.79, CI 95% 1.09-2.96, p = 0.022), residual depressive symptoms (OR = 1.30, CI 95% 1.18-1.43, p < 0.001) and illness severity (OR = 1.24, CI 95% 1.01-1.52, p = 0.037), whilst non-modifiable factor was illness duration (OR = 1.03, CI 95% 1.01-1.05, p = 0.017). Despite intrinsic and non-modifiable illness characteristics, a clinical-wise choice of treatment may help to improve control of manic relapses. Potential improvement of residual depressive symptoms may alleviate the functional burden associated with bipolar disorder.

Depressive residual symptoms are associated with illness course characteristics in a sample of outpatients with bipolar disorder.

Rates of 50-70% of residual symptoms referring to subsyndromal manifestations between episodes that do not meet the required criteria for episode definition were reported in bipolar disorder (BD). However, the specific role of these symptoms on the course of BD patients is poorly understood; thus, we aimed to investigate factors associated with depressive residual symptoms. Overall, 255 currently euthymic BD outpatients on maintenance treatment, including 95 (37.2%) males and 160 (62.8%) females, were consecutively recruited at the Section of Psychiatry, Department of Neuroscience, University of Genoa (Italy) and underwent detailed structured interviews, comprehensive clinical interviews, and clinical record reviews for assessment/collection of relevant information concerning the course of illness and clinical status including cross-referral of all available information. After categorizing subjects according to the presence/absence of residual symptoms, groups were compared along clinical variables and variables associated with residual symptoms were analyzed using multivariate analyses. Subjects with residual symptoms were less likely to report substance abuse (χ2(2) = 11.937, p ≤ 0.005) and lifetime psychotic symptoms (χ2(2) = 10.577, p = 0.005), and more likely to report higher illness episodes, longer duration of illness (t253 = 67.282, p ≤ 0.001; t253 = 10.755, p ≤ 0.001), and longer duration of current illness episode (t253 = 7.707, p ≤ 0.001) than those without residual symptoms. After multivariate analyses, a significant positive contribution to residual symptoms was given only by duration of current illness episode (ß = 0.003; p ≤ 0.05), and lifetime psychotic symptoms (ß = 1.094; p ≤ 0.005). Clinicians have to pay attention to minimize residual symptoms that may significantly impact on the course of BD and achievement of full remission between episodes.

Characteristics and Clinical Outcome of Lyme Neuroborreliosis in a High Endemic Area, 1995-2014: A Retrospective Cohort Study in Denmark.

BACKGROUND: Despite a well-described symptomatology, treatment delay and sequelae are common in patients with Lyme neuroborreliosis (LNB). The aim of this study was to contribute to the knowledge about the symptomatology and epidemiology of LNB. METHODS: We conducted a retrospective study of all LNB cases verified by a positive Borrelia intrathecal antibody index test performed at the Department of Microbiology, Odense University Hospital, Denmark, from 1995 through 2014. RESULTS: The study included 431 patients; 126 were children. The mean incidence was 4.7 per 100 000 inhabitants per year. The median delay from neurological symptom debut to first hospital contact was 20 days and significantly longer for patients with symptom debut in the winter/early spring. The most common clinical symptoms were painful radiculitis (65.9%), cranial nerve palsy (43.4%), and headache (28.3%). A total of 30.6% were seen in >1 hospital department, and 85.6% were admitted during their course of treatment. Serum Borrelia immunoglobulin M and immunoglobulin G at the time of positive Borrelia intrathecal antibody index test were negative in 67 patients (15.5%). We found a median treatment delay of 24 days, with no improvement in our 20-year study period. Residual symptoms following treatment were found in 28.1% of patients, and risk of residual symptoms was significantly associated with delay from symptom debut to initiation of treatment. CONCLUSIONS: The association between treatment delay and residual symptoms and the lack of improvement in treatment delay during the study period highlight the need for standardized diagnostic routines and a better follow-up for LNB patients. Our findings disprove that all patients with LNB develop positive serum Borrelia antibodies within 6 weeks after infection.