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.

Inhibition moderates the effect of attentional bias modification for reducing residual depressive symptoms: A randomized sham-controlled clinical trial.

OBJECTIVES: Residual symptoms represent risk factor for relapse. Attention bias modification (ABM) may reduce clinical and sub-clinical depressive symptoms, indicating that is may be of relevance when preventing relapse. Current evidence suggests that executive functions may moderate the outcome of interventions targeting depressive symptoms. METHODS: We assessed inhibition and shifting as indicators of executive functioning by means of the Color-Word Interference Test (i.e., "Stroop task"). These baseline characteristics were investigated as moderator of the effect of ABM on depression symptoms in a double-blinded randomized sham-controlled trial of ABM including patients with a history of recurrent depression (N = 301). Inclusion and follow-ups took place from January 2015 to October 2016. The trial was retrospectively registered #NCT02658682 January 2016. RESULTS: The moderation analysis was based on the interaction term ABM x Stroop. Scaled inhibition scores ≤10.8, but not shifting ability, moderated the effect of ABM compared to sham on clinician-rated depression (HDRS). The difference from the 15th to the 85th percentile of the inhibition score was about 1 HDRS-point, indicating a small effect size. No moderation was found when self-reported depression and AB were the outcome. Post-hoc power calculation indicates risk of Type-II error. CONCLUSION: When targeting depressive symptoms, ABM seems to be somewhat more effective in patients with weak inhibitory control. This suggests that evaluating the level of inhibition in individual patients could provide some information when making decisions about prescribing ABM to reduce residual symptoms, but the clinical implications of this is uncertain due to an overall small effect size attributable to ABM. Future studies should examine whether inhibitory control still is a relevant moderator when comparing ABM to treatment options other than the sham control condition.

Manic Residual Symptoms Also Deserve Attention: A Symptom Network Analysis of Residual Symptoms in Bipolar Disorder.

Background: Lots of patients with bipolar disorder (BD) continue to have residual symptoms after treatment in their remission, BD exhibits intricate characteristics and transformation patterns in its residual symptoms, residual symptoms of different polarities and degrees can mix with and transform to each other. There is a need for further investigation of BD as a comprehensive multivariate disease system. The current research lacks network analyses focusing on BD's residual and subsyndromal symptoms. Methods: 242 patients were included with bipolar disorder in remission. We compared demographic data and differences in symptoms between populations with and without residual symptoms using t-tests and chi-square tests, with FDR applied for multiple comparison correction. Logistic regression was used to identify influencing factors for residual symptoms. Symptom networks were compared by network analysis to analyze the relationships between different types of residual symptoms. Results: Depressive residual symptoms (N=111) were more common than manic residual symptoms (n=29) in the patients included. The comparison between two groups with and without residual symptoms shows no difference in demographic data and medical history information. The main influencing factors related to residual symptoms were time from diagnosis to first treatment (OR=0.88), the first(OR=1.51) and second (OR=17.1)factors of the Mood Disorder Questionnaire (MDQ), the Quick Inventory of Depressive Symptomatology Self-Report (QIDS)(OR=5.28), the psychological(OR=0.68) and environment (OR=1.53) subscale of the World Health Organization Quality of Life Short Form (WHOQOL-BREF). There was a significant difference in network structure between the groups with and without residual symptoms (network invariance difference=0.4, p =0.025). At the same time, there was no significant difference between the groups with and without depressive residual symptoms. However, the symptom network in patients with depressive residual symptoms is more loosely structured than in those without, with symptoms exhibiting weaker interconnections. When there is no depressive or manic residual symptom, it can still form a symptom network and cause an impact on social function. Conclusion: This study underscores the complexity of bipolar disorder's residual symptoms. Although it primarily manifests as loosely structured depressive residual symptoms, manic residual symptoms should not be ignored. Future research should explore network-based interventions targeting specific symptom clusters or connections to improve residual symptom management and patient outcomes.

Improving Mental Health Outcomes in Patients with Major Depressive Disorder in the Gulf States: A Review of the Role of Electronic Enablers in Monitoring Residual Symptoms.

Up to 75% of individuals with major depressive disorder (MDD) may have residual symptoms such as amotivation or anhedonia, which prevent full functional recovery and are associated with relapse. Globally and in the Gulf region, primary care physicians (PCPs) have an important role in alleviating stigma and in identifying and monitoring the residual symptoms of depression, as PCPs are the preliminary interface between patients and specialists in the collaborative care model. Therefore, mental healthcare upskilling programmes for PCPs are needed, as are basic instruments to evaluate residual symptoms swiftly and accurately in primary care. Currently, few if any electronic enablers have been designed to specifically monitor residual symptoms in patients with MDD. The objectives of this review are to highlight how accurate evaluation of residual symptoms with an easy-to-use electronic enabler in primary care may improve functional recovery and overall mental health outcomes, and how such an enabler may guide pharmacotherapy selection and positively impact the patient journey. Here, we show the potential advantages of electronic enablers in primary care, which include the possibility for a deeper "dive" into the patient journey and facilitation of treatment optimisation. At the policy and practice levels, electronic enablers endorsed by government agencies and local psychiatric associations may receive greater PCP attention and backing, improve patient involvement in shared clinical decision-making, and help to reduce the general stigma around mental health disorders. In the Gulf region, an easy-to-use electronic enabler in primary care, incorporating aspects of the Hamilton Depression Rating Scale to monitor amotivation, and aspects of the Montgomery-Åsberg Depression Rating Scale to monitor anhedonia, could markedly improve the patient journey from residual symptoms through to full functional recovery in individuals with MDD.

Individual Burden of Illness Index in Bipolar Disorder Remission: A Cross-Sectional Study.

BACKGROUND: A population-based method for estimating disease burden is commonly used. Nevertheless, these measurements do not entirely capture the comprehensive burden of illness on an individual patient. To address the problem, the Individual Burden of Illness Index (IBI index) Index was created and validated, specifically for major depressive disorder. The IBI represents the overall influence of the condition, encompassing distress from symptom intensity, functional impairment, and the patient's quality of life. AIM: The aim of the study was to approve and validate the IBI index for the integral assessment of disease burden in patients with bipolar disorder (BD) in remission. METHODS: The cross-sectional study was conducted in the outpatient psychiatric services in Saint Petersburg, Russia, from April through October 2020. Eighty-five patients aged 18 to 45 (mean age 36.6±5.7 years) with BD (type I - 75%, n=64; type II - 25%, n=21) in remission were examined. The study procedure included a structured clinical interview and the use of clinical scales: the World Health Organization's Quality of Life Questionnaire, Hamilton Rating Scale for Depression (HDRS), Young Mania Rating Scale (YMRS), and Personal and the Social Performance Scale. RESULTS: The principal component analysis in accordance with the adjusted one showed that the burden of illness in patients with BD in remission is directly related to the severity of residual depressive symptoms, reflected in the HDRS score: as the HDRS score increases (0.27, p <0.001), residual mania (-0.14, p <0.001), social functioning (-0.06, p <0.001), and quality of life (-0.04, p <0.001) decrease. In contrast, when there are remaining residual mania symptoms, as indicated by the YMRS score, the result tends to be a lower burden, better social functioning, and enhanced quality of life. CONCLUSION: The study has demonstrated through statistical means a successful adaptation and validation of the previously calculated IBI index for patients with BD in remission. Residual affective symptoms were shown to have different impacts on the social functioning of patients with BD in remission, indicating the need for a timely assessment and targeted therapy of these symptoms in such patients.

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.

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.

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.

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.

Effects of Different Durations and Frequencies of Vestibular Rehabilitation in Patients With Residual Symptoms After Benign Paroxysmal Positional Vertigo Repositioning.

OBJECTIVES: This study aimed to explore the effects of different duration and daily frequency of vestibular rehabilitation (VR) in patients with residual symptoms after benign paroxysmal positional vertigo (BPPV) successful repositioning. METHOD: Patients with successful BPPV repositioning (n = 118) were divided into 3 groups according to VR duration and frequency: group A (n = 30; 15 minutes, 3 times/day), group B (n = 30; 30 minutes, 3 times/day), group C (n = 28; 15 minutes, 6 times/day), and control group D (n = 30; no VR). All patients completed the dizziness handicap inventory (DHI) and vestibular rehabilitation benefit questionnaire (VRBQ) at baseline and after 2 and 4 weeks. RESULTS: The emotional scores and the proportion of severe dizziness disability in the DHI scores were significant differences between VR groups A to C and control group D after 2 and 4 weeks (all P < .05). There were significant differences in total DHI and VRBQ scores among the VR groups A to C after 2 and 4 weeks (all P < .05). Interestingly, emotion scores were not significantly different in group A (P = .385), group B (P = .569), and group C (P = .340) between 2 and 4 weeks. Meanwhile at 2 weeks, the difference in motion-provoked dizziness score between group A and B was statistically significant (P = .02). CONCLUSIONS: A total VR duration over 4 weeks can reduce dizziness and improve VR benefits in routine therapy in patients with residual dizziness after successful BPPV repositioning. Emotional improvement can be observed after 2 weeks. VR may help to relieve motion-provoked dizziness earlier if patients are willing to consider increasing the duration to more than 15 minutes.

Comparison of the therapeutic effects of machine and manual reduction for benign paroxysmal positional vertigo / 中国现代医生

@#Objective To compare the therapeutic effects of manual reduction and machine reduction in patients with benign paroxysmal positional vertigo(BPPV)at different ages.Methods Randomly select 300 patients clinically diagnosed with BPPV who visited the Hearing Center of the First Affiliated Hospital of Wenzhou Medical University from April 2022 to December 2023.They were divided into young and middle-aged group of 170 cases(18-59 years old)and elderly group of 130 cases(≥60 years old)according to age.Each group was further divided equally into experimental group and control group based on the diagnosis and treatment methods adopted by the patients.The experimental group patients were treated with a benign paroxysmal positional vertigo diagnosis and treatment system(model/specification:SRM-Ⅳ)for machine reduction.The control group patients were treated with manual reduction.Compare the effective rate of reduction,reduction frequency,incidence of residual dizziness symptoms,and duration of each group.Results In young and middle-aged patients,the incidence and duration of residual dizziness symptoms after reduction in experimental group were significantly lower than those in control group(P<0.05),and there was no statistically significant difference in the effective rate and number of reductions(P>0.05).In elderly group,the reduction efficiency of experimental group was significantly higher than that of control group,and the reduction frequency was lower than that of the control group(P<0.05).There was no statistically significant difference in the incidence and duration of residual dizziness symptoms after reduction(P>0.05).Conclusion Machine reduction can significantly improve the reduction efficiency of elderly BPPV patients,significantly shorten the duration of residual dizziness after reduction treatment in young and middle-aged patients,and reduce its incidence.

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.

Residual symptoms following electroconvulsive therapy: A retrospective cohort study.

BACKGROUND: Residual depressive symptoms following treatment are a burden for patients and are associated with increased risk of relapse. While this phenomenon has been explored following pharmacotherapy, there is little research into residual symptoms following electroconvulsive therapy (ECT). This study quantifies the frequency and type of residual symptoms following ECT treatment. METHODS: This study used retrospective data from patients receiving ECT as part of routine clinical care. Depressive symptomatology was assessed using the Quick Inventory of Depressive Symptomatology - Self-Report 16 item scale (QIDS), which includes 9 symptom domains graded from 0 to 3. We quantified the frequency of mild or greater (QIDS≥1) and moderate or greater (QIDS ≥ 2) residual symptoms following treatment among patients responding to ECT (QIDS decrease ≥50 % from baseline) and non-responders (QIDS decrease <50 %). RESULTS: Among 1799 patients, 1015 (56.4 %) responded to ECT and 784 (43.6 %) did not. Among responders, 99.5 % had at least one residual symptom of mild severity or greater (median = 5, IQR = 3-6) and 83.3 % had at least one residual symptom of moderate severity or greater (median = 1, IQR = 1-2). Among non-responders, 100 % had residual symptoms of mild severity or greater (median = 8, IQR = 7-9), and 99.2 % had a residual symptom of moderate severity or greater (median = 4, IQR = 3-5). The most common residual symptoms among both responders and non-responders were sleep disturbances (93.1 % and 98.7 %, respectively) and sadness (68.9 % and 96.4 %, respectively). LIMITATIONS: Retrospective data from a single freestanding psychiatric hospital. CONCLUSION: Among patients with depression receiving ECT, there were high rates of residual symptoms even among patients responding to treatment.

Corrigendum: Acceptance and commitment therapy preceded by attention bias modification on residual symptoms in depression: a 12-month follow-up.

[This corrects the article DOI: 10.3389/fpsyg.2019.01995.].

Residual insomnia in major depressive disorder: a systematic review.

Introduction: The ultimate goal in major depressive disorder (MDD) treatment is recovery. A proportion of MDD patients with formal remission experience persistent difficulties, which impair their daily functioning. Residual insomnia is one of the most common residual symptoms. Patients with residual insomnia experience relapse significantly earlier and have a poor prognosis. Little is known about possible ways of treatment and what subtype of insomnia is mostly reported. Methods: A systematic literature review was carried out in PubMed and Web of Science to synthesize the current status of knowledge about effective treatment methods and insomnia subtypes in residual insomnia in MDD. Results: A few non-pharmacological treatment methods e.g., Cognitive Behavioral Therapy for Insomnia (CBT-I), Mindfulness-Based Cognitive Therapy (MBCT), behavioral activation (BA) and pharmacological methods (gabapentin, clonazepam) have proven to mitigate residual insomnia. Cognitive Behavioral Therapy for Depression (CBT-D) ameliorates insomnia complaints to a limited extent. Mid-nocturnal insomnia is the most common residual insomnia subtype in MDD patients. Conclusion: Residual insomnia is a very common complaint and most often appears as mid-nocturnal insomnia. Scarce data points out the benefits from pharmacotherapy, psychotherapy, and BA. More research is needed.

[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.

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.

Long-term outcome of patients with neurological form of Wilson's disease compliant to the de-coppering treatment.

BACKGROUND: A substantial proportion of Wilson's disease (WD) patients exhibit residual neurological symptoms. Data on the prognostic value of initial clinical features and treatment choices in WD patients compliant to the therapy is relatively sparse. AIM: The aim of the present study was to identify predictors of the long-term outcome of patients with WD with good treatment adherence. METHODS: Forty patients with neurological form of WD were evaluated before the de-coppering treatment initiation (based on the medical records) and after mean 15.25 ± 11.24 years of the stable treatment. Severity of neurological symptoms were assessed with a tier two of Global Assessment Scale (GAS) for Wilson's Disease. RESULTS: The most frequent symptoms prior to treatment initiation were dysarthria (90%), tremor (90%), clumsiness (67.5%), depression (67.5%), and gait disturbance (62.5%). Significant decrease in the frequency of dysarthria, clumsiness, tremor, gait disturbance, postural instability and an improvement in school/work performance were observed after the long-term treatment, while frequency of dysphagia, drooling, bradykinesia and rigidity, dystonic and choreatic features did not change. Overall symptom severity decreased over time. Presence of dystonia before treatment initiation was the only identified predictor of worse residual GAS score. Greater severity of residual dystonia was associated with female gender and longer disease duration. CONCLUSION: Although patients with neurological form of WD compliant to de-coppering treatment had favorable disease outcome, a significant burden of residual neurological symptoms was observed after the long-term follow-up. Dystonia at disease onset was the only identified predictor of the worse long-term outcome.

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.

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.