Effectiveness of Individual Cognitive-Behavioral Therapy and Predictors of Outcome in Adult Patients with Obsessive-Compulsive Disorder

<b><i>Introduction:</i></b> Cognitive-behavioral therapy (CBT) for obsessive-compulsive disorder (OCD) has proven its efficacy in randomized controlled trials (RCTs). <b><i>Objective:</i></b> To test generalizability to routine care settings, we conducted an effectiveness study to provide naturalistic outcome data and their predictors. <b><i>Methods:</i></b> Pre-post changes in symptoms and impairment as well as response rates were determined in a naturalistic OCD sample (intention-to-treat, ITT, <i>n</i> = 393). Patients received individual CBT for OCD adopting an exposure-based, non-manualized treatment format. Linear and logistic regression analyses were applied to identify associations of sociodemographic and clinical variables with symptom change. <b><i>Results:</i></b> Effect size in ITT patients amounted to <i>d</i> = 1.47 in primary outcome (Yale-Brown Obsessive-Compulsive Scale, Y-BOCS). Remission rates were 46.3% (ITT), 52.0% (completers), and 18.2% (non-completers). The rates of treatment response without remission, no change, and deterioration in the ITT sample were 13.2, 38, and 3%, respectively. Initial symptom severity, comorbid personality disorder, and unemployment were associated with a poorer outcome, and previous medication with a better outcome. Comorbid depressive and anxiety disorders as well as other clinical or sociodemographic variables showed no effects on symptom change. <b><i>Conclusions:</i></b> Outcomes in this large observational trial in a naturalistic setting correspond to available RCT findings suggesting that CBT for OCD should be strongly recommended for dissemination in routine care. Targets for further research include early prediction of non-response and development of alternative treatment strategies for patients who respond insufficiently.

Delays in the presentation and diagnosis of women with breast cancer in Yogyakarta, Indonesia: A retrospective observational study

Purpose To investigate factors associated with delays in presentation and diagnosis of women with confirmed breast cancer (BC). Methods A cross-sectional study nested in an ongoing prospective cohort study of breast cancer patients at Dr Sardjito Hospital, Yogyakarta, Indonesia, was employed. Participants (n = 150) from the main study were recruited, with secondary information on demographic, clinical, and tumor variables collected from the study database. A questionnaire was used to gather data on other socioeconomic variables, herbal consumption, number of healthcare visits, knowledge-attitude-practice of BC, and open-ended questions relating to initial presentation. Presentation delay (time between initial symptom and first consultation) was defined as ≥3 months. Diagnosis delay was defined as ≥1 month between presentation and diagnosis confirmation. Impact on disease stage and determinants of both delays were examined. A Kruskal-Wallis test was used to assess the length and distribution of delays by disease stage. A multivariable logistic regression analysis was conducted to explore the association between delays, cancer stage and factors. Results Sixty-five (43.3%) patients had a ≥3-month presentation delay and 97 (64.7%) had a diagnosis confirmation by ≥1 month. Both presentation and diagnosis delays increased the risk of being diagnosed with cancer stage III-IV (odds ratio/OR 2.21, 95% CI 0.97–5.01, p = 0.059 and OR 3.03, 95% CI 1.28–7.19, p = 0.012). Visit to providers ≤3 times was significantly attributed to a reduced diagnosis delay (OR 0.15, 95% CI 0.06–0.37, p <0.001), while having a family history of cancer was significantly associated with increased diagnosis delay (OR 2.28, 95% CI 1.03–5.04, p = 0.042). The most frequent reasons for delaying presentation were lack of awareness of the cause of symptoms (41.5%), low perceived severity (27.7%) and fear of surgery intervention (26.2%). Conclusions Almost half of BC patients in our setting had a delay in presentation and 64.7% experienced a delay in diagnosis. These delays increased the likelihood of presentation with a more advanced stage of disease. Future research is required in Indonesia to explore the feasibility of evidence-based approaches to reducing delays at both levels, including educational interventions to increase awareness of BC symptoms and reducing existing complex and convoluted referral pathways for patients suspected of having cancer.

Syncope as the Initial Manifestation of Advanced Nasopharyngeal Carcinoma: A Case Report

Carotid sinus syndrome is a principal cause of syncope in the elderly. Syncope, associated with carotid sinus syndrome which is secondary to metastasis of advanced nasopharyngeal carcinoma, rarely occurs. The current study reported a 66-year-old woman, who presented with a history of frequent and recurrent syncope as the initial symptom, and was eventually diagnosed with advanced nasopharyngeal carcinoma. The positron emission tomography scan demonstrated a diagnosis of advanced nasopharyngeal carcinoma with involvement in carotid sheath space, and nasopharyngeal biopsy revealed non-keratinized nasopharyngeal carcinoma. After diagnosis and treatment, the patient had no recurrence of syncope. In summary, our case study suggests that great importance should be attached to potential intrinsic causes of syncope especially in the case of nasopharyngeal carcinoma, as it is an insidious malignancy which needs to be precisely identified.

Accumulation of APP-CTF induces mitophagy dysfunction in the iNSCs model of Alzheimer’s disease

Mitochondrial dysfunction is associated with familial Alzheimer’s disease (fAD), and the accumulation of damaged mitochondria has been reported as an initial symptom that further contributes to disease progression. In the amyloidogenic pathway, the amyloid precursor protein (APP) is cleaved by β-secretase to generate a C-terminal fragment, which is then cleaved by γ-secretase to produce amyloid-beta (Aβ). The accumulation of Aβ and its detrimental effect on mitochondrial function are well known, yet the amyloid precursor protein-derived C-terminal fragments (APP-CTFs) contributing to this pathology have rarely been reported. We demonstrated the effects of APP-CTFs-related pathology using induced neural stem cells (iNSCs) from AD patient-derived fibroblasts. APP-CTFs accumulation was demonstrated to mainly occur within mitochondrial domains and to be both a cause and a consequence of mitochondrial dysfunction. APP-CTFs accumulation also resulted in mitophagy failure, as validated by increased LC3-II and p62 and inconsistent PTEN-induced kinase 1 (PINK1)/E3 ubiquitin ligase (Parkin) recruitment to mitochondria and failed fusion of mitochondria and lysosomes. The accumulation of APP-CTFs and the causality of impaired mitophagy function were also verified in AD patient-iNSCs. Furthermore, we confirmed this pathological loop in presenilin knockout iNSCs (PSEN KO-iNSCs) because APP-CTFs accumulation is due to γ-secretase blockage and similarly occurs in presenilin-deficient cells. In the present work, we report that the contribution of APP-CTFs accumulation is associated with mitochondrial dysfunction and mitophagy failure in AD patient-iNSCs as well as PSEN KO-iNSCs.

Infantile idiopathic intracranial hypertension: case report and review of the literature

Background Idiopathic intracranial hypertension is an infrequent condition of childhood, and is extremely rare in infants, with only 26 cases described. The etiology is still unknown. Typical clinical manifestations change with age, and symptoms are atypical in infants, thus the diagnosis could be late. This is based on increased opening pressure at lumbar puncture, papilloedema and normal cerebral MRI. The measurement of cerebrospinal fluid opening pressure in infants is an issue because many factors may affect it, and data about normal values are scanty. The mainstay of treatment is acetazolamide, which allows to relieve symptoms and to avoid permanent visual loss if promptly administered. Case presentation We report the case of an 8-month-old infant admitted because of vomit, loss of appetite and irritability; later, also bulging anterior fontanel was observed. Cerebral MRI and cerebrospinal fluid analysis resulted negative and after two lumbar punctures he experienced initial symptom relief. Once the diagnosis of idiopathic intracranial hypertension was made, he received oral acetazolamide, and corticosteroids, with progressive symptom resolution. Conclusions Infantile idiopathic intracranial hypertension is extremely rare, and not well described yet. Bulging anterior fontanel in otherwise healthy infants with normal neuroimaging should be always considered suggestive, but can be a late sign, while irritability and anorexia, especially if associated with vomiting, may represent an early sign. In such cases, lumbar puncture should be always done, hopefully with cerebrospinal fluid opening pressure measurement, which is among coded diagnostic criteria, but whose threshold is controversial in infants. Early diagnosis, timely treatment and strict follow-up help to prevent vision loss or death of affected infants.

Local Structure Awareness-Based Retinal Microaneurysm Detection with Multi-Feature Combination

Retinal microaneurysm (MA) is the initial symptom of diabetic retinopathy (DR). The automatic detection of MA is helpful to assist doctors in diagnosis and treatment. Previous algorithms focused on the features of the target itself; however, the local structural features of the target and background are also worth exploring. To achieve MA detection, an efficient local structure awareness-based retinal MA detection with the multi-feature combination (LSAMFC) is proposed in this paper. We propose a novel local structure feature called a ring gradient descriptor (RGD) to describe the structural differences between an object and its surrounding area. Then, a combination of RGD with the salience and texture features is used by a Gradient Boosting Decision Tree (GBDT) for candidate classification. We evaluate our algorithm on two public datasets, i.e., the e-ophtha MA dataset and retinopathy online challenge (ROC) dataset. The experimental results show that the performance of the trained model significantly improved after combining traditional features with RGD, and the area under the receiver operating characteristic curve (AUC) values in the test results of the datasets e-ophtha MA and ROC increased from 0.9615 to 0.9751 and from 0.9066 to 0.9409, respectively.

COVID-19 AND THE HUMAN EYE – CONJUNCTIVITIS A LONE COVID-19 FINDING - A case-control study

Background: The worldwide sudden appearance and drastic increase in the number of infected cases with the severe acute respiratory syndrome-Coronavirus 2 (SARS-CoV-2) determined the World Health Organization to declare it as a pandemic situation. The ‘Corona Virus Disease 2019’ (COVID-19) has varied clinical manifestations, from asymptomatic to severe cases, and conjunctivitis, seems not only to be one of them, but sometimes found to be lone initial symptom present. Aim and method: The aim was to identify the prevalence of conjunctivitis as the first symptom in COVID-19 patients, in a primary healthcare unit. A retrospective study was conducted analyzing the presenting complains/symptoms and results of COVID-19 confirmatory tests. Results: Out of the 672 cases that were sent for RT-PCR testing only 121 (18%) were found to be positive. Among this 2.67% of patients who had both conjunctivitis and COVID-19, 77.77% of patients had unilateral eye affected while 22.22% had bilateral conjunctivitis of varying degrees. 15 patients diagnosed to have both acute conjunctivitis and COVID-19, presented other symptoms associated with COVID-19 infection. While 3 patients had only acute conjunctivitis during their entire course of COVID-19. Conclusions: Conjunctivitis is a symptom of COVID-19 and maybe the first sign of the infection, until the onset of the classical manifestations, the patient serves to be a viral reservoir. The physicians should not miss unilateral conjunctivitis, as it can be the only presenting complain of the COVID-19 disease at the initial phase, which might worsen if underwent undetected and can aid in the spread of the contagion.

Mildly Impaired Foot Control in Long-Term Treated Patients with Wilson’s Disease

Abnormal gait is a common initial symptom of Wilson’s disease, which responds well to therapy, but has not been analyzed in detail so far. In a pilot study, a mild gait disturbance could be detected in long-term treated Wilson patients. The question still is what the underlying functional deficit of this gait disturbance is and how this functional deficit correlates with further clinical and laboratory findings. In 30 long-term treated Wilson patients, the vertical component of foot ground reaction forces (GRF-curves) was analyzed during free walking without aid at the preferred gait speed over a distance of 40 m. An Infotronic® gait analysis system, consisting of soft tissue shoes with solid, but flexible plates containing eight force transducers, was used to record the pressure of the feet on the floor. Parameters of the GRF-curves were correlated with clinical scores as well as laboratory findings. The results of Wilson patients were compared to those of an age- and sex-matched control group. In 24 out of 30 Wilson patients and all controls, two peaks could be distinguished: the first “heel-on” and the second “push-off” peak. The heights of these peaks above the midstance valley were significantly reduced in the patients (p < 0.05). The time differences between peaks 1 or 2 and midstance valley were significantly negatively correlated with the total impairment score (p < 0.05). Gait speed was significantly correlated with the height of the “push-off” peak above the midstance valley (p < 0.045). The GRF-curves of free walking, long-term treated patients with Wilson’s disease showed a reduced “push-off” peak as an underlying deficit to push the center of mass of the body to the contralateral side with the forefoot, explaining the reduction in gait speed during walking.