Determinants of the onset and prognosis of the post-COVID-19 condition: a 2-year prospective observational cohort study.

Background: At least 5-10% of subjects surviving COVID-19 develop the post-COVID-19 condition (PCC) or "Long COVID". The clinical presentation of PCC is heterogeneous, its pathogenesis is being deciphered, and objective, validated biomarkers are lacking. It is unknown if PCC is a single entity or a heterogeneous syndrome with overlapping pathophysiological basis. The large US RECOVER study identified four clusters of subjects with PCC according to their presenting symptoms. However, the long-term clinical implications of PCC remain unknown. Methods: We conducted a 2-year prospective cohort study of subjects surviving COVID-19, including individuals fulfilling the WHO PCC definition and subjects with full clinical recovery. We systematically collected post-COVID-19 symptoms using prespecified questionnaires and performed additional diagnostic imaging tests when needed. Factors associated with PCC were identified and modelled using logistic regression. Unsupervised clustering analysis was used to group subjects with PCC according to their presenting symptoms. Factors associated with PCC recovery were modelled using a direct acyclic graph approach. Findings: The study included 548 individuals, 341 with PCC, followed for a median of 23 months (IQR 16.5-23.5), and 207 subjects fully recovered. In the model with the best fit, subjects who were male and had tertiary studies were less likely to develop PCC, whereas a history of headache, or presence of tachycardia, fatigue, neurocognitive and neurosensitive complaints and dyspnea at COVID-19 diagnosis predicted the development of PCC. The cluster analysis revealed the presence of three symptom clusters with an additive number of symptoms. Only 26 subjects (7.6%) recovered from PCC during follow-up; almost all of them (n = 24) belonged to the less symptomatic cluster A, dominated mainly by fatigue. Recovery from PCC was more likely in subjects who were male, required ICU admission, or had cardiovascular comorbidities, hyporexia and/or smell/taste alterations during acute COVID-19. Subjects presenting with muscle pain, impaired attention, dyspnea, or tachycardia, conversely, were less likely to recover from PCC. Interpretation: Preexisting medical and socioeconomic factors, as well as acute COVID-19 symptoms, are associated with the development of and recovery from the PCC. Recovery is extremely rare during the first 2 years, posing a major challenge to healthcare systems. Funding: Fundació Lluita contra les Infeccions.

Plasma proteomic profiling identifies CD33 as a marker of HIV control in natural infection and after therapeutic vaccination.

BACKGROUND: Biomarkers predicting the outcome of HIV-1 virus control in natural infection and after therapeutic interventions in HIV-1 cure trials remain poorly defined. The BCN02 trial (NCT02616874), combined a T-cell vaccine with romidepsin (RMD), a cancer-drug that was used to promote HIV-1 latency reversal and which has also been shown to have beneficial effects on neurofunction. We conducted longitudinal plasma proteomics analyses in trial participants to define biomarkers associated with virus control during monitored antiretroviral pause (MAP) and to identify novel therapeutic targets that can improve future cure strategies. METHODS: BCN02 was a phase I, open-label, single-arm clinical trial in early-treated, HIV infected individuals. Longitudinal plasma proteomes were analyzed in 11 BCN02 participants, including 8 participants that showed a rapid HIV-1 plasma rebound during a monitored antiretroviral pause (MAP-NC, 'non-controllers') and 3 that remained off ART with sustained plasma viremia <2000 copies/ml (MAP-C, 'controllers'). Inflammatory and neurological proteomes in plasma were evaluated and integration data analysis (viral and neurocognitive parameters) was performed. Validation studies were conducted in a cohort of untreated HIV-1+ individuals (n = 96) and in vitro viral replication assays using an anti-CD33 antibody were used for functional validation. FINDINGS: Inflammatory plasma proteomes in BCN02 participants showed marked longitudinal alterations. Strong proteome differences were also observed between MAP-C and MAP-NC, including in baseline timepoints. CD33/Siglec-3 was the unique plasma marker with the ability to discriminate between MAPC-C and MAP-NC at all study timepoints and showed positive correlations with viral parameters. Analyses in an untreated cohort of PLWH confirmed the positive correlation between viral parameters and CD33 plasma levels, as well as PBMC gene expression. Finally, adding an anti-CD33 antibody to in vitro virus cultures significantly reduced HIV-1 replication and proviral levels in T cells and macrophages. INTERPRETATION: This study indicates that CD33/Siglec-3 may serve as a predictor of HIV-1 control and as potential therapeutic tool to improve future cure strategies. FUNDING: Spanish Science and Innovation Ministry (SAF2017-89726-R and PID2020-119710RB-I00), NIH (P01-AI131568), European Commission (GA101057548) and a Grifols research agreement.

Feasibility of a wearable inertial sensor to assess motor complications and treatment in Parkinson's disease.

BACKGROUND: Wearable sensors-based systems have emerged as a potential tool to continuously monitor Parkinson's Disease (PD) motor features in free-living environments. OBJECTIVES: To analyse the responsivity of wearable inertial sensor (WIS) measures (On/Off-Time, dyskinesia, freezing of gait (FoG) and gait parameters) after treatment adjustments. We also aim to study the ability of the sensor in the detection of MF, dyskinesia, FoG and the percentage of Off-Time, under ambulatory conditions of use. METHODS: We conducted an observational, open-label study. PD patients wore a validated WIS (STAT-ONTM) for one week (before treatment), and one week, three months after therapeutic changes. The patients were analyzed into two groups according to whether treatment changes had been indicated or not. RESULTS: Thirty-nine PD patients were included in the study (PD duration 8 ± 3.5 years). Treatment changes were made in 29 patients (85%). When comparing the two groups (treatment intervention vs no intervention), the WIS detected significant changes in the mean percentage of Off-Time (p = 0.007), the mean percentage of On-Time (p = 0.002), the number of steps (p = 0.008) and the gait fluidity (p = 0.004). The mean percentage of Off-Time among the patients who decreased their Off-Time (79% of patients) was -7.54 ± 5.26. The mean percentage of On-Time among the patients that increased their On-Time (59% of patients) was 8.9 ± 6.46. The Spearman correlation between the mean fluidity of the stride and the UPDRS-III- Factor I was 0.6 (p = <0.001). The system detected motor fluctuations (MF) in thirty-seven patients (95%), whilst dyskinesia and FoG were detected in fifteen (41%), and nine PD patients (23%), respectively. However, the kappa agreement analysis between the UPDRS-IV/clinical interview and the sensor was 0.089 for MF, 0.318 for dyskinesia and 0.481 for FoG. CONCLUSIONS: It's feasible to use this sensor for monitoring PD treatment under ambulatory conditions. This system could serve as a complementary tool to assess PD motor complications and treatment adjustments, although more studies are required.

Sirtuin-2, NAD-Dependent Deacetylase, Is a New Potential Therapeutic Target for HIV-1 Infection and HIV-Related Neurological Dysfunction.

The implementation and access to combined antiretroviral treatment (cART) have dramatically improved the quality of life of people living with HIV (PLWH). However, some comorbidities, such as neurological disorders associated with HIV infection still represent a serious clinical challenge. Soluble factors in plasma that are associated with control of HIV replication and neurological dysfunction could serve as early biomarkers and as new therapeutic targets for this comorbidity. We used a customized antibody array for determination of blood plasma factors in 40 untreated PLWH with different levels of viremia and found sirtuin-2 (SIRT2), an NAD-dependent deacetylase, to be strongly associated with elevated viral loads and HIV provirus levels, as well as with markers of neurological damage (a-synuclein [SNCA], brain-derived neurotrophic factor [BDNF], microtubule-associated protein tau [MAPT], and neurofilament light protein [NFL]). Also, longitudinal analysis in HIV-infected individuals with immediate (n = 9) or delayed initiation (n = 10) of cART revealed that after 1 year on cART, SIRT2 plasma levels differed between both groups and correlated inversely with brain orbitofrontal cortex involution. Furthermore, targeting SIRT2 with specific small-molecule inhibitors in in vitro systems using J-LAT A2 and primary glial cells led to diminished HIV replication and virus reactivation from latency. Our data thus identify SIRT2 as a novel biomarker of uncontrolled HIV infection, with potential impact on neurological dysfunction and offers a new therapeutic target for HIV treatment and cure. IMPORTANCE Neurocognitive disorders are frequently reported in people living with HIV (PLWH) even with the introduction of combined antiretroviral treatment (cART). To identify biomarkers and potential therapeutic tools to target HIV infection in peripheral blood and in the central nervous system (CNS), plasma proteomics were applied in untreated chronic HIV-infected individuals with different levels of virus control. High plasma levels of sirtuin-2 (SIRT2), an NAD+ deacetylase, were detected in uncontrolled HIV infection and were strongly associated with plasma viral load and proviral levels. In parallel, SIRT2 levels in the peripheral blood and CNS were associated with markers of neurological damage and brain involution and were more pronounced in individuals who initiated cART later in infection. In vitro infection experiments using specific SIRT2 inhibitors suggest that specific targeting of SIRT2 could offer new therapeutic treatment options for HIV infections and their associated neurological dysfunction.

Neurocognitive Profile of the Post-COVID Condition in Adults in Catalonia-A Mixed Method Prospective Cohort and Nested Case-Control Study: Study Protocol.

The diagnosis of the post-COVID condition is usually achieved by excluding other diseases; however, cognitive changes are often found in the post-COVID disorder. Therefore, monitoring and treating the recovery from the post-COVID condition is necessary to establish biomarkers to guide the diagnosis of symptoms, including cognitive impairment. Our study employs a prospected cohort and nested case-control design with mixed methods, including statistical analyses, interviews, and focus groups. Our main aim is to identify biomarkers (functional and structural neural changes, inflammatory and immune status, vascular and vestibular signs and symptoms) easily applied in primary care to detect cognitive changes in post-COVID cases. The results will open up a new line of research to inform diagnostic and therapeutic decisions with special considerations for cognitive impairment in the post-COVID condition.

The role of acetylated cyclooxygenase-2 in the biosynthesis of resolvin precursors derived from eicosapentaenoic acid.

Specialized pro-resolving lipid mediators (SPMs) are natural bioactive agents actively involved in inflammation resolution. SPMs act when uncontrolled inflammatory processes are developed, for instance, in patients of COVID-19 or other diseases. The so-called resolution pharmacology aims at developing new treatments based on the use of SPMs as agonists, which promote inflammation resolution without unwanted side effects. It has been shown that the biosynthesis of SPMs called eicosapentaenoic acid (EPA)-derived E-series resolvins is initiated by aspirin-acetylated COX-2 from EPA, leading to 18-hydroperoxy-eicosapentaenoic acid (18-HpEPE). However, there are many open questions concerning the intriguing role of aspirin in the molecular mechanism of resolvin formation. Our MD simulations, combined with QM/MM calculations, show that the potential energy barriers for the H16-abstraction from EPA, required for forming 18-HpEPE, are higher than for the H13-abstraction, thus explaining why 18-HpEPE is a marginal product of COX-2 catalysis. By contrast, in the aspirin-acetylated COX-2/EPA complex, the H16proS-abstraction energy barriers are somewhat lower than the H13proS energy barriers and much smaller than the H16-transfer barriers in the wild type COX-2/EPA system. Those results agree with the experimental observation that aspirin favours the synthesis of several SPMs known as aspirin-triggered resolvins. In the following step of the catalytic mechanism, the calculated O2 addition to C18 is preferred versus the addition to C14 which also agrees with 18R-HEPE and 18S-HEPE being the main products from EPA in aspirin-acetylated COX-2.

Effects of integrase inhibitor-based antiretroviral therapy on brain outcomes according to time since acquisition of HIV-1 infection.

Integrase strand transfer inhibitors (INSTI) are a main component of the current antiretroviral regimens recommended for treatment of HIV infection. However, little is known about the impact of INSTI on neurocognition and neuroimaging. We developed a prospective observational trial to evaluate the effects of INSTI-based antiretroviral therapy on comprehensive brain outcomes (cognitive, functional, and imaging) according to the time since HIV-1 acquisition. We recruited men living with HIV who initiated antiretroviral therapy with INSTI < 3 months since the estimated date of HIV-1 acquisition (n = 12) and > 6 months since estimated date of HIV-1 acquisition (n = 15). We also recruited a group of matched seronegative individuals (n = 15). Assessments were performed at baseline (before initiation of therapy in HIV arms) and at weeks 4 and 48. Baseline cognitive functioning was comparable between the arms. At week 48, we did not find cognitive differences between starting therapy with INSTI earlier than 3 months or later than 6 months after acquisition of HIV-1 infection. Functional status was poorer in individuals diagnosed earlier. This effect recovered 48 weeks after initiation of therapy. Regarding brain imaging, we found that men living with HIV initiating antiretroviral therapy later experienced a greater decrease in medial orbitofrontal cortex over time, with expected negative repercussions for decision-making tasks.

Long-Term Effects in Bone Mineral Density after Different Bariatric Procedures in Patients with Type 2 Diabetes: Outcomes of a Randomized Clinical Trial.

There is scant evidence of the long-term effects of bariatric surgery on bone mineral density (BMD). We compared BMD changes in patients with severe obesity and type 2 diabetes (T2D) 5 years after randomization to metabolic gastric bypass (mRYGB), sleeve gastrectomy (SG) and greater curvature plication (GCP). We studied the influence of first year gastrointestinal hormone changes on final bone outcomes. Forty-five patients, averaging 49.4 (7.8) years old and body mass index (BMI) 39.4 (1.9) kg/m2, were included. BMD at lumbar spine (LS) was lower after mRYGB compared to SG and GCP: 0.89 [0.82;0.94] vs. 1.04 [0.91;1.16] vs. 0.99 [0.89;1.12], p = 0.020. A higher percentage of LS osteopenia was present after mRYGB 78.6% vs. 33.3% vs. 50.0%, respectively. BMD reduction was greater in T2D remitters vs. non-remitters. Weight at fifth year predicted BMD changes at the femoral neck (FN) (adjusted R2: 0.3218; p = 0.002), and type of surgery (mRYGB) and menopause predicted BMD changes at LS (adjusted R2: 0.2507; p < 0.015). In conclusion, mRYGB produces higher deleterious effects on bone at LS compared to SG and GCP in the long-term. Women in menopause undergoing mRYGB are at highest risk of bone deterioration. Gastrointestinal hormone changes after surgery do not play a major role in BMD outcomes.

Unraveling how the Gly526Ser mutation arrests prostaglandin formation from arachidonic acid catalyzed by cyclooxygenase-2: a combined molecular dynamics and QM/MM study.

Cyclooxygenases (COXs) are the enzymes responsible for the biosynthesis of prostaglandins, eicosanoids that play a major role in many physiological processes. Particularly, prostaglandins are known to trigger inflammation, and COX-2, the enzyme isoform associated with this inflammatory response, catalyzes the cyclooxidation of arachidonic acid, leading to prostaglandin G2. For this reason, COX-2 has been a very important pharmacological target for several decades now. The catalytic mechanism of COX-2, a so-called all-radical mechanism, consists of six chemical steps. One of the most intriguing aspects of this mechanism is how COX-2 manages to control the regio- and stereospecificity of the products formed at each step. Mutagenesis experiments have previously been performed in an attempt to find those hot-spot residues that make such control possible. In this context, it is worth mentioning that in experiments with the Gly526Ser COX-2 mutant, prostaglandins were not detected. In this paper, we have combined molecular dynamics simulations and quantum mechanics/molecular mechanics calculations to analyze how the COX-2 catalytic mechanism is modified in the Gly526Ser mutant. Therefore, this study provides new insights into the COX-2 catalytic function.

NEU Screen Shows High Accuracy in Detecting Cognitive Impairment in Older Persons Living With HIV.

The NEUrocognitive (NEU) Screen is a practical tool proposed to screen for HIV-associated cognitive impairment in the clinical setting. This is a pencil-and-paper method that can be applied rapidly (≤10 minutes for administration) and has no copyright limitations. In this study, we aimed at investigating its diagnostic accuracy in an older population of persons living with HIV (PLWH), with cutoffs set at 30, 40, 50, and 60 years. Data were collected from a sample of 368 PLWH who underwent a comprehensive neuropsychological tests battery (gold standard). Results of statistical tests showed that accuracy of the NEU Screen increased with age of the participants. The highest degree of precision, with a sensitivity of 91% and specificity of 92%, was obtained for people ages 60 years or older (correct classification: 91%). These optimal results point to the great potential of the NEU Screen as a tool for detecting cognitive disorders in older PLWH.

A "HOLTER" for Parkinson's disease: Validation of the ability to detect on-off states using the REMPARK system.

The treatment of Parkinson's disease (PD) with levodopa is very effective. However, over time, motor complications (MCs) appear, restricting the patient from leading a normal life. One of the most disabling MCs is ON-OFF fluctuations. Gathering accurate information about the clinical status of the patient is essential for planning treatment and assessing its effect. Systems such as the REMPARK system, capable of accurately and reliably monitoring ON-OFF fluctuations, are of great interest. OBJECTIVE: To analyze the ability of the REMPARK System to detect ON-OFF fluctuations. METHODS: Forty-one patients with moderate to severe idiopathic PD were recruited according to the UK Parkinson's Disease Society Brain Bank criteria. Patients with motor fluctuations, freezing of gait and/or dyskinesia and who were able to walk unassisted in the OFF phase, were included in the study. Patients wore the REMPARK System for 3days and completed a diary of their motor state once every hour. RESULTS: The record obtained by the REMPARK System, compared with patient-completed diaries, demonstrated 97% sensitivity in detecting OFF states and 88% specificity (i.e., accuracy in detecting ON states). CONCLUSION: The REMPARK System detects an accurate evaluation of ON-OFF fluctuations in PD; this technology paves the way for an optimisation of the symptomatic control of PD motor symptoms as well as an accurate assessment of medication efficacy.

Inhibition of Mammalian 15-Lipoxygenase by Three Ebselen-like Drugs. A QM/MM and MM/PBSA Comparative Study.

Ebselen is a potent competitive inhibitor of the active form of rabbit 15-lipoxygenase, an enzyme involved in many inflammatory diseases. Light-induced Z-to-E isomerization of the ebselen-like 2-(3-benzylidene)-3-oxo-2,3-dihydrobenzo[b]thiophene-7-carboxylic acid methyl ester (BODTCM) molecule was used to convert the weak (Z)-BOTDCM inhibitor into the (E)-isomer with much higher inhibitory capacity. In this study, the binding modes of ebselen, (E)-BOTDCM and (Z)-BOTDCM, have been analyzed to provide molecular insights on the inhibitory potency of ebselen and on the geometric-isomer specificity of (E)- and (Z)-BOTDCM inhibitors. The inhibitor-enzyme structures obtained from docking and molecular dynamics simulations as well as from QM/MM calculations show that the inhibitor molecules are not coordinated to the nonheme iron in the active site. Thermal motion allows ebselen and (E)-BOTDCM to visit a wide range of the configurational space competing with the polyunsaturated fatty acid for binding at the active site. Both molecules present similar MM/PBSA binding free energies. The energy penalty for the bigger geometric deformation undergone by (E)-BODTCM would explain its lower inhibitor potency. The (Z)-isomer is the weakest inhibitor because thermal motion moves it to a region very far from the first coordination sphere of Fe, where it could not compete with the fatty acid substrate.

Transdermal rivastigmine for HIV-associated cognitive impairment: A randomized pilot study.

OBJECTIVE: To assess the efficacy and safety of transdermal rivastigmine for the treatment of HIV-associated cognitive impairment. METHODS: We recruited HIV-infected patients with cognitive impairment on stable antiretroviral therapy in a randomized controlled pilot trial with a 48-week follow-up. An additional assessment was held at 12 weeks. Participants received transdermal rivastigmine (9.5 mg daily), lithium (400 mg twice daily, titrated progressively), or remained in a control group (no new medication). The primary efficacy endpoint was change in a global cognitive score (NPZ-7). Secondary endpoints included change in specific cognitive measures, domains, and functional parameters. Safety covered the frequency of adverse events and changes in laboratory results. RESULTS: Seventy-six subjects were screened, and 29 were finally enrolled. Better cognitive outcomes were observed in all groups, although there were no significant differences between the arms (mean NPZ-7 change [SD]): rivastigmine, 0.35 (0.14); lithium, 0.25 (0.40); control, 0.20 (0.44) (p = 0.78). The rivastigmine group showed the highest positive trend (mean NPZ-7 [SD], baseline vs week 48): rivastigmine, -0.47 (0.22) vs -0.11 (0.29), p = 0.06; lithium, -0.50 (0.40) vs -0.26 (0.21), p = 0.22; control, -0.52 (0.34) vs -0.32 (0.52), p = 0.44. The cognitive domains with the highest positive trends were information processing speed at week 12 and executive function at week 48 (rivastigmine vs control): information processing speed, 0.35 (0.64) vs -0.13 (0.25), p = 0.17, d = 0.96; and executive functioning, 0.73 (0.33) vs 0.03 (0.74), p = 0.09, d = 1.18. No relevant changes were observed regarding functional outcomes. A total of 12 (41%) individuals dropped out of the study: 2 (20%) were due to medication-related effects in the rivastigmine group and 4 (36%) in the lithium group. No severe adverse events were reported. CONCLUSIONS: The results from this small randomized trial indicate that transdermal rivastigmine did not provide significant cognitive benefits in people with HAND on stable antiretroviral therapy, even though positive trends were found in specific cognitive domains. Relevant tolerability issues were not observed.

A Waist-Worn Inertial Measurement Unit for Long-Term Monitoring of Parkinson's Disease Patients.

Inertial measurement units (IMUs) are devices used, among other fields, in health applications, since they are light, small and effective. More concretely, IMUs have been demonstrated to be useful in the monitoring of motor symptoms of Parkinson's disease (PD). In this sense, most of previous works have attempted to assess PD symptoms in controlled environments or short tests. This paper presents the design of an IMU, called 9 × 3, that aims to assess PD symptoms, enabling the possibility to perform a map of patients' symptoms at their homes during long periods. The device is able to acquire and store raw inertial data for artificial intelligence algorithmic training purposes. Furthermore, the presented IMU enables the real-time execution of the developed and embedded learning models. Results show the great flexibility of the 9 × 3, storing inertial information and algorithm outputs, sending messages to external devices and being able to detect freezing of gait and bradykinetic gait. Results obtained in 12 patients exhibit a sensitivity and specificity over 80%. Additionally, the system enables working 23 days (at waking hours) with a 1200 mAh battery and a sampling rate of 50 Hz, opening up the possibility to be used for other applications like wellbeing and sports.

Home detection of freezing of gait using support vector machines through a single waist-worn triaxial accelerometer.

Among Parkinson's disease (PD) symptoms, freezing of gait (FoG) is one of the most debilitating. To assess FoG, current clinical practice mostly employs repeated evaluations over weeks and months based on questionnaires, which may not accurately map the severity of this symptom. The use of a non-invasive system to monitor the activities of daily living (ADL) and the PD symptoms experienced by patients throughout the day could provide a more accurate and objective evaluation of FoG in order to better understand the evolution of the disease and allow for a more informed decision-making process in making adjustments to the patient's treatment plan. This paper presents a new algorithm to detect FoG with a machine learning approach based on Support Vector Machines (SVM) and a single tri-axial accelerometer worn at the waist. The method is evaluated through the acceleration signals in an outpatient setting gathered from 21 PD patients at their home and evaluated under two different conditions: first, a generic model is tested by using a leave-one-out approach and, second, a personalised model that also uses part of the dataset from each patient. Results show a significant improvement in the accuracy of the personalised model compared to the generic model, showing enhancement in the specificity and sensitivity geometric mean (GM) of 7.2%. Furthermore, the SVM approach adopted has been compared to the most comprehensive FoG detection method currently in use (referred to as MBFA in this paper). Results of our novel generic method provide an enhancement of 11.2% in the GM compared to the MBFA generic model and, in the case of the personalised model, a 10% of improvement with respect to the MBFA personalised model. Thus, our results show that a machine learning approach can be used to monitor FoG during the daily life of PD patients and, furthermore, personalised models for FoG detection can be used to improve monitoring accuracy.

Los grandes olvidados: Los trastornos cognitivos en la enfermedad de Parkinson / No disponible

Los trastornos cognitivos forman parte de la sintomatología de la enfermedad de Parkinson, son muy frecuentes, heterogéneos y pueden presentarse incluso desde el inicio de la enfermedad. Aunque durante años han recibido poca atención, tanto desde la investigación como desde la práctica clínica, la publicación en 2007 de los criterios de Demencia asociada a la EP y especialmente de Deterioro cognitivo Leve asociado a la EP (DCL-EP) en 2012 ha contribuido a que haya un renovado interés de clínicos y científicos en caracterizar dichos trastornos y en optimizar su tratamiento. Este interés ha hecho que se progrese en pocos años de una manera rápida en esta área. Los datos actuales muestran que es necesario actualizar los criterios de DCL-EP para poder seguir avanzando: requerir una exploración neuropsicológica completa y bien definida, establecer un punto de corte explícito con datos aceptables en sensibilidad y especificidad, y, sobre todo, poder clasificar el DCL-EP en unos subtipos que puedan guiarnos acerca del pronóstico, manejo y tratamiento del paciente

Cognitive disorders are part of the symptomatology of Parkinson’s disease. They are very common, heterogeneous and can be found since the onset of the disease. Nevertheless, for years, cognitive symptoms in PD have received scant attention both from research and from clinical practice. The pu-blication of criteria for dementia associated with PD in 2007 and especially the criteria for Mild Cognitive Impairment associated with PD (PD-MCI) in 2012, has contributed to a renewed interest in clinicians and scientists, to classify these disorders and optimize their treatment. This attention has helped on improving in this area quite fast. Current data show a need to update the criteria for MCI -EP to move forward: Ask for an exhaustive and well defined neuropsychological examination, establish an accurate cut-off with acceptable sensitivity and specificity data, and let classify the DCL-EP in subtypes that can help us the patient’s prognosis, management and treatment

Classification models for neurocognitive impairment in HIV infection based on demographic and clinical variables.

OBJECTIVE: We used demographic and clinical data to design practical classification models for prediction of neurocognitive impairment (NCI) in people with HIV infection. METHODS: The study population comprised 331 HIV-infected patients with available demographic, clinical, and neurocognitive data collected using a comprehensive battery of neuropsychological tests. Classification and regression trees (CART) were developed to obtain detailed and reliable models to predict NCI. Following a practical clinical approach, NCI was considered the main variable for study outcomes, and analyses were performed separately in treatment-naïve and treatment-experienced patients. RESULTS: The study sample comprised 52 treatment-naïve and 279 experienced patients. In the first group, the variables identified as better predictors of NCI were CD4 cell count and age (correct classification [CC]: 79.6%, 3 final nodes). In treatment-experienced patients, the variables most closely related to NCI were years of education, nadir CD4 cell count, central nervous system penetration-effectiveness score, age, employment status, and confounding comorbidities (CC: 82.1%, 7 final nodes). In patients with an undetectable viral load and no comorbidities, we obtained a fairly accurate model in which the main variables were nadir CD4 cell count, current CD4 cell count, time on current treatment, and past highest viral load (CC: 88%, 6 final nodes). CONCLUSION: Practical classification models to predict NCI in HIV infection can be obtained using demographic and clinical variables. An approach based on CART analyses may facilitate screening for HIV-associated neurocognitive disorders and complement clinical information about risk and protective factors for NCI in HIV-infected patients.

A brief and feasible paper-based method to screen for neurocognitive impairment in HIV-infected patients: the NEU screen.

OBJECTIVE: Practical screening methods are necessary to detect neurocognitive impairment (NCI) in HIV-infected patients. We aimed to find a brief and feasible paper-based tool to facilitate the diagnosis of an HIV-associated neurocognitive disorder. METHODS: A total of 106 HIV-infected outpatients with variable clinical characteristics were recruited in a multicenter investigation. NCI was diagnosed using a standardized neuropsychological tests battery (7 areas, 21 measures, ∼2 hours). Multiple score combinations were compared to find a paper-based method that took ≤10 minutes to apply. The presence of NCI was considered the gold standard for comparisons, and the sensitivity and specificity were calculated. RESULTS: Subjects were mostly middle-aged (median, 44 years) men (87%) on antiretroviral treatment. NCI was detected in 51 individuals (48%) and was associated with lower nadir CD4 count (P < 0.001), receiving antiretroviral therapy (P = 0.004), fewer years of education (P = 0.009), and presence of comorbidities (P < 0.001). The score combination that showed the highest sensitivity (74.5%) and specificity (81.8%) detecting NCI included 3 measures of attention/working memory, executive functioning, and verbal fluency (part A of Trail Making Test, part B of Trail Making Test, and Controlled Oral Word Association Test scores). A broader paper-based selection of measures covering 7 areas indicated a sensitivity of 100% and a specificity of 96.3% (7 measures, ∼35 minutes). CONCLUSIONS: The combination of the 3 measures presented in this study seems to be a rapid and feasible screening mean for NCI in HIV-infected patients. This approach, combined with screening for potential comorbidities and daily functioning interference, could help in the initial stages of a HIV-associated neurocognitive disorder diagnosis and in settings with limited access to neuropsychological resources.

Virological efficacy in cerebrospinal fluid and neurocognitive status in patients with long-term monotherapy based on lopinavir/ritonavir: an exploratory study.

BACKGROUND: Data on suppression of HIV replication in the CNS and on the subsequent risk of neurocognitive impairment using monotherapy with boosted protease inhibitors are limited. METHODS: Ours was an exploratory cross-sectional study in patients on lopinavir/ritonavir-based monotherapy (LPV/r-MT) or standard triple therapy (LPV/r-ART) for at least 96 weeks who maintained a plasma viral load <50 copies/mL. HIV-1 RNA in CSF was determined by HIV-1 SuperLow assay (lower limit of detection, 1 copy/mL). Neurocognitive functioning was assessed using a recommended battery of neuropsychological tests covering 7 areas. Neurocognitive impairment (NCI) was determined and also a global deficit score (GDS) for study comparisons. RESULTS: Seventeen patients on LPV/r-MT and 17 on LPV/r-ART were included. Fourteen (82.4%) patients on LPV/r-MT and 16 (94.1%) on LPV/r-ART had HIV-1 RNA <1 copy/mL in CSF (p = 0.601). NCI was observed in 7 patients on LPV/r-MT and in 10 on LPV/r-ART (41% vs 59%; p = 0.494). Mean (SD) GDS was 0.22 (0.20) in patients on LPV/r-MT and 0.47 (0.34) in those on LPV/r-ART (p = 0.012). CONCLUSIONS: Suppression of HIV in CSF is similar in individuals with durable plasma HIV-1 RNA suppression who are receiving LPV/r-MT or LPV/r-ART for at least 96 weeks. Findings for HIV-1 replication in CSF and neurocognitive status indicate that this strategy seems to be safe for CNS functioning.

Consciencia de disfagia en la enfermedad de Parkinson / Awareness of dysphagia in Parkinson's disease

Introducción y objetivo. Con el fin de evaluar el nivel de consciencia de los trastornos de la deglución en la enfermedad de Parkinson (EP), se ha diseñado y validado un cuestionario específico, el Dysphapark. Pacientes y métodos. Un total de 470 afectados de EP han respondido a la pregunta de si creen que tienen o no problemas de deglución, y seguidamente han cumplimentado un cuestionario autoadministrado que valora la eficacia y seguridad de la deglución. Se validó el Dysphapark a través del análisis de Rasch y métodos psicométricos clásicos. Resultados. Las dimensiones de seguridad y eficacia del Dysphapark muestran un buen ajuste al modelo de Rasch. La dimensión eficacia mostró diferencias significativas por género, duración de la enfermedad, consciencia de disfagia y duración de las comidas; la dimensión seguridad, por duración y gravedad de la enfermedad, consciencia de disfagia, logoterapia y conocimiento de espesante. A pesar de que un 90% de los pacientes tenía problemas de eficacia y seguridad en la deglución, un 79,45% no era consciente de padecer disfagia. Conclusiones. El cuestionario Dysphapark es una medida adecuada de la disfagia en EP, según el análisis de Rasch. Una alta proporción de pacientes con EP tiene disfagia, observándose una baja consciencia de la condición, de las consecuencias que puede tener y de la posibilidad de usar espesante. Dado que algunos de los trastornos de la deglución en la EP son asintomáticos y que existe una baja consciencia del trastorno, es recomendable incluir cuestionarios específicos, así como valoración clínica e instrumental de la disfagia en la práctica clínica

Introduction and aim. In order to be able to assess the level of awareness of swallowing disorders in Parkinson’s disease (PD), a specific questionnaire was designed and validated: the Dysphapark questionnaire. Patients and methods. A total of 470 persons with PD were asked whether they believe they have problems swallowing or not, and then they filled in a self-administered questionnaire that evaluates the effectiveness and safety of swallowing. The Dysphapark questionnaire was validated by means of Rasch analysis and classical psychometric methods. Results. The safety and effectiveness dimensions of the Dysphapark fit the Rasch model well. The efficacy dimensionshowed significant differences for gender, length of the illness, awareness of dysphagia and length of meals. Significant differences were also found in the safety dimension for length and severity of illness, awareness of dysphagia, speech therapy and knowledge of thickening agents. Despite the fact that 90% of patients had problems concerning effectiveness and safety in swallowing, 79.45% were not aware that they suffered from dysphagia. Conclusions. The Dysphapark questionnaire is a suitable measure of dysphagia in PD, according to the Rasch analysis. A high proportion of patients with PD have dysphagia, although it has been observed that they have a low level of awareness of the condition, of the consequences it may have and of the possibility of using thickening agents. Given that some of the swallowing disorders in PD are asymptomatic and that the level of awareness of the disorder is low, we recommend including specific questionnaires as well as clinical and instrumental evaluation of dysphagia in clinical practice