A circuit-based approach to modulate hypersexuality in Parkinson's disease.

AIM: Impulse-control disorder is a common neuropsychiatric complication in Parkinson's disease (PD) under dopamine replacement therapy. Prior studies tested the balance between enhanced desire towards reward and cognitive control deficits, hypothesized to be biased towards the former in impulse control disorders. We provide evidence for this hypothesis by measuring behavioral and neural patterns behind the influence of sexual desire over response inhibition and tools towards functional restoration using repetitive transcranial stimulation in patients with hypersexuality as predominant impulsive disorder. METHODS: The effect of sexual cues on inhibition was measured with a novel erotic stop-signal task under on and off dopaminergic medication. Task-related functional and anatomical connectivity models were estimated in 16 hypersexual and 17 nonhypersexual patients with PD as well as in 17 healthy controls. Additionally, excitatory neuromodulation using intermittent theta-burst stimulation (sham-controlled) was applied over the pre-supplementary motor area in 20 additional hypersexual patients with PD aiming to improve response inhibition. RESULTS: Compared with their nonhypersexual peers, patients with hypersexuality recruited caudate, pre-supplementary motor area, ventral tegmental area, and anterior cingulate cortex while on medication. Reduced connectivity was found between pre-supplementary motor area and caudate nucleus in hypersexual compared with nonhypersexual patients (while medicated), a result paralleled by compensatory enhanced anatomical connectivity. Furthermore, stimulation over the pre-supplementary motor area improved response inhibition in hypersexual patients with PD when exposed to sexual cues. CONCLUSION: This study, therefore, has identified a specific fronto-striatal and mesolimbic circuitry underlying uncontrolled sexual responses in medicated patients with PD where cortical neuromodulation halts its expression.

Screening of imported malaria infection in asymptomatic migrants from Sub-Saharan Africa: A retrospective analysis of a 2010-2019 cohort.

BACKGROUND: Up to 40% of cases of imported malaria in Europe are diagnosed in recently arrived migrants, who generally exhibit asymptomatic or mild symptoms and show low parasitaemia (submicroscopic). The study describes the prevalence of malaria infection among asymptomatic Sub-Saharan African migrants (ASSAM) and compares asymptomatic malaria-infected (AMI) vs non-malaria infected patients. METHODS: An observational, comparative, retrospective study was carried out in ASSAM who underwent a medical examination, between 2010 and 2019 at the National Reference Unit for Tropical Diseases (NRU-Trop) in Madrid, Spain. Medical examination and systematic screening protocol for infectious diseases, including screening for malaria infection by Polymerase Chain Reaction (PCR) was performed. RESULTS: During the study period, 632 out of 1061 ASSAM were screened for malaria, median age: 24 years (IQR:1-5); median time from arrival to diagnosis: 2 months (IQR:1-5). P. falciparum was the most frequent species: 61 patients (67.8%). Compared to non-malaria infected, AMI subjects had: higher rate of co-infection with S. stercoralis (41.1%VS 22.9%;p < 0.001) and filariae (8.9% VS 2.4%;p = 0.006), lower erythrocyte corpuscular volume (83.6 VS 84.4;p = 0.008) and lower levels of cholesterol (151.0 VS 167.3;p < 0.001). CONCLUSIONS: We observed a high prevalence of AMI among ASSAM. This highlights the need to consider routing screening of migrants from endemic areas and to study if such screening could avoid the potential morbidities associated with chronic infection, reduce morbi-mortality of acute malaria and the risk of transmission in host communities.

Critical analysis of Chagas disease treatment in different countries.

As a result of globalization and constant migratory flows, Chagas disease is now present in almost all continents. The management and treatment of the disease is often influenced by the economic and social context of the societies that host patients. In this manuscript, we aim to provide a comparative review of approaches to patients with Chagas disease in the Americas and Europe.

Pain management & opioid dose reduction with topical sevoflurane instillations in intractable venous ulcers: a case report

Abstract Vascular ulcers (VU) constitute a major cause of pain and disability, and significantly compromise quality of life. VU have a natural tendency to become chronic and in many cases exhibit anunsatisfactoryresponse to many of the standard therapeutic options.The case of a 73 year-old Caucasian female with severe pain and poorly-controlled pain (Visual Analogic Scale-VAS- of 8-9) due to three lower leg long-standing VUs is reported and discussed herein. The patient was treated with topical instillations of undiluted sevoflurane as per institutional off-label protocol (starting doses of 1mL/cm2 twice a day, and up-titrated according to response to a maximum of 7 mL twice daily). The VAS score dropped to 0-1 shortly after initiation of therapy and remained stable throughout treatment up until the closure of the observations. Subsequently, opioid therapy was gradually tapered down and ultimately abandoned.Sevoflurane application resulted on adequate and sustained pain management of refractory VU, with no significant side effects. On account of its beneficial effectivity and safety profiles, topical sevoflurane emerges as an add-on alternative for the long-term management of VU, and potentially other painful conditions.

Critical analysis of Chagas disease treatment in different countries

As a result of globalization and constant migratory flows, Chagas disease is now present in almost all continents. The management and treatment of the disease is often influenced by the economic and social context of the societies that host patients. In this manuscript, we aim to provide a comparative review of approaches to patients with Chagas disease in the Americas and Europe.

Increased YKL-40 but Not C-Reactive Protein Levels in Patients with Alzheimer's Disease.

Neuroinflammation is a common feature in Alzheimer's (AD) and Parkinson's (PD) disease. In the last few decades, a testable hypothesis was proposed that protein-unfolding events might occur due to neuroinflammatory cascades involving alterations in the crosstalk between glial cells and neurons. Here, we tried to clarify the pattern of two of the most promising biomarkers of neuroinflammation in cerebrospinal fluid (CSF) in AD and PD. This study included cognitively unimpaired elderly patients, patients with mild cognitive impairment, patients with AD dementia, and patients with PD. CSF samples were analyzed for YKL-40 and C-reactive protein (CRP). We found that CSF YKL-40 levels were significantly increased only in dementia stages of AD. Additionally, increased YKL-40 levels were found in the cerebral orbitofrontal cortex from AD patients in agreement with augmented astrogliosis. Our study confirms that these biomarkers of neuroinflammation are differently detected in CSF from AD and PD patients.

Aberrant Salient and Corticolimbic Connectivity in Hypersexual Parkinson's Disease.

Introduction: Impulse control disorders (ICDs) represent a side effect of dopaminergic medication in Parkinson's disease (PD). Patients experience an excessive desire toward natural rewards paired with uncontrolled actions. Yet, the precise neural and behavioral mechanisms associated with ICDs and, importantly, each specific subdomain remain unclear. We aim to decipher resting-state and corticolimbic functional connectivity in PD patients with and without hypersexual ICD. Materials and Methods: Seventeen PD patients with hypersexuality (PD+HS) and 15 PD patients without hypersexuality (PD-HS) underwent two sessions (with and without medication) of resting-state functional magnetic resonance imaging and were compared with 17 healthy controls. Dual-regression independent component analyses extracted salience, sensorimotor, default-mode, and central executive networks. Seed-based functional connectivity with three striatal subdivisions (motor, associative, and limbic) was obtained and significant changes were correlated with key impulsivity and inhibitory measures. Results: Enhanced salience network (SN) activity represented by a significant rise in the right inferior frontal gyrus was found in PD+HS compared with PD-HS. Connectivity analyses revealed a functional disconnection between associative and limbic striatum with precuneus and superior parietal lobe in PD+HS, some connections explained by abnormal sexual behavior and inhibition in PD+HS. Conclusions: Hypersexual ICD is associated with enhanced SN signaling and corticolimbic disconnections, including striatal associative and limbic loops that contribute to altered control of sexually driven behavior and overall severity in PD and ICD. Impact statement We enlarge the neurobiological basis to one specific Parkinson's disease (PD) and impulse control disorder (ICD) (PD+ICD) subtype-that is, hypersexuality-and reveal its associated resting-state functional connectivity linked to altered behavior. We report enhanced salience network and right inferior frontal gyrus as part of the underlying resting-state functional networks in PD patients with hypersexuality (PD+HS). Corticolimbic changes were associated with sexual severity in PD+HS to hypoactive connectivity between associative-limbic striatum with precuneus and superior parietal lobe. The connectivity changes seen in PD+HS could explain baseline differences that engender aberrant control over sexual behavior in ICD.

Seroprevalence of vaccine-preventable and non-vaccine-preventable infections in migrants in Spain.

BACKGROUND: Updated seroprevalence studies of infections in migrants may aid the design of tailored vaccination and prevention programmes. The objective of this study was to describe the seroprevalence rates for potentially transmissible viral infections in migrants attended at a referral centre in a major European city. METHODS: Descriptive analysis of seroprevalence of vaccine-preventable and non-vaccine-preventable infections in migrants attended at a centre in Madrid, Spain (2018-19). Recorded variables included age, gender, country of birth/continent of origin, time from arrival to Spain until first clinic visit, rubella, measles, mumps, varicella (VZV), hepatitis B virus (HBV), hepatitis A virus (HAV), hepatitis C virus (HCV) and HIV serology. RESULTS: In total, 468 patients were included, 135 females (28.8%) and 333 males (71.2%), mean age 30.4 years. The majority of patients were from Africa (52.5%, of which 88.2% from sub-Saharan Africa), followed by Latin America (38.5%) and other areas (9%). Seroprevalence for tested migrants for rubella, measles and mumps was < 95% in the group overall (91% rubella, 88% measles, 83% mumps) and lower rates were observed in migrants >20 years (compared with those ≤ 20 years). Over 10% of females were potentially susceptible (negative/indeterminate serology) to rubella (11.4%), measles (12.7%) or mumps (10.3%). Lowest rates of rubella seropositivity were in Latin American migrants (over 12% potentially susceptible); measles and mumps seropositivity was lowest in migrants from areas other than Africa/Latin America (74% and 68%, respectively). Seroprevalence rates were 91% for VZV, 90% overall for HAV, ~6% for HBV chronic infection (~50% of migrants tested susceptible), 2% for HCV and 6% for HIV. CONCLUSIONS: Differences in seroprevalence for vaccine-preventable and transmissible infections according to gender, age range and area of origin were observed. Tailored screening, vaccination and prevention strategies in potentially vulnerable migrant groups should be designed.

COVID-19 and geographical area of origin.

OBJECTIVES: To describe and compare the main clinical characteristics and outcome measures in hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) according to geographical area of origin. METHODS: A retrospective analysis of patients hospitalized with confirmed COVID-19 at a referral centre in Madrid, Spain, during March-May 2020 was performed. Recorded variables (age, gender, intensive care unit (ICU) admission, outcome), and geographical area of origin were compared for Europeans and non-Europeans (Latin Americans, Asians and Africans). RESULTS: In total, 2345 patients with confirmed COVID-19 hospitalized during the study period were included in the study. Of these, 1956 (83.4%) were European and 389 (16.6%) were non-European (of whom over 90%, 354/389, were Latin American). Non-Europeans were significantly younger than Europeans (mean 54 (SD 13.5) versus 70.4 (SD 15.1) years, p < 0.001); the majority were male (1420/2345, 60.6%), with no significant differences in gender between Europeans and non-Europeans (1197/1956 (61.2%) male in the European group versus 223/389 (57.3%) male in the non-European group, p 0.15). In-hospital mortality overall was higher in Europeans (443/1956, 22.7%) than in non-Europeans (40/389, 10.3%) (p < 0.001), but there were no significant differences when adjusted for age/gender (OR 1.27, 95% CI 0.86-1.88). Non-Europeans were more frequently admitted to ICU (71/389, 18.3%) compared with Europeans (187/1956, 9.6%) (p < 0.001) and a difference in ICU admission rate was also found when adjusted for age/gender (OR 1.43, 95% CI 1.03-1.98). CONCLUSIONS: No significant differences in mortality were observed between Europeans and non-Europeans (mainly Latin Americans), but an increase in ICU admission rate was found in non-Europeans.

Efficacy and Safety of a Novel Submucosal Injection Solution for Resection of Gastrointestinal Lesions.

Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are minimally invasive and efficient techniques for the removal of gastrointestinal (GI) mucosal polyps. In both techniques, submucosal injection solutions are necessary for complete effectiveness and safety during the intervention to be obtained. The main objective of this study was to evaluate the efficacy and safety of a new sterile submucosal injection solution for EMR/ESD used within a clinical protocol in patients with intestinal polyps. We carried out a prospective study between 2016 and 2017 with patients who attended the Endoscopy Consultation-Digestive Department of Primary Hospital. Patients were selected for EMR/ESD after the application of clinical protocols. Thirty-six patients were selected (≥ 66 years with comorbidities and risk factors). Lesions were located mainly in the colon. Our solution presented an intestinal lift ≥ 60 min in EMR/ESD and a high expansion of tissue, optimum viscosity, and subsequent complete resorption. The genes S100A9 and TP53 presented an expression increase in the distal regions. TP53 and PCNA were the only genes whose expression was increased in polyp specimens vs. the surrounding tissue at the mRNA level. In EMR/ESD, our solution presented a prolonged effect at the intestinal level during all times of the intervention. Thus, our solution seems be an effective and safe alternative in cases of flat lesions in both techniques.

Imported Arbovirus Infections in Spain, 2009-2018.

To determine the epidemiologic and clinical characteristics of patients in Spain with imported arbovirus infections, we analyzed 22,655 records from a collaborative network for January 2009-December 2018. Among 861 arbovirus infections, 845 were monoinfections (456 [53%] dengue, 280 [32.5%] chikungunya, 109 [12.7%] Zika) and 16 (1.8%) were co-infections. Most patients were travelers (56.3%) or immigrants returning to Spain after visiting friends or relatives (31.3%). Median patient age was 37 years; most (62.3%) were women and some (28.6%) had received pretravel advice. Only 12 patients were immunosuppressed. Six cases (all dengue monoinfections, none in immunosuppressed patients) were severe. Since 2014, nondengue arbovirus infections increased; until 2016, chikungunya and Zika were most common. Imported arbovirus infections (mostly dengue) were frequently diagnosed, although increased chikungunya and Zika virus infections coincided with their introduction and spread in the Americas. A large proportion of cases occurred in women of childbearing age, some despite receipt of pretravel advice.

Update on the major imported protozoan infections in travelers and migrants.

Globalization has contributed to the emergence of specific parasitic diseases in novel geographical areas, and in these regions, these infections in travelers and immigrants may cause a considerable burden of disease. Timely diagnosis and treatment of protozoan infections to decrease mortality and prevent associated complications are essential. In this respect, the increased availability of specific DNA-detection procedures has improved the diagnosis of many imported parasitic infections. Travelers and immigrants with associated comorbidities or immunosuppression may pose a special challenge regarding management. An updated review of the main protozoan infections in mobile populations (malaria, Chagas disease, leishmaniasis, enteric protozoan infections) is provided, focusing on the changing epidemiology of these diseases, recent developments in diagnosis and management and the possibility of local transmission of imported infections.

Palliative analgesia with topical sevoflurane in cancer-related skin ulcers: a case report.

A Caucasian 39-year-old male patient with a poorly-differentiated infiltrating epidermoid penile carcinoma with urethral invasion was diagnosed. The patient received concomitant adjuvant chemotherapy with radiotherapy in the palliative setting, which produced painful ulceration of tumour lesions at loco-regional level (Numerical Rate Scale, NRS=9). The patient consented for treatment with direct topical sevoflurane instillations, at initial doses of 1 mL/cm2 of ulcerated area, as per unit protocol. The local use of undiluted sevoflurane achieved a marked reduction of the pain score in both nociceptive and irruptive pains (average NRS=3 immediately post-application). This improvement was corroborated by a decline in total morphine needs, any adverse events associated with major opiates. PGI-I and CGI-I scales were used before and after treatment with topical sevoflurane to assess patient and clinician perceptions of improvement in the quality of life. The pharmacy of our hospital had the responsibility to elaborate pre-loaded syringes with sevoflurane so that the patient was instilled simply and comfortably.

Polyols: Is their use safe in enteral nutrition? / Polioles: ¿es seguro su uso en nutrición enteral?

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Identification and prioritisation of risks in a hospital pharmacy using healthcare failure mode and effect analysis.

OBJECTIVES: The goals of this project included identifying the processes and subprocesses performed in hospital pharmacies, identifying potential adverse events, detecting failure modes and the causes of errors, prioritising the risks identified and designing a map of risks for hospital pharmacies. METHODS: A task force composed of hospital pharmacy staff was committed to update the diagram of processes and design a map of processes performed in hospital pharmacies. Risks were identified by failure mode and effect analysis annd prioritised according to their risk priority index (RPI) and criticality. A risk map of adverse events was designed based on the diagram of processes and/or primary activities where the prioritised failure modes were most frequent. RESULTS: In total, 99 failure modes associated with 80 adverse events and 129 causes were identified in eight hospital pharmacy areas/subprocesses. The three areas with the highest percentages of failure modes were inpatient pharmaceutical care, pharmacy laboratory and pharmaceutical technology, and medication management. The 25 failure modes (first quartile) with the highest RPI scores (RPI≥20) and the 25 failure modes with the highest frequency and criticality scores were classified as priority. CONCLUSIONS: According to their RPI, priority failure modes mostly occurred in the area of inpatient pharmaceutical care (92%). However, according to their criticality, priority failure modes were found to homogeneously occur across all pharmaceutical care areas. As general recommendations pharmacists should assume responsibility and leadership in the implementation of safe medication use practices in healthcare centres.

Remote Monitoring of Treatment Response in Parkinson's Disease: The Habit of Typing on a Computer.

OBJECTIVE: The recent advances in technology are opening a new opportunity to remotely evaluate motor features in people with Parkinson's disease (PD). We hypothesized that typing on an electronic device, a habitual behavior facilitated by the nigrostriatal dopaminergic pathway, could allow for objectively and nonobtrusively monitoring parkinsonian features and response to medication in an at-home setting. METHODS: We enrolled 31 participants recently diagnosed with PD who were due to start dopaminergic treatment and 30 age-matched controls. We remotely monitored their typing pattern during a 6-month (24 weeks) follow-up period before and while dopaminergic medications were being titrated. The typing data were used to develop a novel algorithm based on recursive neural networks and detect participants' responses to medication. The latter were defined by the Unified Parkinson's Disease Rating Scale-III (UPDRS-III) minimal clinically important difference. Furthermore, we tested the accuracy of the algorithm to predict the final response to medication as early as 21 weeks prior to the final 6-month clinical outcome. RESULTS: The score on the novel algorithm based on recursive neural networks had an overall moderate kappa agreement and fair area under the receiver operating characteristic (ROC) curve with the time-coincident UPDRS-III minimal clinically important difference. The participants classified as responders at the final visit (based on the UPDRS-III minimal clinically important difference) had higher scores on the novel algorithm based on recursive neural networks when compared with the participants with stable UPDRS-III, from the third week of the study onward. CONCLUSIONS: This preliminary study suggests that remotely gathered unsupervised typing data allows for the accurate detection and prediction of drug response in PD. © 2019 International Parkinson and Movement Disorder Society.

Imported strongyloidiasis: Data from 1245 cases registered in the +REDIVI Spanish Collaborative Network (2009-2017).

BACKGROUND: Imported strongyloidiasis is increasingly being diagnosed in non-endemic areas. The aim of this study was to describe the epidemiological, clinical and microbiological characteristics of patients with imported strongyloidiasis in Spain. METHODOLOGY: This is an observational retrospective study that included all patients diagnosed of strongyloidiasis registered in the +REDIVI Collaborative Network from 2009 to 2017. Demographic, epidemiological and clinical information was collected from the +REDIVI database, and extra information regarding microbiological techniques, treatment and follow-up was requested to participant centers. FINDINGS: Overall, 1245 cases were included. Most of them were immigrants (66.9%), and South America was the most frequent area of origin. Detection of larvae in stool samples was observed in 21.9% of the patients, and serological tests allowed making the diagnosis in the rest of the cases. Eosinophilia was present in 82.2% of cases. Treatment with ivermectin (compared with albendazole) was the most strongly associated factor to achieve the cure (OR 2.34). CONCLUSIONS: Given the long latency of the infection and the risk of developing a severe presentation, screening of S. stercoralis infection should be mandatory in patients coming from or had traveling to endemic areas, especially in those with immunosuppressant conditions.