El uso diario de la profilaxis preexposición para el VIH en hombres gais, bisexuales y otros hombres que tienen sexo con hombres en España: prevalencia y factores asociados / Daily use of HIV pre-exposure prophylaxis among gay, bisexual and other men who have sex with men in Spain: Prevalence and associated factors

Objetivo: Estimar la prevalencia de uso diario de profilaxis preexposición (PrEP) frente al VIH 6 meses después de aprobarse su financiación pública en España e identificar los factores asociados en una muestra nacional de hombres gais, bisexuales y otros hombres que tienen sexo con hombres (GBHSH). Material y métodos: Se analizaron 4.692 hombres GBHSH no diagnosticados de VIH reclutados mediante un cuestionario online difundido a nivel nacional a través de apps y webs de contacto gay entre mayo y julio de 2020. Se estimó la proporción de participantes que usaban PrEP diaria y se identificaron factores asociados mediante regresión de Poisson con variancia robusta. Resultados: El 2,8% (IC 95% 2,3-3,3) de los participantes refirió usar PrEP diariamente. El uso diario de PrEP se asoció de forma independiente con: haber sido reclutado en programas comunitarios, ser mayor de 30 años, residir en grandes ciudades, vivir abiertamente su vida sexual con hombres, haber tenido relaciones anales sin preservativo con más de 10 parejas sexuales, haber consumido drogas para sexo, especialmente drogas chemsex, y haber sido diagnosticado de alguna infección de transmisión sexual. Conclusión: Transcurridos 6 meses desde la aprobación de la PrEP en España, se observa una baja prevalencia de uso diario en una muestra nacional de hombres GBHSH. Es necesario promover el acceso, la demanda y el interés por la PrEP, especialmente entre los hombres GBHSH jóvenes, residentes en ciudades pequeñas y medianas y los que ocultan sus relaciones con otros hombres.(AU)

Objective: We aim to estimate the prevalence of daily HIV pre-exposure prophylaxis (PrEP) use 6 months after public funding approval in Spain and identify associated factors in a national sample of gay, bisexual and other men who have sex with men (GBMSM). Material and methods: We analysed 4692 HIV-undiagnosed GBMSM men recruited via an online questionnaire distributed nationally via gay contact apps and websites between May and July 2020. We estimated the proportion of participants using daily PrEP and identified associated factors using Poisson regression with robust variance. Results: Daily PrEP use was reported by 2.8% (95% CI 2.3-3.3) of all participants. Daily PrEP use was independently associated with being recruited into community programmes, being older than 30 years, living in a large city, living with men, having condomless anal intercourse with more than 10 sexual partners, using drugs for sex, especially chemsex drugs, and being diagnosed with a sexually transmitted infection. Conclusion: Six months after PrEP was approved in Spain, the prevalence of daily use is low in a national sample of GBMSM men. There is a need to promote access, demand and interest in PrEP, especially among young GBMSM men, those living in small and medium-sized cities, and those who hide their relationships with other men.(AU)

[Daily use of HIV pre-exposure prophylaxis among gay, bisexual and other men who have sex with men in Spain: Prevalence and associated factors]. / El uso diario de la profilaxis preexposición para el VIH en hombres gais, bisexuales y otros hombres que tienen sexo con hombres en España: prevalencia y factores asociados.

OBJECTIVE: We aim to estimate the prevalence of daily HIV pre-exposure prophylaxis (PrEP) use 6 months after public funding approval in Spain and identify associated factors in a national sample of gay, bisexual and other men who have sex with men (GBMSM). MATERIAL AND METHODS: We analysed 4692 HIV-undiagnosed GBMSM men recruited via an online questionnaire distributed nationally via gay contact apps and websites between May and July 2020. We estimated the proportion of participants using daily PrEP and identified associated factors using Poisson regression with robust variance. RESULTS: Daily PrEP use was reported by 2.8% (95% CI 2.3-3.3) of all participants. Daily PrEP use was independently associated with being recruited into community programmes, being older than 30 years, living in a large city, living with men, having condomless anal intercourse with more than 10 sexual partners, using drugs for sex, especially chemsex drugs, and being diagnosed with a sexually transmitted infection. CONCLUSION: Six months after PrEP was approved in Spain, the prevalence of daily use is low in a national sample of GBMSM men. There is a need to promote access, demand and interest in PrEP, especially among young GBMSM men, those living in small and medium-sized cities, and those who hide their relationships with other men.

Toward an Automatic Assessment of Cognitive Dysfunction in Relapsing-Remitting Multiple Sclerosis Patients Using Eye Movement Analysis.

Despite the importance of cognitive function in multiple sclerosis, it is poorly represented in the Expanded Disability Status Scale (EDSS), the commonly used clinical measure to assess disability, suggesting that an analysis of eye movement, which is generated by an extensive and well-coordinated functional network that is engaged in cognitive function, could have the potential to extend and complement this more conventional measure. We aimed to measure the eye movement of a case series of MS patients with relapsing−remitting MS to assess their cognitive status using a conventional gaze tracker. A total of 41 relapsing−remitting MS patients and 43 age-matched healthy controls were recruited for this study. Overall, we could not find a clear common pattern in the eye motor abnormalities. Vertical eye movement was more impaired in MS patients than horizontal movement. Increased latencies were found in the prosaccades and reflexive saccades of antisaccade tests. The smooth pursuit was impaired with more corrections (backup and catchup movements, p<0.01). No correlation was found between eye movement variables and EDSS or disease duration. Despite significant alterations in the behavior of the eye movements in MS patients, which are compatible with altered cognitive status, there is no common pattern of these alterations. We interpret this as a consequence of the patchy, heterogeneous distribution of white matter involvement in MS that provokes multiple combinations of impairment at different points in the different networks involved in eye motor control. Further studies are therefore required.

Short-term data on disease activity, cognition, mood, stigma and employment outcomes in a cohort of patients with primary progressive multiple sclerosis (UPPMS study).

BACKGROUND: Primary progressive multiple sclerosis (PPMS) has long been defined by progressive disability accrual in the absence of initial relapses. However, its underlying neurodegenerative process seems to be accompanied by central nervous system inflammation. A new classification defined multiple sclerosis courses according to clinical/radiological activity and progression. We provide further insight into PPMS activity according to this classification and other daily living aspects. METHODS: This was a multicentre, prospective, cohort study including 55 adult patients with PPMS according to 2010 McDonald criteria, within ten years from neurologic symptom onset and not receiving disease-modifying therapies during the past six months, who were followed up for 12 months. The primary study endpoint was the percentage of patients with active disease based on clinical relapses and/or magnetic resonance activity. Disability progression, cognitive function, physical/psychological impact, depression symptoms, stigma and employment were secondary endpoints. RESULTS: Eleven (25.6%) patients exhibited multiple sclerosis activity throughout the 12-month study follow-up. Fourteen showed non-active multiple sclerosis without progression, 11 non-active multiple sclerosis with progression, 6 active multiple sclerosis without progression and 4 active multiple sclerosis with progression; one patient with disease activity was not assessable for progression. Cognitive function scores remained unchanged or increased, disease physical impact was maintained and disease psychological impact significantly decreased. The proportion of patients with depression symptoms or stigma remained without significant changes as well as employment outcomes. CONCLUSION: This study shows that one-fourth of PPMS patients may exhibit disease activity over one year, with disability progression in approximately one-third but without worsening of cognitive function, disease impact, depression, stigma or employment outcomes.

Cancer diagnosis in a Spanish cohort of multiple sclerosis patients under dimethylfumarate treatment.

BACKGROUND: Potential increase of cancer incidence is one of the main safety concerns of the disease-modifying therapies employed in Multiple Sclerosis (MS). OBJECTIVE: Detailed description of patients who developed cancer among a prospective cohort of Spanish MS patients on dimethyl fumarate (DMF) treatment. METHODS: We describe patients who developed cancer among a cohort of 886 MS patients on DMF treatment (2681 patient-years), with a median time of exposure of 39.5 months (IQR 23-51.5), who participated in a multicentre and prospective real-world study conducted in 16 Spanish National Health System hospitals from February 2014 to May 2019. Local researchers were periodically contacted by the investigation team to monitor safety issues. Cancer histories were collected from the medical records and the information was updated at July 30th 2020. RESULTS: Eight Caucasian women developed cancer, which accounts for 0.9% and an accumulated malignancy rate of 298.39 cases per 100,000 patient-years of DMF exposure. At the time of cancer diagnosis, age was between 33 to 67 years and median time on DMF treatment 16.5 months (range 1-53). Two patients had familiar history of cancer. No specific cancer lines were found (breast cancer in 2 cases, thyroid in 3, urothelial carcinoma, cervix and a progression to leiomyosarcoma from a mitotically active leiomyoma). DMF was withdrawn during cancer treatment in 6 patients and reintroduced later. All cancers except one are in complete remission. The patient with leiomyosarcoma died by cancer progression. CONCLUSION: A relationship between cancers and DMF is unlikely because the malignancy rate was similar to that of the age-and sex-matched general population, and because of the absence of specific tumour cell lines. Nevertheless, as with other immunosuppressive DMTs, clinicians treating MS should be aware of any potential cancer symptom and demand proper testing.

Brain region volumes and their relationship with disability progression and cognitive function in primary progressive multiple sclerosis.

BACKGROUND AND PURPOSE: Evidence on regional changes resulting from neurodegenerative processes underlying primary progressive multiple sclerosis (PPMS) is still limited. We assessed brain region volumes and their relationship with disability progression and cognitive function in PPMS patients. METHODS: This was an MRI analysis of 43 patients from the prospective Understanding Primary Progressive Multiple Sclerosis (UPPMS) cohort study. MRI scans were performed within 3 months before enrollment and at month 12. RESULTS: Gray matter volume of declive and white matter volumes adjacent to left straight gyrus, right calcarine sulcus, and right inferior occipital gyrus significantly decreased from baseline to month 12. Baseline white matter volumes adjacent to right amygdala and left cuneus significantly differed between patients with and without disability progression, as well as baseline gray matter volumes of left cuneus, right parahippocampal gyrus, right insula, left superior frontal gyrus, declive, right inferior temporal gyrus, right superior temporal gyrus (pole), and right calcarine sulcus. Baseline gray matter volumes of right cuneus and right superior temporal gyrus positively correlated with 12-month Selective Reminding Test and Word List Generation performance, respectively. Gray matter changes in right superior semilunar lobe and white matter adjacent to left declive and right cerebellar tonsil also positively correlated with Word List Generation scores, while white matter change in left inferior semilunar lobe positively correlated with Symbol Digit Modalities Test performance after 12 months. CONCLUSIONS: White and gray matter volumes of specific brain regions could predict disability progression and cognitive performance of PPMS patients after one year.

Perception of stigma in patients with primary progressive multiple sclerosis.

Stigma associated with neurological disorders may contribute to a poor health-related quality of life. However, limited information is available in primary progressive multiple sclerosis. We investigated the presence and impact of stigma in patients with primary progressive multiple sclerosis. A non-interventional, cross-sectional study was conducted. A total of 55 primary progressive multiple sclerosis patients were studied (mean age 55.8±9.5 years, 56.4% male). The median Expanded Disability Status Scale score was 5.5 (4.0-6.5). Stigma prevalence was 78.2% (n=43). Twenty-four patients (43.6%) were classified as depressed. Scores on the eight-item Stigma Scale for Chronic Illness correlated with physical (rho=0.464, p<0.001) and psychological (rho=0.358, p=0.007) 29-item Multiple Sclerosis Impact Scale subscores. Stigma predicted concurrent depression (odds ratio=1.13; p=0.046). Stigma was highly prevalent with a detrimental effect on quality of life and mood in primary progressive multiple sclerosis.

Hypophonia as a sign of thalamus lesion: a case report.

Hypophonia is a neurological sign usually seen after brainstem or peripheral damage, either at the recurrent laryngeal nerve or vocal cord level. However, it has been described as a sign of supratentorial strokes in a few studies, specifically when anterior and ventral thalamic involvement is reported. In addition, it is a prominent sign of other neurological disorders such as Parkinson disease and other extrapyramidal conditions. We describe a case of hypophonia secondary to a left thalamic hemorrhage, after a careful search of other potential causes of this deficit, and we discuss the underlying neuroanatomical circuits.

Catastrophic outcome of patients with a rebound after Natalizumab treatment discontinuation.

INTRODUCTION: Natalizumab (NTZ) is an effective drug for the treatment of relapsing-remitting multiple sclerosis. In some patients discontinuation is mandatory due to the risk of progressive multifocal leukoencephalopathy. However, severe clinical and radiological worsening has been described after drug cessation. Our aim was to describe the clinical and radiological features of the rebound phenomenon. MATERIAL AND METHODS: Patients switched from NTZ to Fingolimod (FTY) who had presented a rebound after discontinuation were selected. Clinical and magnetic resonance imaging (MRI) data were collected. RESULTS: Four JC virus positive patients were included. The mean disease duration was 9.5 years (SD: 4.12) with a mean time of 3.1 years on NTZ. All patients started FTY within 3-4 months. Neurological deterioration started in a mean time of 3.5 months (SD: 2.08) with multifocal involvement: 75% motor disturbances, 50% cognitive impairment, 25% seizures. The average worsening in Expanded Disability Status Scale [EDSS] was of 3.25 points (SD: 2.33). The MRI showed a very large increase in T2 and gadolinium-enhanced lesions (mean: 23.67, SD: 18.58). All patients received 5 days of IV methylprednisolone, one patient required plasma exchange. All the patients presented neurological deterioration with an EDSS worsening of 1.13 points (SD: 0.48). After the rebound three patients continued treatment with FTY, only one patient restarted NTZ. CONCLUSION: Discontinuation of NTZ treatment may trigger a severe rebound with marked clinical and radiological worsening. A very careful evaluation of benefit-risk should be considered before NTZ withdrawal, and a close monitoring and a short washout period is recommended after drug withdrawal.

Anxiety and depressive symptoms in caregivers of multiple sclerosis patients: The role of information processing speed impairment.

BACKGROUND: Multiple sclerosis (MS) patients have high rates of complications and disability, including cognitive impairment, that often, impact on caregivers' emotional health. Clarification may help identify improved supportive strategies for both caregivers and patients. OBJECTIVE: We aimed to analyse whether MS domain-specific cognitive impairment can influence the severity of psychiatric symptoms of MS caregivers. METHODS: Patients with definite MS (n=63) and their corresponding caregivers (n=63) were recruited. In addition, 59 matched controls were enrolled for establishing normative cognitive data. Each patient underwent a complete neuropsychological testing for cognitive impairment and thorough clinical assessment, including data of disability status (EDSS), affective and emotional symptoms (depression, anxiety, anger) and fatigue. Psychiatric symptoms of the caregivers were assessed with the Beck Anxiety Inventory (BAI) and the Beck Depression Inventory (BDI). RESULTS: In logistic regression analyses, even after controlling for other MS-related symptoms, cognitive deficits, namely impairment on Symbol Digit Modalities Test (OR=8.03, 95% CI=1.27-25.33, p=0.027) and on the Paced Auditory Serial Addition Test (OR=6.86, 95% CI=1.07-21.97, p=0.042), were significant and independent predictors of more severe caregivers' depressive symptoms. CONCLUSIONS: Information processing speed impairment is independently associated with more severe depressive symptoms of caregivers of MS patients, thereby reflecting a further deterioration of family setting.

Impact of anger on the health-related quality of life of multiple sclerosis patients.

BACKGROUND: There is evidence of the presence of a disturbed pattern of anger in multiple sclerosis (MS). Emotion changes, including anger, are thought to influence health-related quality of life (HRQoL). However, although deleterious consequences of anger on physical health have been well reported, there are no studies that have analysed the effects of anger on the HRQoL in patients with MS. Our purpose was to assess the extent to which anger impacts on the HRQoL of a cohort of MS patients. METHODS: One hundred and fifty-seven consecutive MS patients were enrolled in the study. Participants were administered affective trait measures (Beck Depression Inventory, Beck Anxiety Inventory) and anger measures (the Spanish adapted version of the State-Trait Anger Expression Inventory-2). HRQoL was quantified using the Functional Assessment of MS. RESULTS: Linear regression analyses revealed that even after controlling for socio-demographic and clinical variables, higher levels of anger expression-in (tendency to handle anger by keeping it inside) independently predicted worse overall HRQoL of MS patients (ß = -0.15, p = 0.04). We further found that this relationship was moderated by gender, showing that anger expression-in is a more influential predictor of the HRQoL in women with MS. CONCLUSION: The present study provides evidence that anger negatively affects the HRQoL of MS patients. Our results may have implications for those involved in treating emotional complications of MS and especially regarding psychotherapeutic interventions to improve HRQoL of MS patients.

Cognitive impairment in patients with multiple sclerosis predicts worse caregiver's health-related quality of life.

BACKGROUND: Little information exists about how cognitive impairment in multiple sclerosis (MS) patients impacts on their caregivers' health-related quality of life (HRQoL). BACKGROUND: The objective of this paper is to examine the extent to which cognitive impairment in MS patients contributes to caregivers' HRQoL. METHODS: A total of 63 MS patients, 63 caregivers and 59 matched controls were recruited. Patients and controls underwent a neuropsychological assessment, including tests of working memory, speed of information processing, executive function, and verbal fluency. HRQoL of the caregivers was assessed by CAREQOL-MS. In logistic regression models, we adjusted for the effects of confounding variables. In these models, the dependent variable was the CAREQOL-MS (higher median of CAREQOL-MS (worse HRQoL) vs. lower median of CAREQOL-MS (better HRQoL) (reference)), and the independent variable was the impairment on each neuropsychological test vs. its integrity (reference). RESULTS: Cognitive impairment in MS patients was significantly associated with worse caregiver HRQoL (adjusted odds ratio (OR) = 3.10, 95% confidence interval (CI) = 1.07-11.55, p = 0.04). In secondary analyses in which each neuropsychological test was entered in the analyses separately, only Symbol Digit Modalities Test (a measurement of information processing speed) impairment (OR = 4.22, 95%, CI = 1.16-14.53, p = 0.03) was significantly associated with worse caregiver HRQoL. CONCLUSIONS: MS patients' caregivers' HRQoL is significantly influenced by information processing speed impairment of MS patients.

Multiple sclerosis is associated with high trait anger: a case-control study.

INTRODUCTION: In recent years there has been a focus on health-related quality of life in multiple sclerosis (MS) and in particular the importance of non-motor problems such as fatigue, pain, depression, anxiety, and cognitive disorders. However, little attention has been focused on other negative emotions, such as anger. Our purpose was to evaluate whether trait anger (a predisposition to experience frequent and intense episodes of anger over time) is different between persons with and without MS after controlling for depression, anxiety, and other socio-demographic variables. METHODS: 157 consecutive MS patients were enrolled in the study and compared to eighty age, gender, and education-matched healthy controls. Participants were administered affective trait measures (Beck Depression Inventory, Beck Anxiety Inventory) and the trait anger measure (the Spanish adapted version of the State-Trait Anger Expression Inventory-2 [STAXI-2]). RESULTS: MS patients had significantly higher scores on anger intensity (state anger) and trait anger than did controls. They also had a trend to experience direct anger toward other persons or objects in the environment (higher anger expression-out score) and to hold in or suppress angry feelings (higher anger expression-in score). However, in a regression analysis that adjusted for different demographic and clinical variables, we found that diagnosis category (MS patient vs. control) was associated with none of the highest quartiles of STAXI-2 scores, except for the Trait Anger scale (odds ratios between 2.35 and 3.50). CONCLUSIONS: The present study provides further evidence that MS is independently associated with high trait anger.

Blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentration in essential tremor cases in Spain.

BACKGROUND: Environmental correlates for essential tremor (ET) are largely unexplored. The search for such environmental factors has involved the study of a number of neurotoxins. Harmane (1-methyl-9H-pyrido[3,4-b]indole) is a potent tremor-producing toxin. In two prior case-control studies in New York, we demonstrated that blood harmane concentration was elevated in ET patients vs. controls, and especially in familial ET cases. These findings, however, have been derived from a study of cases ascertained through a single tertiary referral center in New York. OBJECTIVE: Our objective was to determine whether blood harmane concentrations are elevated in familial and sporadic ET cases, ascertained from central Spain, compared to controls without ET. METHODS: Blood harmane concentrations were quantified by a well-established high performance liquid chromatography method. RESULTS: The median harmane concentrations were: 2.09 g(-10)/ml (138 controls), 2.41 g(-10)/ml (68 sporadic ET), and 2.90 g(-10)/ml (62 familial ET). In an unadjusted logistic regression analysis, log blood harmane concentration was not significantly associated with diagnosis (familial ET vs. control): odds ratio=1.56, p=0.26. In a logistic regression analysis that adjusted for evaluation start time, which was an important confounding variable, the odds ratio increased to 2.35, p=0.049. CONCLUSIONS: Blood harmane levels were slightly elevated in a group of familial ET cases compared to a group of controls in Spain. These data seem to further extend our observations from New York to a second cohort of ET cases in Spain. This neurotoxin continues to be a source of interest for future confirmatory research.

Akinetic mutism induced by tacrolimus.

Akinetic mutism is an uncommon clinical syndrome characterized by the inability to produce voluntary movements or speech without loss of awareness. Cerebrovascular diseases are the most frequent etiology. It has been reported in cyclosporine-related neurotoxicity, but it is exceptional as the presenting form of tacrolimus intoxication. We report the case of a 66-year-old man who underwent an orthotopic liver transplantation and was treated with intravenous methylprednisolone and tacrolimus. He had an uneventful postoperative course until the third day after surgery, when he developed acute onset mutism, akinesia, and waxy rigidity of passive limb movements. His arterial blood pressure and temperature were normal. Blood analysis and a magnetic resonance image of the brain showed no acute abnormalities. Serum levels of tacrolimus were 20.8 ng/mL, so it was substituted by cyclosporine and mycophenolate mofetil with progressive and complete recovery of akinetic mutism during the following days. Akinetic mutism is an exceptional manifestation of tacrolimus neurotoxicity, but early recognition of the syndrome and withdrawal of the drug are important to avoid persistent cerebral lesions.