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1.
Front Med (Lausanne) ; 11: 1380129, 2024.
Article in English | MEDLINE | ID: mdl-38751980

ABSTRACT

Objective: Arboviruses pose a challenge in ensuring the supply of pathogen-free blood components because they are not routinely screened in blood banks, and blood components from infected asymptomatic donors could be transfused. This study aimed to detect and characterize arboviral infections in Colombian blood donors. Methods: In a cross-sectional study, the prevalence of dengue (DENV), Zika (ZIKV), and chikungunya (CHIKV) viruses and co-infections of blood donors were compared between an epidemic period (November 2019-February 2020, n = 462) and an endemic period (November 2021-August 2022, n = 1,119). Viral RNA from each donor serum was purified, and the viruses were detected using a previously standardized multiplex hemi-nested RT-PCR protocol. Subsequently, donors who tested positive were surveyed 15 days after the detection of the virus to identify clinical characteristics related to the arboviral infection. The prevalences of each virus were presented as percentages and compared between epidemic and endemic periods. Results: Significantly higher prevalences were found in the epidemic period compared with the endemic period for DENV (14.5 vs. 1.9%), ZIKV (7.8 vs. 0.3%), CHIKV (8 vs. 3.3%), and co-infections (4.3 vs. 0.2%). The survey response rate of positive donors in the two periods was 83/175 (47%). In total, 57% of the donors surveyed were asymptomatic. Symptomatic donors most frequently reported headache (31%), malaise (13%), arthralgia (10%), and fever/chills (8%). Conclusion: The prevalence observed in epidemic and endemic periods was higher than that reported in other studies in the Americas. The high proportion of asymptomatic cases found, in addition to the mild and nonspecific manifestations among the symptomatic, may limit the effectiveness of the donor selection criteria used to mitigate the risk of transfusion-transmitted arboviruses.

2.
PLoS Negl Trop Dis ; 18(5): e0012156, 2024 May.
Article in English | MEDLINE | ID: mdl-38709850

ABSTRACT

The multifactorial basis of therapeutic response can obscure the relation between antimicrobial drug susceptibility and clinical outcome. To discern the relationship between parasite susceptibility to meglumine antimoniate (SbV) and therapeutic outcome of cutaneous leishmaniasis, risk factors for treatment failure were considered in evaluating this relationship in ninety-one cutaneous leishmaniasis patients and corresponding clinical strains of Leishmania (Viannia) panamensis. Parasite susceptibility to 32 µg SbV/mL (plasma Cmax) was evaluated in primary human macrophages, PBMCs, and U937 macrophages. Early parasitological response to treatment was determined in lesions of a subgroup of patients, and pathogenicity of Sb-resistant and sensitive clinical strains was compared in BALB/c mice. Parasite survival in cell models and patient lesions was determined by qRT-PCR of Leishmania 7SLRNA transcript. Parasite loads in BALB/c mice were quantified by limiting dilution analysis. The disparate Sb-susceptibility of parasite subpopulations distinguished by isoenzyme profiles (zymodemes) was manifest in all cell models. Notably, Sb-resistance defined by parasite survival, was most effectively discerned in U937 macrophages compared with primary human host cells, significantly higher among strains from patients who failed treatment than cured and, significantly associated with treatment failure. Each unit increase in transformed survival rate corresponded to a 10.6-fold rise in the odds of treatment failure. Furthermore, treatment failure was significantly associated with naturally Sb-resistant zymodeme 2.3 strains, which also produced larger lesions and parasite burdens in BALB/c mice than Sb-sensitive zymodeme 2.2 strains. The confounding effect of host risk factors for treatment failure in discerning this association was evidenced in comparing strains from patients with and without the defined risk factors for treatment failure. These results establish the association of natural resistance to meglumine antimoniate with treatment failure, the importance of host risk factors in evaluating drug susceptibility and treatment outcome, and the clinical and epidemiological relevance of natural Sb-resistance in L. (V.) panamensis subpopulations.


Subject(s)
Antiprotozoal Agents , Drug Resistance , Leishmaniasis, Cutaneous , Macrophages , Meglumine Antimoniate , Meglumine , Mice, Inbred BALB C , Organometallic Compounds , Treatment Failure , Animals , Leishmaniasis, Cutaneous/drug therapy , Leishmaniasis, Cutaneous/parasitology , Meglumine Antimoniate/therapeutic use , Meglumine Antimoniate/pharmacology , Humans , Antiprotozoal Agents/therapeutic use , Antiprotozoal Agents/pharmacology , Female , Meglumine/therapeutic use , Meglumine/pharmacology , Organometallic Compounds/therapeutic use , Organometallic Compounds/pharmacology , Mice , Macrophages/parasitology , Macrophages/drug effects , Macrophages/immunology , Male , Leishmania guyanensis/drug effects , Adult , Middle Aged , Young Adult , Parasite Load , Adolescent
3.
iScience ; 27(5): 109773, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38711445

ABSTRACT

Drug resistance threatens the effective control of infections, including parasitic diseases such as leishmaniases. Neutrophils are essential players in antimicrobial control, but their role in drug-resistant infections is poorly understood. Here, we evaluated human neutrophil response to clinical parasite strains having distinct natural drug susceptibility. We found that Leishmania antimony drug resistance significantly altered the expression of neutrophil genes, some of them transcribed by specific neutrophil subsets. Infection with drug-resistant parasites increased the expression of detoxification pathways and reduced the production of cytokines. Among these, the chemokine CCL3 was predominantly impacted, which resulted in an impaired ability of neutrophils to attract myeloid cells. Moreover, decreased myeloid recruitment when CCL3 levels are reduced was confirmed by blocking CCL3 in a mouse model. Collectively, these findings reveal that the interplay between naturally drug-resistant parasites and neutrophils modulates the infected skin immune microenvironment, revealing a key role of neutrophils in drug resistance.

4.
Pharmaceuticals (Basel) ; 17(3)2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38543177

ABSTRACT

Rheumatoid arthritis (RA) and osteoarthritis (OA) are the most common arthritic diseases. Medical ozone has demonstrated its effectiveness in combination therapy with methotrexate or non-steroidal anti-inflammatory drugs for RA and OA, respectively. Although RA and OA have been compared from different points of view, few studies have considered their redox status in spite of the oxidative processes that are involved in both diseases. The aim of this study was to compare RA with OA, evaluating their redox status and the effects of ozone on their clinical response to combined therapy with ozone. The redox status of 80 patients was determined: antioxidant defenses, injury markers, two subjective variables (pain and disability), and levels of antibodies against cyclic citrullinated peptides were evaluated. Oxidative stress and clinical response to combined therapy with ozone was higher than in the case of RA. After medical ozone treatment, there was an increase in antioxidant defense and a decrease in injury markers as well as pain, disability, and autoantibody concentrations. Redox biomarkers were able to differentiate between both arthritic diseases and combined therapy with ozone (methotrexate + ozone), showing a therapeutic selectivity for RA in comparison with OA.

5.
J Pediatr Psychol ; 49(4): 266-278, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38070171

ABSTRACT

OBJECTIVE: Internet-based interventions may positively impact maternal symptoms of postnatal depression and anxiety. This study assessed the feasibility, acceptability, perceived usefulness, and preliminary effectiveness of an m-Health version of "What Were We Thinking?" (m-WWWT). METHODS: A mixed-methods with a 2-arm randomized parallel design was used. From a total of 477 women, 157 met the inclusion criteria. 128 first-time mothers of full-term infants, aged 4-10 weeks, who received health care at primary public health centers in Chile, were randomly assigned to the experimental (EG, n = 65) or control (CG, n = 63) groups; data of 104 of them (53 and 51, respectively) was analyzed. We used percentages and rates to measure feasibility outcomes and mixed analysis of variance (ANOVA) and latent class analyses (LCA) to assess preliminary effectiveness. Participants completed questionnaires on mental health, social support, and maternal self-efficacy upon recruitment and 3 months after completing the intervention. For the qualitative component, 12 women from the EG were interviewed. RESULTS: Quantitative results show good feasibility outcomes, such as high recruitment (82%), low attrition (EG = 12% and CG = 17%), and high follow-up (EG = 97% and CG = 91%) rates. Qualitative results indicate high acceptability and perceived usefulness of m-WWWT. Mixed ANOVA did not show significant differences between the groups (all p >.05). However, multinomial regression analysis in LCA showed that women with low baseline symptoms of depression and anxiety benefit from the intervention (B = 0.43, 95% confidence interval 1.09-2.16). CONCLUSION: m-WWWT is feasible to be implemented in Chile; future studies are needed to assess the intervention's effectiveness.


Subject(s)
Depression, Postpartum , Internet-Based Intervention , Humans , Female , Depression, Postpartum/therapy , Depression, Postpartum/psychology , Depression/psychology , Chile , Feasibility Studies , Anxiety/psychology
6.
Int J Mol Sci ; 24(21)2023 Oct 30.
Article in English | MEDLINE | ID: mdl-37958730

ABSTRACT

The best form of prevention against human infection through bacteria, viruses, and other parasites is ozone disinfection of wastewater and drinking water as a highly effective, well-known method. Various preclinical studies showed promising results, which are being revisited and reconsidered in times of pandemics and led to interesting results in recent clinical trials and reports, as presented by the example of protective measures against COVID-19 in particularly vulnerable clinical personnel. The application of ozone in the form of the low-dose concept induces its regulation by interference of ozone or its peroxides into the redox equilibrium of the biological system, which finally results in the restoration of the glutathione equilibrium. The antioxidant system is activated, the immune system is modulated, and thus the defense mechanisms are improved. In patients with rheumatoid arthritis, repeated ozone treatments have led to new findings in "immunomodulation" through ozone. The more effective immune response is discussed as the response of innate immune memory and opens interesting aspects for complementary treatment of autoimmune diseases.


Subject(s)
Drinking Water , Ozone , Humans , Ozone/pharmacology , Disinfection/methods , Wastewater , Oxidation-Reduction
7.
Digit Health ; 9: 20552076231203920, 2023.
Article in English | MEDLINE | ID: mdl-37786403

ABSTRACT

Introduction: There is sufficient evidence about the effectiveness of internet-based interventions; however, the users' level of adoption and utilization remains low, with this phenomenon requiring adequate explanation. Objective: The aim of this qualitative study was to explore the users' perceptions and experience of a web-based program (ASCENSO), designed to complement (usual) in-person depression treatment. Method: Twelve participants of the ASCENSO program, comprised of adult individuals (M = 44.3, SD = 13.4) of both genders (67% women) undergoing treatment for depression, were interviewed through semi-structured interviews. The data obtained from these interviews were analyzed utilizing a constructivist grounded theory approach. The interviews were transcribed and analyzed by trained coders. A constant comparative analysis of emergent themes was conducted. Results: These show that users employ and appreciate the program when their interaction with it emulates a "humanized relationship," that is, when the program is proactive in assisting users with their requests and when it responds in a pertinent and individualized manner to their emotional states and needs. Conclusions: Our findings highlight the challenges associated with the development of algorithms capable of attracting different potential users. These should be designed to generate a virtual relationship that emulates human interaction and targets the characteristics of each user, for example, considering the specific phenomenology of their health condition, their present emotional states, and perceived needs. Elements that will vary as mental symptomatology evolve.

8.
Xenotransplantation ; 30(5): e12823, 2023.
Article in English | MEDLINE | ID: mdl-37695105

ABSTRACT

BACKGROUND: The shortage of available transplant organs has made it necessary to search for alternatives, one of which is xenotransplantation. However, the use of animal organs could face rejection from society and the personnel involved in its implementation. OBJECTIVES: (a) to analyze the attitudes of Veterinary Degree students in six Spanish Universities towards xenotransplantation; and (b) to determine the factors that affect its acceptance. METHODS: Of the 2815 students surveyed in the degree program, 2683 valid surveys were obtained. Attitudes towards organ xenotransplantation were evaluated using a validated questionnaire of organ donation. RESULTS: If xenotransplantation was confirmed as a clinical reality, 93% (n = 2493) of those surveyed would accept a xenotransplanted organ, whilst 7% would not. If the results of xenotransplantation were worse than those obtained with human donors and it entailed more risk, 12% (n = 318) would be in favor. 56% (n = 1497) of the students would accept a xenotransplantation provisionally pending the arrival of a human organ. Attitudes towards xenotransplantation were affected by the academic year in which a student was studying, with more favorable attitudes among students in the last year (88% in first year vs. 95% in fifth year; p < .001). More favorable attitudes are also observed depending on the attitude they have towards organ transplantation, with those students being more in favor of donating their organs when they die (94% vs. 88%; p < .001). CONCLUSION: Veterinary students would have a very favorable attitude toward xenotransplantation if these animal organs functioned as well as human organs. Therefore, these students could play an important role in the future promotion of this technique.


Subject(s)
Organ Transplantation , Tissue and Organ Procurement , Animals , Humans , Transplantation, Heterologous , Spain , Attitude , Students , Surveys and Questionnaires
9.
Adv Pharmacol Pharm Sci ; 2023: 1995642, 2023.
Article in English | MEDLINE | ID: mdl-36776283

ABSTRACT

Aims: To evaluate the prevalence and type of adverse drug reactions (ADRs), together with associated risk factors, among Cuban COVID-19 patients treated with chloroquine (CQ), lopinavir/ritonavir (LPV/r), or interferon α2b (IFN α2b), according to the Cuban protocol. Materials and Methods: A prospective descriptive analysis of ADRs was performed on 200 COVID-19 patients who were admitted consecutively to three hospitals in Havana and Pinar del Río from April to July 2020. Information on demographics, ADRs, outcomes, behavioral, and health-related factors was collected using a validated questionnaire and clinical records. Each potential ADR case was assessed for causality based on the WHO-UMC algorithm, concomitant drug influences, and the presence of any drug-drug interactions (DDI). Results: The total frequency of ADRs was 55%, with predominantly gastrointestinal disorders and general symptoms (23% vs 20%). 95.1% of ADRs occurred within 10 days after treatment and 42 potential DDI in 55.5% of patients (61/110) were observed. The prevalence of ADRs was: 44%, 30.4%, and 26.4% for IFN α2b, LPV/r, and CQ, respectively. Sex (odds ratio (OR): 0.40 (95% confidence interval (CI): 0.211-0.742), age (OR: 2.36 (95% CI: 1.02-5.44)), and underlying diseases (OR: 0.12 (95% CI: 0.06-0.23)) were independently associated factors for ADRs (P < 0.05). Conclusions: The frequency of ADRs and potential DDI was high compared to their use during nonpandemic times (e.g., for malaria, HIV, or inflammatory diseases). The safety profile of these drugs when used for COVID-19 treatment showed similar characteristics. Comorbidities, age >37 years old, and female sex were associated with ADRs.

10.
Rev Esp Salud Publica ; 972023 Jan 27.
Article in Spanish | MEDLINE | ID: mdl-36705053

ABSTRACT

OBJECTIVE: The term trans brings together all transgender identities. The early social transition towards the affirmed gender has benefits in the child's development. For families, transit is a period of great uncertainty, requiring support aimed at families of trans minors. The aim of this paper was to explore the needs and experiencies of parents and close-relatives who supported the social transition of their children. METHODS: We worked with focus groups of functional families of transgender minors who had begun the transition (n=14), with a medium-high educational level and who belonged to urban areas of Tenerife. Through a semi-structured interview, they commented on their experiences in the process of supporting the social transition of their children. The data was recorded in a video recording and processed through content analysis and categorization. RESULTS: Early social transition had positive and immediate benefits on child development as well as in the reduction of anxiety. There was a general improvement in mood, self-esteem, and social and family relationships. The accompaniment of specialists and associations helped in the different social situations and favoured resilience. CONCLUSIONS: Early social transition is positive in the personal and socio-family sphere of the minor. To improve their resilience, families demand accompaniment in this process, as well as meeting other trans people who serve as transpositive references. In addition, they point out the need for specific training in health professionals.


OBJETIVO: El término trans aglutina a todas las identidades transgénero. La transición social temprana hacia el género sentido tiene beneficios en el desarrollo del menor. Para las familias, el tránsito es un periodo de grandes incertidumbres, siendo necesario el acompañamiento dirigido a las familias de menores trans. El objetivo del artículo fue explorar, desde una perspectiva paterna y familiar, las necesidades y experiencias sobre el tránsito de menores trans que sirvieran de referente a otros padres/madres que apoyan el tránsito social de sus hijos e hijas. METODOS: Se trabajó con grupos focales de familias funcionales de menores transgénero que habían iniciado la transición (n=14), de nivel educativo medio-alto y que pertenecían a zonas urbanas de Tenerife. Mediante entrevista semiestructurada, comentaron sus experiencias en el proceso de dar soporte al tránsito social de sus hijos e hijas. Los datos fueron registrados en una videograbación y se procesaron mediante análisis de contenido y categorización. RESULTADOS: La transición social temprana tuvo beneficios positivos e inmediatos en el desarrollo del menor, además de en la disminución de la ansiedad. Hubo una mejora general en el humor, la autoestima y las relaciones tanto sociales como familiares. El acompañamiento de especialistas y asociaciones ayudó en las distintas situaciones sociales y favoreció la resiliencia. CONCLUSIONES: El tránsito social temprano es positivo en la esfera personal y sociofamiliar del menor. Para mejorar su resiliencia, las familias demandan acompañamiento en este proceso, así como conocer otras personas trans que les sirvan como referentes transpositivos. Además, señalan la necesidad de formación específica en los profesionales sanitarios.


Subject(s)
Transgender Persons , Transsexualism , Child , Humans , Minors , Spain , Parents , Qualitative Research
11.
Am J Trop Med Hyg ; 108(3): 555-560, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36716739

ABSTRACT

The endosymbiotic Leishmania RNA virus 1 (LRV1) has been associated with severity and clinical manifestations of American tegumentary leishmaniasis caused by species of the Leishmania (Viannia) subgenus. Between and within Leishmania species, and among endemic countries, the prevalence of LRV is highly variable. The LRV virus has not been detected in L. (V.) panamensis, the second-most prevalent species in Central America and Colombia. However, no systematic screening of LRV has been conducted in L. (V.) panamensis, and thus it is still controversial whether this virus is truly absent from the species. We sought to determine the prevalence of LRV1 in L. (V.) panamensis clinical strains isolated from patients with cutaneous leishmaniasis (CL), from different geographic areas of Colombia. We analyzed 219 clinical strains; 78% were L. (V.) panamensis, 18% were L. (V.) braziliensis, and 4% were L. (V.) guyanensis. Screening for LRV1 was performed by quantitative reverse transcription-polymerase chain reaction. The LRV1 was detected in 18% (7 of 40) of L. (V) braziliensis strains, and was not detected in any of the L. (V.) guyanensis or L. (V.) panamensis strains. The LRV1-positive L. (V). braziliensis strains came from the Amazon Basin. Of the seven LRV1-positive strains, two were isolated from patients with mucocutaneous leishmaniasis, and the remaining from patients with CL. Our results confirm the absence of LRV1 in L. (V.) panamensis in Colombia.


Subject(s)
Leishmania braziliensis , Leishmania , Leishmaniasis, Cutaneous , Leishmaniasis, Mucocutaneous , RNA Viruses , Humans , Colombia , Leishmaniasis, Mucocutaneous/epidemiology
12.
Psychother Res ; 33(5): 625-639, 2023 06.
Article in English | MEDLINE | ID: mdl-36404291

ABSTRACT

OBJECTIVE: : The aim of the study was to characterize the subjective experience of recovery from depression based on the perspective of those who suffer from it. METHOD: : Forty participants from two South American countries, who had been or were currently being treated for depression, took part in semi-structured and in-depth interviews. Most participants were female (78%), with ages ranging from 22 to 63 years. Interviews were analyzed using Grounded Theory, creating a hierarchy of categories that represent participants' experience of recovery. The categories were subsequently organized around an emergent central phenomenon. RESULTS: : "Transformation of the experience of the depressed self" was constructed as the main phenomenon that accounts for the subjective understanding of recovery. This transformation consists in an increase in self-acceptance, self-appreciation, and auto-biographical contextualization, coupled with an increase in agency and empowerment. CONCLUSION: : Recovery is experienced as a multidimensional process that goes beyond the absence of symptoms. Change is experienced as a result of active self-management and commitment. The relevance of person-centered perspectives and their subjectivity for managing depression is discussed.


Subject(s)
Depression , Patients , Humans , Female , Male , Depression/therapy , Qualitative Research , Grounded Theory
13.
Nurs Rep ; 14(1): 42-55, 2023 Dec 28.
Article in English | MEDLINE | ID: mdl-38251182

ABSTRACT

BACKGROUND: University education is undergoing a paradigm shift towards active methodologies, such as virtual reality and training videos, which have proven to be valuable resources, especially in the health sciences. The scarcity of existing research on the topic prompted us to conduct this study, which seeks to measure the knowledge gained from the aforementioned tools by users, their level of satisfaction with them, and their perceived utility. METHODS: This is a quasi-experimental intervention study analysing the impact of virtual objects as learning resources for undergraduate nursing students. RESULTS: Fifty-four participants completed the training, yielding highly significant differences between their mean scores, with a high statistical power and a large effect size. A total of 85.46% of participants confirmed that the virtual resources helped them considerably to empathise with the experiences of trans people in healthcare settings. Students were comfortable using the virtual resources, very satisfied with the methodology employed, and would recommend the training received. CONCLUSIONS: University teaching must adapt to meet the current legislations and changing health needs of society, and teaching staff must be prepared to implement new active teaching methodologies that make learning a more dynamic process. Considering these results, our study serves as a guide for other nursing educators who seek to promote inclusive healthcare regarding gender diversity. This study is not registered.

14.
Front Physiol ; 13: 1029805, 2022.
Article in English | MEDLINE | ID: mdl-36406985

ABSTRACT

Medical ozone reestablishes cellular redox balance so that it may be a valid therapeutic approach in the prevention and management of age-related diseases with oxidative etiology in older people. The aim of this study is to evaluate oxidative stress and some vasoactive substances in elderly (60-70 years) rheumatoid arthritis patients with diabetes and hypertension, as well as another group with bronchial asthma patients in order to demonstrate the beneficial effects of medical ozone in the prevention and therapy of age-related diseases in these age groups. A randomized clinical study with 45 older patients (60-70 years) was performed. Group I (n = 15) with rheumatoid arthritis + diabetes and hypertension received no ozone treatment, and group II (n = 30) was treated with medical ozone. This group was divided into two subgroups (n = 15 each), group IIa: the same as group I + medical ozone and group IIb: bronchial asthma patients. Indicators of RA in I and IIa groups were evaluated. Redox balance was assessed through defense and injury biomarkers. Thromboxane A2 (TXA2) and prostacyclin levels were assessed in group IIb patients. Medical ozone arrested oxidative injury progression in the Ia group and decreased thromboxane levels and the TXA2/6-keto PGF1α ratio in the IIb group. Medical ozone arrested the progression of oxidative damage and modulated those endogenous mechanisms that promote a suitable redox status and TXA2/PGI2 balance. These results suggest that medical ozone may become a standard approach in the prevention and management of age-related oxidative diseases in elderly people.

15.
Health Informatics J ; 28(4): 14604582221135440, 2022.
Article in English | MEDLINE | ID: mdl-36300324

ABSTRACT

Symptoms of postpartum depression and anxiety in new mothers are prevalent and negatively impact maternal emotional wellbeing and infant development. Barriers to accessing treatment prevent women from receiving mental health care, a situation that has worsened due to the COVID-19 pandemic. mHealth interventions hold the potential to support women during the transition to parenthood despite these barriers and to promote the use of preventive interventions. This study uses a mixed methods design to assess the feasibility and preliminary effectiveness of a psychoeducational, guided mHealth intervention to prevent postpartum mental health difficulties in women who receive care in primary health centers in Chile. The study will contribute to evidence-based research on the effectiveness of mHealth interventions for new mothers from an understudied cultural background. The findings will also enable the development of a larger randomized controlled trial to assess the effectiveness of the intervention, which, if effective, could significantly contribute to the emotional wellbeing of women and their families.


Subject(s)
COVID-19 , Depression, Postpartum , Internet-Based Intervention , Child , Female , Humans , Anxiety/prevention & control , Chile , COVID-19/prevention & control , Depression, Postpartum/prevention & control , Feasibility Studies , Mothers/psychology , Pandemics
16.
Front Psychol ; 13: 979872, 2022.
Article in English | MEDLINE | ID: mdl-35967668

ABSTRACT

[This corrects the article DOI: 10.3389/fpsyg.2021.712087.].

17.
Pathogens ; 11(3)2022 Mar 21.
Article in English | MEDLINE | ID: mdl-35335703

ABSTRACT

Addition of the immunomodulator pentoxifylline (PTX) to antimonial treatment of mucosal leishmaniasis has shown increased efficacy. This randomized, double-blind, placebo-controlled trial evaluated whether addition of pentoxifylline to meglumine antimoniate (MA) treatment improves therapeutic response in cutaneous leishmaniasis (CL) patients. Seventy-three patients aged 18−65 years, having multiple lesions or a single lesion ≥ 3 cm were randomized to receive: intramuscular MA (20 mg/kg/day × 20 days) plus oral PTX 400 mg thrice daily (intervention arm, n = 36) or MA plus placebo (control arm, n = 37), between 2012 and 2015. Inflammatory gene expression was evaluated by RT-qPCR in peripheral blood mononuclear cells from trial patients, before and after treatment. Intention-to-treat failure rate was 35% for intervention vs. 25% for control (OR: 0.61, 95% CI: 0.21−1.71). Per-protocol failure rate was 32% for PTX, and 24% for placebo (OR: 0.50, 95% CI: 0.13−1.97). No differences in frequency or severity of adverse events were found (PTX = 142 vs. placebo = 140). Expression of inflammatory mediators was unaltered by addition of PTX to MA. However, therapeutic failure was associated with significant overexpression of il1ß and ptgs2 (p < 0.05), irrespective of study group. No clinical benefit of addition of PTX to standard treatment was detected in early mild to moderate CL caused by Leishmania (V.) panamensis.

18.
Antimicrob Agents Chemother ; 66(1): e0142521, 2022 01 18.
Article in English | MEDLINE | ID: mdl-34694879

ABSTRACT

Failure of treatment of cutaneous leishmaniasis with antimonial drugs and miltefosine is frequent. Use of oral combination therapy represents an attractive strategy to increase efficacy of treatment and reduce the risk of drug resistance. We evaluated the potency of posaconazole, itraconazole, voriconazole, and fluconazole and the potential synergy of those demonstrating the highest potency, in combination with miltefosine (HePC), against infection with Leishmania (Viannia) panamensis. Synergistic activity was determined by isobolograms and calculation of the fractional inhibitory concentration index (FICI), based on parasite quantification using an ex vivo model of human peripheral blood mononuclear cells (PBMCs) infected with a luciferase-transfected, antimony and miltefosine sensitive line of L. panamensis. The drug combination and concentrations that displayed synergy were then evaluated for antileishmanial effect in 10 clinical strains of L. panamensis by reverse transcription-quantitative (qRT-PCR) of Leishmania 7SLRNA. High potency was substantiated for posaconazole and itraconazole against sensitive as well as HePC- and antimony-resistant lines of L. panamensis, whereas fluconazole and voriconazole displayed low potency. HePC combined with posaconazole (Poz) demonstrated evidence of synergy at free drug concentrations achieved in plasma during treatment (2 µM HePC plus 4 µM Poz). FICI, based on 70% and 90% reduction of infection, was 0.5 for the sensitive line. The combination of 2 µM HePC plus 4 µM Poz effected a significantly greater reduction of infection by clinical strains of L. panamensis than individual drugs. Orally administrable miltefosine/posaconazole combinations demonstrated synergistic antileishmanial capacity ex vivo against L. panamensis, supporting their potential as a novel therapeutic strategy to improve efficacy and effectiveness of treatment.


Subject(s)
Antiprotozoal Agents , Leishmania guyanensis , Antiprotozoal Agents/pharmacology , Antiprotozoal Agents/therapeutic use , Azoles/pharmacology , Humans , Leukocytes, Mononuclear , Phosphorylcholine/analogs & derivatives , Phosphorylcholine/therapeutic use
19.
JMIR Ment Health ; 8(12): e26814, 2021 Dec 16.
Article in English | MEDLINE | ID: mdl-34927594

ABSTRACT

BACKGROUND: Internet-based interventions promise to enhance the accessibility of mental health care for a greater number of people and in more remote places. Their effectiveness has been shown for the prevention and treatment of various mental disorders. However, their potential when delivered as add-on to conventional treatment (ie, blended care) is less clear. OBJECTIVE: The aim of this study is to study the effectiveness of an internet intervention (ASCENSO) implemented in addition to face-to-face treatment as usual (TAU) for depression. METHODS: A 2-arm, parallel-group, randomized controlled trial was conducted in an outpatient private mental health care center in Chile. In all, 167 adults, diagnosed with major depressive disorder, without severe comorbidities, and with internet access, were included. Eighty-four participants were assigned to the intervention group and received medical and psychological TAU from the mental health center plus access to the ASCENSO online platform. The control group (n=83) received only TAU. The ASCENSO platform includes psycho-educational information, depressive symptom monitoring and feedback, and managing emergencies based on the principles of cognitive behavioral therapy. Emergency management was mental health provider-assisted. TAU includes access to primary care physicians and psychiatrists, to a brief individual psychotherapy, and to medication when needed. The baseline questionnaires were administered in person, and 6- and 9-months assessments were conducted online. Depression symptoms and quality of life were measured by self-administered questionnaires, and treatment adherence was determined via the Mental Health Center's internal records. The usage of ASCENSO was assessed by server logs. Reduction on depressive symptomatology was considered as the primary outcome of the intervention and quality of life as a secondary outcome. RESULTS: Of the 84 participants in the intervention group, 5 participants (6%) never accessed the online platform. Of the remaining 79 participants who accessed ASCENSO, 1 (1%, 1/79) did not answer any of the symptom questionnaire, and most participants (72/79, 91%) answered the monitoring questionnaires irregularly. The ASCENSO intervention implemented in addition to face-to-face care did not improve the outcome of the usual care delivered at the mental health center, either in terms of reduction of depressive symptoms (F2,6087= 0.48; P=.62) or in the improvement of quality of life (EQ-5D-3L: F2,7678=0.24; P=.79 and EQ-VAS: F2,6670= 0.13; P=.88). In contrast, for the primary (F2,850=78.25; P<.001) and secondary outcomes (EQ-5D-3L: F2,1067=37.87; EQ-VAS: F2,4390= 51.69; P<.001) in both groups, there was an improvement from baseline to 6 months (P<.001), but there was no change at 9 months. In addition, no effects on adherence to or use of TAU were found. Finally, the dropout rate for the face-to-face treatment component was 54% (45/84) for the intervention group versus 39% (32/83) for the control group (P=.07). CONCLUSIONS: The fact that the adjunctive access to ASCENSO did not improve outcome could be due to both the rather high effectiveness of TAU and to patients' limited use of the online platform. TRIAL REGISTRATION: ClinicalTrials.gov NCT03093467; https://clinicaltrials.gov/ct2/show/NCT03093467.

20.
Ter. psicol ; 39(3): 445-465, dic. 2021. tab, ilus
Article in Spanish | LILACS | ID: biblio-1390469

ABSTRACT

Resumen: Antecedentes: El principal factor de riesgo para suicidio consumado es el Intento Suicida (IS) previo. La hospitalización psiquiátrica es un recurso terapéutico utilizado en adolescentes para proteger su integridad. Objetivo: Describir y comprender la experiencia de hospitalización psiquiátrica por intento de suicidio y los cambios asociados a ésta, desde la perspectiva de lo/as adolescentes implicados. Método: Estudio cualitativo descriptivo que entrevista a 10 adolescentes que fueron hospitalizados por IS en un centro psiquiátrico. Las entrevistas semiestructuradas fueron codificadas según los criterios de codificación abierta y axial de la Teoría Fundamentada. Resultados: Se presentan dos categorías descriptivas: a) Hospitalización: "lo peor que me ha pasado en la vida… pero tuvo cosas buenas", y b) "Una vez afuera, pienso que me sirvió para cambiar". Luego, se presenta un esquema relacional que articula ambos fenómenos, "de la conmoción a la contención reflexiva". Conclusiones: La experiencia de hospitalización psiquiátrica por IS constituye una experiencia de alto impacto existencial, que brinda posibilidades de movilizar cambios personales y familiares. Sólo post-hospitalización lo/as adolescentes visualizan y desarrollan estos cambios, adhiriendo a los tratamientos indicados y apoyo familiar. Sin embargo, la indicación y gestión de este recurso terapéutico debe ponderarse, para evitar riesgos asociados.


Abstract: Background: Previous suicide attempt (SA) is the main risk factor for completed suicide. Psychiatric hospitalization is a therapeutic resource used in adolescents to protect their integrity. Aim: To describe and understand the experience of psychiatric hospitalization due to SA and the changes associated with it, from the perspective of adolescents involved. Method: Descriptive qualitative study that interviews 10 adolescents who were hospitalized for SA in a psychiatric center. Semi-structured interviews were coded according to Grounded Theory's open and axial coding criteria. Results: Two descriptive categories are presented: a) Hospitalization: "the worst thing that has happened to me in my life… but it had something positive", and b) "Once outside, I think it helped me to change". Then, a relational scheme that articulates both phenomena is presented, "from shock to reflective containment". Conclusions: The experience of psychiatric hospitalization for SA constitutes an experience with a high existential impact, which offers possibilities to mobilize personal and family changes. Only after hospitalization adolescents visualize and develop these changes, adhering to the indicated treatments and family support. However, the indication and management of this therapeutic resource must be considered, to avoid associated risks.


Subject(s)
Humans , Male , Female , Adolescent , Evaluation Studies as Topic
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