Home- vs clinic-based daylight photodynamic therapy with 5-aminolevulinic acid nanoemulsion (BF-200 ALA) for actinic keratosis: A randomized, single-blind, prospective study.

BACKGROUND: Daylight photodynamic therapy (DL-PDT) has become one of the most effective treatments for the resolution of actinic keratosis (AK) of Olsen grade 1 and 2. Generally, PDT it is carried out in a clinic setting, which involves the patient's and their caregivers commuting to the hospital as well as a significant use of resources to carry it out within the clinic setting. OBJECTIVES: To determine the efficacy and safety of a home-based treatment of AK with DL-PDT with the BF-200 ALA gel compared to a clinic-based setting. METHODS: The study was performed as a randomized, single-center, non-inferiority clinical trial with two parallel groups. 9 patients received one clinic-based DL-PDT (group 1) and 11 patients received one session of home-based DL-PDT (group 2). The primary endpoints were the mean AK clearance per patient and the total AK lesion clearance rate 12 weeks after treatment. The secondary endpoints were the number of remaining AKs and new AKs appearing in the treatment field 12 weeks after one PDT session. The pain during and 24 h after PDT as well as the local skin reactions were also assessed. RESULTS: The overall reduction of AK lesions per patient was similar in both groups with one PDT session. An overall AK clearance per patient of 10 ± 4.33 for group 1 versus 9.73 ± 2.9 for group 2 without statistically significant differences (p = 0.868). Regarding the clearance rate, although it was slightly higher in group 2 (71.58 ± 22.51 vs 82.1 ± 11.13), the analysis did not show statistically significant differences. The mild pain recorded during the treatment course and the mild local skin reactions were similar in both groups. Patient satisfaction was high for both groups without statistically significant differences. CONCLUSION: Self-performed home-based DL-PDT with BF-200 ALA gel is as effective as the one performed in a clinic-based setting, with a comparable safety profile, high levels of patient satisfaction and with advantages for the patients and their caregivers that can enhance patient´s adherence to the treatment.

Placental concentrations of xenoestrogenic organochlorine pesticides and polychlorinated biphenyls and assessment of their xenoestrogenicity in the PA-MAMI mother-child cohort.

BACKGROUND: Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCB), they have contributed to the exposure of women to persistent organic pollutants (POPs). These compounds can cross the placental barrier and interfere with the hormonal system of newborns. AIM: To determine concentrations of OCPs and PCBs and their xenoestrogenic activity in placentas of women from the PA-MAMI cohort of Panama. METHODS: Thirty-nine placenta samples from women in the Azuero peninsula (Panama) were analyzed. Five OCPs [p-p'-dichlorodiphenyldichloroethylene (p-p'-DDE), beta-hexachlorohexane (ß-HCH), γ-hexachlorohexane (lindane), hexachlorobenzene (HCB) and mirex] and three PCB congeners (PCB-138, PCB-153 and PCB-180) were quantified in placenta extracts. The xenoestrogenic activity of extracts was assessed with the E-Screen bioassay to estimate the total effective xenoestrogen burden (TEXB). RESULTS: All placental samples were positive for at least three POP residues and >70% for at least six. The frequencies of quantified OCPs ranged from 100% for p,p'-DDE and HCB to 30.8% for ß-HCH. The highest median concentration was for lindane (380.0 pg/g placenta), followed by p,p'-DDE (280.0 pg/g placenta), and HCB (90.0 pg/g placenta). Exposure to p,p'-DDE was associated with greater meat consumption, suggesting that animal fat is a major source of exposure to DDT metabolites. The frequency of detected PCBs ranged between 70 and 90%; the highest median concentration was for PCB 138 (17.0 pg/g placenta), followed by PCB 153 (16.0 pg/g placenta). All placentas were positive in the estrogenicity bioassay with a median TEXB-α of 0.91 pM Eeq/g of placenta. Exposure to lindane was positively associated with the xenoestrogenicity of TEXB- α, whereas this association was negative in the case of exposure to PCB 153. CONCLUSIONS: To our best knowledge, this study contributes the first evidence on the presence of POPs and xenoestrogenic burden in placentas from Latin-American women. Given concerns about the consequences of prenatal exposure to these compounds on children's health, preventive measures are highly recommended to eliminate or minimize the risk of OCP exposure during pregnancy.

Perception of PrEP-related stigma in PrEP users: Results from the ANRS-PREVENIR cohort.

INTRODUCTION: Since the advent of HIV pre-exposure prophylaxis (PrEP), stigma has been shown to be a major barrier to its uptake and adherence. It is therefore essential to define the proportion of users who consider that PrEP can negatively impact their image and the factors associated with this perception. METHOD: We performed a multivariable logistic regression on data from the 2567 participants in the ANRS-PREVENIR study who answered the outcome question. RESULTS: Almost one-third of the sample (comprising mostly cisgender men who have sex with men [94.3%]) considered that taking PrEP could give others a negative image of them. Younger participants (adjusted odds ratio [aOR] 0.98; 95% confidence interval [CI] 0.97-0.99) and more psychologically vulnerable participants (i.e., lower self-esteem score [aOR 0.98; 95% CI 0.96-0.99] and higher depression score [aOR 1.02; 95% CI 1.00-1.03]) were also more likely to have this perception. In contrast, participants encouraged to take PrEP by their main partner (aOR 0.67; 95% CI 0.51-0.88) and friends (aOR 0.79; 95% CI 0.66-0.95), and those who protected themselves more because they had knowledge of their most recent sexual partner's HIV status (aOR 0.83; 95% CI 0.69-0.99) and systematic use of PrEP and/or condoms during intercourse in the previous 3 months (aOR 0.80; 95% CI 0.67-0.96) were less likely to have this perception. DISCUSSION: Given the strong interrelation between stigmatization (real or perceived), risky behaviours and adherence, our results emphasize the need for HIV prevention campaigns to promote a positive image of PrEP users. They also show that stigmatization and its effects need to be fully considered to improve HIV prevention offers to current and potential PrEP users who are most likely to be psychologically vulnerable.

Immunization with thiol-binding proteins from Haemonchus contortus adult worms partially protects goats against infection during prepatency.

To contribute of the knowledge of the immune mechanisms underlying the response to the immunization of goats with thiol-binding proteins fractions (PBS-TSBP) from Haemonchus contortus (H. contortus) adult worms, this study analyzed the degree of protection and the immune responses developed against the parasite after vaccination with this antigenic complex during the time-elapsing between challenge with L3 of the parasite and the development of adult worms, evidenced by the appearance of first faecal eggs (prepatent period or prepatency). Goat kids immunized with PBS-TBSP generated an immune response during the prepatency which translates into a reduction in the number of worms, as well as a lower reduction on packed cell volume and plasma protein levels in relation to the non-vaccinated animals. As previously described in other studies carried out after the prepatent period, this protection was associated with a systemic humoral response. At the local level, a specific humoral response was also observed, together with an immune-inflammatory infiltrate in the gastric mucosa of MCH-II + cells and CD4+ lymphocytes, whose number was associated with a reduction in the number of worms and an increase in plasma proteins. A high peripheral eosinophilia was detected, but no corresponding increased infiltration of the gastric mucosa by eosinophils or globular leukocytes was observed. In agreement with previous data on the immunolocalization of the antigens used here, the results obtained contribute to the idea that these may be excretion/secretion (E/S) products necessary for parasite survival, whose inactivation during the larval and/or pre-adult stages may have contributed to immunoprotection.

Population pharmacokinetics and pharmacodynamics of imipenem in neutropenic adult patients.

OBJECTIVE: Imipenem is recommended in patients with chemotherapy-induced febrile neutropenia. Although alterations of antibiotic pharmacokinetic parameters have been reported in such patients, little data is available on imipenem. METHODS: Prospective, single-center, non-interventional pharmacokinetic cohort study in adults with chemotherapy-induced febrile neutropenia. Critically ill patients were excluded. Imipenem was administered as a 30-min infusion of 1000 mg/8h. Total imipenem plasma concentrations were assayed by high-performance liquid chromatography during neutropenia and just after neutrophil recovery. We estimated population pharmacokinetic parameters of imipenem by non-linear mixed-effect modelling using the SAEM algorithm. RESULTS: Sixteen patients were included in the study, including nine women (56.3%), median age 37 years (range, 18.3; 78.3). Eight patients had an hematological malignancy (50.0%) and seven had a solid tumor (43.8%). Imipenem pharmacokinetics were best described by a one-compartment model with first-order elimination. Mean values for imipenem were: clearance 14.3L/h and 10.9L/h and volume of distribution 20.7L and 14.5 L during neutropenia and after recovery, respectively. Imipenem plasma area under the curve at steady state was reduced by 23% during neutropenia. However, all patients achieved a pharmacodynamic target of %fT>MIC ≥ 40% with a regimen of 1000 mg/8 h or 500 mg/6 h, for MICs up to 2 mg/L. The pharmacodynamics profile for a target of %fT > MIC = 100% was however less favorable with 500 mg/6 h or 1000 mg/8 h either during or after neutropenia. CONCLUSION: Pharmacokinetic/pharmacodynamic goals for imipenem were similar in patients during and after neutropenia, despite reduced plasma exposure.

Treatment With a Three-Drug Regimen for Pulmonary Tuberculosis Based on Rapid Molecular Detection of Isoniazid Resistance: A Noninferiority Randomized Trial (FAST-TB).

Background: The rationale behind the use of ethambutol in the standard tuberculosis treatment is to prevent the emergence of resistance to rifampicin in case of primary resistance to isoniazid. We evaluated whether early detection of isoniazid resistance using molecular testing allows the use an ethambutol-free regimen. Methods: FAST-TB, a phase 4, French, multicenter, open-label, non-inferiority trial, compared 2 strategies: (1) polymerase chain reaction (PCR)-based detection of isoniazid and rifampicin resistance at baseline using Genotype MTBDRplus version 2.0 followed by ethambutol discontinuation if no resistance was detected (PCR arm) and (2) a standard 4-drug combination, pending phenotypic drug-susceptibility results (C arm). Adult patients with smear-positive pulmonary tuberculosis were enrolled. The primary endpoint was the proportion of patients with treatment success defined as bacteriological or clinical cure at the end of treatment. A non-inferiority margin of 10% was used. Results: Two hundred three patients were randomized, 104 in the PCR arm and 99 in the C arm: 26.6% were female, median age was 37 (interquartile range, 28-51) years, 72.4% were born in Africa, and 5.4% were infected with human immunodeficiency virus. Chest x-ray showed cavities in 64.5% of the cases. Overall, 169 patients met criteria of treatment success: 87 of 104 (83.7%) in the PCR arm and 82 of 99 (82.8%) in the C arm with a difference of +0.8% (90% confidence interval, -7.9 to 9.6), meeting the noninferiority criteria in the intention-to-treat population (P = .02). Conclusions: In a setting with low prevalence of primary isoniazid resistance, a 3-drug combination with isoniazid, rifampicin, and pyrazinamide, based on rapid detection of isoniazid resistance using molecular testing, was noninferior to starting the recommended 4-drug regimen.

What Dermatologists Should Know About Thiazides. / Tiazidas: lo que el dermatólogo debería saber.

Hydrochlorothiazide and other thiazide diuretics have been used for decades to treat high blood pressure, heart failure, and chronic kidney disease. Thiazides have been linked to photosensitivity with heterogeneous clinical manifestations and recovery times. Diagnosis can be aided by phototesting, photopatch testing, and skin biopsy. Long-term use of hydrochlorothiazide has been linked to an increased dose-dependent risk of certain types of skin cancer in recent years. In this review, we also look at other less common or lesser-known adverse effects of thiazide diuretics that have been described in isolated reports.

Tiazidas: lo que el dermatólogo debería saber / What Dermatologists Should Know About Thiazides

La hidroclorotiazida (HCTZ) y otros diuréticos tiazídicos son fármacos que se han empleado desde hace décadas para el tratamiento de la hipertensión arterial, la insuficiencia cardíaca o la enfermedad renal crónica. Las tiazidas se han asociado con reacciones de fotosensibilidad, siendo heterogéneas en cuanto a manifestación clínica y tiempo de recuperación, y en las cuales, el fototest, el fotoparche y la biopsia cutánea nos pueden ser útiles en el diagnóstico. En relación con estos fármacos, en los últimos años se ha evidenciado también un mayor riesgo dosis-dependiente de desarrollar determinados tipos de cáncer cutáneo en pacientes tratados de forma crónica con HCTZ. En esta revisión se comentan, asimismo, otros efectos adversos menos habituales o reconocidos de los diuréticos tiazídicos reportados de forma aislada en la literatura (AU)

Hydrochlorothiazide and other thiazide diuretics have been used for decades to treat high blood pressure, heart failure, and chronic kidney disease. Thiazides have been linked to photosensitivity with heterogeneous clinical manifestations and recovery times. Diagnosis can be aided by phototesting, photopatch testing, and skin biopsy. Long-term use of hydrochlorothiazide has been linked to an increased dose-dependent risk of certain types of skin cancer in recent years. In this review, we also look at other less common or lesser-known adverse effects of thiazide diuretics that have been described in isolated reports (AU)

[Translated article] What Dermatologists Should Know About Thiazides / Tiazidas: lo que el dermatólogo debería sabers

Hydrochlorothiazide and other thiazide diuretics have been used for decades to treat high blood pressure, heart failure, and chronic kidney disease. Thiazides have been linked to photosensitivity with heterogeneous clinical manifestations and recovery times. Diagnosis can be aided by phototesting, photopatch testing, and skin biopsy. Long-term use of hydrochlorothiazide has been linked to an increased dose-dependent risk of certain types of skin cancer in recent years. In this review, we also look at other less common or lesser-known adverse effects of thiazide diuretics that have been described in isolated reports (AU)

La hidroclorotiazida (HCTZ) y otros diuréticos tiazídicos son fármacos que se han empleado desde hace décadas para el tratamiento de la hipertensión arterial, la insuficiencia cardíaca o la enfermedad renal crónica. Las tiazidas se han asociado con reacciones de fotosensibilidad, siendo heterogéneas en cuanto a manifestación clínica y tiempo de recuperación, y en las cuales, el fototest, el fotoparche y la biopsia cutánea nos pueden ser útiles en el diagnóstico. En relación con estos fármacos, en los últimos años se ha evidenciado también un mayor riesgo dosis-dependiente de desarrollar determinados tipos de cáncer cutáneo en pacientes tratados de forma crónica con HCTZ. En esta revisión se comentan, asimismo, otros efectos adversos menos habituales o reconocidos de los diuréticos tiazídicos reportados de forma aislada en la literatura (AU)

Consecuencias de la fractura de pene: complicaciones y resultados funcionales a largo plazo / Consequences of penile fracture: Complications and long-term functional outcomes

Introducción La fractura de pene (FP) es una urgencia urológica con baja incidencia, por lo que existe poca evidencia de los resultados a largo plazo. Este estudio se centra en las complicaciones postoperatorias y los resultados funcionales a largo plazo en pacientes que han sufrido una FP reparada quirúrgicamente en nuestro centro.Materiales y métodos Los registros clínicos de pacientes sometidos a cirugía urgente por FP en un hospital de tercer nivel entre 2006 y 2020 se revisaron retrospectivamente. Los resultados funcionales se evaluaron con visitas telefónicas voluntarias desde junio del 2020 a febrero del 2021. Se realizó un cribado de sintomatología del tracto urinario inferior mediante el cuestionario IPSS, de función sexual mediante el EHS y el IIEF-5, y de alteraciones morfológicas mediante pregunta directa a los pacientes.ResultadosCuarenta y un pacientes fueron sometidos a cirugía por FP; 11 de ellos además asociaron lesión uretral (mayor incidencia si había lesión de ambos cuerpos cavernosos, 19,4 vs. 80%, p<0,05). Solo un paciente presentó una complicación Clavien-Dindo tipo 3a por dehiscencia de la herida, 4 (13%) tipo 2 y 9 (29%) tipo 1. Realizaron seguimiento a largo plazo 24 pacientes, de los cuales 20 (83,3%) presentaban una función sexual normal. Doce (50%) presentaban un nódulo palpable en la zona de la fractura, 8 (33,3%) curvatura peneana de nueva aparición y un paciente con lesión uretral previa presentó estenosis de uretra.Conclusión En la fractura de pene, hay más incidencia de lesión uretral si se afectan ambos cuerpos cavernosos. Las secuelas funcionales a largo plazo tras la reparación quirúrgica de una FP son poco frecuentes (AU)

Introduction Penile fracture (PF) is a urological emergency with low incidence, and evidence of its long-term outcomes is scarce. This study focuses on postoperative complications and long-term functional outcomes in patients with PF and surgical repair at our center.Materials and method Clinical records of patients undergoing urgent surgery for PF at a third level hospital between 2006 and 2020 were retrospectively reviewed. Functional outcomes were assessed with voluntary telephone interviews from June 2020 to February 2021. Lower urinary tract symptoms were screened by IPSS questionnaire, sexual function by EHS and IIEF-5, and morphological alterations by direct questions to patients.ResultsA total of 41 patients underwent surgery for PF. Eleven of them also had urethral injury (higher incidence if there was bilateral corpora cavernosa injury, 19.4 vs. 80%, P<.05). Only one patient presented a Clavien-Dindo type 3a complication due to wound dehiscence, 4 (13%) type 2 and 9 (29%) type 1. Twenty-four patients underwent long-term follow-up, of whom 20 (83.3%) presented normal sexual function. Twelve patients (50%) had a palpable nodule at the fracture site, 8 (33.3%) had new onset penile curvature and one patient with previous urethral injury presented urethral stricture.Conclusion In cases of penile fracture, there is a higher incidence of urethral injury if both corpora cavernosa are affected. Long-term functional sequelae after surgical repair of a PF are rare (AU)

Consequences of penile fracture: Complications and long-term functional outcomes.

INTRODUCTION: Penile fracture (PF) is a urological emergency with low incidence, and evidence of its long-term outcomes is scarce. This study focuses on postoperative complications and long-term functional outcomes in patients with PF and surgical repair at our center. MATERIALS AND METHOD: Clinical records of patients undergoing urgent surgery for PF at a third level hospital between 2006 and 2020 were retrospectively reviewed. Functional outcomes were assessed with voluntary telephone interviews from June 2020 to February 2021. Lower urinary tract symptoms were screened by IPSS questionnaire, sexual function by EHS and IIEF-5 and morphological alterations by direct questions to patients. RESULTS: A total of 41 patients underwent surgery for PF. Eleven of them also had urethral injury (higher incidence if there was bilateral corpora cavernosa injury, 19.4% vs. 80%, p < 0.05). Only 1 patient presented a Clavien-Dindo type 3a complication due to wound dehiscence, 4 (13%) type 2 and 9 (29%) type 1. Twenty-four patients underwent long-term follow-up, of whom 20 (83.3%) presented normal sexual function. Twelve patients (50%) had a palpable nodule at the fracture site, 8 (33.3%) had new onset penile curvature and 1 patient with previous urethral injury presented urethral stricture. CONCLUSION: In cases of penile fracture, there is a higher incidence of urethral injury if both corpora cavernosa are affected. Long-term functional sequelae after surgical repair of a PF are rare.

[Teledermatology in the Health Center West Area of Granada: From primary to specialized care]. / Teledermatología en el Área Sanitaria Centro Oeste de Granada: desde atención primaria a especializada.

INTRODUCTION: Teledermatology (TD) is a health tool based on the application of information and communication technologies (ICT) for the care of skin diseases at a distance, allowing a better connection between primary care professionals (PCP) and specialized care. The objective of this study was to analyze the characteristics of the teleconsultations made to our service in a period of 2years (January 1, 2018 to December 31, 2019). MATERIAL AND METHODS: The data was obtained from a TD system with dermoscopy that allows teleconsultations to be carried out asynchronously. Data were analyzed over 24months. The variables studied were the health centre of origin, the diagnostic suspicion of the PCP, the time and type of response, and the clinical judgment issued by the dermatologist. RESULTS: Between January 1, 2018 and December 31, 2019, a total of 3,294 teleconsultations were received. 24.76% were referred to the dermatology consultation, while 25.63% required subsequent follow-up electronically. The most frequent diagnostic suspicion by the PCP was that of benign pathology (54.71%). The most frequent dermatological clinical judgment was that of seborrheic keratosis (20.19%), followed by actinic keratosis (14.02%), acquired common melanocytic nevi (13.24%) and basal cell carcinoma (8.98%). CONCLUSIONS: The TD system is a useful tool that allowed a quick response to a high percentage of consultations, helping to avoid unnecessary referrals and easy communication between primary and specialized care. It also allows prioritizing those patients with malignant tumour pathology.

A Randomized Placebo-Controlled Efficacy Study of a Prime Boost Therapeutic Vaccination Strategy in HIV-1-Infected Individuals: VRI02 ANRS 149 LIGHT Phase II Trial.

In this placebo-controlled phase II randomized clinical trial, 103 human immunodeficiency virus type 1 (HIV-1)-infected patients under cART (combined antiretroviral treatment) were randomized 2:1 to receive either 3 doses of DNA GTU-MultiHIV B (coding for Rev, Nef, Tat, Gag, and gp160) at week 0 (W0), W4, and W12, followed by 2 doses of LIPO-5 vaccine containing long peptides from Gag, Pol, and Nef at W20 and W24, or placebo. Analytical treatment interruption (ATI) was performed between W36 to W48. At W28, vaccinees experienced an increase in functional CD4+ T-cell responses (P < 0.001 for each cytokine compared to W0) measured, predominantly against Gag and Pol/Env, and an increase in HIV-specific CD8+ T cells producing interleukin 2 (IL-2) and tumor necrosis factor alpha (TNF-α) (P = 0.001 and 0.013, respectively), predominantly against Pol/Env and Nef. However, analysis of T-cell subsets by mass cytometry in a subpopulation showed an increase in the W28/W0 ratio for memory CD8+ T cells coexpressing exhaustion and senescence markers such as PD-1/TIGIT (P = 0.004) and CD27/CD57 (P = 0.044) in vaccinees compared to the placebo group. During ATI, all patients experienced viral rebound, with the maximum observed HIV RNA level at W42 (median, 4.63 log10 copies [cp]/ml; interquartile range [IQR], 4.00 to 5.09), without any difference between arms. No patient resumed cART for CD4 cell count drop. Globally, the vaccine strategy was safe. However, a secondary HIV transmission during ATI was observed. These data show that the prime-boost combination of DNA and LIPO-5 vaccines elicited broad and polyfunctional T cells. The contrast between the quality of immune responses and the lack of potent viral control underscores the need for combined immunomodulatory strategies. (This study has been registered at ClinicalTrials.gov under registration no. NCT01492985.)IMPORTANCE In this placebo-controlled phase II randomized clinical trial, we evaluated the safety and immunogenicity of a therapeutic prime-boost vaccine strategy using a recombinant DNA vaccine (GTU-MultiHIV B clade) followed by a boost vaccination with a lipopeptide vaccine (HIV-LIPO-5) in HIV-infected patients on combined antiretroviral therapy. We show here that this prime-boost strategy is well tolerated, consistently with previous studies in HIV-1-infected individuals and healthy volunteers who received each vaccine component individually. Compared to the placebo group, vaccinees elicited strong and polyfunctional HIV-specific CD4+ and CD8+ T-cell responses. However, these immune responses presented some qualitative defects and were not able to control viremia following antiretroviral treatment interruption, as no difference in HIV viral rebound was observed in the vaccine and placebo groups. Several lessons were learned from these results, pointing out the urgent need to combine vaccine strategies with other immune-based interventions.