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INTRODUCTION The monoclonal antibodies Aducanumab, Lecanemab, Gantenerumab, and Donanemab were developed for the treatment of Alzheimer's disease (AD). METHODS We used single‐molecule detection and super‐resolution imaging to characterize the binding of these antibodies to diffusible amyloid beta (Aβ) aggregates generated in‐vitro and harvested from human brains. RESULTS Lecanemab showed the best performance in terms of binding to the small‐diffusible Aβ aggregates, affinity, aggregate coating, and the ability to bind to post‐translationally modified species, providing an explanation for its therapeutic success. We observed a Braak stage–dependent increase in small‐diffusible aggregate quantity and size, which was detectable with Aducanumab and Gantenerumab, but not Lecanemab, showing that the diffusible Aβ aggregates change with disease progression and the smaller aggregates to which Lecanemab preferably binds exist at higher quantities during earlier stages. DISCUSSION These findings provide an explanation for the success of Lecanemab in clinical trials and suggests that Lecanemab will be more effective when used in early‐stage AD. Highlights Anti amyloid beta therapeutics are compared by their diffusible aggregate binding characteristics. In‐vitro and brain‐derived aggregates are tested using single‐molecule detection. Lecanemab shows therapeutic success by binding to aggregates formed in early disease. Lecanemab binds to these aggregates with high affinity and coats them better.

Purpose: This study aimed to review the demographics, clinical characteristics, and long-term outcomes of therapeutic penetrating keratoplasty (TPK) performed in a tertiary eye care hospital. Methods: Case records of 149 therapeutic transplants (135 patients) that were performed during the calendar year 2016 were retrospectively analyzed, and outcomes were measured until 3 years of follow-up. Information on demographics, presentation characteristics, keratoplasty indications, offending microbe, and secondary surgical interventions was studied. The final outcome was classified in terms of therapeutic, anatomical, and functional outcomes. Results: The median age of the recipients was 55 years with 61% men. The most common indications for TPK were perforated infectious ulcer (45.9%), nonhealing ulcers (29.9%), and graft infections (17.4%). Fungal etiology was noted in 61.2% and bacterial etiology in 17.4% of the eyes. Therapeutic success was achieved in 130 eyes (89%) at the end of 1 month. Anatomical success was achieved in 130 (98.5%) and 88 patients (86.3%) at the end of 1 and 6 months, respectively. At the 6-month time point, 78 patients (76.5%) attained functional success with vision better than light perception. Three-year follow-up data were available for 23.7% of recipients, of which only 12 patients (37.5%) retained a clear graft either after a primary therapeutic or secondary optical keratoplasty. Conclusion: Therapeutic keratoplasty is highly effective in eradicating infection and providing anatomical integrity. However, timely intervention can aid in achieving the best functional outcome.

Purpose Symptomatic internal hemorrhoids affect up to 40% of people in Western society. Patients with grade I–III hemorrhoids, who fail lifestyle and medical management, may benefit from office-based procedures. As per the American Society of Colon and Rectum Surgeons (ASCRS), rubber band ligation (RBL) is the first-line office-based treatment. Polidocanol sclerotherapy is a relatively new approach for these patients. The aim of this systematic review is to compare the efficacy of RBL and polidocanol sclerotherapy with the treatment of symptomatic grade I–III internal hemorrhoids. Methods The systematic review was completed by searching MEDLINE, Embase, and CENTRAL databases from inception to August 2022 for prospective studies comparing RBL and polidocanol sclerotherapy or evaluating the efficacy of polidocanol sclerotherapy alone for adult (> 18 years) patients with grade I–III internal hemorrhoids. Treatments were evaluated for therapeutic success and post-procedure morbidity. Results Of 155 citations obtained, 10 studies (3 comparative and 7 single-arm studies) and 4 abstracts (2 comparative and 2 single arm) were included in the study. The patients undergoing sclerotherapy had a 93% (151/163) therapeutic success rate compared to 75% (68/91) in the RBL group (OR 3.39, 95% CI 1.48–7.74, p  < 0.01). The post-procedure morbidity was 8% (17/200) in the sclerotherapy group and 18% (23/128) in the RBL group (OR 0.53, 95% CI 0.15–1.82, p  = 0.31). Conclusion This study highlights that polidocanol sclerotherapy may be associated with higher therapeutic success in patients with symptomatic grade I–III internal hemorrhoids. Further evaluations in the form of randomized trials are required to evaluate patient populations, which may benefit more from sclerotherapy.

This study aimed to evaluate the anatomical, therapeutic, and functional outcome of therapeutic penetrating keratoplasty (TPK) in terms of success and failure. In this retrospective study 57 eyes of 57 patients were reviewed. They had undergone TPK from December 2012 to June 2017. Data analyzed included the baseline demographic features and characteristics, preoperative diagnosis, and postoperative outcomes. The baseline characteristics included age, gender, laterality, indications of TPK, lens status, size of the recipient, grade of the graft, organisms identified, preoperative best corrected visual acuity (BCVA), secondary procedures, adjunctive surgical procedure, postoperative BCVA at last follow-up, intraocular pressure (IOP), and long-term complications of TPK. The ultimate outcome of TPK was observed in terms of anatomical, therapeutic, and functional outcome which indicated the success and failure. A total of 57 eyes of 57 with an age range of 2–76-year-old patients who underwent TPK were included in the study. Perforated corneal ulcer was a major indication of TPK in 32 (56.1%) cases. Anatomical success was obtained overall in 49 (85.96%) cases. Indications of TPK and preoperative visual acuity, complications of TPK, and ultimate graft clarity showed significant impact on the anatomical outcome (P = 0.03, P = 0.00, P = 0.00, and P = 0.05), respectively. The therapeutic and functional success was observed in 51 (89.47%) and 40 (70.17%) cases, respectively. Perforated corneal ulcers was the major indication for TPK. Indications and complications significantly affect the anatomical, therapeutic, and functional outcome.

The main objective of this study was to evaluate the variables influencing the efficacy of different approaches to addressing the problem of drug use among juvenile offenders. A longitudinal study was conducted with 79 adolescent internees at the Teresa de Calcuta CEMJ (Centro de Ejecución de Medidas Judiciales) in Madrid. Therapeutic interventions were conducted with adolescents with severe drug-related problems. For data analysis, binary logistic regression analysis was used. Therapeutic success after a three-month follow-up period was 53.2%. The regression analysis correctly classified 86.1% of the cases, effectively predicting 85.7% of therapeutic success and 86.5% of therapeutic failure. The analysis identified 4 predictive factors: the number of criminal charges resulting in internment, number of minor infractions committed during detention, prior consumption of ecstasy and risk factors in personality and/or behavioural issues. The results suggest that judicial and therapeutic interventions should be based on the chronicity of delinquency and other individual personality traits.

Previous research suggests that psychotherapists' readiness to treat traumatized patients varies according to patient and therapist characteristics, including the patient's refugee background. : This study aims to examine the relationship between psychotherapists' readiness to treat patients with symptoms of post-traumatic stress disorder and various patient and therapist characteristics, including refugee background and country of origin. : In our vignette study with a nationwide online survey in Germany (  = 871), we assessed the readiness of licensed psychotherapists (LPTs) and therapists in training (PiTs) to treat patients with PTSD. Vignettes described patients with PTSD who differed in gender, refugee background, and country of origin (Syria vs. Ukraine). Participants rated treatment readiness and expected treatment success based on the vignette they received. : Treatment readiness and expected success were significantly lower for refugee patients. There was no difference in treatment readiness between refugees from Syria and Ukraine, but therapists expected less therapeutic success for Syrian patients compared to Ukrainian patients. Gender did not influence the results. The study shows that refugee background and country of origin influence psychotherapists' readiness to treat PTSD and their expectations of treatment success. These findings highlight potential reasons for the undertreatment of refugees and suggest opportunities for intervention and training, such as informing therapists about effective treatments for refugee patients.

Patients with psoriasis often have comorbidities and are at increased risk of developing several complications compared with the general population. Knowledge on the role of immune mediators and systemic inflammation in psoriasis has led to the hypothesis that early intervention with systemic therapy has the potential to modify the course of the disease and reduce the risk of long-term adverse outcomes. In this article, we address some potential issues that need to be considered before early intervention can be implemented routinely. The first is determining what constitutes “early” intervention for psoriasis. A second point is whether the intervention should be considered for patients with early disease or for selected subsets based on risk stratification. A third important consideration is defining success for early intervention. Finally, adoption of early and effective intervention should be based on high-level evidence. Ideally, randomized trials would be the best strategy to compare early vs. late systemic treatment in patients with psoriasis, probably using the frequency of long-term outcomes as primary endpoint, with cutaneous and pharmacoeconomic outcomes assessed secondarily.

Background/Objectives: Since 28 January 2022, veterinary medicinal products (VMPs) must be used in accordance with the conditions of the marketing authorisation (Regulation (EU) 2019/6, Article 106). This entails further restrictions on therapeutic freedom, for example, with regard to dose deviations. Off-label use is any use of a product that deviates from the Summary of Product Characteristics (SPCs). To date, there are no data available on the type and extent of off-label use on the basis of which the feasibility of the new regulation in Germany can be assessed. Methods: Therefore, a Germany-wide anonymous online survey was conducted as a quantitative cross-sectional study comprising 196 questions according to off-label use in dogs and cats. Results: In quantitative terms, the survey was representative of 358 participants but limited due to the demographic characteristics of the participants. A total of 91.3% (326/357) veterinarians stated that they had used antibiotics off-label. Fusidic acid, chloramphenicol, tylosin, and florfenicol were most frequently reclassified with regard to animal species. Authorised drugs for cats and dogs such as amoxicillin/clavulanic acid, doxycycline, metronidazole, and fluoroquinolones, like enrofloxacin and marbofloxacin, were also used off-label, often with regard to indication and treatment duration. Conclusions: Although there are comparatively many antibacterial preparations available for cats and dogs, off-label use is common practice. In many cases, special circumstances of the individual case justify the off-label use of authorised preparations for cats and dogs. The survey results indicate that some dose revisions are recommended. Guidance for specific indications in cats and dogs could contribute to greater legal certainty in small animal practice with regard to the justification of off-label use.

Background HIV-1 DNA persists in infected cells, forming viral reservoirs. Pre-antiretroviral treatment (ART) HIV-1 DNA load was reported to predict ART success in European severely immunocompromised patients. The aim of this study was to determine whether HIV-1 DNA levels are associated with virological success in less severely immunocompromised patients who receive early ART in sub-Saharan Africa. Methods The association between pre-ART HIV-1 DNA and the virological response after 30 months on ART was studied in multivariate logistic regression in patients randomised to immediate ART groups in the Temprano trial, which assessed the benefits of early ART in HIV-infected adults in Côte d’Ivoire. HIV-1 DNA was quantified in peripheral blood mononuclear cell (PBMC) using real-time PCR. Results HIV-1 DNA levels were measured in 1013 patients. Their medians [IQR] of pre-ART CD4 count, HIV-1 RNA and HIV-1 DNA levels were 465 [379–578]/mm 3 , 4.7 [4.0–5.3] log 10 copies/ml and 2.9 [2.5–3.2] log 10 copies/million PBMC, respectively. Pre-ART HIV-1 DNA was significantly correlated with pre-ART HIV-1 RNA (R = 0.59, p < 0.0001). In multivariate analysis, HIV-1 DNA < 3 log 10 copies/million PBMC was significantly associated with virological success at M30 after adjustment for other key variables (ART regimen, IPT, sex, age, WHO clinical stage, CD4 and HIV-1 RNA; aOR 1.57; 95% CI 1.08–2.30; p = 0.02). Conclusion Low HIV-1 DNA was statistically associated with virological success in this population of sub-Saharan African adults who started treatment with a median pre-ART CD4 count at 465/mm 3 . HIV-1 DNA could become a useful tool for guiding some therapeutic decisions in the test-and-treat era. Trial registration TEMPRANO ANRS 12136 ClinicalTrials.gov, number NCT00495651, date of registration 03/07/2007.

The use of natural products, such as essential oils (EOs), is a potential novel approach to treat fish bacterial infections with a lower risk of developing resistance. There has been a number of studies reporting the activity of EOs as those obtained from the species Achyrocline satureioides, Aniba parviflora, Aniba rosaeodora, Anthemis nobilis, Conobea scoparioides, Cupressus sempervirens, Illicium verum, Lippia origanoides, and Melaleuca alternifolia against bacteria. However, there are few studies investigating the effect of these EOs against fish bacteria. Therefore, the aim of this study was to evaluate the in vitro antibacterial activity of EOs against the following fish bacteria, Aeromonas hydrophila, Citrobacter freundii, and Raoultella ornithinolytica. Additionally, the in vivo antibacterial activity of the EO L. origanoides was evaluated against experimentally induced A. hydrophila infection of silver catfish (Rhamdia quelen). The EO of L. origanoides was chosen as it showed the highest in vitro antibacterial activity, with minimum inhibitory concentrations ranging from 0.2 to 0.8 mg mL-1. This EO also presented a therapeutic success of 58.33%, on a 30 day A. hydrophila infection. Therefore, we suggested that the EO of L. origanoides may be a viable alternative as a treatment for A. hydrophila infection. RESUMO: O uso de produtos naturais, como óleos essenciais (OEs), é uma nova abordagem potencial para o tratamento de infecções bacterianas em peixes com um baixo risco de desenvolvimento de resistência. Existem estudos reportando a atividade de OEs como aqueles obtidos das espécies Achyrocline satureioides, Aniba parviflora, Aniba rosaeodora, Anthemis nobilis, Conobea scoparioides, Cupressus sempervirens, Illicium verum, Lippia origanoides e Melaleuca alternifolia contra bactérias. Porém, existem poucos estudos investigando o efeito desses OEs supracitados contra bactérias isoladas de peixes. Portanto, o objetivo desse estudo foi avaliar a atividade antibacteriana in vitro desses OEs contra bactérias isoladas de peixes (Aeromonas hydrophila, Citrobacter freundii e Raoultella ornithinolytica). Assim como avaliar a atividade antibacteriana in vivo do OE de L. origanoides contra uma infecção por A. hydrophila experimentalmente induzida em jundiá (Rhamdia quelen). O OE de L. origanoides foi escolhido porque apresentou a melhor atividade antibacteriana in vitro, com concentrações inibitórias mínimas variando de 0,2 a 0,8 mg mL-1. Esse OE apresentou sucesso terapêutico de 58,33% no dia 30 pós-infecção. Portanto, sugerimos que o OE de L. origanoides possa ser uma alternativa viável no tratamento da infecção por A. hydrophila em peixes.