Search

Abstract Introduction The efficacy of galcanezumab has been demonstrated in randomized controlled trials, but evidence about its use under clinical practice conditions is still limited. This study aimed to describe the characteristics of the patients treated with galcanezumab in routine clinical practice in Spain as well as treatment patterns, persistence, and effectiveness. Methods A retrospective chart review study was carried out in six hospitals. Information of adults with migraine, who started treatment with galcanezumab between November 2019 and September 2021, was analyzed until end or loss of follow-up. Continuous variables were described as mean (standard deviation, SD) and median (interquartile range, IQR), and categorical variables as frequency and percentages. Persistence to treatment was estimated using Kaplan–Meier analysis. Results A total of 314 patients were analyzed over median follow-up period of 17.5 months (13.8–20.7), with a mean age of 46.3 (12.6), 85% women, 80.6% chronic migraine, and reporting a mean of monthly migraine days of 16.7 (7.8). Overall, 72.9% had comorbid conditions, with anxiety and depression disorders being the most frequent. More than 60% had received ≥ 6 previous preventive drugs, the most common being antiepileptics, antidepressants, and botulinum toxin (95.2%, 89.8% and 84.1%, respectively). Overall, 60.3% of the patients with other preventive treatments maintained them after galcanezumab initiation. The median time on galcanezumab was 14.6 months (9.4–22.8); 95.7%, 82.0%, 76.2% and 59.8% of patients were persistent to treatment at 3, 6, 9 and 12 months, respectively. Of the patients who discontinued (151: 48.1%), 57.6% were due to lack of effectiveness and 31.1% were due to improvement in migraine. The average reduction of monthly migraine days at 3, 6, 9 and 12 months was 7.9 (7.2), 9.1 (7.5), 8.8 (6.6) and 9.0 (6.9) days, respectively. Conclusions In real clinical practice, galcanezumab is an effective treatment and has a high persistence in patients with migraine, mostly chronic and with multiple use of previous preventive treatments.

ABSTRACT Peru holds a high mammalian diversity in its Amazonian region, with 326 species. However, our knowledge about the actual diversity is still considered incomplete, and the molecular information for those species in genetic databases is even less comprehensive. To assess the availability of genetic information for Peruvian Amazonian mammals relative to known diversity, we surveyed the Amazonian mammals with at least one molecular marker in the most widely used repositories for nucleotide sequences, GenBank and BOLD Systems. Our survey focused on widely used molecular markers in evolutionary biology-cytochrome b [cyt-b], cytochrome oxidase I [COI], 12S ribosomal RNA [12S], and the mitogenome [mit]-derived from Peruvian Amazon mammals. Additionally, to gain insights into the current mammalian sampling effort in Peruvian Amazonia, we generated a map of unique sampling localities and a heat map, utilizing 41951 records, which identified six major information gaps. This comprehensive analysis found 1597 genetic sequences corresponding to 180 mammalian species (55.2% of Peruvian Amazonian species): COI (38 species), cyt-b (167 species), 12S (56 species), and mitogenome (16 species). Taxonomically, Rodentia (53 species, four markers), Chiroptera (63 species, three markers), and Didelphimorphia (27 species, four markers) represented most molecular data, with a concentration of molecular markers in the orders Chiroptera (703) and Rodentia (499). Geographically, the Loreto department has the largest genetic information (530 records, 99 species). These results confirm a worrying underrepresentation of Peruvian Amazonian diversity in molecular databases. Consequently, we advocate for the use of scientific collections as an alternative source to systematically generate genetic information for the Amazonian mammal diversity in Peru to compensate for the current underrepresentation.

En este artículo reflexivo se ofrece una visión panorámica de los estudios realizados sobre la Manosfera y el antifeminismo en el contexto europeo y español en los últimos cinco años. Para ello, se han revisado los estudios más recientes y relevantes realizados en Europa centrados en comprender la misoginia online organizada y las tecnoculturas tóxicas. Además, se han analizado los trabajos incipientes sobre la manosfera española realizados en España con el fin de conectar el conocimiento europeo con los avances locales. Esta revisión crítica ofrece un estado de la cuestión que incluye: una definición de la manosfera, una propugnación de la importancia de su estudio, una revisión de los temas tratados por áreas temáticas, un diagnóstico de lo que queda por hacer y un aviso ético-epistemológico para aquellas investigadoras que se quieran comprometer con el trabajo de desentrañar qué es la manosfera.

Sylvilagus andinus (Thomas, 1897) is a highland lagomorph from the Ecuadorean Paramos. Its distribution was tentatively believed to extend to northwestern Peru on the basis of ecological niche modeling and the inclusion of the Peruvian S. capsalis Thomas, 1913 as a synonym. Here, we confirm the occurrence of S. andinus in Peru by a morphological examination of seven new records from northwestern Peru and one new record from Ancash department in central Peru.

En el presente trabajo, presentamos una lista actualizada de mamíferos mayores para Loreto compuesta por 72 especies en 8 órdenes y 25 familias. Esta lista fue elaborada a partir de la minuciosa revisión de bases de datos, colecciones zoológicas y publicaciones científicas. En Loreto se encuentran 5 especies endémicas nacionales: Lagothrix flavicauda, Saguinus (Leontocebus) illigeri, Saguinus (Leontocebus) nigrifrons, Pithecia aequatorialis y Pithecia isabela, siendo las tres últimas también endémicas para Loreto. Se encontraron 292 localidades diferentes a partir de 3286 registros de mamíferos mayores. Se presenta un mapa de distribución de las localidades analizadas remarcando ecorregiones y registros históricos (antes del 2001) y contemporáneos (después del 2001). Asimismo, se presentan mapas con la distribución de las localidades donde han sido registradas las 72 especies estudiadas, y un mapa de densidad de las localidades registradas, el cual permite identificar dos zonas con vacíos de información: 1) la zona Datem del Marañón-Loreto y 2) la zona Alto Amazonas-Ucayali. Estas zonas requieren evaluaciones urgentes para complementar el conocimiento de la biodiversidad de Loreto y sustentar adecuadamente los planes de conservación y desarrollo sustentable.

En este trabajo presentamos una lista actualizada de los murciélagos de Loreto basada en la revisión de bases de datos, colecciones científicas y literatura especializada. Encontramos que Loreto es el departamento con mayor diversidad de murciélagos del Perú, con 114 especies agrupadas en 7 familias (19.9% de la mastofauna peruana), y que incluyen dos de las nueve especies endémicas para Perú: Micronycteris (Micronycteris) matses y Hsunycteris dashe. Además, se encontraron 444 localidades diferentes con registros de especímenes, principalmente ubicadas a lo largo de ríos. Las especies registradas en cuatro o menos localidades únicas fueron consideradas como raras, mientras que las especies registradas en 111 o más localidades únicas fueron consideradas comunes. Presentamos un mapa de las ecorregiones de Loreto con las localidades únicas, tanto históricas como contemporáneas, además de un mapa de densidad de localidades por cada 25 km2 donde se identifican 6 zonas de vacíos de información: 1) norte y centro de Putumayo 2) noroeste de Maynas y noreste de Loreto, 3) centro de Maynas, 4) centro-norte del Datem del Marañón, norte de Alto Amazonas y extremo occidental de Loreto, 5) centro-sur de Requena y extremo oriental de Ucayali y 6) extremo occidental de Ucayali. Finalmente presentamos mapas de distribución para cada especie aquí reportada para Loreto.

En este trabajo realizamos una revisión exhaustiva de bases de datos de colecciones científicas y literatura especializada con el objetivo de actualizar la lista de los mamíferos menores no voladores (

La lista de mamíferos del Perú más reciente, publicada en el año 2020, compiló un total de 569 especies y 82 especies endémicas, sin embargo, en corto tiempo varios cambios taxonómicos han ocurrido y obligan a presentar otra lista actualizada de todas las especies de mamíferos con registros en el Perú. Esta nueva lista actualizada hasta noviembre de 2021 incluye 573 especies, 223 géneros, 51 familias y 13 órdenes: Didelphimorphia (47), Paucituberculata (2), Sirenia (1), Cingulata (5), Pilosa (7), Primates (42), Lagomorpha (2), Eulipotyphla (3), Carnivora (33), Perissodactyla (2), Artiodactyla (46, incluyendo 32 cetáceos), Rodentia (194) y Chiroptera (189); de las cuales, 87 especies son endémicas para el país. Por otro lado, la necesidad de contar con listas taxonómicas válidas y actualizadas para el uso en toma de decisiones, nos lleva a proponer como una estrategia óptima que la Asociación de Mastozoólogos del Perú (AMP) asuma el rol de mantener actualizada una lista que cubra las necesidades de los diferentes usuarios, tal como organizaciones similares lo vienen haciendo en países vecinos con el apoyo del Estado y ONGs.

There is growing evidence that autophagy might serve specialized functions in neurons besides its role in protein homeostasis. In this study, authors demonstrate that axonal retrograde transport of BDNF/TrkB in neuronal amphisomes is involved in plasticity-relevant local signaling at presynaptic boutons and that SIPA1L2, a member of the SIPA1L family of neuronal RapGAPs, associates via LC3b to TrkB-containing amphisomes to regulate its motility and signaling at the axon terminals

Infectious diseases are emerging and re-emerging due to climate change. Understanding how climate variability affects the transmission of infectious diseases is important for both researchers and the general public. Yet, the widespread knowledge of the general public on this matter is unknown, and quantitative research is still lacking. A survey was designed to assess the knowledge and perception of 1) infectious diseases, 2) climate change and 3) the effect of climate change on infectious diseases. Participants were recruited via convenience sampling, and an anonymous cross-sectional survey with informed consent was distributed to each participant. Descriptive and inferential analyses were performed primarily focusing on the occupational background as well as nationality of participants. A total of 458 individuals participated in this study, and most participants were originally from Myanmar, the Netherlands, Spain, United Kingdom and the United States. Almost half (44%) had a background in natural sciences and had a higher level of knowledge on infectious diseases compared to participants with non-science background (mean score of 12.5 and 11.2 out of 20, respectively). The knowledge of the effect of climate change on infectious diseases was also significantly different between participants with and without a background in natural sciences (13.1 and 11.8 out of 20, respectively). The level of knowledge on various topics was highly correlated with nationality but not associated with age. The general population demonstrated a high awareness and strong knowledge of climate change regardless of their background in natural sciences. This study exposes a knowledge gap in the general public regarding the effect of climate change on infectious diseases, and highlights that different levels of knowledge are observed in groups with differing occupations and nationalities. These results may help to develop awareness interventions for the general public.

The emergence and spread of antibiotics resistance in wastewater treatment systems have been pointed as a major environmental health problem. Nevertheless, research about adaptation and antibiotics resistance gain in wastewater treatment systems subjected to antibiotics has not been successfully developed considering bioreactor performance, microbial community dynamics and microbial activity dynamics at the same time. To observe this in autotrophic nitrogen removal systems, a partial-nitritation biofilter was subjected to a continuous loading of antibiotics mix of azithromycin, norfloxacin, trimethoprim, and sulfamethoxazole. The effect of the antibiotics mix over the performance, bacterial communities and bacterial activity in the system was evaluated. The addition of antibiotics caused a drop of ammonium oxidation efficiency (from 50 to 5%) and of biomass concentration in the bioreactor, which was coupled to the loss of ammonium oxidizing bacteria Nitrosomonas in the bacterial community from 40 to 3%. Biomass in the partial nitritation biofilter experienced a sharp decrease of about 80% due to antibiotics loading, but the biomass adapted and experienced a growth by stabilization under antibiotics feeding. During the experiment several bacterial genera appeared, such as Alcaligenes, Paracoccus, and Acidovorax, clearly dominating the bacterial community with >20% relative abundance. The system reached around 30% ammonium oxidation efficiency after adaptation to antibiotics, but no effluent nitrite was found, suggesting that dominant antibiotics-resistant phylotypes could be involved in nitrification–denitrification metabolisms. The activity of ammonium oxidation measured as amoA and hao gene expression dropped a 98.25% and 99.21%, respectively, comparing the system before and after the addition of antibiotics. On the other hand, denitrifying activity increased as observed by higher expression of nir and nos genes (83.14% and 252.54%, respectively). In addition, heterotrophic nitrification cyt c-551 was active only after the antibiotics addition. Resistance to the antibiotics was presumably given by ermF, carA and msrA for azithromycin, mutations of the gyrA and grlB for norfloxacin, and by sul123 genes for sulfamethoxazole. Joined physicochemical and microbiological characterization of the system were used to investigate the effect of the antibiotics over the bioprocess. Despite the antibiotics resistance, activity of Bacteria decreased while the activity of Archaea and Fungi increased.

Pyrrole-imidazole (Py-Im) polyamides are synthetic non-genotoxic minor groove-binding small molecules. We hypothesized that Py-Im polyamides can modulate the cellular response to ionizing radiation. Pre-treatment of cells with a Py-Im polyamide prior to exposure to ionizing radiation resulted in a delay in resolution of phosphorylated γ-H2AX foci, increase in XRCC1 foci, and reduced cellular replication potential. RNA-sequencing of cell lines exposed to the polyamide showed induction of genes related to the ultraviolet radiation response. We observed that the polyamide is almost 10-fold more toxic to a cell line deficient in DNA ligase 3 as compared to the parental cell line. Alkaline single cell gel electrophoresis reveals that the polyamide induces genomic fragmentation in the ligase 3 deficient cell line but not the corresponding parental line. The polyamide interferes directly with DNA ligation in vitro. We conclude that Py-Im polyamides may be further explored as sensitizers to genotoxic therapies.

Background: Data on dental anomaly prevalence is instrumental to diagnosis and treatment in different populations. A retrospective study was done to determine dental anomaly prevalence and associations in a group of orthodontic patients in a Mexican population. Methods: Number, shape, eruption and structural dental anomalies were assessed from the records of 670 subjects. Prevalence, distribution, and associations between the different anomalies were calculated. Chi-squared and Fisher’s exact tests (p

The diameter of long-period fiber gratings (LPFGs) fabricated in optical fibers with a low cutoff wavelength was be reduced by hydrofluoric acid etching, enhancing the sensitivity to refractive index by more than a factor of 3, to 2611 nm/refractive index unit in the range from 1.333 to 1.4278. The grating period selected for the LPFGs allowed access to the dispersion turning point at wavelengths close to the visible range of the optical spectrum, where optical equipment is less expensive. As an example of an application, a pH sensor based on the deposition of a polymeric coating was analyzed in two situations: with an LPFG without diameter reduction and with an LPFG with diameter reduction. Again, a sensitivity increase of a factor of near 3 was obtained, demonstrating the ability of this method to enhance the sensitivity of thin-film-coated LPFG chemical sensors.

In this work, the monitoring of the etching process up to a diameter of 30 µm of two LPFG structures has been compared, one of them had initially 125 µm, whereas the second one had 80 µm. By tracking the wavelength shift of the resonance bands during the etching process it is possible to check the quality of etching process (the 80 µm fibre performs better than de 125 µm fibre), and to stop for a specific cladding mode coupling, which permits to obtain an improved sensitivity compared to the initial structure.

La enseñanza de la Geografía Física dentro del marco de la Geografía ha pasado por diferentes etapas cada una de las cuales se ha caracterizado por las tendencias geográficas del momento, así como del desarrollo y evolución del pensamiento geográfico. Siendo la envoltura geográfica del planeta Tierra, por su esencia, el medio natural en el que habita la sociedad humana, constituye el objeto natural de las actividades productivas y la frente de recursos naturales De modo que la disciplina Geografía Física queda conformada por las asignaturas que representan los componentes naturales que quedan integrados en la Geografía de los Paisajes, todas ellas interrelacionadas por una concepción ecólogo-ambiental. En el presente trabajo hacemos algunos análisis y reflexiones sobre la trayectoria en la impartición de esta disciplina, así como el comportamiento actual de corrientes y tendencias en su enseñanza, complementado por la experiencia de los profesores y egresados.

Virtual tours with 360 photos present a quick, easy and accessible way to create immersive experiences. The visualization on diverse devices provides a user experience that can be different. A virtual tour with 360 photos of the Chapel of Dolores (Tenerife) has been created. Access is limited to specific days, so the creation of a virtual tour allows you to visit it at any time; in addition, a pilot test has been carried out with students of the degree of restoration and conservation of cultural heritage in order to measure the user experience of the virtual tour, depending on the device used. The participants took a virtual tour of the Dolores Chapel, first with a cell phone and then with the virtual reality headset, and then completed a user experience questionnaire. The results obtained comparing both visualization technologies are detailed, highlighting the fact that when using the virtual reality headset no better results are obtained on the immersion subscale; in addition, the visualization on a smartphone is more comfortable and obtains better results for consequences such as dizziness and vertigo. Therefore, it may be an interesting strategy to have simple versions that work quickly on cell phones.

Documentar los retablos atendiendo a sus características formales y tridimensionalidad es un reto que a día de hoy podemos abordar mediante el uso de técnicas de documentación ya utilizadas en el ámbito de los bienes inmuebles. Este estudio aborda el proceso de elaboración de un modelo digital de un retablo que, mediante una aproximación a la metodología HBIM, captura su configuración física para convertirlo en contenedor de información relativa a aspectos técnicos, estado de conservación e intervenciones realizadas. Dicho proceso contempla una fase previa de aproximación al objeto de estudio, definición de los usos del modelo, y configuración de un entorno de gestión colaborativa a partir del cual poder añadir e intercambiar información. El uso académico del modelo tridimensional garantizará el conocimiento exhaustivo del retablo, siendo inicialmente modelo de consulta y posteriormente de gestión, al registrar las intervenciones llevadas a cabo por el alumnado, con fines didácticos y de divulgación.

Abstract Introduction Ixekizumab (IXE) is an IgG4-type monoclonal antibody targeting IL-17A indicated alone or in combination with methotrexate, for the treatment of active psoriatic arthritis (PsA) in adult patients with insufficient response or with intolerance to one or more disease-modifying anti-rheumatic drug (DMARD) therapy. The PRO-STIP study aimed to describe persistence, patient characteristics, treatment patterns, and effectiveness in patients with PsA receiving IXE in a real-world clinical setting in Spain. Methods This was an observational, multicentric, retrospective, longitudinal study in adult PsA patients who started IXE between January 2019 and December 2020, with at least 24 weeks of follow-up. A descriptive analysis of patient characteristics and treatment patterns was performed. The primary objective, treatment persistence, was estimated by Kaplan–Meier survival curve. Effectiveness was evaluated by Disease Activity in Psoriatic Arthritis (DAPSA) scores at baseline and at 12 and 24 weeks. Results Eighty-nine patients met the selection criteria (55.1% women and mean age 51.5 years). The median time from PsA diagnosis to starting IXE was 7.7 years (IQR 3.4–14.6). Prior to IXE, 95.5% patients had been treated with at least one biologic or targeted synthetic DMARD (b/tsDMARD). The observed persistence rates were 95.5%, 84.3% and 68.5% at 24, 48, and 104 weeks, respectively. The median persistence was not reached in the study period (mean persistence, 86.9 [95% CI 80.6–93.2] weeks). Twenty-eight (31.5%) patients discontinued IXE, 19 patients (21.3%) due to loss of effectiveness and two patients (2.2%) due to adverse events. In patients receiving treatment and with available effectiveness assessment (n = 24), DAPSA decreased significantly from baseline 23.7 (95% CI 19.5–27.9) to 14.8 (95% CI 10.5–19.2) at 12 weeks (p = 0.005) and 14.3 (95% CI 11.1–17.4) at 24 weeks (p = 0.004). Conclusions PsA patients treated with IXE in a real-world setting show high treatment persistence through 104 weeks and improvements in disease activity after treatment initiation. This suggests that IXE could be an effective treatment for patients with PsA. Retrospectively registered Date of registration: 25th May 2021.

Abstract Introduction This analysis aimed to evaluate demographics, migraine-related disability, symptoms, diagnosis and healthcare consultation, work productivity, and treatment patterns according to headache frequency in adults with migraine in the OVERCOME (ObserVational survey of the Epidemiology, tReatment and Care Of MigrainE) (Spain) study. Methods Data were obtained from an observational, cross-sectional, web-based survey conducted between October 2020–February 2021 in Spain. Eligible participants were adult members of online survey panels living in Spain who were able to read and write Spanish and fulfilled the International Classification of Headache Disorders, third edition (ICHD-3) criteria for migraine or had a self-reported physician diagnosis. Results In total, 10,229 patients comprised the Spanish sample. Only 56.2% of respondents had a confirmed healthcare professional (HCP) diagnosis of migraine, despite almost all meeting modified ICHD-3 criteria. Pain severity, migraine-related disability, and interictal burden increased with increasing number of headache days per month. Migraine impacted on respondents’ work productivity, with increases in presenteeism, work productivity loss, and daily activity impairment at higher headache frequencies. Over the past year, 66.2% of all HCP visits were specifically due to migraine, most commonly with a general practitioner or pharmacist. A subgroup of 1277 patients (12.5% of the total survey population) met eligibility criteria for migraine preventive medications, of whom only 36.6% were currently taking a preventive. Conclusions Results of the OVERCOME (Spain) survey reveal the substantial burden of migraine, which is directly linked to headache frequency. However, most patients experiencing frequent headaches and eligible for migraine preventives are currently not taking them. Findings highlight the importance of addressing unmet needs for people with migraine in Spain.

Abstract Introduction Insulin lispro 100 units/mL Jr KwikPen is the first prefilled, disposable, half‐unit insulin pen that delivers 0.5–30 units in increments of 0.5 units for the treatment of patients with diabetes. This study describes the profile of patients in Spain who initiated insulin therapy with Jr KwikPen in a real‐world setting. Methods This retrospective, observational study based on IQVIA's electronic medical records database included patients with Type 1 (T1D) or Type 2 (T2D) diabetes who initiated therapy with Jr KwikPen between May 2018 and December 2020. Sociodemographic, clinical, and treatment characteristics at treatment initiation were analysed descriptively. Results A total of 416 patients were included. The main characteristics of the T1D/T2D groups (N = 326/90), respectively were as follows: female sex, 61.7%/65.6%; mean age (standard deviation [SD]), 32.5 (20.7)/55.5 (16.6) years; body mass index, 20.9 (4.2)/25.2 (4.6) kg/m2 (N = 239/77); HbA1c, 7.8 (1.7)%/8.0 (1.5)% (N = 141/64); and presence of diabetes‐associated comorbidities, 27.9%/64.4%. Only 32.8% of patients with T1D were

AimsAfter a few passages of in vitro culture, primary human articular chondrocytes undergo senescence and loss of their phenotype. Most of the available chondrocyte cell lines have been obtained from cartilage tissues different from diarthrodial joints, and their utility for osteoarthritis (OA) research is reduced. Thus, the goal of this research was the development of immortalized chondrocyte cell lines proceeded from the articular cartilage of patients with and without OA.MethodsUsing telomerase reverse transcriptase (hTERT) and SV40 large T antigen (SV40LT), we transduced primary OA articular chondrocytes. Proliferative capacity, degree of senescence, and chondrocyte surface antigen expression in transduced chondrocytes were evaluated. In addition, the capacity of transduced chondrocytes to synthesize a tissue similar to cartilage and to respond to interleukin (IL)-1β was assessed.ResultsCoexpression of both transgenes (SV40 and hTERT) were observed in the nuclei of transduced chondrocytes. Generated chondrocyte cell lines showed a high proliferation capacity and less than 2% of senescent cells. These cell lines were able to form 3D aggregates analogous to those generated by primary articular chondrocytes, but were unsuccessful in synthesizing cartilage-like tissue when seeded on type I collagen sponges. However, generated chondrocyte cell lines maintained the potential to respond to IL-1β stimulation.ConclusionThrough SV40LT and hTERT transduction, we successfully immortalized chondrocytes. These immortalized chondrocytes were able to overcome senescence in vitro, but were incapable of synthesizing cartilage-like tissue under the experimental conditions. Nonetheless, these chondrocyte cell lines could be advantageous for OA investigation since, similarly to primary articular chondrocytes, they showed capacity to upregulate inflammatory mediators in response to the IL-1β cytokine.Cite this article: Bone Joint Res 2023;12(1):46–57.

This research studies the dose–plasma level (PL) relationship of second-generation antipsychotics, together with the treatment outcomes achieved, in seriously ill people with schizophrenia. An observational, prospective, one-year follow-up study was carried out with patients (N = 68) with severe schizophrenia treated with paliperidone three-month (PP3M) or aripiprazole one-month (ARIM). Participants were divided into standard-dose or high-dose groups. PLs were divided into “standard PL” and “high PL” (above the therapeutic reference range, TRR) groups. The dose/PL relationship, and severity, hospitalizations, tolerability, compliance, and their relationship with doses and PLs were evaluated. There was no clear linear relationship between ARIM or PP3M doses and the PLs achieved. In half of the subjects, standard doses reached PLs above the TRR. The improvements in clinical outcomes (decrease in clinical severity and relapses) were related to high PLs, without worse treatment tolerability or adherence. All participants remained in the study, regardless of dose or PL. Clinical severity and hospitalizations decreased significantly more in those patients with high PLs. Considering the non-linear dose–PL relationship of ARIM and PP3M in people with severe schizophrenia, PLs above the TRR are linked to better treatment outcomes, without worse tolerability. The need in a notable number of cases for high doses to reach those effective PLs is highlighted.