Reconstruction of neocortex: Organelles, compartments, cells, circuits, and activity.

We assembled a semi-automated reconstruction of L2/3 mouse primary visual cortex from ∼250 × 140 × 90 µm3 of electron microscopic images, including pyramidal and non-pyramidal neurons, astrocytes, microglia, oligodendrocytes and precursors, pericytes, vasculature, nuclei, mitochondria, and synapses. Visual responses of a subset of pyramidal cells are included. The data are publicly available, along with tools for programmatic and three-dimensional interactive access. Brief vignettes illustrate the breadth of potential applications relating structure to function in cortical circuits and neuronal cell biology. Mitochondria and synapse organization are characterized as a function of path length from the soma. Pyramidal connectivity motif frequencies are predicted accurately using a configuration model of random graphs. Pyramidal cells receiving more connections from nearby cells exhibit stronger and more reliable visual responses. Sample code shows data access and analysis.

Connectomic reconstruction of a female Drosophila ventral nerve cord.

A deep understanding of how the brain controls behaviour requires mapping neural circuits down to the muscles that they control. Here, we apply automated tools to segment neurons and identify synapses in an electron microscopy dataset of an adult female Drosophila melanogaster ventral nerve cord (VNC)1, which functions like the vertebrate spinal cord to sense and control the body. We find that the fly VNC contains roughly 45 million synapses and 14,600 neuronal cell bodies. To interpret the output of the connectome, we mapped the muscle targets of leg and wing motor neurons using genetic driver lines2 and X-ray holographic nanotomography3. With this motor neuron atlas, we identified neural circuits that coordinate leg and wing movements during take-off. We provide the reconstruction of VNC circuits, the motor neuron atlas and tools for programmatic and interactive access as resources to support experimental and theoretical studies of how the nervous system controls behaviour.

Synaptic architecture of leg and wing premotor control networks in Drosophila.

Animal movement is controlled by motor neurons (MNs), which project out of the central nervous system to activate muscles1. MN activity is coordinated by complex premotor networks that facilitate the contribution of individual muscles to many different behaviours2-6. Here we use connectomics7 to analyse the wiring logic of premotor circuits controlling the Drosophila leg and wing. We find that both premotor networks cluster into modules that link MNs innervating muscles with related functions. Within most leg motor modules, the synaptic weights of each premotor neuron are proportional to the size of their target MNs, establishing a circuit basis for hierarchical MN recruitment. By contrast, wing premotor networks lack proportional synaptic connectivity, which may enable more flexible recruitment of wing steering muscles. Through comparison of the architecture of distinct motor control systems within the same animal, we identify common principles of premotor network organization and specializations that reflect the unique biomechanical constraints and evolutionary origins of leg and wing motor control.

FlyWire: online community for whole-brain connectomics.

Due to advances in automated image acquisition and analysis, whole-brain connectomes with 100,000 or more neurons are on the horizon. Proofreading of whole-brain automated reconstructions will require many person-years of effort, due to the huge volumes of data involved. Here we present FlyWire, an online community for proofreading neural circuits in a Drosophila melanogaster brain and explain how its computational and social structures are organized to scale up to whole-brain connectomics. Browser-based three-dimensional interactive segmentation by collaborative editing of a spatially chunked supervoxel graph makes it possible to distribute proofreading to individuals located virtually anywhere in the world. Information in the edit history is programmatically accessible for a variety of uses such as estimating proofreading accuracy or building incentive systems. An open community accelerates proofreading by recruiting more participants and accelerates scientific discovery by requiring information sharing. We demonstrate how FlyWire enables circuit analysis by reconstructing and analyzing the connectome of mechanosensory neurons.

Oligodendrocyte precursor cells ingest axons in the mouse neocortex.

Neurons in the developing brain undergo extensive structural refinement as nascent circuits adopt their mature form. This physical transformation of neurons is facilitated by the engulfment and degradation of axonal branches and synapses by surrounding glial cells, including microglia and astrocytes. However, the small size of phagocytic organelles and the complex, highly ramified morphology of glia have made it difficult to define the contribution of these and other glial cell types to this crucial process. Here, we used large-scale, serial section transmission electron microscopy (TEM) with computational volume segmentation to reconstruct the complete 3D morphologies of distinct glial types in the mouse visual cortex, providing unprecedented resolution of their morphology and composition. Unexpectedly, we discovered that the fine processes of oligodendrocyte precursor cells (OPCs), a population of abundant, highly dynamic glial progenitors, frequently surrounded small branches of axons. Numerous phagosomes and phagolysosomes (PLs) containing fragments of axons and vesicular structures were present inside their processes, suggesting that OPCs engage in axon pruning. Single-nucleus RNA sequencing from the developing mouse cortex revealed that OPCs express key phagocytic genes at this stage, as well as neuronal transcripts, consistent with active axon engulfment. Although microglia are thought to be responsible for the majority of synaptic pruning and structural refinement, PLs were ten times more abundant in OPCs than in microglia at this stage, and these structures were markedly less abundant in newly generated oligodendrocytes, suggesting that OPCs contribute substantially to the refinement of neuronal circuits during cortical development.

Opioid Prescribing Rate for Nonoperative Distal Radius Fractures and Clinician Response to a Clinical Decision Support Alert.

BACKGROUND: Opioids are commonly prescribed for the management of acute orthopedic trauma pain, including nonoperative distal radius fractures. OBJECTIVES: This prospective study aimed to determine if a clinical decision support intervention influenced prescribing decisions for patients with known risk factors. We sought to quantify frequency of opioid prescriptions for acute nonoperative distal radius fractures treated. METHODS: We performed a prospective study at one large health care system. Utilizing umbrella code S52.5, we identified all distal radius fractures treated nonoperatively, and the encounters were merged with the Prescription Reporting with Immediate Medication Mapping (PRIMUM) database to identify encounters with opioid prescriptions and patients with risk factors for opioid use disorder. We used multivariable logistic regression to determine patient characteristics associated with the prescription of an opioid. Among encounters that triggered the PRIMUM alert, we calculated the percentage of encounters where the PRIMUM alert influenced the prescribing decision. RESULTS: Of 2984 encounters, 1244 (41.7%) included an opioid prescription. Age increment is a significant factor to more likely receive opioid prescriptions (p < 0.0001) after adjusting for other factors. Among encounters where the physician received an alert, those that triggered the alert for early refill were more likely to influence physicians' opioid prescribing when compared with other risk factors (p = 0.0088). CONCLUSION: Over 90% of patients (106/118) continued to receive an opioid medication despite having a known risk factor for abuse. Additionally, we found older patients were more likely to be prescribed opioids for nonoperatively managed distal radius fractures.

Verteporfin is a substrate-selective γ-secretase inhibitor that binds the amyloid precursor protein transmembrane domain.

This work reports substrate-selective inhibition of a protease with broad substrate specificity based on direct binding of a small-molecule inhibitor to the substrate. The target for these studies was γ-secretase protease, which cleaves dozens of different single-span membrane protein substrates, including both the C99 domain of the human amyloid precursor protein and the Notch receptor. Substrate-specific inhibition of C99 cleavage is desirable to reduce production of the amyloid-ß polypeptide without inhibiting Notch cleavage, a major source of toxicity associated with broad specificity γ-secretase inhibitors. In order to identify a C99-selective inhibitors of the human γ-secretase, we conducted an NMR-based screen of FDA-approved drugs against C99 in model membranes. From this screen, we identified the small-molecule verteporfin with these properties. We observed that verteporfin formed a direct 1:1 complex with C99, with a KD of 15-47 µM (depending on the membrane mimetic used), and that it did not bind the transmembrane domain of the Notch-1 receptor. Biochemical assays showed that direct binding of verteporfin to C99 inhibits γ-secretase cleavage of C99 with IC50 values in the range of 15-164 µM, while Notch-1 cleavage was inhibited only at higher concentrations, and likely via a mechanism that does not involve binding to Notch-1. This work documents a robust NMR-based approach to discovery of small-molecule binders to single-span membrane proteins and confirmed that it is possible to inhibit γ-secretase in a substrate-specific manner.

Standardization of Trauma, General Surgical Morbidity and Mortality Conferences: Development and Dissemination of a "Toolkit" in Peru.

BACKGROUND: Morbidity and Mortality (M&M) conferences allow clinicians to review adverse events and identify areas for improvement. There are few reports of structured M&M conferences in low- and middle-income countries and no report of collaborative efforts to standardize them. METHODS: The present study aims to gather general surgeons representing most of Peru's urban surgical care and, in collaboration, with trauma quality improvement experts develop a M&M conferences toolkit with the expectation that its diffusion impacts their reported clinical practice. Fourteen general surgeons developed a toolkit as part of a working group under the auspices of the Peruvian General Surgery Society. After three years, we conducted an anonymous written questionnaire to follow-up previous observations of quality improvement practices. RESULTS: A four-component toolkit was developed: Toolkit component #1: Conference logistics and case selection; Toolkit component #2: Documenting form; Toolkit component #3: Presentation template; and Toolkit component #4: Code of conduct. The toolkit was disseminated to 10 hospitals in 2016. Its effectiveness was evaluated by comparing the results of surveys on quality improvement practices conducted in 2016, before toolkit dissemination (101 respondents) and 2019 (105 respondents). Lower attendance was reported by surgeons in 2019. However, in 2019, participants more frequently described "improve the system" as the perceived objective of M&M conferences (70.5% vs. 38.6% in 2016; p < 0.001). CONCLUSION: We established a toolkit for the national dissemination of a standardized M&M conference. Three years following the initial assessment in Peru, we found similar practice patterns except for increased reporting of "system improvement" as the goal of M&M conferences.

Urban effluents affect the invasive bivalve Limnoperna fortunei (Dunker 1857) fitness in a large Pampasic river (Río Negro, Uruguay).

Invasive alien species (IAS) exert a negative impact on native ecosystems and on various human activities. Limnoperna fortunei (Dunker 1857), a sessile mytilid introduced from Asia in the Río de la Plata, demonstrates a high dispersal capacity, growing over other organisms and artificial structures. Understanding its behavior is crucial for developing appropriate control and mitigating its detrimental effects. This study investigated the population dynamics of this mollusk in response to urban effluents in a large river. Water and population parameters of L. fortunei were measured both upstream and downstream of a small town from July to December 2020. Downstream areas exhibited increased temperature and decreased transparency compared to upstream locations, while pH, conductivity, and dissolved oxygen remained relatively constant. However, downstream, the L. fortunei population comprised fewer and smaller individuals, displaying high width-to-length ratios. Most measured water parameters exhibited significant differences between sampling months. The abundance of L. fortunei remained relatively stable over time due to its nearly continuous reproduction in Uruguay. Nonetheless, shell elongation (15.3-22.8 mm) coincided with an increase in dry weight (0.009-0.038 g) from winter to spring. Allometric relationships, primarily following a power-law model, varied between months, ranging from H = 0.39L1.04 to H = 1.36L0.57. This study contributes to the comprehension of the population dynamics and life history of L. fortunei, thereby aiding in the conservation of invaded aquatic systems. Moreover, it provides valuable insights into the effects of urban effluents on this species, contributing to our understanding of its potential role as a bioindicator.

[Obstetric violence in Chile: women's perceptions and differences among health centersViolência obstétrica no Chile: percepção das mulheres e diferenças entre os serviços de saúde]. / Violencia obstétrica en Chile: percepción de las mujeres y diferencias entre centros de salud.

Objective: The objective of this article is to report the results of the first survey on obstetric violence in Chile, to bring to light a reality more common than we think, and to compare its occurrence by the type of service (public or private) where the birth was attended. Methods: This is a descriptive and cross-sectional study conducted from December 2019 to May 2020. The sample was composed of 2 105 women from all regions of Chile. Results: Data analyses indicate that 79.3% of women believe they have experienced some form of obstetric violence. Despite the many reports of violence in public and private health centers, significant statistical differences were detected between the two, with higher numbers of reports for public centers. Similarly, more reports of obstetric violence were detected in young women (aged 18-29 years), in those who identify as indigenous, and among those with a non-heterosexual sexual orientation. Conclusions: Obstetric violence is part of the continuum of violence against women and is systematically reported by those who give birth in both public and private health services. This form of violence has serious consequences for women, due to both their difference in position with respect to the medical team and the importance of the birthing event in the life of any woman.

Objetivo: Informar os resultados obtidos na primeira pesquisa sobre violência obstétrica realizada no Chile, com o propósito de dar visibilidade a uma realidade mais comum do que se acredita e comparar sua ocorrência por categoria de serviço de assistência ao parto (rede pública ou privada). Métodos: Estudo descritivo transversal realizado entre dezembro de 2019 e maio de 2020. A amostra incluiu 2 105 mulheres provenientes de todas as regiões do país. Resultados: Os dados analisados indicam que 79,3% das mulheres entrevistadas acreditam ter sofrido alguma forma de violência obstétrica. Apesar do alto índice de relatos de violência tanto em serviços públicos quanto privados, observam-se diferenças estatísticas significativas entre eles, com maior ocorrência na rede pública. A violência obstétrica foi relatada com mais frequência entre as jovens (18 a 29 anos), as que se identificam com os povos nativos e as que são de orientação sexual não heterossexual. Conclusões: A violência obstétrica faz parte do ciclo de violência contra a mulher e é sistematicamente relatada pelo pessoal que presta assistência ao parto em serviços públicos e particulares. Trata-se de uma forma de violência com consequências sérias devido à posição ocupada pela equipe médica e à importância do parto na vida da mulher.

Validating a measurement of psychological, physical and sexual abuse against women in gynecological care within the Chilean health system.

Our objective was to create and validate a scale that would allow us to investigate women's experiences of violent practices in healthcare System. The scale was applied to large sample of women (N = 4563) from Chile. We analyzed data and conclude that the final instrument shows good reliability (α = .876 y ω = .921) and a factorial structure of three correlated factors referring to psychological, physical and sexual violence. Similarly, our analysis of the data -using a confirmatory factor analysis and multi-group factor analysis- reveals good fit indexes (CFI = .94 y RSMEA = .06) and supports the scale's metric invariance between groups in age (18 - 31 and 32 - 82) and healthcare centers (public and private). The prevalence rates of the different forms of violence predicted by the scale are reported.

Ecological integrity assessment of streams in the light of natural ecoregions and anthropic land use.

Reference conditions for river bioassessment should be established inside ecoregions. Our objectives were (1) to implement a bioassessment methodology for Uruguayan prairie streams regarding ecoregions and land use and (2) to assess the ecological integrity of streams of the Río Negro basin in Uruguay. Due to logistical constraints, sampling was divided into two collection trips: one including the upper basin in fall 2015 and the other including the lower basin in spring 2016. Basins were analyzed separately due to seasonal and geographical differences. In the streams sampled in fall 2015, conductivity, total nitrogen (TN), and total phosphorus (TP) were higher in sedimentary ecoregions than in crystalline ones, independent on land use. In those sampled in spring 2016, these variables showed the highest values in the ecoregions dominated by agriculture. Eighty percent of the sampled streams presented the impact of cattle in their riparian zone. Discriminant analysis showed a similar composition of macroinvertebrates among ecoregions in 2015, but different composition between land uses. Conversely, in 2016, there were differences among some ecoregions, but not between land uses. Agriculture was correlated with tolerant invertebrates, while natural land use and afforestation were correlated with sensitive ones. The BMWP-Colombia showed the impact of livestock on streams, but in general good water quality, while an index of genera for Uruguay, indicated that all streams are eutrophic, thereby confirming the importance of using different types of metrics. Due to its geographical homogeneity and small size, a smaller number of ecoregions could be defined for stream assessments in the Río Negro basin.

Effect of hemodiafiltration on measured physical activity: primary results of the HDFIT randomized controlled trial.

BACKGROUND: Dialysis patients are typically inactive and their physical activity (PA) decreases over time. Uremic toxicity has been suggested as a potential causal factor of low PA in dialysis patients. Post-dilution high-volume online hemodiafiltration (HDF) provides greater higher molecular weight removal and studies suggest better clinical/patient-reported outcomes compared with hemodialysis (HD). METHODS: HDFIT was a randomized controlled trial at 13 clinics in Brazil that aimed to investigate the effects of HDF on measured PA (step counts) as a primary outcome. Stable HD patients (vintage 3-24 months) were randomized to receive HDF or high-flux HD. Treatment effect of HDF on the primary outcome from baseline to 3 and 6 months was estimated using a linear mixed-effects model. RESULTS: We randomized 195 patients (HDF 97; HD 98) between August 2016 and October 2017. Despite the achievement of a high convective volume in the majority of sessions and a positive impact on solute removal, the treatment effect HDF on the primary outcome was +538 [95% confidence interval (CI) -330 to 1407] steps/24 h after dialysis compared with HD, and was not statistically significant. Despite a lack of statistical significance, the observed size of the treatment effect was modest and driven by steps taken between 1.5 and 24.0 h after dialysis, in particular between 20 and 24 h (+197 steps; 95% CI -95 to 488). CONCLUSIONS: HDF did not have a statistically significant treatment effect on PA 24 h following dialysis, albeit effect sizes may be clinically meaningful and deserve further investigation.

Sociodemographic Characteristics, Gender Identification, and Gender Affirmation Pathways in Transgender People: A Survey Study in Chile.

Understanding the internal diversity of transgender communities is essential for developing optimal, inclusive policies and service provision. To date, research on this topic remains scarce in Chile. We conducted a survey study describing sociodemographic characteristics (age, sex assigned at birth, onset age, nationality, education, sex work, having a partner, having children, sexual orientation, religiousness, gender identification, and gender affirmation pathways). A snowball sample of 377 self-identified transgender adults living in Chile (Mage = 31.88, rangeage = 18-67) was collected for the purpose of this study. According to their sex assigned at birth, 139 participants were female and 238 male. Results revealed that sex assigned at birth was significantly associated with almost all the sociodemographic variables. Eight gender self-identification categories were obtained based on self-declaration. These gender identification categories varied according to sex assigned at birth. Finally, four patterns (clusters) of gender affirmative actions were identified among participants. These patterns indicated that the longer the gender affirmation pathway time, the greater the invasiveness level of the medical procedures used. Sex assigned at birth moderated the association between gender affirmation pathways and gender identity categories. Results were discussed highlighting the heterogeneity found in terms of sociodemographic characteristics, gender identification, and gender affirmation pathways.

Molecular characterization and antibacterial activity of oral antibiotics and copper nanoparticles against endodontic pathogens commonly related to health care-associated infections.

OBJECTIVE: To carry out molecular characterization and determine the antibacterial activity of oral antibiotics and copper nanoparticles (Cu-NPs) against endodontic strains isolated from persistent infections. MATERIALS AND METHODS: Root canal samples from 24 teeth in different patients with persistent endodontic infections were obtained. The isolated strains were identified by biochemical tests and 16S rDNA sequencing. Genotyping was achieved by molecular methods. The antibacterial activity of antibiotics and copper nanostructures was determined by using minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values. Furthermore, a time-kill kinetics assay was evaluated. Nonparametric tests (Kruskal-Wallis ANOVA) were performed (p value <0.05). RESULTS: Twenty-one isolated strains were identified. Six isolates of Enterococcus faecalis were grouped into two clusters of three isolates each, two of which were clones. All were clarithromycin-resistant and erythromycin. Eight Pseudomonas putida presented two clusters, two Pseudomonas spp. were not clonal, and all were resistant to the tested antibiotics except tetracycline. Two of five strains of Cutibacterium acnes were clonal, and all were resistant only to metronidazole. The lowest MIC and MBC values were obtained with Cu-NPs. Time-kill kinetics using Cu-NPs showed a significant decrease in all tested species within 4 h and reached 100% in 2 h for C. acnes. CONCLUSION: In this study, in relation to health care-associated infections, endodontic strains of each species isolated at least in one patient were polyclonal. In Pseudomonas spp., at least one clone was shared between patients. E. faecalis and C. acnes strains were susceptible to low Cu-NP concentrations, while Pseudomonas spp. strains were resistant. CLINICAL RELEVANCE: Assessing and keeping track of the susceptibility of clinical strains to antimicrobial compounds is important for the clinical outcome. Based on our results, Cu-NPs could be an alternative for endodontic treatment, in order to avoid selection of resistant strains.

Synthesis and Biological Assessment of 4,1-Benzothiazepines with Neuroprotective Activity on the Ca2+ Overload for the Treatment of Neurodegenerative Diseases and Stroke.

In excitable cells, mitochondria play a key role in the regulation of the cytosolic Ca2+ levels. A dysregulation of the mitochondrial Ca2+ buffering machinery derives in serious pathologies, where neurodegenerative diseases highlight. Since the mitochondrial Na+/Ca2+ exchanger (NCLX) is the principal efflux pathway of Ca2+ to the cytosol, drugs capable of blocking NCLX have been proposed to act as neuroprotectants in neuronal damage scenarios exacerbated by Ca2+ overload. In our search of optimized NCLX blockers with augmented drug-likeness, we herein describe the synthesis and pharmacological characterization of new benzothiazepines analogues to the first-in-class NCLX blocker CGP37157 and its further derivative ITH12575, synthesized by our research group. As a result, we found two new compounds with an increased neuroprotective activity, neuronal Ca2+ regulatory activity and improved drug-likeness and pharmacokinetic properties, such as clog p or brain permeability, measured by PAMPA experiments.

Bismuth quadruple regimen with tetracycline or doxycycline versus three-in-one single capsule as third-line rescue therapy for Helicobacter pylori infection: Spanish data of the European Helicobacter pylori Registry (Hp-EuReg).

BACKGROUND: Different bismuth quadruple therapies containing proton-pump inhibitors, bismuth salts, metronidazole, and a tetracycline have been recommended as third-line Helicobacter pylori eradication treatment after failure with clarithromycin and levofloxacin. AIM: To evaluate the efficacy and safety of third-line treatments with bismuth, metronidazole, and either tetracycline or doxycycline. METHODS: Sub-study with Spanish data of the "European Registry on H pylori Management" (Hp-EuReg), international multicenter prospective non-interventional Registry of the routine clinical practice of gastroenterologists. After previous failure with clarithromycin- and levofloxacin-containing therapies, patients receiving a third-line regimen with 10/14-day bismuth salts, metronidazole, and either tetracycline (BQT-Tet) or doxycycline (BQT-Dox), or single capsule (BQT-three-in-one) were included. Data were registered at AEG-REDCap database. Univariate and multivariate analyses were performed. RESULTS: Four-hundred and fifty-four patients have been treated so far: 85 with BQT-Tet, 94 with BQT-Dox, and 275 with BQT-three-in-one. Average age was 53 years, 68% were women. Overall modified intention-to-treat and per-protocol eradication rates were 81% (BQT-Dox: 65%, BQT-Tet: 76%, BQT-three-in-one: 88%) and 82% (BQT-Dox: 66%, BQT-Tet: 77%, BQT-three-in-one: 88%), respectively. By logistic regression, higher eradication rates were associated with compliance (OR = 2.96; 95% CI = 1.01-8.84) and no prior metronidazole use (OR = 1.96; 95% CI = 1.15-3.33); BQT-three-in-one was superior to BQT-Dox (OR = 4.46; 95% CI = 2.51-8.27), and BQT-Tet was marginally superior to BQT-Dox (OR = 1.67; 95% CI = 0.85-3.29). CONCLUSION: Third-line H pylori eradication with bismuth quadruple treatment (after failure with clarithromycin and levofloxacin) offers acceptable efficacy and safety. Highest efficacy was found in compliant patients and those taking 10-day BQT-three-in-one or 14-day BQT-Tet. Doxycycline seems to be less effective and therefore should not be recommended.

Assessment of Rehabilitation Infrastructure in Peru.

OBJECTIVE: To assess rehabilitation infrastructure in Peru in terms of the World Health Organization (WHO) health systems building blocks. DESIGN: Anonymous quantitative survey; questions were based on the WHO's Guidelines for Essential Trauma Care and rehabilitation professionals' input. SETTING: Large public hospitals and referral centers and an online survey platform. PARTICIPANTS: Convenience sample of hospital personnel working in rehabilitation and neurology (N=239), recruited through existing contacts and professional societies. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Outcome measures were for 4 WHO domains: health workforce, health service delivery, essential medical products and technologies, and health information systems. RESULTS: Regarding the domain of health workforce, 47% of physical therapists, 50% of occupational therapists, and 22% of physiatrists never see inpatients. Few reported rehabilitative nurses (15%) or prosthetist/orthotists (14%) at their hospitals. Even at the largest hospitals, most reported ≤3 occupational therapists (54%) and speech-language pathologists (70%). At hospitals without speech-language pathologists, physical therapists (49%) or nobody (34%) perform speech-language pathology roles. At hospitals without occupational therapists, physical therapists most commonly (59%) perform occupational therapy tasks. Alternate prosthetist/orthotist task performers are occupational therapists (26%), physical therapists (19%), and physicians (16%). Forty-four percent reported interdisciplinary collaboration. Regarding the domain of health services, the most frequent inpatient and outpatient rehabilitation barriers were referral delays (50%) and distance/transportation (39%), respectively. Regarding the domain of health information systems, 28% reported rehabilitation service data collection. Regarding the domain of essential medical products and technologies, electrophysical agents (88%), gyms (81%), and electromyography (76%) were most common; thickened liquids (19%), swallow studies (24%), and cognitive training tools (28%) were least frequent. CONCLUSIONS: Rehabilitation emphasis is on outpatient services, and there are comparatively adequate numbers of physical therapists and physiatrists relative to rehabilitation personnel. Financial barriers seem low for accessing existing services. There appear to be shortages of inpatient rehabilitation, specialized services, and interdisciplinary collaboration. These may be addressed by redistributing personnel and investing in education and equipment for specialized services. Further examination of task sharing's role in Peru's rehabilitation services is necessary to evaluate its potential to address deficiencies.

Mixed-Methods Assessment of Trauma and Acute Care Surgical Quality Improvement Programs in Peru.

BACKGROUND: Evidence for the positive impact of quality improvement (QI) programs on morbidity, mortality, patient satisfaction, and cost is strong. Data regarding the status of QI programs in low- and middle-income countries, as well as in-depth examination of barriers and facilitators to their implementation, are limited. METHODS: This cross-sectional, descriptive study employed a mixed-methods design, including distribution of an anonymous quantitative survey and individual interviews with healthcare providers who participate in the care of the injured at ten large hospitals in Lima, Peru. RESULTS: Key areas identified for improvement in morbidity and mortality (M&M) conferences were the standardization of case selection, incorporation of evidence from the medical literature into case presentation and discussion, case documentation, and the development of a clear plan for case follow-up. The key barriers to QI program implementation were a lack of prioritization of QI, lack of sufficient human and administrative resources, lack of political support, and lack of education on QI practices. CONCLUSIONS: A national program that makes QI a required part of all health providers' professional training and responsibilities would effectively address a majority of identified barriers to QI programs in Peru. Specifically, the presence of basic QI elements, such as M&M conferences, should be required at hospitals that train pre-graduate physicians. Alternatively, short of this national-level organization, efforts that capitalize on local examples through apprenticeships between institutions or integration of QI into continuing medical education would be expected to build on the facilitators for QI programs that exist in Peru.

Fourteen-day high-dose esomeprazole, amoxicillin and metronidazole as third-line treatment for Helicobacter pylori infection.

INTRODUCTION: The efficacy of currently recommended third-line therapies for Helicobacter pylori is suboptimal, even that of culture-guided treatments. Resistance to multiple antibiotics is the major factor related to treatment failure. The aim of this study was to evaluate the effectiveness and safety of a 14-day therapy using high-dose of amoxicillin, metronidazole and esomeprazole. MATERIAL AND METHODS: Multicenter open-label study as a register in routine clinical practice in patients with two previous failures of eradication therapy. A triple therapy with esomeprazole 40 mg b.d., amoxicillin 1 g t.d.s and metronidazole 500 mg t.d.s for 2 weeks was administered as a third-line therapy after a first treatment including clarithromycin and a second treatment including a quinolone. Helicobacter pylori status was determined by either histology or 13 C-UBT both before and after treatment. RESULTS: A total of 68 patients were included in this study. An interim analysis showed that only three out of eight patients who had received metronidazole in previous eradication regimens were cured (37%, 95% CI 8-75); as a result, after this interim analysis only metronidazole-naïve patients were included. The ITT eradication rate in metronidazole-naive patients was 64% (95% CI 51-76). Adverse events occurred in 58% of patients, all of them mild-to-moderate. Two patients (3%) did not complete >90% of the treatment because of side effects. No severe adverse events occurred. CONCLUSION: Cure rates of this 14-day schedule using high-dose esomeprazole, amoxicillin and metronidazole as a third-line eradication regimen were suboptimal, especially in patients who had received metronidazole in previous failed eradication regimens.