Alginate microbeads and hydrogels delivering meropenem and bacteriophages to treat Pseudomonas aeruginosa fracture-related infections.

Bacteriophage (phage) therapy has shown promise in treating fracture-related infection (FRI); however, questions remain regarding phage efficacy against biofilms, phage-antibiotic interaction, administration routes and dosing, and the development of phage resistance. The goal of this study was to develop a dual antibiotic-phage delivery system containing hydrogel and alginate microbeads loaded with a phage cocktail plus meropenem and evaluate efficacy against muti-drug resistant Pseudomonas aeruginosa. Two phages (FJK.R9-30 and MK.R3-15) displayed enhanced antibiotic activity against P. aeruginosa biofilms when tested in combination with meropenem. The antimicrobial activity of both antibiotic and phage was retained for eight days at 37 °C in dual phage and antibiotic loaded hydrogel with microbeads (PA-HM). In a mouse FRI model, phages were recovered from all tissues within all treatment groups receiving dual PA-HM. Moreover, animals that received the dual PA-HM either with or without systemic antibiotics had less incidence of phage resistance and less serum neutralization compared to phages in saline. The dual PA-HM could reduce bacterial load in soft tissue when combined with systemic antibiotics, although the infection was not eradicated. The use of alginate microbeads and injectable hydrogel for controlled release of phages and antibiotics, leads to the reduced development of phage resistance and lower exposure to the adaptive immune system, which highlights the translational potential of the dual PA-HM. However, further optimization of phage therapy and its delivery system is necessary to achieve higher bacterial killing activity in vivo in the future.

Novel Bacteriophage Specific against Staphylococcus epidermidis and with Antibiofilm Activity.

Staphylococcus epidermidis has emerged as the most important pathogen in infections related to indwelling medical devices, and although these infections are not life-threatening, their frequency and the fact that they are extremely difficult to treat represent a serious burden on the public health system. Treatment is complicated by specific antibiotic resistance genes and the formation of biofilms. Hence, novel therapeutic strategies are needed to fight these infections. A novel bacteriophage CUB-EPI_14 specific to the bacterial species S. epidermidis was isolated from sewage and characterized genomically and phenotypically. Its genome contains a total of 46,098 bp and 63 predicted genes, among which some have been associated with packaging and lysis-associated proteins, structural proteins, or DNA- and metabolism-associated proteins. No lysogeny-associated proteins or known virulence proteins were identified in the phage genome. CUB-EPI_14 showed stability over a wide range of temperatures (from -20 °C to 50 °C) and pH values (pH 3-pH 12) and a narrow host range against S. epidermidis. Potent antimicrobial and antibiofilm activities were observed when the phage was tested against a highly susceptible bacterial isolate. These encouraging results open the door to new therapeutic opportunities in the fight against resilient biofilm-associated infections caused by S. epidermidis.

What you need to know about scoping reviews. / Lo que tienes que saber sobre las revisiones panorámicas.

The increasing amount of evidence has caused an increasing amount of literature reviews. There are different types of reviews systematic reviews are the best known, and every type of review has different purposes. The scoping review is a recent model that aims to answer broad questions and identify and expose the available evidence for a broader question, using a rigorous and reproducible method. In the last two decades, researchers have discussed the most appropriate method to carry out scoping reviews, and recently the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for scoping reviews (PRISMA-ScR) reporting guideline was published. This is the fifth article of a methodological collaborative series of narrative reviews about general topics on biostatistics and clinical epidemiology. This review aims to describe what scoping reviews are, identify their objectives, differentiate them from other types of reviews, and provide considerations on how to carry them out.

La cantidad creciente de evidencia ha provocado a su vez un aumento en el número de revisiones de la literatura. Existen distintos tipos de revisiones donde las más conocidas son las revisiones sistemáticas, y cada tipo de revisión posee objetivos distintos. La revisión panorámica (o scoping review) es un modelo reciente que busca dar respuestas a preguntas amplias, a la vez que intenta identificar y exponer la evidencia disponible para una pregunta en particular, a través de un método riguroso y reproducible. En las últimas dos décadas se ha discutido cuál es el método más apropiado para realizarlas, siendo la extensión de Preferred Reporting Items For Systematic Reviews and Meta-Analyses para Scoping reviews (PRISMA-ScR) la guía de reporte más recientemente incorporada. Este artículo es el quinto de una serie metodológica colaborativa de revisiones narrativas sobre temáticas de bioestadística y epidemiología clínica. Esta revisión tiene como objetivo describir qué son las revisiones panorámicas, identificar sus objetivos, diferenciarlas de otros tipos de revisiones de literatura, y dar algunas consideraciones sobre cómo estas se pueden llevar a cabo.

Rapid reviews: definitions and uses. / Revisiones rápidas: definiciones y usos.

This article is the first in a collaborative methodological series of narrative reviews on biostatistics and clinical epidemiology. This review aims to present rapid reviews, compare them with systematic reviews, and mention how they can be used. Rapid reviews use a methodology like systematic reviews, but through shortcuts applied, they can attain answers in less than six months and with fewer resources. Decision-makers use them in both America and Europe. There is no consensus on which shortcuts have the least impact on the reliability of conclusions, so rapid reviews are heterogeneous. Users of rapid reviews should identify these shortcuts in the methodology and be cautious when interpreting the conclusions, although they generally reach answers concordant with those obtained through a formal systematic review. The principal value of rapid reviews is to respond to health decision-makers needs when the context demands answers in limited time frames.

Este artículo es el primero de una serie metodológica colaborativa de revisiones narrativas sobre temáticas de bioestadística y epidemiología clínica. El objetivo de esta revisión es presentar las revisiones rápidas, compararlas con las revisiones sistemáticas y mencionar su uso actual. Las revisiones rápidas utilizan una metodología similar a las revisiones sistemáticas, pero mediante atajos utilizados en su desarrollo; permiten alcanzar respuestas en menos de seis meses y con menos recursos, por lo que son utilizadas por tomadores de decisiones tanto en América como Europa. No existe consenso sobre cuáles atajos tienen menor impacto en la confiabilidad de las conclusiones, por lo que las revisiones rápidas son heterogéneas entre sí. Los consumidores deben identificar estos atajos en la metodología y ser precavidos en la interpretación de las conclusiones, aunque generalmente alcanzan respuestas concordantes con las obtenidas mediante una revisión sistemática tradicional. Su principal atractivo es ajustarse a las necesidades de los tomadores de decisiones en salud, cuando el contexto exige respuestas en plazos de tiempo acotados.

Revisiones rápidas: definiciones y usos / Rapid reviews: definitions and uses

Este artículo es el primero de una serie metodológica colaborativa de revisiones narrativas sobre temáticas de bioestadística y epidemiología clínica. El objetivo de esta revisión es presentar las revisiones rápidas, compararlas con las revisiones sistemáticas y mencionar su uso actual. Las revisiones rápidas utilizan una metodología similar a las revisiones sistemáticas, pero mediante atajos utilizados en su desarrollo; permiten alcanzar respuestas en menos de seis meses y con menos recursos, por lo que son utilizadas por tomadores de decisiones tanto en América como Europa. No existe consenso sobre cuáles atajos tienen menor impacto en la confiabilidad de las conclusiones, por lo que las revisiones rápidas son heterogéneas entre sí. Los consumidores deben identificar estos atajos en la metodología y ser precavidos en la interpretación de las conclusiones, aunque generalmente alcanzan respuestas concordantes con las obtenidas mediante una revisión sistemática tradicional. Su principal atractivo es ajustarse a las necesidades de los tomadores de decisiones en salud, cuando el contexto exige respuestas en plazos de tiempo acotados.

This article is the first in a collaborative methodological series of narrative reviews on biostatistics and clinical epidemiology. This review aims to present rapid reviews, compare them with systematic reviews, and mention how they can be used. Rapid reviews use a methodology like systematic reviews, but through shortcuts applied, they can attain answers in less than six months and with fewer resources. Decision-makers use them in both America and Europe. There is no consensus on which shortcuts have the least impact on the reliability of conclusions, so rapid reviews are heterogeneous. Users of rapid reviews should identify these shortcuts in the methodology and be cautious when interpreting the conclusions, although they generally reach answers concordant with those obtained through a formal systematic review. The principal value of rapid reviews is to respond to health decision-makers' needs when the context demands answers in limited time frames.

Outreach training and supportive supervision for malaria case management in Zambia: the effects of focused capacity building on indicators of diagnostic and clinical performance.

BACKGROUND: Accurate diagnosis of malaria and reduced reliance on presumptive treatment are crucial components of quality case management. From 2008 to 2012, the Improving Malaria Diagnostics project, in collaboration with the Zambia National Malaria Control Centre, implemented an external quality assurance scheme partially comprised of outreach training and supportive supervision (OTSS) in an effort to improve malaria case management across a spectrum of health facilities performing laboratory-based malaria diagnostics. OTSS assessments were conducted by project-trained laboratory and clinical supervisors on a regular basis and measured changes in health facility staff performance over time. Standardized supervision tools were used for data collection and guided OTSS teams to assess health facility infrastructure, record keeping practices, stores of supplies and consumables, good laboratory practices, and staff adherence to guidelines for the case management and diagnosis of suspected malaria cases via direct observations or record reviews. The structure of OTSS also allowed supervisors to provide ongoing support to clinicians and laboratory staff through regular mentoring and on-the-job training. RESULTS: This analysis included 88 laboratories and 64 clinics each with four repeated supervisory assessments. Over the course of the project there were significant declines in the number of laboratories experiencing stock-outs of microscopy reagents/consumables (p < 0.001) and significant increases in the number of laboratories instituting the use of microscopy positive controls (p < 0.01), conducting parasite counting (p < 0.05), and converting from a semi-quantitative to a quantitative parasite counting methodology (p < 0.001). Performance in malaria diagnostic and clinical practices [i.e. RDT use (mean(diff) = 14.3%, p < 0.001), blood slide preparation (mean(diff) = 14.7%, p < 0.001), blood slide staining and reading (mean(diff) = 14.0%, p < 0.001), fever case management (mean(diff) = 7.3%, p < 0.01)] and prescriber adherence to negative diagnostic test results (mean(diff) = 7.2%, p < 0.05) showed modest, but significant gains from assessment 1 to assessment 4. CONCLUSION: The external quality assurance scheme provided periodic representations of clinical and laboratory staff performance. OTSS-enrolled health facilities demonstrated improvements to malaria diagnostic skills, adoption of laboratory best practices, strengthened fever case management practices, and improved prescriber adherence to negative malaria test results.

Frequency and coinfection between genotypes of human papillomavirus in a population of asymptomatic women in northern Peru.

OBJECTIVE: Describe the prevalence of HPV genotypes via PCR and DNA sequencing in 397 women who attended to the gynecological outpatient center in the Hospital Regional Docente de Cajamarca from March to September 2017. RESULTS: A positive PCR result for HPV was observed in 121 cervical samples. A high-risk genotype was found in 63.6% (77/121) of patients, a probably oncogenic type in 23.1% (28/121) and a low-risk type in 7.4%. Among the high-risk genotypes, HPV-31 was the most common one present in 20% (21/77), followed by HPV-16 in 11.4% (12/77). Coinfections between two or more genotypes were observed in 12 cases.

Primary intestinal lymphoma in patients with inflammatory bowel disease: a descriptive series from the prebiologic therapy era.

BACKGROUND: Primary intestinal lymphoma in the setting of inflammatory bowel disease (IBD) is uncommon and may be associated with immune suppressive therapy. We report clinical features and outcomes in patients with both conditions prior to use of biologic therapy. METHODS: All patients with primary intestinal lymphoma and IBD at our institution from 1960-2000 were retrospectively identified. Data reported are frequency (proportion) or median (interquartile range). Kaplan-Meier analysis was performed. RESULTS: Fifteen patients were identified: 14 (93%) were male, 10 (66%) had Crohn's disease. Median age at diagnosis of IBD and lymphoma was 30 (22-51) and 47 (28-68) years, respectively, with bloody diarrhea the most common presenting symptom for each diagnosis. Lymphoma location was colorectal in nine (60%), small bowel in four (27%), and one (6.25%) each: stomach, duodenum, and ileal pouch. Treatments were surgery plus chemotherapy (n = 6), surgery alone (n = 3), chemotherapy alone (n = 2), chemotherapy and radiation (n = 1), surgery and radiation (n = 1); two patients died before treatment. Most patients (n = 11, 73%) were Ann Arbor stages I or II. Large cell B-type histology was most common (n = 9, 60%). Three patients died within 30 days of lymphoma diagnosis. Survival free of death from lymphoma at 1- and 5-years was 78% and 63%, respectively, and was associated with advanced lymphoma stage (P = 0.004). CONCLUSIONS: Diagnosis and treatment of primary intestinal lymphoma in patients with IBD can be challenging and requires a high index of suspicion. Optimal survival requires multimodality therapy.

Marked increase in child survival after four years of intensive malaria control.

In malaria-endemic countries in Africa, a large proportion of child deaths are directly or indirectly attributable to infection with Plasmodium falciparum. Four years after high coverage, multiple malaria control interventions were introduced on Bioko Island, Equatorial Guinea, changes in infection with malarial parasites, anemia, and fever history in children were estimated and assessed in relation to changes in all-cause under-5 mortality. There were reductions in prevalence of infection (odds ratio [OR] = 0.31, 95% confidence interval [CI] = 0.2-0.46), anemia (OR = 0.11, 95% CI = 0.07-0.18), and reported fevers (OR = 0.41, 95% CI = 0.22-0.76) in children. Under-5 mortality fell from 152 per 1,000 births (95% CI = 122-186) to 55 per 1,000 (95% CI = 38-77; hazard ratio = 0.34 [95% CI = 0.23-0.49]). Effective malaria control measures can dramatically increase child survival and play a key role in achieving millennium development goals.

Factors influencing the effectiveness of malaria control in Bioko Island, equatorial Guinea.

The Bioko Island Malaria Control Project (BIMCP) has carried out intensive interventions since early 2004 to reduce malaria transmission through indoor residual spraying (IRS) and case management. Annual parasite prevalence surveys have been carried out to monitor the effectiveness of the program. Significant overall reductions in prevalence of infection have been observed, with 42% fewer infections occurring in 2006 compared with baseline. Nevertheless, there is evidence of considerable heterogeneity in impact of the intervention. Prevalence of infection was significantly associated with spray status of the child's house, spray coverage with effective insecticide of the neighborhood of the house, bed net use, and time elapsed since last spray. Careful scheduling of spray coverage is therefore essential to maximize the effectiveness of IRS and to ensure consistent reductions in parasite prevalence. This can only be achieved if comprehensive monitoring systems are in place for both the management and evaluation of the intervention.

Reduction in infection with Plasmodium falciparum one year after the introduction of malaria control interventions on Bioko Island, Equatorial Guinea.

The Bioko Island Malaria Control Project was initiated in 2003 to substantially reduce malaria on the island of Bioko in Equatorial Guinea. The intervention consisted of generalized indoor residual spraying during the first year of the project. Case management and related measures were introduced during the second year. Two large household and parasitemia surveys of children 2 to < 15 years of age were carried out in 2004 and 2005, respectively, to assess the effect of the intervention after the first year. Patient records were collected retrospectively from one district hospital and analyzed for a comparison of pre-intervention and post-intervention periods. Overall mean prevalence of P. falciparum infection reduced from 46% (95% confidence interval [CI] = 40-51%) at baseline in 2004 to 31% (95% CI = 24-40%) in 2005 (P < 0.001). When the 12-month pre-intervention period was compared with the 12-month post-intervention period, there was a modest but statistically significant reduction in the number of malaria cases among hospital patients.

[Giant uterine myoma]. / Mioma uterino gigante.

Giant uterine tumors, defined as weighing 11.4 kg (25 lb) or more, are uncommon. The last cases reported were published on May, 2003 by Oelsner and collaborators. We report the case of a 45-year old woman with a large abdominal mass and three-day history of constipation and respiratory difficulty. Total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed, and a giant uterine myoma, which weighted 12.4 kg (27.3 lb), was found. The patient's postoperative course was uneventful and she was discharged on the fourth postoperative day.

Evaluación del desarrollo psicomotor en niños de Lima Metropolitana / Evaluation of the children psychomotor devolopment in Metropolitan Lima

En un intento por mejorar nuestra comprensión del crecimiento y desarrollo infantil en el Perú, durante 1991-1992 se realizó un estudio descriptivo del nivel de desarrollo psicomotor alcanzado por 1039 niños de 12 a 35 meses de Lima Metropolitana. El diseño permite hacer inferencias a nivel poblacional, teniendo en consideración tres estratos socioeconómicos y cuatro grupos etáreos. El desarrollo psicomotor fue medido a través de la Prueba de Brunet-Lezine, y los valores de talla y peso mediante antropometría, aplicándose además una entrevista estructurada. Las prevalencias de desarrollo psicomotor deficiente resultaron máximas en el área de lenguaje y particularmente en el estrato socioeconómico bajo. Al explorarse la relación entre el estado nutricional y un conjunto de variables, controlando por nivel socioeconómico, se encontró que el nivel educativo de los padres era importante en los estratos superior y medio, mientras otros indicadores socieconómicos tales como el material del piso de la vivienda lo eran más en el estrato bajo. Los indicadores antropométricos se asociaron débilmente a los niveles de desarrollo psicomotor. En general, la fuerza de las asociaciones existentes entre este último y las variables investigadas mostró dependencia del nivel socioeconómico

Crescimento e estado nutricional de pre-escolares resistentes na regiao amazonica do peru

Foi estudado o estado nutricional de 1684 pre-escolares menores de 5 anos (862 meninos 2 822 meninas), residentes na Regiao Amazonica do Peru. Os dados foram obtidos da Pesquisa Nacional de Nutricao e Saude (ENNSSA), realizada no Peru, em 1984. O crecismento e estado nutricional foi avaliado atraves dos seguintes indicadores: peso para idade, altura para idade, peso para altura e perimetro braquial. Os resultados mostram uma levada prevalencia de baixa estatura (porcentagem de adequacao a mediana menor que 95 por cento para indice altura para idade) e baixa prevalencia de inadequacao de peso (porcentagem de adequacao a mediana menor que 80 por cento para o indice peso para altura). De acordo com o indice peso para idade, 38 por cento das criancas estiveram adequadamente nutridas e apenas 0,8 por cento apresentaram desnutricao grave.

Prevalencia del déficit de peso y estatura en niños pre-escolares residentes en la selva baja Peruana / Prevalence of weight and hight deficiency in children living at the Peruvian Amazon jungle

Se midió el peso y estatura de 1699 niños menores de 6 años residentes en la selva amazónica del Perú, los datos fueron obtenidos en la Encuesta Nacional de Nutrición y Salud realizada en Perú en el año de 1984. Para evaluar la prevalencia de problemas de crecimiento en estos niños. El peso y la talla fueron presentadas en relación a las curvas de crecimiento de la NCHS-USA/OMS (Centro Nacional de estadística en Salud de los Estados Unidos y la Organización Mundial de Salud). Los resultados muestran una elevada prevalencia de déficit de estatura sobre todo en los niños mayores de un año. Se encontró que la prevalencia de déficit de peso y sobrepeso es baja

Estudio seroepidemiológico de fiebre tifoidea en población escolar en el área norte de Lima metropolitana / Sero-epidemiological study of thyphoid fever in schoolchildren of the northern area of Lima

Entre los meses de setiembre y noviembre de 1989, se realizó un estudio transversal en 1322 escolares supuestos sanos, del distrito de San Juan de Lurigancho, sin antecedentes de inmunización contra fiebre tifoidea, seleccionados mediante muestreo por conglomerados, con el objetivo de estimar las prevalencias de serología positiva para antígeno O y H de Salmonella typhi y su distribución según sexo, grupo etáreo y tipo de colegio. La determinación de los títulos se hizo con la técnica de microaglutinación en placa, que tiene una sensibilidad de 84 por ciento y una especificidad del 87 por ciento para un punto de corte mayor e igual 1:160 para el diagnóstico de fiebre tifoidea. Las prevalencias de serología O positiva para los diferentes tipos de corte (mayor e igual 1:20, mayor o igual 1:40, mayor o igual 1:80), fue significativamente mayor en mujeres (41.6 por ciento, 12.4 por ciento, 3.9 por ciento) que en hombres (41.1 por ciento, 9.1 por ciento, 1.1 por ciento) (p<0.05). Las prevalencias de serología H para los puntos de corte mencionados fueron similares en mujeres (69.0 por ciento, 18.8 por ciento, y 5.6 por ciento) y en hombres (73.1 por ciento, 16.5 por ciento, y 6.4 por ciento) (p>0.05). Ambas prevalencias positivas O y H fueron estadísticamente diferentes según grupo etáreo; pero, similares según tipo de colegio. Las altas proporciones de prevalencia encontradas, sugieren frecuente infección subclínica lo cual perpetúa la endemicidad de esta enfermedad

Eficacia de la bacampicilina en fiebre tifoidea / Efficiency of bacampicililin in typhoid fever

Cincuenta y siete pacientes cuyas edades fluctuaban entre 14 a 60 años de edad y en quienes se aisló Salmonella typhi o Salmonella paratyphi fueron incluidos en un estudio abierto para valorar la eficacia de clorhidrato de bacampicilina oral en el tratamiento de fiebre tifoidea, en especial causado por S. typhi. Los pacientes fueron valorados tanto clínica como bacteriológicamente y dividios en tres grupos de tratamiento para recibir bacampicilina oral de acuerdo a uno de los tres esquemas de dosis, durante 14 días. Cuarenta y nueve de los 57 (86.0%) pacientes fueron tratados de manera satisfactoria, tres (5.3%) se consideraron como fallas de tratamiento, y cinco (8.8%) experimentaron efectos indeseables que requirieron la descontinuación del fármaco. No hubo recaídas en un periodo de dos meses de seguimiento en 47 pacientes que fueron tratados de manera satisfactoria con bacampicilina. Los datos de cultivos negativos de heces y bilis en la fase temprana del tratamiento y la ausencia de recaídas, muestran que la terapéutica con clorhidrato de bacampicilina es eficaz en este padecimiento

Estado nutricional en menores de 6 años en el Perú / Nutritional state in children under 6 years in Peru

La presente publicación recoge información básica de población que habita en viviendas particulares, sobre: sexo, edad, nivel de estudios, morbilidad sentida en los últimos 15 días, atención de salud en los últimos 90 días e ingresos; de las mujeres en edad f´´ertil (de 12 a 49 años) y en los menores de 6 años. Asimismo, información referente a percepción de problemas de salud, y participación de la familia en actividades comunales

Estado nutricional en menores de 6 años en el Perú / Nutritional state in children under 6 years in Peru

La presente publicación recoge información básica de población que habita en viviendas particulares, sobre: sexo, edad, nivel de estudios, morbilidad sentida en los últimos 15 días, atención de salud en los últimos 90 días e ingresos; de las mujeres en edad f´´ertil (de 12 a 49 años) y en los menores de 6 años. Asimismo, información referente a percepción de problemas de salud, y participación de la familia en actividades comunales(AU)