Feasibility and Acceptability of Virtual Implementation of a Sexual Reproductive Health Teen Pregnancy Prevention Program for Native Youth.

American Indian/Alaska Native (Native) youth face high rates of substance use, teen pregnancy and sexually transmitted infections. In response to the COVID-19 pandemic, Respecting the Circle of Life (RCL), a sexual reproductive health and teen pregnancy prevention program for Native youth and their trusted adult, was adapted and delivered in a virtual format with Native youth in a rural, reservation-based Native community. This manuscript describes the adaptation process, feasibility, and acceptability of virtual program implementation. The manuscript describes the process of rapidly shifting the RCL program into a virtual format. In addition, a mixed-methods process evaluation of implementation forms, program feedback forms, in-depth interviews with participants, and staff debriefing sessions was completed. Results show virtual implementation of RCL is both feasible and acceptable for Native youth and their trusted adults. A key benefit of virtual implementation is the flexibility in scheduling and ability to have smaller groups of youth, which offers greater privacy for youth participants compared to in-person implementation with larger groups. However, internet connectivity did present a challenge for virtual implementation. Ultimately, sexual and reproductive health programs seeking to reach Native youth and families should consider virtual implementation methods, both during and outside of pandemic situations.

Microdosing and standard-dosing take-home buprenorphine from the emergency department: A feasibility study.

OBJECTIVE: Emergency department (ED)-initiated buprenorphine may prevent overdose. Microdosing is a novel approach that does not require withdrawal, which can be a barrier to standard inductions. We aimed to evaluate the feasibility of an ED-initiated buprenorphine/naloxone program providing standard-dosing and microdosing take-home packages and of randomizing patients to either intervention. METHODS: We broadly screened patients ≥18 years old for opioid use disorder at a large, urban ED. In a first phase, we provided consecutive patients with 3-day standard-dosing packages, and then we provided a subsequent group with 6-day microdosing packages. In a second phase, we randomized patients to standard dosing or microdosing. We attempted 7-day telephone follow-ups and 30-day in-person community follow-ups. The primary feasibility outcome was number of patients enrolled and accepting randomization. Secondary outcomes were numbers screened, follow-up rates, and 30-day opioid agonist therapy retention. RESULTS: We screened 3954 ED patients and identified 94 with opioid use disorders. Of the patients, 26 (27.7%) declined participation: 10 identified a negative prior experience with buprenorphine/naloxone as the reason, 5 specifically cited precipitated withdrawal, and none cited randomization. We enrolled 68 patients. A total of 14 left the ED against medical advice, 8 were excluded post-enrollment, 21 received standard dosing, and 25 received microdosing. The 7-day and 30-day follow-up rates were 9/46 (19.6%) and 15/46 (32.6%), respectively. At least 5/21 (23.8%) provided standard dosing and 8/25 (32.0%) provided microdosing remained on opioid agonist therapy at 30 days. CONCLUSIONS: ED-initiated take-home standard-dosing and microdosing buprenorphine/naloxone programs are feasible, and a randomized controlled trial would be acceptable to our target population.

Casting Is Effective for Recurrence Following Ponseti Treatment of Clubfoot.

BACKGROUND: Up to 40% of patients with idiopathic clubfoot who are treated with the Ponseti method experience recurrence of deformity. Many of these patients receive surgery (e.g., anterior tibial tendon transfer). An alternative approach for recurrent clubfoot is repeat Ponseti casting. The purpose of this study was to evaluate the outcome of repeat Ponseti casting in the treatment of recurrent clubfoot. METHODS: Patients with recurrent idiopathic clubfoot who were treated at our hospital, between 2004 and 2012, with repeat serial casting and bracing (the recurrent group) were eligible for inclusion in the study. The recurrent group and a control group of randomly selected patients seen during the same period who had not had recurrence were compared with respect to demographic data, age at the time of treatment, number of casts, subsequent surgical intervention(s), and the Disease-Specific Instrument (DSI) clubfoot scale. Patients were deemed to have a successful outcome if they had a well-corrected foot (defined as dorsiflexion of ≥10°, hindfoot in valgus, and a straight lateral border) at the time of follow-up. RESULTS: Of a total of 71 eligible patients with clubfeet, 35 patients participated. At the time of follow-up, success rates were 74% for the recurrent group and 83% for the control group. Dorsiflexion past neutral was significantly higher in the control group than the patient group (20° versus 12°, respectively; p < 0.001). Ninety-five percent of the control subjects had a straight lateral border in comparison with 78% in the recurrent group (p = 0.004). Likewise, 97% of controls had the hindfoot in valgus in comparison with 80% of the recurrent group (p = 0.02). There was a significant difference in the ability to squat (76% in the control group and 43% in the recurrent group; p = 0.03). There was no difference between groups in the total outcome of the DSI. CONCLUSIONS: Recurrence was seen in 19% (71) of 382 children who were eligible for our study who were typically discharged after the age of 5 years from our clinic, indicating the importance of continued follow-up until after that age. Treatment with casting was successful in many patients and may be a reasonable choice for recurrent idiopathic clubfeet. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Enfermedad meningocóccica en la Región Metropolitana de Chile y su correlación con factores ambientales / Meningococcal disease in the Metropolitan Region of Chile and its correlation with environmental factors

Introduction: Meningococcal disease (MD) is a public health problem worldwide, due to its high morbidity and mortality. Most cases occur in sub-Saharan Africa, where there is a marked seasonal pattern with predominance during the dry season. Objectives: To describe the morbidity of MD in the Metropolitan Region (MR) of Chile and explore whether there is a correlation between the number of cases with the levels of atmospheric particulate matter PM 10 and PM 2.5, relative humidity (RH), temperature and total environmental pollen. Materials and Methods: Ecological time series study, statistical analysis with R 3.0.1, graphics with Excel 2013. Results: Between 2010 and 2013, 234 MD cases were reported in the MR with an increasing trend. There is a seasonal pattern with an increase of cases from August to October, and a decrease from March to April. There is no correlation with the levels of PM10 and PM2.5. There is a slight positive correlation with RH and a slight negative correlation with temperature. There is a moderate positive correlation with the levels of total environmental pollens. Discussion: Overcrowding and the winter viral infections could explain the increased incidence of MD and the slight correlation with RH and temperature. The moderate correlation with the pollens could be explained by an effect of irritation of the upper airway. Conclusions: More epidemiological studies whose designs allow a greater causal inference are required.

Introducción: La enfermedad meningocóccica (EM) constituye un problema de salud pública mundial debido a su alta morbi-mortalidad. La mayor cantidad de casos ocurre en África subsahariana, donde existe un marcado patrón estacional en la estación seca. Objetivos: Describir la morbilidad de la EM en la Región Metropolitana (RM) de Chile y explorar si existe correlación entre el número de casos con PM 10, PM 2,5 humedad relativa (HR), temperatura y pólenes ambientales totales. Materiales y Métodos: Estudio ecológico tipo series de tiempo, análisis estadístico con R 3.0.1, gráficos con Excel 2013. Resultados: En el período 2010-2013 se notificaron 234 casos de EM en la RM, con una tendencia al alza. Se observa un patrón estacional con aumento de casos entre agosto y octubre y una disminución entre marzo y abril. No existe correlación con los niveles de PM 10 ni de PM 2,5. Se describe una correlación positiva leve con la HR y negativa leve con la temperatura. Existe correlación moderada positiva con los niveles de pólenes totales ambientales. Discusión: El hacinamiento y las infecciones virales de invierno podrían explicar el aumento de casos de EM y la correlación leve con la HR y la temperatura. La correlación moderada con los pólenes podría explicarse por un efecto de irritación de la vía aérea superior. Conclusiones: Se requieren más estudios epidemiológicos cuyos diseños permitan una mayor inferencia causal.

Characteristics of a pediatric hospice palliative care program over 15 years.

OBJECTIVES: Pediatric palliative care has seen the adoption of several service provision models, yet there is minimal literature describing them. Canuck Place Children's Hospice (CPCH) is North America's first freestanding pediatric hospice. This study describes the characteristics of and services delivered to all children on the CPCH program from 1996 to 2010. METHODS: A retrospective review of all patient medical records CPCH was conducted. Analyses examined trends and correlations between 40 selected data points: linear regression modeling was used to assess trends over time; t tests were used to examine significant associations between independent means; and the Kaplan-Meier method was used to measure survival probabilities. RESULTS: The study cohort included 649 children. The majority of diagnoses belonged to cancers (30%), and diseases of the neuromuscular (20%), and central nervous systems (18%). The majority of deaths occurred among the cancer (45%), central nervous system (15%), and metabolic disease groups (14%). By study end date, 24% of children were still alive, 61% died, and 15% transitioned to adult services (more than half of whom were cognitively competent). On average, 1024 days were spent on the CPCH program (median = 301). The majority of inpatient hospice discharges were for respite (82%); only 7% were for end-of-life care. Location of death was shared between CPCH (61%), hospital (22%), and home (16%). CONCLUSIONS: Diagnostic groups largely determine the nature and magnitude of services used, and our involvement with pediatric life-threatening conditions is increasing. Reviews of pediatric palliative programs can help evaluate the services needed by the population served.

A community of practice: librarians in a biomedical research network.

Providing library and reference services within a biomedical research community presents special challenges for librarians, especially those in historically lower-funded states. These challenges can include understanding needs, defining and communicating the library's role, building relationships, and developing and maintaining general and subject specific knowledge. This article describes a biomedical research network and the work of health sciences librarians at the lead intensive research institution with librarians from primarily undergraduate institutions and tribal colleges. Applying the concept of a community of practice to a collaborative effort suggests how librarians can work together to provide effective reference services to researchers in biomedicine.

[Meningococcal disease in the Metropolitan Region of Chile and its correlation with environmental factors]. / Enfermedad meningocóccica en la Región Metropolitana de Chile y su correlación con factores ambientales.

INTRODUCTION: Meningococcal disease (MD) is a public health problem worldwide, due to its high morbidity and mortality. Most cases occur in sub-Saharan Africa, where there is a marked seasonal pattern with predominance during the dry season. OBJECTIVES: To describe the morbidity of MD in the Metropolitan Region (MR) of Chile and explore whether there is a correlation between the number of cases with the levels of atmospheric particulate matter PM 10 and PM 2.5, relative humidity (RH), temperature and total environmental pollen. MATERIALS AND METHODS: Ecological time series study, statistical analysis with R 3.0.1, graphics with Excel 2013. RESULTS: Between 2010 and 2013, 234 MD cases were reported in the MR with an increasing trend. There is a seasonal pattern with an increase of cases from August to October, and a decrease from March to April. There is no correlation with the levels of PM10 and PM2.5. There is a slight positive correlation with RH and a slight negative correlation with temperature. There is a moderate positive correlation with the levels of total environmental pollens. DISCUSSION: Overcrowding and the winter viral infections could explain the increased incidence of MD and the slight correlation with RH and temperature. The moderate correlation with the pollens could be explained by an effect of irritation of the upper airway. CONCLUSIONS: More epidemiological studies whose designs allow a greater causal inference are required.

Comparison of surgeon and physiotherapist-directed Ponseti treatment of idiopathic clubfoot.

BACKGROUND: Increasingly, the Ponseti method has been adopted worldwide as the preferred method of managing idiopathic clubfoot deformity. Following the successful implementation of the Ponseti method by orthopaedic surgeons in our institution, a clubfoot clinic was established in 2003. This clinic is directed by a physiotherapist who, using the Ponseti protocol, performs the serial cast treatment and supervises the brace management of all children with idiopathic clubfoot deformity. The purpose of this study was to compare the outcomes of physiotherapist-directed with surgeon-directed Ponseti cast treatment of idiopathic clubfeet. METHODS: We performed a retrospective cohort study of all patients with idiopathic clubfoot deformity treated from 2002 to 2006 and followed for a minimum of two years. Twenty-five children (thirty-four clubfeet) treated by surgeons were compared with ninety-five children (137 clubfeet) treated by a physiotherapist. The outcomes that were evaluated included the number of casts required, the rate of percutaneous Achilles tenotomy, the rate of recurrence, the failure rate, and the need for additional surgical procedures. RESULTS: At the time of presentation, the patients in the two groups were similar in terms of age, sex distribution, laterality of the clubfoot, and history of treatment. The mean duration of follow-up was thirty-four months in the physiotherapist-directed group and forty-eight months in the surgeon-directed group. No significant difference was found between the two groups with regard to the mean number of initial casts, the Achilles tenotomy rate, or the failure rate. Recurrence requiring additional treatment occurred in 14% of the feet in the physiotherapist-directed group and in 26% of the feet in the surgeon-directed group (p = 0.075). Additional procedures, including repeat Achilles tenotomy or a limited posterior or posteromedial release, were required in 6% of the feet in the physiotherapist-directed group and in 18% of those in the surgeon-directed group (p = 0.025). CONCLUSIONS: In our institution, the Ponseti method of cast treatment of idiopathic clubfeet was as effective when it was directed by a physiotherapist as it was when it was directed by a surgeon, with fewer recurrences and a less frequent need for additional procedures in the physiotherapist-directed group. The introduction of the physiotherapist-supervised clubfoot clinic at our institution has been effective without compromising the quality of care of children with clubfoot deformity.

Treatment of neuromuscular and syndrome-associated (nonidiopathic) clubfeet using the Ponseti method.

BACKGROUND: Clubfeet are associated with many neuromuscular and congenital conditions. Nonidiopathic clubfeet are typically thought to be resistant to nonoperative management. The Ponseti method has revolutionized the treatment of patients with idiopathic clubfeet. The purpose of this study was to describe the use of the Ponseti method in the treatment of patients whose clubfeet are associated with a neuromuscular diagnosis or a syndrome. METHODS: All patients with clubfeet who were treated at the Hospital for Sick Children, Toronto, from 2001 to 2005 were reviewed. Patients were included only if a neuromuscular condition or a syndrome associated with clubfeet could be identified and if the primary treatment was at our institution. Twenty-three patients with 40 nonidiopathic clubfeet and 171 patients with 249 idiopathic clubfeet have been treated with a minimum follow-up time of 1 year. The outcomes evaluated included the number of casts, the percentage of patients requiring percutaneous Achilles tendon lengthening (tenotomy of the Achilles tendon [TAT]), rate of recurrences, rate of failures, and the need for additional secondary procedures. RESULTS: The mean age at presentation for nonidiopathic clubfeet was 11 weeks. The mean follow-up time was 33 months, and the mean number of casts was 6.4; a percutaneous TAT was necessary in 27 (68%) of 40 feet. Failure of the Ponseti casting occurred in 4 (10%) of the 40 feet. Recurrence requiring additional treatment occurred in 16 (44%) of 36 feet. Additional procedures included second percutaneous TAT, limited posterior/plantar release, or complete posteromedial release totaling 11 (28%) of 40. When compared with idiopathic clubfeet, nonidiopathic clubfeet required more casts and had a higher rate of failures, recurrences, and additional procedures than idiopathic clubfeet. CONCLUSIONS: Although not as successful as for idiopathic clubfeet, when the Ponseti technique is applied to nonidiopathic clubfeet, correction can be achieved and maintained in most patients. LEVEL OF EVIDENCE: Prognostic level 2.

Insights into polyether biosynthesis from analysis of the nigericin biosynthetic gene cluster in Streptomyces sp. DSM4137.

Nigericin was among the first polyether ionophores to be discovered, but its biosynthesis remains obscure. The biosynthetic gene cluster for nigericin has been serendipitously cloned from Streptomyces sp. DSM4137, and deletion of this gene cluster abolished the production of both nigericin and the closely related metabolite abierixin. Detailed comparison of the nigericin biosynthetic genes with their counterparts in the biosynthetic clusters for other polyketides has prompted a significant revision of the proposed common pathway for polyether biosynthesis. In particular, we present evidence that in nigericin, nanchangmycin, and monensin, an unusual ketosynthase-like protein, KSX, transfers the initially formed linear polyketide chain to a discrete acyl carrier protein, ACPX, for oxidative cyclization. Consistent with this, deletion of either monACPX or monKSX from the monensin gene cluster effectively abolished monensin A biosynthesis.

Evidence that a novel thioesterase is responsible for polyketide chain release during biosynthesis of the polyether ionophore monensin.

Polyether ionophores, such as monensin A, are known to be biosynthesised, like many other antibiotic polyketides, on giant modular polyketide synthases (PKSs), but the intermediates and enzymes involved in the subsequent steps of oxidative cyclisation remain undefined. In particular there has been no agreement on the mechanism and timing of the final polyketide chain release. We now report evidence that MonCII from the monensin biosynthetic gene cluster in Streptomyces cinnamonensis, which was previously thought to be an epoxide hydrolase, is a novel thioesterase that belongs to the alpha/beta-hydrolase structural family and might catalyse this step. Purified recombinant MonCII was found to hydrolyse several thioester substrates, including an N-acetylcysteamine thioester derivative of monensin A. Further, incubation with a hallmark inhibitor of such enzymes, phenylmethanesulfonyl fluoride, led to inhibition of the thioesterase activity and to the accumulation of an acylated form of MonCII. These findings require a reassessment of the role of other enzymes implicated in the late stages of polyether ionophore biosynthesis.

Evidence for the role of the monB genes in polyether ring formation during monensin biosynthesis.

Ionophoric polyethers are produced by the exquisitely stereoselective oxidative cyclization of a linear polyketide, probably via a triepoxide intermediate. We report here that deletion of either or both of the monBI and monBII genes from the monensin biosynthetic gene cluster gave strains that produced, in place of monensins A and B, a mixture of C-3-demethylmonensins and a number of minor components, including C-9-epi-monensin A. All the minor components were efficiently converted into monensins by subsequent acid treatment. These data strongly suggest that epoxide ring opening and concomitant polyether ring formation are catalyzed by the MonB enzymes, rather than by the enzyme MonCII as previously thought. Consistent with this, homology modeling shows that the structure of MonB-type enzymes closely resembles the recently determined structure of limonene-1,2-epoxide hydrolase from Rhodococcus erythropolis.

Structure, biosynthetic origin, and engineered biosynthesis of calcium-dependent antibiotics from Streptomyces coelicolor.

The calcium-dependent antibiotic (CDA), from Streptomyces coelicolor, is an acidic lipopeptide comprising an N-terminal 2,3-epoxyhexanoyl fatty acid side chain and several nonproteinogenic amino acid residues. S. coelicolor grown on solid media was shown to produce several previously uncharacterized peptides with C-terminal Z-dehydrotryptophan residues. The CDA biosynthetic gene cluster contains open reading frames encoding nonribosomal peptide synthetases, fatty acid synthases, and enzymes involved in precursor supply and tailoring of the nascent peptide. On the basis of protein sequence similarity and chemical reasoning, the biosynthesis of CDA is rationalized. Deletion of SCO3229 (hmaS), a putative 4-hydroxymandelic acid synthase-encoding gene, abolishes CDA production. The exogenous supply of 4-hydroxymandelate, 4-hydroxyphenylglyoxylate, or 4-hydroxyphenylglycine re-establishes CDA production by the DeltahmaS mutant. Feeding analogs of these precursors to the mutant resulted in the directed biosynthesis of novel lipopeptides with modified arylglycine residues.