Using the Food and Drug Administration´s Sentinel System for surveillance of TB infection.

BACKGROUND: We examined patterns in care for individuals treated for latent TB infection (LTBI) in the US Food and Drug Administration´s Sentinel System.METHODS: Using administrative claims data, we identified patients who filled standard LTBI treatment prescriptions during 2008-2019. In these cohorts, we assessed LTBI testing, clinical management, and treatment duration.RESULTS: Among 113,338 patients who filled LTBI prescriptions, 80% (90,377) received isoniazid (INH) only, 19% (21,235) rifampin (RIF) only, and 2% (1,726) INH + rifapentine (RPT). By regimen, the proportion of patients with documented prior testing for TBI was 79%, 54%, and 91%, respectively. Median therapy duration was 84 days (IQR 35-84) for the 3-month once-weekly INH + RPT regimen, 60 days (IQR 30-100) for the 6- to 9-month INH regimen, and 30 days (IQR 2-60) for the 4-month RIF regimen.CONCLUSIONS: Among the cohorts, INH-only was the most commonly prescribed LTBI treatment. Most persons who filled a prescription for LTBI treatment did not have evidence of completing recommended treatment duration. These data further support preferential use of shorter-course regimens such as INH + RPT.

Use of an electronic medical record dashboard to identify gaps in osteoporosis care.

Using an electronic medical record (EMR)-based dashboard, this study explored osteoporosis care gaps in primary care. Eighty-four physicians shared their practice activities related to bone mineral density testing, 10-year fracture risk calculation and treatment for those at high risk. Significant gaps in fracture risk calculation and osteoporosis management were identified. PURPOSE: To identify care gaps in osteoporosis management focusing on Canadian clinical practice guidelines (CPG) related to bone mineral density (BMD) testing, 10-year fracture risk calculation and treatment for those at high risk. METHODS: The ADVANTAGE OP EMR tool consists of an interactive algorithm to facilitate assessment and management of fracture risk using CPG. The FRAX® and Canadian Association of Radiologists and Osteoporosis Canada (CAROC) tools were embedded to facilitate 10-year fracture risk calculation. Physicians managed patients as clinically indicated but with EMR reminders of guideline recommendations; participants shared practice level data on management activities after 18-month use of the tool. RESULTS: Eighty-four physicians (54%) of 154 who agreed to participate in this study shared their aggregate practice activities. Across all practices, there were 171,310 adult patients, 40 years of age and older, of whom 17,214 (10%) were at elevated risk for fracture. Sixty-two percent of patients potentially at elevated risk for fractures did not have BMD testing completed; most common reasons for this were intention to order BMD later (48%), physician belief that BMD was not required (15%) and patient refusal (20%). For patients with BMD completed, fracture risk was calculated in 29%; 19% were at high risk, of whom 37% were not treated with osteoporosis medications as recommended by CPG. CONCLUSION: Despite access to CPG and fracture risk calculators through the ADVANTAGE OP EMR tool, significant gaps remain in fracture risk calculation and osteoporosis management. Additional strategies are needed to address this clinical inertia among family physicians.

Changes in tuberculosis epidemiology, United States, 1993-2017.

BACKGROUND: After 20 years of steady decline, the pace of decline of tuberculosis (TB) incidence in the United States has slowed.METHODS: Trends in TB incidence rates and case counts since 1993 were assessed using national US surveillance data. Patient characteristics reported during 2014-2017 were compared with those for 2010-2013.RESULTS: TB rates and case counts slowed to an annual decline of respectively 2.2% (95%CI -3.4 to -1.0) and 1.5% (95%CI -2.7 to -0.3) since 2012, with decreases among US-born persons and no change among non-US-born persons. Overall, persons with TB diagnosed during 2014-2017 were older, more likely to have combined pulmonary and extra-pulmonary disease than extra-pulmonary disease alone, more likely to be of non-White race, and less likely to have human immunodeficiency virus infection, or cavitary pulmonary disease. During 2014-2017, non-US-born persons with TB were more likely to have diabetes mellitus, while the US-born were more likely to have smear-positive TB and use non-injecting drugs.CONCLUSION: Changes in epidemiologic trends are likely to affect TB incidence in the coming decades. The Centers for Disease Control and Prevention has called for increased attention to TB prevention through the detection and treatment of latent tuberculous infection.

Chrysotile and chrysophosphate chemical modification of the chrysotile surface and its effect on biological behavior.

Chrysotile asbestos was reacted with phosphorus oxychloride (POC) gas to produce a chemically modified fiber referred to as chrysophosphate. The presence of phosphorus and chlorine on the fiber surface and in small fiber bundles was verified by means of energy dispersive x-ray spectrometry and laser mass spectrometry. The altered fiber exhibits different physical-chemical properties when compared with the unaltered precursor material. In addition to marked surface changes, fibrils of the reacted material appear to be cross-linked increasing the size of particulates, fiber bundles and increasing their mechanical stability. The reacted specimens exhibit fewer fibrils reducing their surface area. In vitro testing using the human erythrocyte model showed the membranolytic activity of the reacted fiber to be substantially reduced to the background level measured for mechanical membrane breakage during manipulation. Membranolytic activity of unreacted chrysotile displayed values reported previously in the literature. These data support the observation made in other studies that fiber surface modification by means of an industrial process may be a method for reducing the biological potential of mineral particles. The membrane model is considered a useful and preliminary examination. These materials will require further testing in more complex in vivo systems. Some in vivo assays were performed on chrysophosphate with results that appeared to differ from our membrane tests. These differences are described and the variation of batch chemistry, stability of the reacted surface, and the resulting surface chemistry, are discussed.

Association with pregnancy increases the risk of local recurrence but does not impact overall survival in breast cancer: A case-control study of 87 cases.

Pregnancy-associated breast cancer (PABC) constitutes 7% of all BCs in young women. The prognosis of PABC remains controversial. In this study, we evaluated the impact of the association of pregnancy with BC on the rates of overall survival (OS), disease free survival (DFS), and distant and local recurrence-free survival. We conducted a retrospective unicenter case-control study. We enrolled PABC patients treated at our institution between 1992 and 2009. For each case, 2 BC controls were matched for age and year of diagnosis. Univariate and multivariate analyses were performed to assess the parameters associated with prognosis. Eighty-seven PABC patients were enrolled and matched with 174 controls. The univariate analysis did not reveal any significant differences in OS, DFS or distant recurrence rates between the 2 groups. Pregnancy associated status, a tumor larger than T2 and neoadjuvant chemotherapy as the primary treatment were significantly associated with an increased risk of local relapse. The multivariate analysis showed that the pregnancy associated status and the tumor size were strong prognostic factors of local recurrence. Pregnancy associated status negates the prognostic value of tumor size, as both T0-T2 and T3-T4 PABC patients have the same poor prognosis as control BC patients with T3-T4 tumors. Interestingly, although PABC patients have more locally advanced tumors, they did not have a higher rate of radical surgery than the control BC patients. Pregnancy associated status is a strong prognostic factor of local relapse in BC. In PABC patients, when possible, radical surgery should be the preferred first treatment step.

Antenatal and postnatal care: a review of innovative models for improving availability, accessibility, acceptability and quality of services in low-resource settings.

UNLABELLED: Key lessons can be drawn from innovative approaches that have been implemented to ensure access to better antenatal care (ANC) and postnatal care (PNC). This paper examines the successes and challenges of ANC and PNC delivery models in several settings around the world; discusses the lessons to be learned from them; and makes recommendations for future programmes. Based on this review, we conclude that close monitoring of ANC and PNC quality and delivery models, health workforce support, appropriate use of electronic technologies, integrated care, a woman-friendly perspective, and adequate infrastructure are key elements of successful programmes that benefit the health and wellbeing of women, their newborns and families. However, a full evaluation of care delivery models is needed to establish their acceptability, accessibility, availability and quality. TWEETABLE ABSTRACT: New paper examines global innovations in antenatal/postnatal care @MHTF @ICS_Integrare #MNCH #healthsystems.

Breast lumps in pregnant women.

Breast lumps detected during pregnancy are generally benign and reflect fibroadenoma, lactating adenoma, cysts, infarction of the breast or galactocele. Although rare, the possibility of breast cancer must also be considered to avoid any delays in diagnosis. After patient questioning and clinical examination, the first imaging modality to use is ultrasound. No further assessment is called for if lesions are categorized as BI-RADS 2 and no suspicious clinical signs are observed. Depending on the clinical setting, lesions classified BI-RADS 3 require monitoring and mammographic assessment (which can be helpful in diagnosing cancer and incurs no risk to the embryo or fetus). If the clinical signs are unclear and/or the lesion(s) are categorized as ≥ BI-RADS 4a, then mammography and often biopsy should be performed. Strict BI-RADS scoring (American College of Radiology) should be applied, bearing in mind that benign lesions can appear suspicious during pregnancy, and some cancers can exhibit what seem to be reassuring characteristics.

A single-institution study of 117 pregnancy-associated breast cancers (PABC): Presentation, imaging, clinicopathological data and outcome.

BACKGROUND: This retrospective single-institution study was designed to describe the main clinical, radiological and histological features, as well as the outcome of pregnancy-associated breast cancer (PABC), with a special emphasis on imaging and diagnostic difficulties. MATERIAL AND METHODS: We reviewed all breast cancers diagnosed during pregnancy or during the 12 months following delivery at our institution, between 1993 and 2009. Out of a total of 16,555 new cases of breast cancer observed during this period, 117 PABC (0.7%) were diagnosed. RESULTS: Mean age at diagnosis was 33.7 years. Most cancers (81.2%) were diagnosed after delivery. Intermediate or high family risk was frequent (27.5%). The most common mode of presentation was a palpable mass (89.7%). Mean time to diagnosis was 5.8 months. Sensitivity for mammography was 80.9% and for ultrasound 77%. Most prognostic factors were unfavourable: frequent lymph node involvement (51.8%), high-grade tumours, hormone receptor negativity (45.9%) and HER2 positivity (38.7%). Treatments generally included surgery (61.7% mastectomies), radiotherapy (96%) and chemotherapy (79.6%). Overall 5-year survival was 81.8%. CONCLUSION: PABC is an uncommon but aggressive form of breast cancer and must be considered in the presence of any breast abnormality during pregnancy or the months following delivery. Mammography and ultrasound should both be performed at the slightest clinical suspicion. Radiologists must be aware that masses may lack typical malignant ultrasound characteristics. Biopsies should be largely performed.

Molecular dynamics of DNA-protein conjugates on electrified surfaces: solutions to the drift-diffusion equation.

Self-assembled monolayers of charged polymers are an integral component of many state-of-the-art nanobiosensors. Electrical interactions between charged surfaces and charged biomolecules, adopting the roles of linkers or capture molecules, are not only crucial to the sensor performance but may also be exploited for novel sensing concepts based on electrically actuated interfaces. Here we introduce an analytical model describing the behavior of double-stranded DNA and proteins tethered to externally biased microelectrodes. Continuum electrostatic Poisson-Boltzmann models and the drift-diffusion (Smoluchowski) equation are used to calculate the steady state as well as the dynamic behavior of oligonucleotide rods in DC and AC electric fields. The model predicts the oligonucleotide orientation on the surface and calculates how the increased hydrodynamic drag caused by a protein bound to the DNA's distal end affects the molecular dynamics of the DNA-protein complex. The results of the model are compared to experiments with electrically switchable DNA layers, and very good agreement between theory and experiment is found. The hydrodynamic diameter of the bound protein can be analyzed from experimental data of the slowed motion of the DNA-protein conjugate with angstrom precision.

Recognition of pulmonary hypertension in the rheumatology community: lessons from a Quality Enhancement Research Initiative.

OBJECTIVES: The aim of this study was to utilise the Quality Enhancement Research Initiative in Systemic Sclerosis (QuERI-SSc) to measure and reduce a perceived gap in the diagnosis of pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc). METHODS: Rheumatologists enrolled patients with SSc (aged ≥ 18 years) and provided data on a panel of diagnostic tests over 3 years. Pulmonary function testing, echocardiography, 6-minute walk distance, N-terminal pro-brain natriuretic peptide assays, high-resolution computed tomography of the lungs, and ventilation/perfusion scan plus right heart catheterisation (RHC; when appropriate) were emphasised. Exclusion criteria included previously documented PAH, interstitial lung disease, and SSc overlapping with other connective tissue disease. RESULTS: Participating rheumatologists enrolled 207 patients with SSc (90% female; 80% white), with a median age of 57 years and median disease duration of 5 years. A total of 82% of patients were classified as New York Heart Association functional class I and II; of these patients, 177 had an echocardiogram at enrolment and 191 at any time during the study. Of those who met study-specified criteria for RHC at enrolment, only 3 of 7 patients underwent RHC. CONCLUSIONS: The screening algorithm was successful in identifying patients with mild impairment. Although specific tools were recommended for screening PAH in patients with SSc, results indicate that significant diagnostic care gaps still exist in the general rheumatology community. Better understanding and adherence to guidelines could improve the care and, ideally, outcomes of these high-risk patients.

Translating research into practice: the introduction of the INTERGROWTH-21st package of clinical standards, tools and guidelines into policies, programmes and services.

The INTERGROWTH-21(st) Project has generated a package of international clinical standards, tools and guidelines. It is now necessary to plan for the next phase of the project: the translation of the research findings into practice through its global dissemination. The plan is to pre-empt barriers to implementation by drawing from the published literature; gathering views and perspectives from policy makers, programmers and practitioners; incorporating input from local 'champions', and collecting and analysing data generated by a monitoring and evaluation system. Working at the global, regional, national and local levels will enable wide dissemination of the package, as well as increase the scope for adaptation and integration in diverse clinical contexts. We seek maximum uptake of the package in policies, guidelines and clinical practice to improve the quality of care offered to mothers and newborns. The strategy will also enhance our understanding of the effectiveness of different approaches to the translation of evidence into practice.

A comparison of the assessment and management of cardiometabolic risk in patients with and without type 2 diabetes mellitus in Canadian primary care.

AIM: To investigate the cardiometabolic risk (CMR) assessment and management patterns for individuals with and without type 2 diabetes mellitus (T2DM) in Canadian primary care practices. METHODS: Between April 2011 and March 2012, physicians from 9 primary care teams and 88 traditional non-team practices completed a practice assessment on the management of 2461 patients >40 years old with no clinical evidence of cardiovascular disease and diagnosed with at least one of the following risk factor-T2DM, dyslipidaemia or hypertension. RESULTS: There were 1304 individuals with T2DM and 1157 without. Pharmacotherapy to manage hyperglycaemia, dyslipidaemia and hypertension was widely prescribed. Fifty-eight percent of individuals with T2DM had a glycated haemoglobin (HbA1c) ≤7.0%. Amongst individuals with dyslipidaemia, median low-density lipoprotein cholesterol (LDL-C) was 1.8 mmol/l for those with T2DM and 2.8 mmol/l for those without. Amongst individuals with hypertension, 30% of those with T2DM achieved the <130/80 mmHg target, whereas 60% of those without met the <140/90 mmHg target. The composite glycaemic, LDL-C and blood pressure (BP) target outcome was achieved by 12% of individuals with T2DM. Only 17% of individuals with T2DM and 11% without were advised to increase their physical activity. Dietary modifications were recommended to 32 and 10% of those with and without T2DM, respectively. CONCLUSIONS: Patients at elevated CMR were suboptimally managed in the primary care practices surveyed. There was low attainment of recommended therapeutic glycaemic, lipid and BP targets. Advice on healthy lifestyle changes was infrequently dispensed, representing a missed opportunity to educate patients on the long-term benefits of lifestyle modification.

From the transcription of genes involved in ectodermal dysplasias to the understanding of associated dental anomalies.

Orodental anomalies are one aspect of rare diseases and are increasingly identified as diagnostic and predictive traits. To understand the rationale behind gene expression during tooth or other ectodermal derivative development and the disruption of odontogenesis or hair and salivary gland formation in human syndromes we analyzed the expression patterns of a set of genes (Irf6, Nfkbia, Ercc3, Evc2, Map2k1) involved in human ectodermal dysplasias in mouse by in situ hybridization. The expression patterns of Nfkbia, Ercc3 and Evc2 during odontogenesis had never been reported previously. All genes were indeed transcribed in different tissues/organs of ectodermal origin. However, for Nfkbia, Ercc3, Evc2, and Map2k1, signals were also present in the ectomesenchymal components of the tooth germs. These expression patterns were consistent in timing and localization with the known dental anomalies (tooth agenesis, microdontia, conical shape, enamel hypoplasia) encountered in syndromes resulting from mutations in those genes. They could also explain the similar orodental anomalies encountered in some of the corresponding mutant mouse models. Translational approaches in development and medicine are relevant to gain understanding of the molecular events underlying clinical manifestations.

Poor achievement of guidelines-recommended targets in type 2 diabetes: findings from a contemporary prospective cohort study.

AIMS: To prospectively evaluate diabetes management in the primary care setting and explore factors related to guideline-recommended triple target achievement [blood pressure (BP) ≤ 130/80 mmHg, A1C ≤ 7% and low-density lipoprotein (LDL)-cholesterol < 2.5 mmol/l]. METHODS: Baseline, 6 and 12 month data on clinical and laboratory parameters were measured in 3002 patients with type 2 diabetes enrolled as part of a prospective quality enhancement research initiative in Canada. A generalised estimating equation model was fitted to assess variables associated with triple target achievement. RESULTS: At baseline, 54%, 53% and 64% of patients, respectively, had BP, A1C and LDL-cholesterol at target; all three goals were met by 19% of patients. The percentage of individuals achieving these targets significantly increased during the study [60%, 57%, 76% and 26%, respectively, at the final visit, p < 0.0001 except for A1C, p = 0.27]. A much smaller proportion of patients had adequate control during the entire study period [30%, 39%, 53% and 7%, respectively]. In multivariable analysis, women, patients younger than 65 years and patients of Afro-Canadian origin were less likely to achieve the triple target. DISCUSSION: As part of a quality enhancement research initiative, we observed important improvements in the attainment of guidelines-recommended targets in patients with type 2 diabetes followed for a 12-month period in the primary care setting; however, many individuals still failed to achieve and especially maintain optimal goals for therapy, particularly the triple target. Results of the multivariable analysis reinforce the need to address barriers to improve diabetes care, particularly in more susceptible groups.

Multistate outbreak of Escherichia coli O157:H7 infections associated with a national fast-food chain, 2006: a study incorporating epidemiological and food source traceback results.

A multistate outbreak of Escherichia coli O157:H7 infections occurred in the USA in November-December 2006 in patrons of restaurant chain A. We identified 77 cases with chain A exposure in four states - Delaware, New Jersey, New York, and Pennsylvania. Fifty-one (66%) patients were hospitalized, and seven (9%) developed haemolytic uraemic syndrome; none died. In a matched analysis controlling for age in 31 cases and 55 controls, illness was associated with consumption of shredded iceberg lettuce [matched odds ratio (mOR) 8·0, 95% confidence interval (CI) 1·1-348·1] and shredded cheddar cheese (mOR 6·2, CI 1·7-33·7). Lettuce, an uncooked ingredient, was more commonly consumed (97% of patients) than cheddar cheese (84%) and a single source supplied all affected restaurants. A single source of cheese could not explain the regional distribution of outbreak cases. The outbreak highlights challenges in conducting rapid multistate investigations and the importance of incorporating epidemiological study results with other investigative findings.

Effect of atorvastatin on circulating hsCRP concentrations: a sub-study of the achieve cholesterol targets fast with atorvastatin stratified titration (ACTFAST) study.

BACKGROUND: Elevated C-reactive protein (CRP) concentration is a risk factor for cardiovascular events that may add prognostic information. Statin treatment is associated with significant reductions in CRP concentrations, which appear to be unrelated to the magnitude of LDL-cholesterol reduction. We investigated the effect of atorvastatin, across its dose range, on high sensitivity (hs)CRP in subjects at high cardiovascular risk. METHODS: ACTFAST was a 12 week, prospective, multicenter, open-label trial in which high-risk subjects were assigned a starting dose of atorvastatin (10, 20, 40 or 80 mg/d) based on LDL-C and status of statin use at screening (1345 statin-free [SF] and 772 previously statin-treated [ST]). RESULTS: At baseline, ST subjects had significantly lower hsCRP levels than SF subjects (ST group 2.31, 95% CI 2.15, 2.48 mg/L vs. SF group 3.16, 95% CI 2.98, 3.34 mg/L, p<0.05). In the SF group, atorvastatin 10 to 80 mg significantly (p<0.01) reduced hsCRP levels in a dose dependent-manner. In ST group, additional hsCRP reductions were observed over the statin used at baseline, which were not dose-dependent. Atorvastatin significantly decreased hsCRP concentrations in subjects with or without diabetes or the metabolic syndrome. CONCLUSIONS: Atorvastatin treatment at different doses, particularly 80 mg, significantly reduced hsCRP serum concentrations. This reduction was observed in both SF and ST groups and was independent of the presence of metabolic syndrome and/or diabetes. The beneficial effect of atorvastatin was evident at 6 weeks, supporting the practice of early introduction of higher doses of atorvastatin in high-risk patients.

Self-limited febrile syndromes temporally associated with the use of propofol for sedation in gastrointestinal endoscopic procedures.

PURPOSE: To investigate cases of febrile illnesses in patients who received propofol for sedation during gastrointestinal endoscopy. METHODS: Active case finding for patients who underwent endoscopy between 1 April and 30 May 2007 and suffered unexplained fever, chills, or myalgia within 48 hour after the procedure. We reviewed medications and clinical practices to find factors associated with the reactions. RESULTS: Seventy-four cases at eight facilities in five states were identified yielding a rate of 36 reactions per 1000 procedures, compared with a baseline rate of 0.6 per 1000. The majority of patients experienced self-limited fever (89.2%), chills (73.0%), or myalgia (63.5%). Blood samples from five patients were collected for culture; no organisms grew. All health care facilities that reported cases and fully participated in the investigation (n = 7) had received a common lot of propofol just before recognition of the first case. Bacterial endotoxin and sterility testing on unopened vials from this lot of propofol showed no abnormalities. Cases terminated after facilities stopped using the associated lot of propofol. CONCLUSIONS: We found a temporal association between a particular lot of propofol and an outbreak of febrile illnesses at several healthcare facilities performing endoscopy. When propofol is used to sedate patients for endoscopy, fever is a rare outcome and healthcare professionals should investigate clusters of these reactions. Post-procedure surveillance is important to identify possible medication reactions.

[Mammographic evaluation of dense breasts: techniques and limits]. / Exploration des seins denses en mammographie: techniques et limites.

Breast density is a radiological concept based on the proportion of radiopaque glandular tissue relative to radiolucent fatty tissue. Mammographic evaluation of dense breasts is more difficult, related to technical difficulties, with decreased rates for detection and characterization of breast lesions, resulting in reduced sensitivity with increased number of interval cancers at routine follow-up when compared to radiolucent breasts. We will review the definition of dense breasts and their frequency, especially their relationship with the age of patients. We will discuss the current technical problems and the impact of breast density on the efficacy of conventional mammography. We will discuss the value of digital mammography, the role of computer assisted diagnosis (CAD) systems and tomosynthesis in the evaluation of dense breasts.