Cost-effectiveness of expanded latent TB infection testing and treatment: Lynn City, Massachusetts, USA.

BACKGROUND: Between October 2016 and March 2019, Lynn Community Health Center in Massachusetts implemented a targeted latent TB infection testing and treatment (TTT) program, increasing testing from a baseline of 1,200 patients tested to an average of 3,531 patients tested, or 9% of the population per year.METHODS: We compared pre-implementation TTT, represented by the first two quarters of implementation data, to TTT, represented by 12 quarters of data. Time, diagnostic, and laboratory resources were estimated using micro-costing. Other cost and testing data were obtained from the electronic health record, pharmaceutical claims, and published reimbursement rates. A Markov cohort model estimated future health outcomes and cost-effectiveness from a societal perspective in 2020 US dollars. Monte Carlo simulation generated 95% uncertainty intervals.RESULTS: The TTT program exhibited extended dominance over baseline pre-intervention testing and had an incremental cost-effectiveness ratio (ICER) of US$52,603 (US$22,008â-"US$95,360). When compared to baseline pre-TTT testing, the TTT program averted an estimated additional 7.12 TB cases, 3.49 hospitalizations, and 0.16 deaths per lifetime cohort each year.CONCLUSIONS: TTT was more cost-effective than baseline pre-implementation testing. Lynn Community Health Centerâ-™s experience can help inform other clinics considering expanding latent TB infection testing.

The adequacy of tissue microarrays in the assessment of inter- and intra-tumoural heterogeneity of infiltrating lymphocyte burden in leiomyosarcoma.

The characterisation and clinical relevance of tumour-infiltrating lymphocytes (TILs) in leiomyosarcoma (LMS), a subtype of soft tissue sarcoma that exhibits histological heterogeneity, is not established. The use of tissue microarrays (TMA) in studies that profile TIL burden is attractive but given the potential for intra-tumoural heterogeneity to introduce sampling errors, the adequacy of this approach is undetermined. In this study, we assessed the histological inter- and intra-tumoural heterogeneity in TIL burden within a retrospective cohort of primary LMS specimens. Using a virtual TMA approach, we also analysed the optimal number of TMA cores required to provide an accurate representation of TIL burden in a full tissue section. We establish that LMS have generally low and spatially homogenous TIL burdens, although a small proportion exhibit higher levels and more heterogeneous distribution of TILs. We show that a conventional and practical number (e.g. ≤3) of TMA cores is adequate for correct ordinal categorisation of tumours with high or low TIL burden, but that many more cores (≥11) are required to accurately estimate absolute TIL numbers. Our findings provide a benchmark for the design of future studies aiming to define the clinical relevance of the immune microenvironments of LMS and other sarcoma subtypes.

Disparities in disease presentation in the four screenable cancers according to health insurance status.

OBJECTIVES: Current guidelines support the use of screening for early detection in breast, prostate, colorectal and cervical cancer. The purpose of this study was to evaluate whether insurance status predicts for more advanced disease in these four currently screened cancers. STUDY DESIGN: The Surveillance, Epidemiology, and End Results (SEER) database was queried for breast, prostate, colorectal and cervix in patients aged 18-64 years. The database was queried from 2007 to 2011, with 425,614 patients with known insurance status included. METHODS: Multinomial logistic regression was used to evaluate insurance status and cancer presentation. RESULTS: Under multivariate analysis for breast cancer, uninsured patients more often had invasive disease (odds ratio [OR]: 1.55), T- (OR: 2.00), N- (OR: 1.59) stage, and metastatic disease (OR: 3.48), and were more often high-grade (OR: 1.21). For prostate cancer, uninsured patients again presented more commonly with higher T-stage (OR: 1.45), nodal (OR: 2.90) and metastatic (OR: 4.98) disease, in addition to higher prostate-specific antigen (OR: 2.85) and Gleason score (OR: 1.65). Colorectal cancer had similar findings with uninsured individuals presenting with more invasive disease (OR: 1.78), higher T (OR: 1.86), N (OR: 1.22), and M (OR: 1.58) stage, in addition to higher carcinoembryonic antigen levels (OR: 1.66). Similar results were seen for cervical cancer with uninsured having higher T (OR: 2.03), N (OR: 1.21), and M (OR: 1.45) stage. CONCLUSION: In the four cancers detected by screening exams, those without health insurance present with more advanced disease, with higher stage and grade, and more elevated tumour markers.

Predicting intensive care and hospital outcome with the Dalhousie Clinical Frailty Scale: a pilot assessment.

Frailty may help to predict intensive care unit (ICU) patient outcome. The Dalhousie Clinical Frailty Scale (DCFS) is validated to assess frailty in ambulatory settings but has not been investigated in Australian ICUs. We conducted a prospective three-month study of patients admitted to a tertiary level ICU. Within 24 hours of ICU admission, the next of kin or nurse in charge assigned a DCFS score to the patient. Data were obtained to assess the association between frailty and patient outcome. The DCFS score was completed in 205 of 348 (59%) of eligible patient admissions. The mean DCFS score was 3.2 (±1.6). Overall frailty (DCFS>4) occurred in 28 of 205 patients (13%, confidence interval 9% to 17%), 13 of 93 (15%, confidence interval 10% to 25%) in patients aged >65 years and 5 of 11 (45%, confidence interval 21% to 71%) in those>85 years. Patients with chronic liver disease (P<0.001) and end-stage renal failure (P=0.009) were more likely to be frail. The DCFS score was not significantly associated with ICU or hospital mortality: odds ratio 0.98 (95% confidence interval 0.6 to 1.6) and odds ratio 1.07 (95% confidence interval 0.8 to 1.4), respectively. However, after adjustment for illness severity and requirement for palliative care, the DCFS score was significantly associated with increased (log) hospital length-of-stay (P=0.04) and age (P=0.001). Approximately 1 in 10 ICU patients were frail and this frequency increased with age. The DCFS was associated with patient age and comorbidities and potentially predicts increased hospital length-of-stay but not other outcomes. Strategies to improve compliance with DCFS completion are needed.

Obstetric complications and psychological well-being: experiences of Bangladeshi women during pregnancy and childbirth.

Women in developing countries experience postnatal depression at rates that are comparable with or higher than those in developed countries. However, their personal experiences during pregnancy and childbirth have received little attention in relation to postnatal depression. In particular, the contribution of obstetric complications to their emotional well-being during the postpartum period is still not clearly understood. This study aimed to (a) describe the pregnancy and childbirth experiences among women in Bangladesh during normal childbirth or obstetric complications and (b) examine the relationship between these experiences and their psychological well-being during the postpartum period. Two groups of women--one group with obstetric complications (n=173) and the other with no obstetric complications (n=373)--were selected from a sample of women enrolled in a community-based study in Matlab, Bangladesh. The experiences during pregnancy and childbirth were assessed in terms of a five-point rating scale from 'severely uncomfortable=1' to 'not uncomfortable at all=5'. The psychological status of the women was assessed using a validated local version of the Edinburgh Postnatal Depression Scale (EPDS) at six weeks postpartum. Categorical data were analyzed using the chi-square test and continuous data by analysis of variance. Women with obstetric complications reported significantly more negative experiences during their recent childbirth [95% confidence interval (CI) 1.36-1.61, p<0.001] compared to those with normal childbirth. There was a significant main effect on emotional well-being due to experiences of pregnancy [F (4,536)=4.96, p=0.001] and experiences of childbirth [F (4,536)=3.29, p=0.01]. The EPDS mean scores for women reporting severe uncomfortable pregnancy and childbirth experiences were significantly higher than those reporting no such problems. After controlling for the background characteristics, postpartum depression was significantly associated with women reporting a negative childbirth experience. Childbirth experiences of women can provide important information on possible cases of postnatal depression.

Evaluation of certain food additives and contaminants.

This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives, including flavouring agents, with a view to recommending acceptable daily intakes (ADIs) and to preparing specifications for identity and purity. The Committee also evaluated the risk posed by two food contaminants, with the aim of advising on risk management options for the purpose of public health protection. The first part of the report contains a general discussion of the principles governing the toxicological evaluation and assessment of intake of food additives (in particular flavouring agents) and contaminants. A summary follows of the Committee's evaluations of technical, toxicological and intake data for certain food additives (acidified sodium chlorite, asparaginase from Aspergillus oryzae expressed in Aspergillus oryzae, carrageenan and processed Eucheuma seaweed, cyclotetraglucose and cyclotetraglucose syrup, isoamylase from Pseudomonas amyloderamosa, magnesium sulfate, phospholipase A1 from Fusarium venenatum expressed in Aspergillus oryzae, sodium iron(III) ethylenediaminetetraacetic acid (EDTA) and steviol glycosides); eight groups of related flavouring agents (linear and branched-chain aliphatic, unsaturated, unconjugated alcohols, aldehydes, acids and related esters; aliphatic acyclic and alicyclic terpenoid tertiary alcohols and structurally related substances; simple aliphatic and aromatic sulfides and thiols; aliphatic acyclic dials, trials and related substances; aliphatic acetals; sulfur-containing heterocyclic compounds; aliphatic and aromatic amines and amides; and aliphatic alicyclic linear alpha, beta -unsaturated di- and trienals and related alcohols, acids and esters); and two food contaminants (aflatoxin and ochratoxin A). Specifications for the following food additives were revised: maltol and ethyl maltol, nisin preparation, pectins, polyvinyl alcohol, and sucrose esters of fatty acids. Specifications for the following flavouring agents were revised: maltol and ethyl maltol, maltyl isobutyrate, 3-acetyl-2,5-dimethylfuran and 2,4,5-trimethyl-delta-oxazoline (Nos 1482, 1506 and 1559), and monomenthyl glutarate (No. 1414), as well as the method of assay for the sodium salts of certain flavouring agents. Annexed to the report are tables summarizing the Committee's recommendations for intakes and toxicological evaluations of the food additives and contaminants considered.

Synovial sarcoma: a clinicopathologic, staging, and prognostic assessment.

PURPOSE: Synovial sarcoma (SS) is a common soft tissue sarcoma (STS) with a propensity for young adults and notable sensitivity to chemotherapy (CT). This study provides a current clinicopathologic, staging, and prognostic assessment for SS. The problems with the current American Joint Committee for Cancer (AJCC) Staging System in relation to SS are discussed. METHODS: Review of a prospective database supplemented by retrospective data. RESULTS: One hundred fifty patients were assessed; median age was 30 years and median follow-up was 52 months. Overall actuarial 5-year survival rate was 57%. Size trend, but not a cutoff of less than 5 cm versus > or = 5 cm, was a prognostic indicator (P <.001). The current AJCC/International Union Against Cancer Staging System differentiated prognosis less well than the recently proposed Royal Marsden Hospital Staging System. Age greater than 20 years at diagnosis implied worse prognosis. A local recurrence event was associated with a worse survival (P <.001). Therapeutic CT was administered to 55 patients. Eleven of 19 patients had an objective response to a combination of ifosfamide and doxorubicin. Four cases had complete response after CT. Twenty-one patients had pulmonary metastasectomy, with an actuarial 5-year survival rate of 23%. CONCLUSION: SS tends to affect young people. In this subtype of STS, size trend is the most significant influence on stage and hence survival; however, smaller SSs have an unexpectedly poor prognosis. Adequate local control may affect survival. SS is often chemosensitive, and given its poor prognosis, multicenter trials of adjuvant therapy are warranted.

Nomograms used to define the short-term treatment with PGE(1) in patients with intermittent claudication and critical ischemia. The ORACL.E (Occlusion Revascularization in the Atherosclerotic Critical Limb) Study Group. The European Study.

Infusional, cyclic PGE1 treatment is effective in patients with intermittent claudication and critical limb ischemia (CLI). One of the problems related to chronic PGE1 treatment in vascular diseases due to atherosclerosis is to evaluate the variations of clinical conditions due to treatment in order to establish the number of cycles per year or per period (in severe vascular disease reevaluation of patients should be more frequent) needed to achieve clinical improvement. In a preliminary pilot study a group of 150 patients (mean age 67+/-12 years) with intermittent claudication (walking range from 0 to 500 m) and a group of 100 patients with CLI (45% with rest pain, and 55% gangrene; mean age 68 +/-11 years) the number of PGE1 cycles according to the short-term protocol (STP) needed to produce significant clinical improvement was preliminarily evaluated. Considering these preliminary observations, the investigators established a research plan useful to produce nomograms indicating the number of cycles of PGE1-STP per year needed to improve the clinical condition (both in intermittent claudication and CLI). A significant clinical improvement was arbitrarily defined as the increase of at least 35% in walking distance (on treadmill) and/or the disappearance of signs and symptoms of critical ischemia in 6 months of treatment in at least 75% of the treated patients. With consideration of the results obtained with the preliminary nomograms a larger validation of the nomograms is now advisable. A cost-effectiveness analysis is also useful to define the efficacy of treatment on the basis of its costs. The publication of this report in two angiological journals (Angeiologie and Angiology) will open the research on nomograms to all centers willing to collaborate to the study. The data are being collected in the ORACL.E database and will be analyzed within 12 months after the publication of this report.

Toward a science for and of the people: promoting civil society through the application of developmental science.

Applied developmental science (ADS) is scholarship that seeks to advance the integration of developmental research with actions-policies and programs-that promote positive development and/or enhance the life chances of vulnerable children and families. Through this integration ADS may become a major means to foster a science for and of the people. It may serve as an exemplar of the means through which scholarship, with community collaboration, may contribute directly to social justice. In so doing, ADS helps shift the model of amelioration, prevention, or optimization research from one demonstrating efficacy to one promoting outreach. When this contribution occurs in the context of university-community partnerships, ADS may serve also as a model of how higher education may engage policy makers, contribute to community capacity to sustain valued programs, and maintain and perpetuate civil society through knowledge-based, interinstitutional systems change.

External cephalic version with epidural anaesthesia after failure of a first trial with beta-mimetics.

OBJECTIVE: To assess the efficacy, tolerance, and cost of external version under epidural anaesthesia and beta-mimetic tocolysis after the failure of an initial attempt with tocolysis alone. DESIGN: Prospective open study. PARTICIPANTS: Sixty-eight women with breech presentation at around 36 weeks of gestation and an attempted external cephalic version under salbutamol that failed, who consented to try a second attempt under epidural anaesthesia. RESULTS: The overall success rate under epidural anaesthesia was 39.7% (27/68), and complications occurred in two cases. The total cost of attempting external version was higher than the cost of expectant management. CONCLUSIONS: The efficacy of external cephalic version under epidural reduces the rate of caesarean sections associated with breech presentation, but its relative safety remains in question. Moreover, our economic analysis discourages the hope of lowered costs suggested by earlier reports that this technique is more expensive than expectant management, except in institutions with a policy of systematic caesarean sections when version fails.

Thalassaemia in Sri Lanka: implications for the future health burden of Asian populations. Sri Lanka Thalassaemia Study Group.

BACKGROUND: Thalassaemias pose an increasing problem for the Indian subcontinent and many Asian countries. We analysed the different types of thalassaemia in the Sri Lankan population, surveyed gene frequencies in schoolchildren, and estimated the burden of disease and requirements for its control. METHODS: We analysed blood samples from patients attending clinics in nine hospitals and defined the different types of beta thalassaemia by high-performance liquid chromatography (HPLC) and DNA analysis. The range of mutations was obtained by analysis of beta-globin genes. Capillary blood was obtained from schoolchildren from different parts of the island and analysed by HPLC to provide an approximate assessment of the carrier frequency of beta thalassaemia and haemoglobin E (HbE). To estimate the frequency of alpha thalassaemia the alpha-globin genotypes were also analysed when it was possible. FINDINGS: Blood samples were obtained from 703 patients with beta thalassaemia and from 1600 schoolchildren. The thalassaemia mutations were unevenly spread. Although 23 different beta-thalassaemia mutations were found, three accounted for the thalassaemia phenotype in about 70% of the patients, most whom are homozygotes or compound heterozygotes for IVS1-5 (G-->C) or IVS1-1 (G-->A). The third common mutation, codon 26 (G-->A), which produces HbE, interacts with one or other of these mutations to produce HbE/beta thalassaemia; this comprises 13.0-30.9% of cases in the main centres. Samples from 472 patients were analysed to determine the alpha-globin genotype. Overall, 15.5% patients were carriers for deletion forms of alpha+ thalassaemia. Average gene frequencies showed that there will be more than 2000 patients requiring treatment at any one time, in the future, of whom those with HbE/beta thalassaemia will account for about 40%. INTERPRETATION: In Sri Lanka, interactions of the two common beta-thalassaemia alleles will nearly always result in a transfusion-dependent disorder. However, about 40% of patients will have HbE/beta thalassaemia, which has a variable course. The management of these disorders could require about 5% of the total health budget. We need to learn more about the natural history and appropriate management of HbE/beta thalassaemia if resources are to be used effectively.