Abstract A commercially available software platform, Explorys (Explorys, Inc., Cleveland, OH), was used to mine a pooled electronic healthcare database consisting of the medical records of more than ...27 million patients. A total of 229,420 patients had undergone a total knee arthroplasty; 3470 (1.51%) patients were identified to have undergone manipulation under anesthesia. Individual risk factors of being female, African American race, age less than 60, BMI > 30 and nicotine dependence were determined to have relative risk of 1.25, 2.20, 3.46, 1.33 and 1.32 respectively. Depressive disorder, diabetes mellitus, opioid abuse/dependence and rheumatoid arthritis were not significant risk factors. African Americans under the age of 60 at time of TKA had the greatest incidence of MUA (5.17%) and relative risk of 3.73 (CI: 3.36, 4.13).
Objective Identify overlap of the transcriptome of myometrium and cervix in association with human labor. Study Design The transcriptional profile of myometrial and cervical biopsies obtained from ...women in spontaneous labor at term (n = 9) and not in labor (n = 9) were characterized by Affymetrix v2 U133 plus 2 arrays. Common canonical pathways and functional groups were identified by Ingenuity Pathway Analysis. Results One hundred ten genes (false discovery rate < 1%) were commonly up-regulated by myometrium and cervix in association with labor and 29 genes (false discovery rate < 1%) down-regulated. Fold change in expression of up-regulated genes was strongly correlated; myometrium vs cervix (r = 0.51; P < .001), with no relationship in down-regulated genes (r = 0.26; P = .16). Canonical pathway analysis established up-regulation of inflammatory pathway signaling, with greatest increases in cellular movement and immune response gene ontology groups. Conclusion Gestational tissues exhibit a core inflammatory response in association with human parturition, with pathways regulating cellular trafficking dominating.
Background Asthma is a heterogeneous disease in which there is a differential response to asthma treatments. This heterogeneity needs to be evaluated so that a personalized management approach can be ...provided. Objectives We stratified patients with moderate-to-severe asthma based on clinicophysiologic parameters and performed an omics analysis of sputum. Methods Partition-around-medoids clustering was applied to a training set of 266 asthmatic participants from the European Unbiased Biomarkers for the Prediction of Respiratory Diseases Outcomes (U-BIOPRED) adult cohort using 8 prespecified clinic-physiologic variables. This was repeated in a separate validation set of 152 asthmatic patients. The clusters were compared based on sputum proteomics and transcriptomics data. Results Four reproducible and stable clusters of asthmatic patients were identified. The training set cluster T1 consists of patients with well-controlled moderate-to-severe asthma, whereas cluster T2 is a group of patients with late-onset severe asthma with a history of smoking and chronic airflow obstruction. Cluster T3 is similar to cluster T2 in terms of chronic airflow obstruction but is composed of nonsmokers. Cluster T4 is predominantly composed of obese female patients with uncontrolled severe asthma with increased exacerbations but with normal lung function. The validation set exhibited similar clusters, demonstrating reproducibility of the classification. There were significant differences in sputum proteomics and transcriptomics between the clusters. The severe asthma clusters (T2, T3, and T4) had higher sputum eosinophilia than cluster T1, with no differences in sputum neutrophil counts and exhaled nitric oxide and serum IgE levels. Conclusion Clustering based on clinicophysiologic parameters yielded 4 stable and reproducible clusters that associate with different pathobiological pathways.
The CardioMetabolic Health Alliance Sperling, Laurence S., MD; Mechanick, Jeffrey I., MD; Neeland, Ian J., MD ...
Journal of the American College of Cardiology,
09/2015, Letnik:
66, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Abstract The Cardiometabolic Think Tank was convened on June 20, 2014, in Washington, DC, as a “call to action” activity focused on defining new patient care models and approaches to address ...contemporary issues of cardiometabolic risk and disease. Individual experts representing >20 professional organizations participated in this roundtable discussion. The Think Tank consensus was that the metabolic syndrome (MetS) is a complex pathophysiological state comprised of a cluster of clinically measured and typically unmeasured risk factors, is progressive in its course, and is associated with serious and extensive comorbidity, but tends to be clinically under-recognized. The ideal patient care model for MetS must accurately identify those at risk before MetS develops and must recognize subtypes and stages of MetS to more effectively direct prevention and therapies. This new MetS care model introduces both affirmed and emerging concepts that will require consensus development, validation, and optimization in the future.
The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with ...differences in symptoms or disease course, reinfection rates, or transmissibility.
We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, Rt, for the two incidence estimates.
From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. For the same period, possible reinfections were identified in 249 (0·7% 95% CI 0·6–0·8) of 36 509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Reinfection occurrences were more positively correlated with the overall regional rise in cases (Spearman correlation 0·56–0·69 for South East, London, and East of England) than with the regional increase in the proportion of infections with the B.1.1.7 variant (Spearman correlation 0·38–0·56 in the same regions), suggesting B.1.1.7 does not substantially alter the risk of reinfection. We found a multiplicative increase in the Rt of B.1.1.7 by a factor of 1·35 (95% CI 1·02–1·69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant.
The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant.
Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society.
Summary Background Childhood-cancer survival is dismal in most low-income countries, but initiatives for treating paediatric cancer have substantially improved care in some of these countries. The My ...Child Matters programme was launched to fund projects aimed at controlling paediatric cancer in low-income and mid-income countries. We aimed to assess baseline status of paediatric cancer care in ten countries that were receiving support (Bangladesh, Egypt, Honduras, Morocco, the Philippines, Senegal, Tanzania, Ukraine, Venezuela, and Vietnam). Methods Between Sept 5, 2005, and May 26, 2006, qualitative face-to-face interviews with clinicians, hospital managers, health officials, and other health-care professionals were done by a multidisciplinary public-health research company as a field survey. Estimates of expected numbers of patients with paediatric cancer from population-based data were used to project the number of current and future patients for comparison with survey-based data. 5-year survival was postulated on the basis of the findings of the interviews. Data from the field survey were statistically compared with demographic, health, and socioeconomic data from global health organisations. The main outcomes were to assess baseline status of paediatric cancer care in the countries and postulated 5-year survival. Findings The baseline status of paediatric oncology care varied substantially between the surveyed countries. The number of patients reportedly receiving medical care (obtained from survey data) differed markedly from that predicted by population-based incidence data. Management of paediatric cancer and access to care were poor or deficient (ie, nonexistent, unavailable, or inconsistent access for most children with cancer) in seven of the ten countries surveyed, and accurate baseline data on incidence and outcome were very sparse. Postulated 5-year survival were: 5–10% in Bangladesh, the Philippines, Senegal, Tanzania, and Vietnam; 30% in Morocco; and 40–60% in Egypt, Honduras, Ukraine, and Venezuela. Postulated 5-year survival was directly proportional to several health indicators (per capita annual total health-care expenditure Pearson's r2 =0·760, p=0·001, per capita gross domestic product r2 =0·603, p=0·008, per capita gross national income r2 =0·572, p=0·011, number of physicians r2 =0·560, p=0·013 and nurses r2 =0·506, p=0·032 per 1000 population, and most significantly, annual government health-care expenditure per capita r2 =0·882, p<0·0001). Interpretation Detailed surveys can provide useful data for baseline assessment of the status of paediatric oncology, but cannot substitute for national cancer registration. Alliances between public, private, and international agencies might rapidly improve the outcome of children with cancer in these countries. Funding National Institutes of Health (grant CA21765; Bethesda, MD, USA), American Lebanese Syrian Associated Charities (ALSAC; Memphis, TN, USA), and Sanofi-Aventis Sponsorship Department (Paris, France).
Background While many diffusion tensor imaging (DTI) investigations have noted disruptions to white matter integrity in individuals with chronic psychotic disorders, fewer studies have been conducted ...in young people at the early stages of disease onset. Using whole tract reconstruction techniques, the aim of this study was to identify the white matter pathology associated with the common clinical symptoms and executive function impairments observed in young people with psychosis. Methods We obtained MRI scans from young people with psychosis and healthy controls. Eighteen major white matter tracts were reconstructed to determine group differences in fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD) and then were subsequently correlated with symptomatology and neurocognitive performance. Results Our study included 42 young people with psychosis (mean age 23 yr) and 45 healthy controls (mean age 25 yr). Compared with the control group, the psychosis group had reduced FA and AD in the left inferior longitudinal fasciculus (ILF) and forceps major indicative of axonal disorganization, reduction and/or loss. These changes were associated with worse overall psychiatric symptom severity, increases in positive and negative symptoms, and worse current levels of depression. The psychosis group also showed FA reductions in the left superior longitudinal fasciculus that were associated with impaired neurocognitive performance in attention and semantic fluency. Limitations Our analysis grouped 4 subcategories of psychosis together, and a larger follow-up study comparing affective and nonaffective psychoses is warranted. Conclusion Our findings suggest that impaired axonal coherence in the left ILF and forceps major underpin psychiatric symptoms in young people in the early stages of psychosis.
Background Data on endoscopic stenting of malignant gastric outlet obstruction (GOO) are based on studies predominantly involving patients with pancreatic adenocarcinoma. Objective To compare ...survival and clinical outcome after stent placement for GOO due to pancreatic cancer compared with nonpancreatic cancer. Design Retrospective study. Setting Single tertiary hospital. Patients A total of 292 patients with malignant GOO. Intervention Stent placement. Main Outcome Measurements Post–stent placement survival and clinical outcome. Results In 196 patients with pancreatic cancer and 96 with nonpancreatic cancer, median post–stent placement survival was similar (2.7 months in pancreatic cancer vs 2.4 months in nonpancreatic cancer). Overall survival was shorter in patients with pancreatic cancer (13.7 vs 17.1 months; P = .004). Clinical success rates at 2 months (71% vs 91%) and reintervention rates (30% vs 23%) were comparable. Post–stent placement chemotherapy and the absence of distant metastasis were associated with better post–stent placement survival in both groups (pancreatic cancer: chemotherapy vs no chemotherapy, 5.4 vs 1.5 months, P < .0001; metastasis vs no metastasis, 1.8 vs 4.6, P = .005; nonpancreatic cancer: chemotherapy vs no chemotherapy, 9.2 vs 1.8, P = .001; metastasis vs no metastasis, 2.1 vs 6.1, P = .009). Limitations Retrospective study. Conclusions In this large series of patients undergoing stent placement for malignant GOO in North America, we observed no difference in post–stent placement survival despite better overall survival in patients with nonpancreatic cancer. GOO is a marker for poor survival in malignancy, regardless of the type. Chemotherapy and the absence of distant metastasis were associated with better post–stent placement survival in both groups.
Abstract Objectives To explore an alternative approach to quantifying the burden of side effects at 1 year after treatment for prostate cancer among both patients and their partners. Methods We ...analyzed data from 75 couples in the Family and Cancer Therapy Selection study. Paired patients and family members were independently asked about their willingness to pay (WTP) for a hypothetical new treatment that cures prostate cancer without side effects if they could reconsider their treatment decision by indicating the maximum amount they would be willing to pay given 11 separate “bids” ranging from $0 to $1500 per month. Descriptive and regression analyses were conducted for patients and family members controlling for sociodemographic characteristics and health status; Spearman correlations were also examined. Results Among 75 couples analyzed, the income-adjusted mean WTP estimates per month were $400.8 (standard error SE $54.3) for patients and $650.2 (SE 72.2) for family members. The WTP between patients and family members was correlated (Pearson ρ 0.30; P = 0.01). After adjusting for covariates, the adjusted mean WTP per month was $588.1 (SE 65.77) for patients and $819.4 (SE 74.33) for family members. Wanting to avoid side effects at baseline predicted higher WTP for patients ( P = 0.010). Experiencing sexual side effects was predictive of higher WTP for family members ( P = 0.047). Conclusions Fairly high WTP amounts for a hypothetical treatment without side effects suggests that patients and their partners are experiencing important burdens 1 year after treatment. The higher amounts partners are willing to pay and the correlation with sexual side effects suggest that they are perceptive of significant treatment burdens.
Abstract Rheumatoid arthritis (RA) is a long-term condition causing joint pain and swelling and sometimes systemic involvement. The aims of treatment are, first, to reduce the impact the disease has ...on a patient and, second, to halt progression of disease. The advent of intensive therapy, including biologics, has led to a major improvement in outcome. To assess treatment impact, formal outcome measures have been developed. Traditionally, these focussed on the clinical aspects such as disease activity and joint damage. More recently, there has been an increased focus on patient-related outcome measures including quality-of-life measures. These enable illness evaluation from patients’ perspectives, examination of care quality and comparison of the effectiveness and cost-effectiveness of treatment. This article examines advantages and disadvantages of the various outcome measures which are generally used in RA, with a focus on quality of life and patient-related measures.
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