Patients with cirrhosis are classified in a compensated and a decompensated stage. Portal hypertension is responsible for most of the complications of cirrhosis that mark the transition from compensated to decompensated cirrhosis. The objectives of this study were (a) to analyse survival of the different stages and substages of cirrhosis and (b) to examine the prognostic value of the hepatic venous pressure gradient (HVPG) at each of the stages.
A total of 729 patients with suspected cirrhosis underwent routine measurement of portal pressure and systemic haemodynamics between 11/1995 and 12/2004. The primary end-point of the study was death, collected until November 30th, 2006. Multivariable analysis was performed using two models to determine predictors of death at each stage.
A total of 443 patients were included in the study. The 1-year mortality was 5.4% in compensated and 20.2% in decompensated patients. Compensated patients in stage 1 (no varices) had a longer survival than stage 2 patients (varices present) (P = 0.015). In decompensated patients, survival was not different between stage 3 (ascites, with or without varices) and stage 4 (variceal haemorrhage, with or without ascites). Age and HVPG (cut-off 10 mmHg) were independent predictors of death in compensated patients, whereas MELD was in decompensated patients.
Survival rates and predictors of death are different between patients with compensated and decompensated cirrhosis. Unlike the Italian cohort staging system, ascites is a better stratifying clinical event than variceal haemorrhage in patients with decompensated cirrhosis. The presence of clinically significant portal hyper-tension has prognostic value in compensated cirrhosis.
ascites; cirrhosis; oesophageal varices; variceal haemorrhage
To investigate whether treatment initiated with an angiotensin-converting enzyme inhibitor (ACE-I) or an angiotensin II receptor blocker (ARB) for patients with ischemic heart disease, hypertension, or diabetes causes a reduction in hemoglobin (Hb) levels.
Patients and Methods
This was a retrospective cohort analysis using the computerized database of a large health maintenance organization. Included were all adults with a first purchase of an ACE-I, an ARB, or a calcium channel blocker (CCB) between January 1, 2004, and December 31, 2009, defined as the index date. Measures of Hb levels before and 1 year after the index date were reviewed, and the change was calculated. All the analyses were stratified by pharmaceutical class. The main exposure variables were the proportion of days covered (PDC) by these drugs and the mean enalapril dosage (for enalapril users only).
Levels of Hb before and after treatment were available for 14,754 patients taking ACE-Is, 751 taking ARBs, and 3087 taking CCBs. A high PDC was significantly associated with greater yearly reductions in Hb levels compared with a low PDC for CCB use, but was more pronounced for ACE-I and ARB use. A high PDC was also associated with a higher odds of developing anemia in ACE-I users (odds ratio [OR], 1.59; P<.001) and ARB users (OR, 2.21; P=.05). In nonanemic enalapril users, every 10-mg increment in daily dose was associated with an OR of 1.45 for the development of anemia (P<.001). The association remained after excluding nonadherent patients.
Levels of Hb are reduced during the first year of use of ACE-Is and to a lesser extent with use of ARBs. This association is dose dependent and is not explained by patient adherence.
ACE-I, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; CCB, calcium channel blocker; Hb, hemoglobin; IHD, ischemic heart disease; MHS, Maccabi Healthcare Services; OR, odds ratio; PDC, proportion of days covered; WHO, World Health Organization
There is now ample evidence that motor imagery (MI) contributes to enhance motor performance. Previous research also demonstrated that directing athletes’ attention to the effects of their movements on the environment is more effective than focusing on the action per se. The present study aimed therefore at evaluating whether adopting an external focus during MI contributes to enhance tennis serve performance. Twelve high-level young tennis players were included in a test-retest procedure. The effects of regular training were first evaluated. Then, players were subjected to a MI intervention during which they mentally focused on ball trajectory and specifically visualized the space above the net where the serve can be successfully hit. Serve performance was evaluated during both a validated serve test and a real match. The main results showed a significant increase in accuracy and velocity during the ecological serve test after MI practice, as well as a significant improvement in successful first serves and won points during the match. Present data therefore confirmed the efficacy of MI in combination of physical practice to improve tennis serve performance, and further provided evidence that it is feasible to adopt external attentional focus during MI. Practical applications are discussed.
Motor imagery contributes to enhance tennis serve performance.
Data provided evidence of the benefits of adopting an external focus of attention during imagery.
Results showed significant improvement in successful first serves and won points during a real match.
Movement imagery; motor performance; focus of attention; safety window
This study aimed at investigating the influence of three rackets on shoulder net joint moments, power and muscle activity during the flat tennis serve under field- conditions. A 6-camera Eagle® motion analysis system, operating at 256 Hz, captured racket and dominant upper limb kinematics of the serve in five tennis players under three racket conditions (A: low mass, high balance and polar moment, B: low three moments of inertia, and C: high mass, swingweight and twistweight). The electromyographic activity of six trunk and arm muscles was simultaneously recorded. Shoulder net joint moments and power were computed by 3D inverse dynamics. The results showed that greater shoulder joint power and internal/external rotation peak moments were found to accelerate and decelerate racket A in comparison with the racket C. Moreover, serving with the racket A resulted in less activity in latissimus dorsi muscle during the acceleration phase, and biceps brachii muscle during the follow-through phase when compared with racket C. These initial findings encourage studying the biomechanical measurements to quantify the loads on the body during play in order to reduce them, and then prevent shoulder injuries. Racket specifications may be a critical point for coaches who train players suffering from shoulder pain and chronic upper limb injuries should be considered in relation to the racket specifications of the players.
Light racket required more joint power than heavy one to achieve similar post impact ball velocity.
Serving with a light racket resulted in higher shoulder internal and external rotation moments than using a heavy one for similar performance.
Chronic shoulder pain should encourage coaches to check for potentially inappropriate racket specifications of their players.
EMG; inverse dynamics; joint power; joint moment; tennis serve
Data regarding the safety of endoscopic skull base exploration are very scarce. With this method, fragile vital structures (cranial nerves, the optic complex, brainstem, hypothalamus or cerebral ventricles) are exposed to direct illumination within a closed space. Also, high-speed drills, cauterization and ultrasonic aspiration deliver a significant load of thermal energy. The aim of this study was to record the temperature close to the structures of the skull base and in the intradural space during the procedures performed using extended endoscopic transnasal approaches.
The temperature of the skull base was continuously recorded during six transnasal endoscopic procedures. Implantable copper-constantan thermocouples were inserted: one into the esophagus and another through the nostril to reach the operative field at the skull base.
At the beginning of the procedure, the temperature of the operative field was on average 36.8 °C ± 0.80 °C, i.e. only 1 °C higher than the esophageal temperature. Then it grew continuously during the whole procedure, to eventually reach a level of 42–43 °C at the final stage, whereas the esophageal temperature remained stable. Occasionally, the temperature increased up to 45 °C during cauterization and ultrasonic aspiration, and even up to 62 °C during high-speed drilling.
Endoscopic skull base surgery is associated with an incessant increase of the temperature of the intraoperative field. The temperature can peak suddenly to levels which can potentially harm neural structures and influence the rate of postoperative complications.
Endoscopy; Transnasal; Extended approach; Cranial base; Temperature
This phase 2 study evaluated trebananib (AMG 386), an investigational peptide-Fc fusion protein that neutralises the interaction between angiopoietins-1/2 and the Tie2 receptor, plus FOLFIRI as second-line treatment for patients with metastatic colorectal cancer.
Patients had adenocarcinoma of the colon or rectum with progression within 6 months of receiving only one prior fluoropyrimidine/oxaliplatin-based chemotherapy regimen for metastatic disease. All patients received FOLFIRI and were randomised 2 : 1 to also receive intravenous trebananib 10 mg kg−1 once weekly (QW) (Arm A) or placebo QW (Arm B). The primary end point was investigator-assessed progression-free survival (PFS).
One hundred and forty-four patients were randomised (Arms A/B, n=95/49). Median PFS in Arms A and B was 3.5 and 5.2 months (hazard ratio (HR) 1.23; 95% CI, 0.81–1.86; P=0.33) and median overall survival (OS) was 11.9 and 8.8 months, respectively (HR 0.90; 95% CI; 0.53–1.54; P=0.70). Objective response rate (ORR) was 14% and 0% in Arms A and B, respectively. Incidence of grade ⩾3 adverse events was similar between treatment arms (Arm A, 61% Arm B, 65%) and included pulmonary embolism (1%/4%), deep vein thrombosis (5%/2%), and hypertension (1%/0%).
Administration of trebananib plus FOLFIRI did not prolong PFS compared with placebo plus FOLFIRI. Toxicities were manageable and consistent with those known for FOLFIRI and trebananib.
AMG 386; trebananib; angiopoietin inhibitor; metastatic colorectal carcinoma
Background: Carbohydrate binding modules (CBMs) contribute to the enzymatic degradation of complex polysaccharide structures.
Results: New CBMs display specificity for decorated glucans through an extensive hydrophobic platform that interacts with both backbone and side chain structures.
Conclusion: CBMs that bind to complex β-glucans exploit different components of these ligands as specificity determinants.
Significance: CBMs can utilize the side chains of decorated glucans as specificity determinants.
Plant biomass is central to the carbon cycle and to environmentally sustainable industries exemplified by the biofuel sector. Plant cell wall degrading enzymes generally contain noncatalytic carbohydrate binding modules (CBMs) that fulfil a targeting function, which enhances catalysis. CBMs that bind β-glucan chains often display broad specificity recognizing β1,4-glucans (cellulose), β1,3-β1,4-mixed linked glucans and xyloglucan, a β1,4-glucan decorated with α1,6-xylose residues, by targeting structures common to the three polysaccharides. Thus, CBMs that recognize xyloglucan target the β1,4-glucan backbone and only accommodate the xylose decorations. Here we show that two closely related CBMs, CBM65A and CBM65B, derived from EcCel5A, a Eubacterium cellulosolvens endoglucanase, bind to a range of β-glucans but, uniquely, display significant preference for xyloglucan. The structures of the two CBMs reveal a β-sandwich fold. The ligand binding site comprises the β-sheet that forms the concave surface of the proteins. Binding to the backbone chains of β-glucans is mediated primarily by five aromatic residues that also make hydrophobic interactions with the xylose side chains of xyloglucan, conferring the distinctive specificity of the CBMs for the decorated polysaccharide. Significantly, and in contrast to other CBMs that recognize β-glucans, CBM65A utilizes different polar residues to bind cellulose and mixed linked glucans. Thus, Gln106 is central to cellulose recognition, but is not required for binding to mixed linked glucans. This report reveals the mechanism by which β-glucan-specific CBMs can distinguish between linear and mixed linked glucans, and show how these CBMs can exploit an extensive hydrophobic platform to target the side chains of decorated β-glucans.
Carbohydrate-binding Protein; Isothermal Titration Calorimetry; Plant Cell Wall; Protein Structure; X-ray Crystallography
We reported that Notch-1, a potent breast oncogene, is activated in response to trastuzumab and contributes to trastuzumab resistance in vitro. We sought to determine the preclinical benefit of combining a Notch inhibitor (γ-secretase inhibitor (GSI)) and trastuzumab in both trastuzumab-sensitive and trastuzumab-resistant, ErbB-2-positive, BT474 breast tumours in vivo. We also studied if the combination therapy of lapatinib plus GSI can induce tumour regression of ErbB-2-positive breast cancer.
We generated orthotopic breast tumour xenografts from trastuzumab- or lapatinib-sensitive and trastuzumab-resistant BT474 cells. We investigated the antitumour activities of two distinct GSIs, LY 411 575 and MRK-003, in vivo.
Our findings showed that combining trastuzumab plus a GSI completely prevented (MRK-003 GSI) or significantly reduced (LY 411 575 GSI) breast tumour recurrence post-trastuzumab treatment in sensitive tumours. Moreover, combining lapatinib plus MRK-003 GSI showed significant reduction of tumour growth. Furthermore, a GSI partially reversed trastuzumab resistance in resistant tumours.
Our data suggest that a combined inhibition of Notch and ErbB-2 signalling pathways could decrease recurrence rates for ErbB-2-positive breast tumours and may be beneficial in the treatment of recurrent trastuzumab-resistant disease.
ErbB-2; trastuzumab; Notch-1; GSI; recurrence; resistance
We investigated the status of estrogen receptor alpha (ERα), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) in primary tumor and in the corresponding brain metastases in a consecutive series of breast cancer patients. Additionally, we studied factors potentially influencing conversion and evaluated its association with survival.
The study group included 120 breast cancer patients. ERα, PR, and HER2 status in primary tumors and in matched brain metastases was determined centrally by immunohistochemistry and/or fluorescence in situ hybridization.
Using the Allred score of ≥ 3 as a threshold, conversion of ERα and PR in brain metastases occurred in 29% of cases for both receptors, mostly from positive to negative. Conversion of HER2 occurred in 14% of patients and was more balanced either way. Time to brain relapse and the use of chemotherapy or trastuzumab did not influence conversion, whereas endocrine therapy induced conversion of ERα (P = 0.021) and PR (P = 0.001), mainly towards their loss. Receptor conversion had no significant impact on survival.
Receptor conversion, particularly loss of hormone receptors, is a common event in brain metastases from breast cancer, and endocrine therapy may increase its incidence. Receptor conversion does not significantly affect survival.
Caenorhabditis elegans sarcomeres have been studied extensively utilizing both forward and reverse genetic techniques to provide insight into muscle development and the mechanisms behind muscle contraction. A previous genetic screen investigating early muscle development produced 13 independent mutant genes exhibiting a Pat (paralyzed and arrested elongation at the two-fold length of embryonic development) muscle phenotype. This study reports the identification and characterization of one of those genes, pat-9.
Positional cloning, reverse genetics, and plasmid rescue experiments were used to identify the predicted C. elegans gene T27B1.2 (recently named ztf-19) as the pat-9 gene. Analysis of pat-9 showed it is expressed early in development and within body wall muscle lineages, consistent with a role in muscle development and producing a Pat phenotype. However, unlike most of the other known Pat gene family members, which encode structural components of muscle attachment sites, PAT-9 is an exclusively nuclear protein. Analysis of the predicted PAT-9 amino acid sequence identified one putative nuclear localization domain and three C2H2 zinc finger domains. Both immunocytochemistry and PAT-9::GFP fusion expression confirm that PAT-9 is primarily a nuclear protein and chromatin immunoprecipitation (ChIP) experiments showed that PAT-9 is present on certain gene promoters.
We have shown that the T27B1.2 gene is pat-9. Considering the Pat-9 mutant phenotype shows severely disrupted muscle attachment sites despite PAT-9 being a nuclear zinc finger protein and not a structural component of muscle attachment sites, we propose that PAT-9 likely functions in the regulation of gene expression for some necessary structural or regulatory component(s) of the muscle attachment sites.
Sarcomere; Muscle; Zinc finger; Pat
Introduction. Different anthropometric variables have been shown to be related to cardiovascular morbidity and mortality. Our aim was to compare the association between different anthropometric measurements and inflammatory status. Methods and results. A cross-sectional study design in which we analyzed the data collected during a five-year period in the Tel Aviv Medical Center Inflammation Survey (TAMCIS). Included in the study were 13,033 apparently healthy individuals at a mean (SD) age of 43. Of these, 8,292 were male and 4,741 female. A significant age-adjusted and multiple-adjusted partial correlation was noted between all anthropometric measurements and all inflammatory biomarkers. There was no significant difference in the correlation coefficients between different biomarkers and anthropometric variables. Conclusion. Most of the common used anthropometric variables are similarly correlated with inflammatory variables. The clinician can choose the variable that he/she finds easiest to use.
The definition of “genetic testing” is not a simple matter, and the term is often used with different meanings. The purpose of this work was the collection and analysis of European (and other) legislation and policy instruments regarding genetic testing, to scrutinise the definitions of genetic testing therewith contained the following: 60 legal documents were identified and examined—55 national and five international ones. Documents were analysed for the type (context) of testing and the material tested and compared by legal fields (privacy and confidentiality, data protection, biobanks, insurance and labour law, forensic medicine); some instruments are very complex and deal with various legal fields at the same time. There was no standard for the definitions used, and different approaches were identified (from wide general, to some very specific and technically based). Often, legal documents did not contain any definitions, and many did not distinguish between genetic testing and genetic information. Genetic testing was more often defined in non-binding legal documents than in binding ones. Definitions are core elements of legal documents, and their accuracy and harmonisation (particularly within a particular legal field) is critical, not to compromise their enforcement. We believe to have gathered now the evidence for adopting the much needed differentiation between (a) “clinical genetics testing”, (b) “genetics laboratory-based genetic testing” and (c) “genetic information”, as proposed before.
Electronic supplementary material
The online version of this article (doi:10.1007/s12687-012-0077-1) contains supplementary material, which is available to authorized users.
Legislation; Definition; Genetic test; Genetic information; EuroGentest
To strengthen existing evidence on the role of neighborhoods in chronic disease onset in later life, we investigated associations between multiple neighborhood features and 2-year onset of 6 common conditions using a national sample of older adults.
Neighborhood features for adults aged 55 years or older in the 2002 Health and Retirement Study were measured by use of previously validated scales reflecting the built, social, and economic environment. Two-level random-intercept logistic models predicting the onset of heart problems, hypertension, stroke, diabetes, cancer, and arthritis by 2004 were estimated.
In adjusted models, living in more economically disadvantaged areas predicted the onset of heart problems for women (odds ratio [OR]=1.20; P<.05). Living in more highly segregated, higher-crime areas was associated with greater chances of developing cancer for men (OR=1.31; P<.05) and women (OR=1.25; P<.05).
The neighborhood economic environment is associated with heart disease onset for women, and neighborhood-level social stressors are associated with cancer onset for men and women. The social and biological mechanisms that underlie these associations require further investigation.
The diagnostic process and the surgical procedures in patients with snoring and obstructive sleep apnea syndrome (OSAS) are crucial. The aim of this study was to assess the efficacy of surgical treatment in snoring and OSAS patients.
A precise laryngological examination and screening polysomnography (Poly-Mesam) were performed in all patients with mild, moderate and severe OSAS before and 6 months after surgery. The patients completed questionnaires concerning their complaints. We included patients qualified to septoplasty, laser-assisted uvulopalatoplasty (LAUP), uvulopalatopharyngoplasty (UPPP) and radiofrequency-induced thermotherapy of the tongue base (RITT). Outcome evaluation of surgery was performed on the basis of data received from follow-up laryngological examinations, selected parameters obtained from the Poly-Mesam test and follow-up questionnaires.
In most cases we observed improvement, defined as decreasing some sleep parameters, such as a respiratory disturbance index (RDI), by more than 50%, decreasing the loudness of snoring, decreasing the number of hypopneas, and obtaining better blood saturation values. After UPPP we noticed changes in retropalatal space, soft palate dimensions and uvula-posterior pharyngeal wall distance. In the postoperative period we did not observe severe complications. In some cases we found short-lived palatal deficiency after UPPP. Patients after RITT experienced discomfort and throat pain lasting from 2 to 4 days. In 2 patients we observed swelling of the tongue base, which decreased after few days.
Surgery in OSAS contributes to normalization of some sleep parameters. The majority of patients experienced improvement after surgery.
snoring; sleep apnea syndrome; septoplasty; uvulopalatoplasty; uvulopalatopharyngoplasty; radiofrequency-induced thermotherapy
Lysosomal exoglycosidases, such as α-mannosidases (MAN) and β-galactosidases (GAL), are found in different glycoside hydrolase sequence-based families. Considerable research has proved plays the role of MAN, which play a key role in the modification and diversification of hybrid N-glycans, processes with strong cellular links to cancer. Therefore the study aim was to investigate the activities of MAN and GAL in larynx cancer compared to controls.
Material and methods
Larynx cancer (n = 21) and normal healthy tissue (n = 21) were collected from patients during total laryngectomy. A biopsy of macroscopically healthy tissue in the area of the lower 1/3 of omohyoid muscle was taken for frozen sections in each case and these served as controls. The release of p-nitrophenol from p-nitrophenol derivatives of MAN and GAL was used.
In all specimens we observed significantly higher activity of investigated enzymes in larynx cancer compared with controls. The mean release of MAN from activated cells was 3.702 ±1.3245 nkat/g wet tissue compared to controls (1.614 ±0.8220 nkat/g wet tissue). The mean release of GAL from the activated cells was 3.383 ±2.1980 nkat/g wet tissue compared to controls (2.137 ±1.3685 nkat/g wet tissue). Differences in observed activity were statistically significant.
The present data indicate that MAN and GAL are significantly and consistently elevated in larynx cancer growth. It also means that catabolic reactions involving glycoproteins, glycolipids and proteoglycans may play a role in larynx cancer. Further research should also evaluate the relative importance of these particular exoglycosidases in indicating the progress of the disease in considering the spectrum of identified marker mediators.
α-mannosidase; β-galactosidase; laryngeal cancer; exoglycosidase activity
To explore the influence of the communities in which Hispanics live on their access to health care.
1996–2002 Medical Expenditure Panel Survey data, linked to secondary data sources and including 14,504 observations from 8,371 Mexican American respondents living in metropolitan areas.
We use multivariate probit regression models, stratified by individuals' insurance status, for analyses of four dependent variables measuring access to health care. We measure community characteristics at the zip code tabulation area level, and key independent variables of interest are the percentage of the population that speaks Spanish and percentage of the population that is immigrant Hispanic. Each of these measures is interacted with individual-level measures of nativity and length of U.S. residency.
For Mexican American immigrants, living in an area populated by relatively more Spanish speakers or more Hispanic immigrants is associated with better access to care. The associations are generally stronger for more recent immigrants compared with those who are better established. Among U.S.-born Mexican Americans who are uninsured, living in areas more heavily populated with Spanish-speaking immigrants is negatively associated with access to care.
The results suggest that characteristics of the local population, including language and nativity, play an important role in access to health care among U.S. Hispanics, and point to the need for further study, including analyses of other racial and ethnic groups, using different geographic constructs for describing the local population, and, to the extent possible, more specific exploration of the mechanisms through which these characteristics may influence access to care.
Access; insurance; immigrant; Hispanic; community
Women with triple-negative breast cancer have the worst prognosis, frequently present with metastatic tumors and have few targeted therapy options. Notch-1 and Notch-4 are potent breast oncogenes that are overexpressed in triple-negative and other subtypes of breast cancer. PEA3, an ETS transcription factor, is also overexpressed in triple-negative and other breast cancer subtypes. We investigated whether PEA3 could be the critical transcriptional activator of Notch receptors in MDA-MB-231 and other breast cancer cells.
Real-time PCR and Western blot analysis were performed to detect Notch-1, Notch-2, Notch-3 and Notch-4 receptor expression in breast cancer cells when PEA3 was knocked down by siRNA. Chromatin immunoprecipitation was performed to identify promoter regions for Notch genes that recruited PEA3. TAM-67 and c-Jun siRNA were used to identify that c-Jun was necessary for PEA3 enrichment on the Notch-4 promoter. A Notch-4 luciferase reporter was used to confirm that endogenous PEA3 or AP-1 activated the Notch-4 promoter region. Cell cycle analysis, trypan blue exclusion, annexin V flow cytometry, colony formation assay and an in vivo xenograft study were performed to determine the biological significance of targeting PEA3 via siRNA, Notch signaling via a γ-secretase inhibitor, or both.
Herein we provide new evidence for transcriptional regulation of Notch by PEA3 in breast cancer. PEA3 activates Notch-1 transcription in MCF-7, MDA-MB-231 and SKBr3 breast cancer cells. PEA3 activates Notch-4 transcription in MDA-MB-231 cells where PEA3 levels are endogenously high. In SKBr3 and BT474 breast cancer cells where PEA3 levels are low, overexpression of PEA3 increases Notch-4 transcripts. Chromatin immunoprecipitation confirmed the enrichment of PEA3 on Notch-1 and Notch-4 promoters in MDA-MB-231 cells. PEA3 recruitment to Notch-1 was AP-1-independent, whereas PEA3 recruitment to Notch-4 was c-JUN-dependent. Importantly, the combined inhibition of Notch signaling via a γ-secretase inhibitor (MRK-003 GSI) and knockdown of PEA3 arrested growth in the G1 phase, decreased both anchorage-dependent and anchorage-independent growth and significantly increased apoptotic cells in vitro. Moreover, either PEA3 knockdown or MRK-003 GSI treatment significantly reduced tumor growth of MDA-MB-231 xenografts in vivo.
Taken together, the results from this study demonstrate for the first time that Notch-1 and Notch-4 are novel transcriptional targets of PEA3 in breast cancer cells. Targeting of PEA3 and/or Notch pathways might provide a new therapeutic strategy for triple-negative and possibly other breast cancer subtypes.
To determine whether Medicare enrollment at age 65 has an effect on the health trajectory of the near-elderly uninsured.
Eight biennial waves (1992–2006) of the Health and Retirement Study, a nationally representative panel survey of noninstitutionalized 51–61 year olds and their spouses.
We use a quasi-experimental approach to compare the health effects of insurance for the near-elderly uninsured with previously insured contemporaneous controls. The primary outcome measure is overall self-reported health status combined with mortality (i.e., excellent to very good, good, fair to poor, dead).
The change in the trajectory of overall health status for the previously uninsured that can be attributed to Medicare is small and not statistically significant. For every 100 persons in the previously uninsured group, joining Medicare is associated with 0.6 fewer in excellent or very good health (95 percent CI: −4.8, 3.3), 0.3 more in good health (95 percent CI: −3.8, 4.1), 2.5 fewer in fair or poor health (95 percent CI: −7.4, 2.3), and 2.8 more dead (−4.0, 10.0) by age 73. The health trajectory patterns from physician objective health measures are similarly small and not statistically significant.
Medicare coverage at age 65 for the previously uninsured is not linked to improvements in overall health status.
Uninsured; Medicare; health insurance; health status
Isolated sphenoid sinus pathologies are relatively rare. In the majority of cases, symptoms do not arise in the early stages of the disease or are non-specific, therefore making diagnosis difficult. The aim of this study was to investigate the diagnostic process and the reasons for development of complications in patients with isolated sphenoid sinus pathology.
The clinical data and observation charts of 32 patients were investigated to determine how long the main symptoms of sphenoid pathology had been present before the patients were referred for medical treatment, and the time that elapsed from the first ambulatory medical assessment to the initial diagnosis.
Complaints and symptoms of sphenoid sinus pathology had been present for 10.2 months before the diagnosis was established. Although the duration of complaints in “ORL” (diagnosed by otorhinolaryngologist) and “non-ORL” (diagnosed by other specialists) group of patients was similar (10.8 and 9.5 months on average, respectively), unexpectedly, in the “non-ORL” group of patients, the time necessary for making the initial diagnosis was actually shorter than in the “ORL” group (1.8 vs 4.1 months). At the time of hospital admission, endoscopic examination revealed no abnormalities in 31.2% of patients. In 28.1% of patients the pathological process in the sphenoid sinus was diagnosed only after the onset of complications.
The occult character of the disease and the lack of severe and specific symptoms, rather than the delay in getting extensive diagnostic tests, are responsible for the delayed diagnosis and treatment.
sphenoiditis; isolated lesion; complications
Microtubules with long polyglutamylated C-terminal tails are more prone to severing by spastin, establishing the importance of tubulin posttranslational modifications.
Posttranslational glutamylation of tubulin is present on selected subsets of microtubules in cells. Although the modification is expected to contribute to the spatial and temporal organization of the cytoskeleton, hardly anything is known about its functional relevance. Here we demonstrate that glutamylation, and in particular the generation of long glutamate side chains, promotes the severing of microtubules. In human cells, the generation of long side chains induces spastin-dependent microtubule disassembly and, consistently, only microtubules modified by long glutamate side chains are efficiently severed by spastin in vitro. Our study reveals a novel control mechanism for microtubule mass and stability, which is of fundamental importance to cellular physiology and might have implications for diseases related to microtubule severing.
The use of predictive genetic tests is expanding rapidly. Given limited health care budgets and few national coverage decisions specifically for genetic tests, evidence of benefits and harms is a key requirement in decision making; however, assessing the benefits and harms of genetic tests raises a number of challenging issues. Frequently, evidence of medical benefits and harms is limited due to practical and ethical limitations of conducting meaningful clinical trials. Also, clinical endpoints frequently do not capture the benefit appropriately because the main purpose of many genetic tests is personal utility of knowing the test results, and costs of the tests and counseling can be insufficient indicators of the total costs of care. This study provides an overview of points to consider for the assessment of benefits and harms from genetic tests in an ethically and economically reflected manner. We discuss whether genetic tests are sufficiently exceptional to warrant exceptional methods for assessment and appraisal.
Resource allocation; Genetic testing; Costs and cost analysis
Data for predicting which patients with pandemic influenza A (H1N1) infection are likely to run a complicated course are sparse. We retrospectively studied whether the admission serum C-reactive protein (CRP) levels can serve as a predictor of illness severity.
Included were all consecutive adult patients who presented to the emergency department (ED) between May-December, 2009 with a flu-like illness, a confirmed diagnosis of pandemic influenza A (H1N1) infection and a serum CRP level measured within 24 hours of presentation. Patients with a proven additional concurrent acute illness (e.g., bacteremia) were excluded. We used the ROC curve analysis, Kaplan-Meier curves and the Cox proportional hazard model to evaluate the predictive ability of CRP as a prognostic factor.
Seventeen (9%) of the 191 enrolled patients were admitted to the intensive care unit (ICU), of whom eight (4%) required mechanical ventilation and three (2%) died. The median admission serum CRP levels were significantly higher among patients who required subsequent ICU care and mechanical ventilation than among patients who did not (123 mg/L and 112 mg/L vs. 40 mg/L, p < .001 and 43 mg/L, p = .017, respectively). A Cox proportional hazard model identified admission serum CRP levels and auscultatory findings over the lungs as independent prognostic factors for ICU admission. Admission serum CRP levels were the only independent prognostic factor for mechanical ventilation. Thirty days after presenting to the ED, none of the patients with admission serum CRP level <28 mg/L (lower tertile) required either ICU admission or mechanical ventilation. At the same time point, 19% of the patients with admission serum CRP level ≥70 mg/L (upper tertile) needed to be admitted to the ICU and 8% of the same upper tertile group required mechanical ventilation. The differences in the rates between the lower vs. upper tertile groups were significant (Log-Rank p < .001 for ICU and p < .024 for mechanical ventilation).
In our study group, serum CRP levels obtained in the early ED admission stage from patients presenting with pandemic H1N1 influenza A infection were found to serve as a useful gauge for predicting disease course and assisting in patient management.
Objective and background
To explore the possibility that increased resting heart rate (HR) is associated with a microinflammatory response. Such an association could explain, at least in part, the recently described worse cardiovascular prognosis in individuals with increased HR.
Concentrations of fibrinogen and high‐sensitivity C‐reactive protein, as well as the absolute number of polymorphonuclear leucocytes, were analysed in a cohort of 4553 apparently healthy men and in those with atherothrombotic risk factors.
Following adjustment for age and body mass index, lipid profile and cardiovascular risk factors, a significant (p<0.001) difference was noted between individuals in the first quintile of HR (⩽58 beats/min) and those in the fifth quintile (⩾79 beats/min) regarding all the above‐mentioned inflammatory biomarkers, the respective mean values being 7.38 and 8.11 μmol/l, 1.12 and 1.61 mg/l, and 4.23 and 4.74×109/l.
Resting HR is associated with a microinflammatory response in apparently healthy men and in those with atherothrombotic risk factors. Sympathetic activation might be a common factor explaining such an association. If confirmed in additional studies, this association might be a relevant target for therapeutic manipulations.