Novel parameters indicate significant differences in severity of obstructive sleep apnea with patients having similar apnea–hypopnea index

Sleep apnea–hypopnea syndrome (SAHS) causes impairment of daytime functions and increases risk of cardiovascular diseases. Apnea–hypopnea index (AHI), currently used for the estimation of the severity of SAHS, does not contain information on the morphology or duration aspects of the breathing cessations and related oxygen desaturations. Longer breathing cessations and deeper desaturations may have more severe consequences than shorter and shallower ones. To address these issues, novel parameters containing information on the duration and morphology of breathing cessations and oxygen desaturations were calculated and evaluated on 160 male patients (40 patients in normal, mild, moderate and severe AHI severity categories). Obstruction and desaturation duration parameters consist of sum of event durations normalized with the total analysed time. Desaturation severity is a sum of desaturation event areas normalized with total analysed time and obstruction severity parameter is a sum of the products of apnea and hypopnea durations and related desaturation areas normalized with total analysed time. The median follow-up time of the patients was 183 months (range 154–215 months). The 40 patients in each category were further divided into subgroups A and B with lowest and highest novel parameter values, respectively. AHI showed no differences between the subgroups. Mortality was increased in subgroups B compared to subgroups A. The correlation of the novel parameters with AHI was only moderate and the parameter values were partially overlapping between the AHI severity categories. This suggests that patients with similar AHI may in fact suffer from SAHS of very different severity. Thus, the present results suggest that the novel parameters could bring new insight to the individual estimation of the severity of SAHS.     

In search of a cut-off apnea–hypopnea index in type 3 home portable monitors to diagnose and treat obstructive sleep apnea: a mathematical simulation

The American Academy of Sleep Medicine (AASM) uses similar apnea–hypopnea index (AHI) cut-off values to diagnose and define severity of sleep apnea independent of the technique used: in-hospital polysomnography (PSG) or type 3 portable monitoring (PM). Taking into account that PM theoretically might underestimate the AHI, we explored whether a lower cut-off would be more appropriate. We performed mathematical re-calculations on the diagnostic PSG-AHI (scored using AASM 1999 rules) of 865 consecutive patients with an AHI of ≥20 events/h who started continuous positive airway pressure (CPAP). For a PSG-AHI of ≥15 events/h re-scored using AASM 2012 rules (PSG-AHI^AASM2012), a PM-respiratory event index (REI)^AASM2012 cut-off point of ≥15 events/h resulted in a post-test probability of 100% of having the disease, but with negative tests in 57.1%. A PM-REI^AASM2012 cut-off of 8 events/h, still resulted in a positive post-test probability of 100% but with negative tests in only 34.3%. Combination of the cut-off values with clinical estimation of being ‘at high risk’ based on Epworth Sleepiness Scale (ESS) and Berlin Questionnaire scores only resulted in a small reduction in the percentage of negative tests (respectively 52.7% and 32.7%). After 6 months, CPAP adherence was not lower using the PM-REI^{AASM 2012} cut-off ≥8 events/h in comparison to ≥15 events/h (median 5.7 vs. 5.8 h/night, p = 0.368) and the reduction in ESS was similar too (median –4 and –5 points, p = 0.083). Consequently, using a lower PM-REI^AASM2012 cut-off could result in cost savings because of less negative studies and lesser need for a confirmatory PSG or a performance of a CPAP trial.     

Clinical relevance of genotype–phenotype correlations beyond vascular events in a cohort study of 1500 Marfan syndrome patients with FBN1 pathogenic variants

PurposeMarfan syndrome (MFS) is a connective tissue disorder in which several systems are affected with great phenotypic variability. Although known to be associated with pathogenic variants in the FBN1 gene, few genotype–phenotype correlations have been found in proband studies only.MethodsIn 1,575 consecutive MFS probands and relatives from the most comprehensive database worldwide, we established survival curves and sought genotype–phenotype correlations.ResultsA risk chart could be established with clinical and genetic data. Premature termination codon variants were not only associated with a shorter life expectancy and a high lifelong risk of aortic event, but also with the highest risk of severe scoliosis and a lower risk for ectopia lentis (EL) surgery. In-frame variants could be subdivided according to their impact on the cysteine content of fibrillin-1 with a global higher severity for cysteine loss variants and the highest frequency of EL surgery for cysteine addition variants.ConclusionThis study shows that FBN1 genotype–phenotype correlations exist for both aortic and extra-aortic features. It can be used for optimal risk stratification of patients with a great importance for genetic counseling and personalized medicine. This also provides additional data for the overall understanding of the role of fibrillin-1 in various organs.     

Is CONUT score a prognostic index in patients with diffuse large cell lymphoma?

Background/aimThe aim of the study was to evaluate the effect of Controlling Nutritional Status (CONUT) score on the prognosis in patients with diffuse large B-cell lymphoma (DLBCL). Materials and methods The present study was a retrospective study. The CONUT score was calculated based on serum albumin, total cholesterol and lymphocyte levels. This study included a total of 266 patients, 131 (49.2%) were female and 135 (50.8%) were male. The median follow-up period was 51 months (range: 1–190).Results The median age was 64 years. The cut off CONUT was 1.5. There was a significant difference between patients with high (≥ 2) or low (< 2) CONUT scores in terms of overall survival (OS) and progression-free survival (PFS). The 5-year OS and PFS in patients with high CONUT score was 52.1% and 49.7%. The 5-year OS and PFS in patients with low CONUT score was 79.8% and 75.6% (p < 0.001). In the multivariate analysis for OS, age ≥ 65 years (HR = 1.80, p = 0.028), Eastern Cooperative Oncology Group (ECOG) > 1 (HR = 2.04, p = 0.006), stage IIIA–IVB disease (HR = 2.75, p = 0.001) and the CONUT score (HR = 1.15, p = 0.003) were found statistically significant. In the multivariate analysis for PFS, age ≥ 65 years (HR = 2.02, p = 0.007), stage IIIA–IVB disease (HR = 2.42, p = 0.002) and the CONUT score (HR = 1.19, p = 0.001) were found to be significant parameters. ConclusionHigh CONUT score reduces OS and PFS in DLBCL. CONUT score is an independent, strong prognostic index in patients with DLBCL.     

Worrying in the wings? Negative emotional birth memories in mothers and fathers show similar associations with perinatal mood disturbance and delivery mode

Archives of Women's Mental Health - Negative birth experiences can lead to symptoms of post-traumatic stress disorder in new mothers but have received much less attention in new fathers. A...     

Globulin–platelet model predicts significant fibrosis and cirrhosis in CHB patients with high HBV DNA and mildly elevated alanine transaminase levels

The globulin–platelet model (GP) is a new noninvasive liver fibrosis model developed in chronic hepatitis B (CHB) patients. This study aimed to evaluate the diagnostic performance of GP model for liver fibrosis and cirrhosis in CHB patients with high HBV DNA and mildly elevated alanine transaminase (ALT) levels. We enrolled 316 CHB patients with HBV DNA ≥ 4 log 10 copies/mL and 40 IU/L < ALT ≤ 80 IU/L. The GP, aspartate transaminase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4) were calculated. Using liver histology as a gold standard, the diagnostic performances of noninvasive fibrosis models were compared by the area under receiver operating characteristic curves (AUROCs). Of 316 patients, 146 (46.2%), 64 (20.3%) and 40 (12.7%) were classified as having significant fibrosis, severe fibrosis and cirrhosis, respectively. To predict significant fibrosis, the AUROC of GP was lower than APRI (0.64 vs 0.76, p < 0.001) and equivalent to FIB-4 (0.64 vs 0.66, p = 0.366). To predict severe fibrosis, the AUROC of GP was equivalent to APRI (0.82 vs 0.79, p = 0.409) and FIB-4 (0.82 vs 0.77, p = 0.224). To predict cirrhosis, the AUROC of GP was higher than APRI (0.91 vs 0.84, p = 0.033) and FIB-4 (0.91 vs 0.80, p = 0.004). GP is a more accurate noninvasive fibrosis model than APRI and FIB-4 to diagnose cirrhosis in CHB patients with high HBV DNA and mildly elevated ALT levels. The clinical application of GP model may reduce the need for liver biopsy in CHB patients.     

Does the presence of a current psychiatric disorder in AIDS patients affect the initiation of antiretroviral treatment and duration of therapy?

BACKGROUND: Psychiatric disorders are common in HIV patients, and previous work suggests that these patients experience delays in treatment with highly active antiretroviral therapy (HAART). We investigated whether a current psychiatric disorder (1) affected the time to initiation of HAART, (2) predicted the likelihood of being prescribed HAART for at least 6 months, and (3) affected survival in urban AIDS patients. METHODS: We conducted a retrospective cohort study of AIDS patients with no prior history of HAART who were enrolled and followed at the Johns Hopkins University HIV clinic between January 1996 and January 2002. Patients were stratified based on the presence of a psychiatric disorder. Cox proportional hazards regression models estimated the relative risk of receiving HAART and survival, whereas multivariate logistic regression models estimated the relative odds of remaining on HAART. RESULTS: During the study period, 549 patients with AIDS and no prior antiretroviral treatment were enrolled in the clinic. Eighteen percent (n = 100) were defined as having a current psychiatric disorder, 39% (n = 215) were defined as having no psychiatric disorder, and 43% (n = 34) were indeterminate. Patients with a psychiatric disorder were 37% more likely to receive HAART (Cox adjusted hazard ratio [95% confidence interval (CI)]: 1.37 [1.01-1.87]), had greater than twice the odds of being prescribed HAART for at least 6 months (adjusted odds ratio [95% CI]: 2.14 [1.24-3.69]), and were 40% more likely to survive (Cox adjusted hazard ratio [95% CI]: 0.61[0.37-0.99]) as compared with those without a psychiatric disorder. CONCLUSION: Patients with psychiatric disorders are receiving HAART and are able to reap the survival benefit by remaining on it.     

IFN-α-based treatment of patients with chronic HCV show increased levels of cells with myeloid-derived suppressor cell phenotype and of IDO and NOS

Introduction: Hepatitis C virus (HCV) infection causes chronic hepatitis, which is often associated with suppressed anti-HCV immune responses. We have recently reported accumulation of myeloid-derived suppressor cells (MDSCs) and suppressed immunity in cancer patients.

Aim: The main aim of this study was to determine whether chronic HCV patients harbor high of MDSCs in general and in nonresponders to IFN-based therapy in particular as well as to analyze the immune suppressive molecules.

Methods: Peripheral blood samples withdrawn from 154 patients with chronic HCV infection and were categorized into responders and nonresponders based on viral titer upon IFN-α treatment.

Results: The relative and absolute numbers of MDSCs defined as Lin^?/HLA-DR^?/CD33⁺/CD11b⁺ increased in all HCV patients, where they were higher in nonresponders than in responders. Additionally, the levels of MDSCs after 4–6 months of treatment in responders were lower than during the course of treatment. The responders also showed higher levels of IL-2 coincided with increased numbers of dendritic cells (DCs), CD4⁺ and CD8⁺ T cells. The levels of total NOS and IDO were also higher in nonresponders as compared to responders and healthy controls, while the expression levels of CD3ζ was lower in responders as compared to nonresponders and healthy volunteers.

Conclusion: Chronic HCV patients harbor high numbers of MDSCs, which are higher in nonresponders than in responders. The higher numbers of MDSCs associated with increases in the suppressing factors.     

Genetic variation and significant association of polymorphism rs7700944 G>A of TIM-4 gene with rheumatoid arthritis susceptibility in Chinese Han and Hui populations

The T‐cell immunoglobulin and mucin domains 1 (TIM‐1) and 3 (TIM‐3) have been shown to be associated with susceptibility to rheumatoid arthritis (RA) in many ethnicities. In this study, we investigated the rs7700944 polymorphism of the intron region of TIM‐4 gene in Chinese Han and Hui populations, with and without RA in Ningxia Hui Autonomous Region of China. Our results demonstrated genetic variations of the TIM‐4 gene, along with significantly different distributions of genotypes and alleles at rs7700944 site in these two populations, with or without RA (P < 0.01). In addition, a strong association between the polymorphism with RA susceptibility was found in the studies of Chinese Han and Hui ethnic groups (P < 0.01), although the risk genotype contributed to RA susceptibility was different between the Han and Hui groups (P < 0.01). The AG was the risk genotype for RA in Han population, while GG was the risk genotype at rs7700944 site of TIM‐4 gene in Hui ethnicity. In addition to the genotype, the risk alleles of this single nucleotide polymorphism for RA in these two populations were also different, individuals with A allele was more susceptible to RA in Chinese Han [odds ratio (OR) = 1.930; 95% CI 1.412, 2.636; P < 0.01], but the risk allele in Hui was G in this study (OR = 1.823; 95% CI 1.330, 2.498; P < 0.01). These findings strongly suggest that polymorphism of rs7700944 of TIM‐4 may be a potential genetic variant among distinguished populations, as well as an important genetic factor associated with the RA susceptibility in many ethnicities.     

Autoimmune hepatitis in patients with primary Sj?gren's syndrome: a series of two-hundred and two patients

Based on the revised criteria of the American-European Consensus Group, we retrospectively established the diagnosis of primary or secondary Sjögren''s syndrome for 202 patients referred to a Sjögren''s syndrome clinic. Of these, 58 patients and 8 patients fulfilled criteria for primary and secondary Sjögren''s syndrome, respectively. Of the 58 patients with primary Sjögren''s syndrome, one (1.7%) had definite autoimmune hepatitis, as defined by the International Autoimmune Hepatitis Group diagnostic criteria. One additional symptomatic patient who did not fulfill criteria for primary Sjögren''s syndrome had definite autoimmune hepatitis. None of the patients with secondary Sjögren''s syndrome had definite autoimmune hepatitis. Two (1%) of the 194 patients with primary Sjögren''s syndrome or clinical symptoms had primary biliary cirrhosis. These values are lower than those reported by prior studies with smaller patient populations and likely represent a more accurate estimate of the true prevalence of these diseases in patients with primary Sjögren''s syndrome.     

Is gender a factor in psychiatrists' evaluation and treatment of patients with major depression?

BACKGROUND: Gender differences in clinical assessment and treatment have been reported in several areas of medicine. We examine whether differences exist in the routine outpatient psychiatric management of men and women with major depression. METHODS: Psychiatrists practicing in the community completed case forms on a systematic sample of their adult outpatients with major depression. Comparisons are presented between male (n=261) and female (n=472) patients focusing on their background characteristics, clinical presentation, assessment, and treatment. Significant gender disparities in assessment and treatment are also examined with respect to the gender of the treating psychiatrist. RESULTS: Although male and female patients had generally similar clinical profiles, a significantly greater proportion of males than females had psychomotor retardation and substance use disorders. No significant gender differences were observed in the assessment of depressive symptoms, psychiatric comorbidities, and treatment with antidepressant medications or psychotherapy. However, a significantly smaller percentage of depressed women than men received assessments of sexual function and medication-related sexual side effects. Female patients were also less likely to have discussed their treatment preferences with their psychiatrists. LIMITATIONS: Only a minority (33.2%) of psychiatrists invited to participate contributed patients to this study. The results are based on structured assessments completed by practicing psychiatrists rather than patient self-assessments or independent research assessments. CONCLUSIONS: Although we find overall little evidence of gender bias in the clinical management of major depression, both male and female psychiatrists need to further explore sexual function and treatment preferences in female patients.     

A comparison of efficacy and safety of 2-year telbivudine and entecavir treatment in patients with chronic hepatitis B: a match–control study

There are limited data comparing the clinical outcomes between telbivudine and entecavir. We consecutively enrolled 115 telbivudine-naive and 115 entecavir-naive chronic hepatitis B patients, who were matched for age, sex, hepatitis B e antigen (HBeAg) status and cirrhosis, and treated for at least 2 years or less than 2 years but had developed resistance. Except for the rate of HBeAg seroconversion, which was similar, patients in the entecavir group had better clinical outcomes than those in the telbivudine group for alanine aminotransferase normalization (85.2% vs 78.4%, p <0.048), undetectable HBV DNA (96.5% vs 74.8%, p <0.001), and viral resistance (0.9% vs 21.7%, p <0.001) after 2 years of treatment, After applying roadmap or super-responders concepts, entecavir still had better outcomes than telbivudine in undetectable HBV DNA and viral resistance. The cumulative incidence of hepatocellular carcinoma development was similar between telbivudine-naive and entecavir-naive patients (p 0.565). In renal function analysis, there were significantly more patients with estimated glomerular filtration rate (eGFR) category improvement in both the telbivudine and entecavir groups at year 1 (p 0.006 and p 0.047, respectively). The rate of virological improvement was significantly higher with entecavir than with telbivudine after 2 years of treatment, whether applying the concepts of roadmap or super-responders. The incidence of hepatocellular carcinoma was similar between telbivudine and entecavir. Both telbivudine and entecavir were associated with eGFR improvement, especially in patients with renal insufficiency.     

Which memory processes are affected in patients with obstructive sleep apnea? An evaluation of 3 types of memory

STUDY OBJECTIVE: To investigate which memory processes are affected by obstructive sleep apnea (OSA). DESIGN: Three separate memory systems were investigated in patients with OSA and normal subjects. Verbal episodic memory was tested after forced encoding, in order to control the level of attention during item presentation; procedural memory was tested using a simplified version of a standard test with an interfering task; lastly, working memory was examined with validated paradigms based on a theoretical model. SETTING: Sleep laboratory and outpatient sleep clinic in a French tertiary-care university hospital. PARTICIPANTS: Ninety-five patients with OSA and 95 control subjects matched for age and level of education. Group 1 (54 patients, 54 controls) underwent an extensive battery of tasks evaluating verbal episodic, procedural, and working memory. Group 2 (16 patients, 16 controls) underwent procedural memory tests only, and group 3 (25 patients, 25 controls) working memory tests only. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Compared with matched controls, patients with OSA exhibited a retrieval deficit of episodic memory but intact maintenance, recognition, and forgetfulness; decreased overall performance in procedural memory, although pattern learning did occur; and impairment of specific working memory capabilities despite normal short-term memory. No consistent correlation was found between OSA severity and memory deficit. The long duration of the test session did not negatively impact the patients' performance. CONCLUSIONS: Memory impairment in OSA is mild and does not affect all memory processes but, rather, specific aspects, underscoring the need for extensive and specific memory testing in clinical and research settings.     

Seasonal and weather variation of sleep and physical activity in 12–14-year-old children

Background: Understanding variation in physical activity (PA) and sleep is necessary to develop novel intervention strategies targeting adolescents’ health behaviors. We examined the extent to which PA and sleep vary by aspects of the physical environment. Participants: We performed a cross-sectional analysis of 669 adolescents in the Project Viva cohort. Methods: We estimated total PA, sleep duration, sleep efficiency, and sleep midpoint timing from wrist accelerometers. We used multivariable linear regression models and generalized estimated equations to assess associations of PA and sleep with season and daily weather conditions obtained from the National Oceanic and Atmospheric Administration archive. Results: Mean age was 12.9 (SD 0.6) years; 51% were female and 68% were white. Mean sleep duration was 466 (SD 42) min per night and total PA was 1,652 (SD 431) counts per min per day. Sleep midpoint time was 41 (95% CI: 27 to 54) min later in summer, 28 (95% CI: ?41 to ?14) min earlier in spring, and 29 (95% CI: ?43 to ?15) min earlier in autumn compared to winter. Higher temperature and longer day length both were associated with small reductions of nightly sleep duration. Adolescents were less physically active during winter and on rainy and short sunlight days. There was an inverse U-shaped relationship between PA and mean temperature. Conclusions: Season was associated with large changes in sleep timing, and smaller changes in other sleep and PA measurements. Given the importance of sleep and circadian alignment, future health behavioral interventions may benefit by targeting “season-specific” interventions.