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AbstractIntroduction. We report a very rare case of familial breast cancer and diffuse gastric cancer, with germline pathogenic variants in both BRCA1 and CDH1 genes. To the best of our knowledge, this is the first report of such an association.Family description.

The proband is a woman diagnosed with breast cancer at the age of 52 years. She requested genetic counselling in 2012, at the age of 91 years, because of a history of breast cancer in her daughter, her sister, her niece and her paternal grandmother and was therefore concerned about her relatives. Her sister and maternal aunt also had gastric cancer.

She was tested for several genes associated with hereditary breast cancer.Results. A large deletion of BRCA1 from exons 1 to 7 and two CDH1 pathogenic cis variants were identified.Conclusion. This complex situation is challenging for genetic counselling and management of at-risk individuals.cancer.

Breastcancer. Gastricclinical geneticsgenetic screening/counsellingmolecular geneticsIntroductionGLI-Kruppel family member 3 (GLI3) encodes for a zinc finger transcription factor which plays a key role in the sonic hedgehog (SHH) signalling pathway essential in both limb and craniofacial development.1 2 In hand development, SHH is expressed in the zone of polarising activity (ZPA) on the posterior side of the handplate. The ZPA expresses SHH, creating a gradient of SHH from the posterior to the anterior side of the handplate.

In the presence of SHH, full length GLI3-protein is produced (GLI3A), whereas absence of SHH causes cleavage of GLI3 into its repressor form (GLI3R).3 4 Abnormal expression of this SHH/GLI3R gradient can cause both preaxial and postaxial polydactyly.2Concordantly, pathogenic DNA variants in the GLI3 gene are known to cause multiple syndromes with craniofacial and limb involvement, such as. Acrocallosal syndrome5 (OMIM. 200990), Greig cephalopolysyndactyly syndrome6 (OMIM.

175700) and Pallister-Hall syndrome7 (OMIM. 146510). Also, in non-syndromic polydactyly, such as preaxial polydactyly-type 4 (PPD4, OMIM.

174700),8 pathogenic variants in GLI3 have been described. Out of these diseases, Pallister-Hall syndrome is the most distinct entity, defined by the presence of central polydactyly and hypothalamic hamartoma.9 The other GLI3 syndromes are defined by the presence of preaxial and/or postaxial polydactyly of the hand and feet with or without syndactyly (Greig syndrome, PPD4). Also, various mild craniofacial features such as hypertelorism and macrocephaly can occur.

Pallister-Hall syndrome is caused by truncating variants in the middle third of the GLI3 gene.10–12 The truncation of GLI3 causes an overexpression of GLI3R, which is believed to be the key difference between Pallister-Hall and the GLI3-mediated polydactyly syndromes.9 11 Although multiple attempts have been made, the clinical and genetic distinction between the GLI3-mediated polydactyly syndromes is less evident. This has for example led to the introduction of subGreig and the formulation of an Oro-facial-digital overlap syndrome.10 Other authors, suggested that we should not regard these diseases as separate entities, but as a spectrum of GLI3-mediated polydactyly syndromes.13Although phenotype/genotype correlation of the different syndromes has been cumbersome, clinical and animal studies do provide evidence that distinct regions within the gene, could be related to the individual anomalies contributing to these syndromes. First, case studies show isolated preaxial polydactyly is caused by both truncating and non-truncating variants throughout the GLI3 gene, whereas in isolated postaxial polydactyly cases truncating variants at the C-terminal side of the gene are observed.12 14 These results suggest two different groups of variants for preaxial and postaxial polydactyly.

Second, recent animal studies suggest that posterior malformations in GLI3-mediated polydactyly syndromes are likely related to a dosage effect of GLI3R rather than due to the influence of an altered GLI3A expression.15Past attempts for phenotype/genotype correlation in GLI3-mediated polydactyly syndromes have directly related the diagnosed syndrome to the observed genotype.10–12 16 Focusing on individual hand phenotypes, such as preaxial and postaxial polydactyly and syndactyly might be more reliable because it prevents misclassification due to inconsistent use of syndrome definition. Subsequently, latent class analysis (LCA) provides the possibility to relate a group of observed variables to a set of latent, or unmeasured, parameters and thereby identifying different subgroups in the obtained dataset.17 As a result, LCA allows us to group different phenotypes within the GLI3-mediated polydactyly syndromes and relate the most important predictors of the grouped phenotypes to the observed GLI3 variants.The aim of our study was to further investigate the correlation of the individual phenotypes to the genotypes observed in GLI3-mediated polydactyly syndromes, using LCA. Cases were obtained by both literature review and the inclusion of local clinical cases.

Subsequently, we identified two subclasses of limb anomalies that relate to the underlying GLI3 variant. We provide evidence for two different phenotypic and genotypic groups with predominantly preaxial and postaxial hand and feet anomalies, and we specify those cases with a higher risk for corpus callosum anomalies.MethodsLiterature reviewThe Human Gene Mutation Database (HGMD Professional 2019) was reviewed to identify known pathogenic variants in GLI3 and corresponding phenotypes.18 All references were obtained and cases were included when they were diagnosed with either Greig or subGreig syndrome or PPD4.10–12 Pallister-Hall syndrome and acrocallosal syndrome were excluded because both are regarded distinct syndromes and rather defined by the presence of the non-hand anomalies, than the presence of preaxial or postaxial polydactyly.13 19 Isolated preaxial or postaxial polydactyly were excluded for two reasons. The phenotype/genotype correlations are better understood and both anomalies can occur sporadically which could introduce falsely assumed pathogenic GLI3 variants in the analysis.

Additionally, cases were excluded when case-specific phenotypic or genotypic information was not reported or if these two could not be related to each other. Families with a combined phenotypic description, not reducible to individual family members, were included as one case in the analysis.Clinical casesThe Sophia Children’s Hospital Database was reviewed for cases with a GLI3 variant. Within this population, the same inclusion criteria for the phenotype were valid.

Relatives of the index patients were also contacted for participation in this study, when they showed comparable hand, foot, or craniofacial malformations or when a GLI3 variant was identified. Phenotypes of the hand, foot and craniofacial anomalies of the patients treated in the Sophia Children's Hospital were collected using patient documentation. Family members were identified and if possible, clinically verified.

Alternatively, family members were contacted to verify their phenotypes. If no verification was possible, cases were excluded.PhenotypesThe phenotypes of both literature cases and local cases were extracted in a similar fashion. The most frequently reported limb and craniofacial phenotypes were dichotomised.

The dichotomised hand and foot phenotypes were preaxial polydactyly, postaxial polydactyly and syndactyly. Broad halluces or thumbs were commonly reported by authors and were dichotomised as a presentation of preaxial polydactyly. The extracted dichotomised craniofacial phenotypes were hypertelorism, macrocephaly and corpus callosum agenesis.

All other phenotypes were registered, but not dichotomised.Pathogenic GLI3 variantsAll GLI3 variants were extracted and checked using Alamut Visual V.2.14. If indicated, variants were renamed according to standard Human Genome Variation Society nomenclature.20 Variants were grouped in either missense, frameshift, nonsense or splice site variants. In the group of frameshift variants, a subgroup with possible splice site effect were identified for subgroup analysis when indicated.

Similarly, nonsense variants prone for nonsense mediated decay (NMD) and nonsense variants with experimentally confirmed NMD were identified.21 Deletions of multiple exons, CNVs and translocations were excluded for analysis. A full list of included mutations is available in the online supplementary materials.Supplemental materialThe location of the variant was compared with five known structural domains of the GLI3 gene. (1) repressor domain, (2) zinc finger domain, (3) cleavage site, (4) activator domain, which we defined as a concatenation of the separately identified transactivation zones, the CBP binding domain and the mediator binding domain (MBD) and (5) the MID1 interaction region domain.1 6 22–24 The boundaries of each of the domains were based on available literature (figure 1, exact locations available in the online supplementary materials).

The boundaries used by different authors did vary, therefore a consensus was made.In this figure the posterior probability of an anterior phenotype is plotted against the location of the variant, stratified for the type of mutation that was observed. For better overview, only variants with a location effect were displayed. The full figure, including all variant types, can be found in the online supplementary figure 1.

Each mutation is depicted as a dot, the size of the dot represents the number of observations for that variant. If multiple observations were made, the mean posterior odds and IQR are plotted. For the nonsense variants, variants that were predicted to produce nonsense mediated decay, are depicted using a triangle.

Again, the size indicates the number of observations." data-icon-position data-hide-link-title="0">Figure 1 In this figure the posterior probability of an anterior phenotype is plotted against the location of the variant, stratified for the type of mutation that was observed. For better overview, only variants with a location effect were displayed. The full figure, including all variant types, can be found in the online supplementary figure 1.

Each mutation is depicted as a dot, the size of the dot represents the number of observations for that variant. If multiple observations were made, the mean posterior odds and IQR are plotted. For the nonsense variants, variants that were predicted to produce nonsense mediated decay, are depicted using a triangle.

Again, the size indicates the number of observations.Supplemental materialLatent class analysisTo cluster phenotypes and relate those to the genotypes of the patients, an explorative analysis was done using LCA in R (R V.3.6.1 for Mac. Polytomous variable LCA, poLCA V.1.4.1.). We used our LCA to detect the number of phenotypic subgroups in the dataset and subsequently predict a class membership for each case in the dataset based on the posterior probabilities.In order to make a reliable prediction, only phenotypes that were sufficiently reported and/or ruled out were feasible for LCA, limiting the analysis to preaxial polydactyly, postaxial polydactyly and syndactyly of the hands and feet.

Only full cases were included. To determine the optimal number of classes, we fitted a series of models ranging from a one-class to a six-class model. The optimal number of classes was based on the conditional Akaike information criterion (cAIC), the non adjusted and the sample-size adjusted Bayesian information criterion (BIC and aBIC) and the obtained entropy.25 The explorative LCA produces both posterior probabilities per case for both classes and predicted class membership.

Using the predicted class membership, the phenotypic features per class were determined in a univariate analysis (χ2, SPSS V.25). Using the posterior probabilities on latent class (LC) membership, a scatter plot was created using the location of the variant on the x-axis and the probability of class membership on the y-axis for each of the types of variants (Tibco Spotfire V.7.14). Using these scatter plots, variants that give similar phenotypes were clustered.Genotype/phenotype correlationBecause an LC has no clinical value, the correlation between genotypes and phenotypes was investigated using the predictor phenotypes and the clustered phenotypes.

First, those phenotypes that contribute most to LC membership were identified. Second those phenotypes were directly related to the different types of variants (missense, nonsense, frameshift, splice site) and their clustered locations. Quantification of the relation was performed using a univariate analysis using a χ2 test.

Because of our selection criteria, meaning patients at least have two phenotypes, a multivariate using a logistic regression analysis was used to detect the most significant predictors in the overall phenotype (SPSS V.25). Finally, we explored the relation of the clustered genotypes to the presence of corpus callosum agenesis, a rare malformation in GLI3-mediated polydactyly syndromes which cannot be readily diagnosed without additional imaging.ResultsWe included 251 patients from the literature and 46 local patients,10–12 16 21 26–43 in total 297 patients from 155 different families with 127 different GLI3 variants, 32 of which were large deletions, CNVs or translocations. In six local cases, the exact variant could not be retrieved by status research.The distribution of the most frequently observed phenotypes and variants are presented in table 1.

Other recurring phenotypes included developmental delay (n=22), broad nasal root (n=23), frontal bossing or prominent forehead (n=16) and craniosynostosis (n=13), camptodactyly (n=8) and a broad first interdigital webspace of the foot (n=6).View this table:Table 1 Baseline phenotypes and genotypes of selected populationThe LCA model was fitted using the six defined hand/foot phenotypes. Model fit indices for the LCA are displayed in table 2. Based on the BIC, a two-class model has the best fit for our data.

The four-class model does show a gain in entropy, however with a higher BIC and loss of df. Therefore, based on the majority of performance statistics and the interpretability of the model, a two-class model was chosen. Table 3 displays the distribution of phenotypes and genotypes over the two classes.View this table:Table 2 Model fit indices for the one-class through six-class model evaluated in our LCAView this table:Table 3 Distribution of phenotypes and genotypes in the two latent classes (LC)Table 1 depicts the baseline phenotypes and genotypes in the obtained population.

Note incomplete data especially in the cranium phenotypes. In total 259 valid genotypes were present. In total, 289 cases had complete data for all hand and foot phenotypes (preaxial polydactyly, postaxial polydactyly and syndactyly) and thus were available for LCA.

Combined, for phenotype/genotype correlation 258 cases were available with complete genotypes and complete hand and foot phenotypes.Table 2 depicts the model fit indices for all models that have been fitted to our data.Table 3 depicts the distribution of phenotypes and genotypes over the two assigned LCs. Hand and foot phenotypes were used as input for the LCA, thus are all complete cases. Malformation of the cranium and genotypes do have missing cases.

Note that for the LCA, full case description was required, resulting in eight cases due to incomplete phenotypes. Out of these eight, one also had a genotype that thus needed to be excluded. Missingness of genotypic data was higher in LC2, mostly due to CNVs (table 1).In 54/60 cases, a missense variant produced a posterior phenotype.

Likewise, splice site variants show the same phenotype in 23/24 cases (table 3). For both frameshift and nonsense variants, this relation is not significant (52 anterior vs 54 posterior and 26 anterior vs 42 posterior, respectively). Therefore, only for nonsense and frameshift variants the location of the variant was plotted against the probability for LC2 membership in figure 1.

A full scatterplot of all variants is available in online supplementary figure 1.Figure 1 reveals a pattern for these nonsense and frameshift variants that reveals that variants at the C-terminal of the gene predict anterior phenotypes. When relating the domains of the GLI3 protein to the observed phenotype, we observe that the majority of patients with a nonsense or frameshift variant in the repressor domain, the zinc finger domain or the cleavage site had a high probability of an LC2/anterior phenotype. This group contains all variants that are either experimentally determined to be subject to NMD (triangle marker in figure 1) or predicted to be subject to NMD (diamond marker in figure 1).

Frameshift and nonsense variants in the activator domain result in high probability for an LC1/posterior phenotype. These variants will be further referred to as truncating variants in the activator domain.The univariate relation of the individual phenotypes to these two groups of variants are estimated and presented in table 4. In our multivariate analysis, postaxial polydactyly of the foot and hand are the strongest predictors (Beta.

2.548, p<0001 and Beta. 1.47, p=0.013, respectively) for patients to have a truncating variant in the activator domain. Moreover, the effect sizes of preaxial polydactyly of the hand and feet (Beta.

ˆ’0.797, p=0123 and −1.772, p=0.001) reveals that especially postaxial polydactyly of the foot is the dominant predictor for the genetic substrate of the observed anomalies.View this table:Table 4 Univariate and multivariate analysis of the phenotype/genotype correlationTable 4 shows exploration of the individual phenotypes on the genotype, both univariate and multivariate. The multivariate analysis corrects for the presence of multiple phenotypes in the underlying population.Although the craniofacial anomalies could not be included in the LCA, the relation between the observed anomalies and the identified genetic substrates can be studied. The prevalence of hypertelorism was equally distributed over the two groups of variants (47/135 vs 21/47 respectively, p<0.229).

However for corpus callosum agenesis and macrocephaly, there was a higher prevalence in patients with a truncating variant in the activator domain (3/75 vs 11/41, p<0.001. OR. 8.8, p<0.001) and 42/123 vs 24/48, p<0.05).

Noteworthy is the fact that 11/14 cases with corpus callosum agenesis in the dataset had a truncating variant in the activator domain.DiscussionIn this report, we present new insights into the correlation between the phenotype and the genotype in patients with GLI3-mediated polydactyly syndromes. We illustrate that there are two LCs of patients, best predicted by postaxial polydactyly of the hand and foot for LC1, and the preaxial polydactyly of the hand and foot and syndactyly of the foot for LC2. Patients with postaxial phenotypes have a higher risk of having a truncating variant in the activator domain of the GLI3 gene which is also related to a higher risk of corpus callosum agenesis.

These results suggest a functional difference between truncating variants on the N-terminal and the C-terminal side of the GLI3 cleavage site.Previous attempts of phenotype to genotype correlation have not yet provided the clinical confirmation of these assumed mechanisms in the pathophysiology of GLI3-mediated polydactyly syndromes. Johnston et al have successfully determined the Pallister-Hall region in which truncating variants produce a Pallister-Hall phenotype rather than Greig syndrome.11 However, in their latest population study, subtypes of both syndromes were included to explain the full spectrum of observed malformations. In 2015, Demurger et al reported the higher incidence of corpus callosum agenesis in the Greig syndrome population with truncating mutations in the activator domain.12 Al-Qattan in his review summarises the concept of a spectrum of anomalies dependent on haplo-insufficiency (through different mechanisms) and repressor overexpression.13 However, he bases this theory mainly on reviewed experimental data.

Our report is the first to provide an extensive clinical review of cases that substantiate the phenotypic difference between the two groups that could fit the suggested mechanisms. We agree with Al-Qattan et al that a variation of anomalies can be observed given any pathogenic variant in the GLI3 gene, but overall two dominant phenotypes are present. A population with predominantly preaxial anomalies and one with postaxial anomalies.

The presence of preaxial or postaxial polydactyly and syndactyly is not mutually exclusive for one of these two subclasses. Meaning that preaxial polydactyly can co-occur with postaxial polydactyly. However, truncating mutations in the activator domain produce a postaxial phenotype, as can be derived from the risk in table 4.

The higher risk of corpus callosum agenesis in this population shows that differentiating between a preaxial phenotype and a postaxial phenotype, instead of between the different GLI3-mediated polydactyly syndromes, might be more relevant regarding diagnostics for corpus callosum agenesis.We chose to use LCA as an exploratory tool only in our population for two reasons. First of all, LCA can be useful to identify subgroups, but there is no ‘true’ model or number of subgroups you can detect. The best fitting model can only be estimated based on the available measures and approximates the true subgroups that might be present.

Second, LC membership assignment is a statistical procedure based on the posterior probability, with concordant errors of the estimation, rather than a clinical value that can be measured or evaluated. Therefore, we decided to use our LCA only in an exploratory tool, and perform our statistics using the actual phenotypes that predict LC membership and the associated genotypes. Overall, this method worked well to differentiate the two subgroups present in our dataset.

However, outliers were observed. A qualitative analysis of these outliers is available in the online supplementary data.The genetic substrate for the two phenotypic clusters can be discussed based on multiple experiments. Overall, we hypothesise two genetic clusters.

One that is due to haploinsufficiency and one that is due to abnormal truncation of the activator. The hypothesised cluster of variants that produce haploinsufficiency is mainly based on the experimental data that confirms NMD in two variants and the NMD prediction of other nonsense variants in Alamut. For the frameshift variants, it is also likely that the cleavage of the zinc finger domain results in functional haploinsufficiency either because of a lack of signalling domains or similarly due to NMD.

Missense variants could cause haploinsufficiency through the suggested mechanism by Krauss et al who have illustrated that missense variants in the MID1 domain hamper the functional interaction with the MID1-α4-PP2A complex, leading to a subcellular location of GLI3.24 The observed missense variants in our study exceed the region to which Krauss et al have limited the MID-1 interaction domain. An alternative theory is suggested by Zhou et al who have shown that missense variants in the MBD can cause deficiency in the signalling of GLI3A, functionally implicating a relative overexpression of GLI3R.22 However, GLI3R overexpression would likely produce a posterior phenotype, as determined by Hill et al in their fixed homo and hemizygous GLI3R models.15 Therefore, our hypothesis is that all included missense variants have a similar pathogenesis which is more likely in concordance with the mechanism introduced by Krauss et al. To our knowledge, no splice site variants have been functionally described in literature.

However, it is noted that the 15 and last exon encompasses the entire activator domain, thus any splice site mutation is by definition located on the 5′ side of the activator. Based on the phenotype, we would suggest that these variants fail to produce a functional protein. We hypothesise that the truncating variants of the activator domain lead to overexpression of GLI3R in SHH rich areas.

In normal development, the presence of SHH prevents the processing of full length GLI34 into GLI3R, thus producing the full length activator. In patients with a truncating variant of the activator domain of GLI3, thus these variants likely have the largest effect in SHH rich areas, such as the ZPA located at the posterior side of the hand/footplate. Moreover, the lack of posterior anomalies in the GLI3∆699/- mouse model (hemizygous fixed repressor model) compared with the GLI3∆699/∆699 mouse model (homozygous fixed repressor model), suggesting a dosage effect of GLI3R to be responsible for posterior hand anomalies.15 These findings are supported by Lewandowski et al, who show that the majority of the target genes in GLI signalling are regulated by GLI3R rather than GLI3A.44 Together, these findings suggest a role for the location and type of variant in GLI3-mediated syndromes.Interestingly, the difference between Pallister-Hall syndrome and GLI3-mediated polydactyly syndromes has also been attributed to the GLI3R overexpression.

However, the difference in phenotype observed in the cases with a truncating variant in the activator domain and Pallister-Hall syndrome suggest different functional consequences. When studying figure 1, it is noted that the included truncating variants on the 3′ side of the cleavage site seldomly affect the CBP binding region, which could provide an explanation for the observed differences. This binding region is included in the Pallister-Hall region as defined by Johnston et al and is necessary for the downstream signalling with GLI1.10 11 23 45 Interestingly, recent reports show that pathogenic variants in GLI1 can produce phenotypes concordant with Ellis von Krefeld syndrome, which includes overlapping features with Pallister-Hall syndrome.46 The four truncating variants observed in this study that do affect the CBP but did not result in a Pallister-Hall phenotype are conflicting with this theory.

Krauss et al postulate an alternative hypothesis, they state that the MID1-α4-PP2A complex, which is essential for GLI3A signalling, could also be the reason for overlapping features of Opitz syndrome, caused by variants in MID1, and Pallister-Hall syndrome. Further analysis is required to fully appreciate the functional differences between truncating mutations that cause Pallister-Hall syndrome and those that result in GLI3-mediated polydactyly syndromes.For the clinical evaluation of patients with GLI3-mediated polydactyly syndromes, intracranial anomalies are likely the most important to predict based on the variant. Unfortunately, the presence of corpus callosum agenesis was not routinely investigated or reported thus this feature could not be used as an indicator phenotype for LC membership.

Interestingly when using only hand and foot phenotypes, we did notice a higher prevalence of corpus callosum agenesis in patients with posterior phenotypes. The suggested relation between truncating mutations in the activator domain causing these posterior phenotypes and corpus callosum agenesis was statistically confirmed (OR. 8.8, p<0.001).

Functionally this relation could be caused by the GLI3-MED12 interaction at the MBD. Pathogenic DNA variants in MED12 can cause Opitz-Kaveggia syndrome, a syndrome in which presentation includes corpus callosum agenesis, broad halluces and thumbs.47In conclusion, there are two distinct phenotypes within the GLI3-mediated polydactyly population. Patients with more posteriorly and more anteriorly oriented hand anomalies.

Furthermore, this difference is related to the observed variant in GLI3. We hypothesise that variants that cause haploinsufficiency produce anterior anomalies of the hand, whereas variants with abnormal truncation of the activator domain have more posterior anomalies. Furthermore, patients that have a variant that produces abnormal truncation of the activator domain, have a greater risk for corpus callosum agenesis.

Thus, we advocate to differentiate preaxial or postaxial oriented GLI3 phenotypes to explain the pathophysiology as well as to get a risk assessment for corpus callosum agenesis.Data availability statementData are available upon reasonable request.Ethics statementsPatient consent for publicationNot required.Ethics approvalThe research protocol was approved by the local ethics board of the Erasmus MC University Medical Center (MEC 2015-679)..

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American Institute of Physics, news release, Sept. 14, 2021 Steven Reinberg Copyright © 2021 HealthDay. All rights reserved.Latest Pregnancy News THURSDAY, Sept. 16, 2021 (HealthDay News) The erectile dysfunction treatment levitra has many women thinking twice about having more kids. In a survey of close to 1,200 New York City women with young children, one-third of respondents who had been thinking about having another baby before the levitra but hadn't started trying said they were no longer considering it.

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15, 2021 Cara Murez Copyright © 2021 HealthDay. All rights reserved. QUESTION The first sign of pregnancy is most often. See AnswerLatest Cancer News THURSDAY, Sept. 16, 2021 (HealthDay News) Multiple sclerosis (MS) patients diagnosed with colon cancer may have a greater risk of dying from cancer or other causes in the next six months to year than colon cancer patients without MS, a Canadian study finds.

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The researchers found that people with MS were 45% more likely to die of any cause six months after their cancer diagnosis than people without MS. They were also 34% more likely to die of any cause in a year. After that, the risk of death was the same for both groups. Also, people with MS were more likely to die of cancer than people without MS only at six months after diagnosis, when their risk was 29% higher. "Understanding more about the factors involved in treating cancer in people with MS and their outcomes will be helpful for people with MS and their doctors as they balance the benefits of cancer treatment with the potential adverse effects and consider life expectancy and quality of life," Marrie said in a news release from the American Academy of Neurology.

The findings were published online Sept. 15 in the journal Neurology. More information To learn more about MS, visit the National Multiple Sclerosis Society. SOURCE. American Academy of Neurology, news release, Sept.

15, 2021 Steven Reinberg Copyright © 2021 HealthDay. All rights reserved. SLIDESHOW What Is Multiple Sclerosis?. MS Symptoms, Causes, Diagnosis See SlideshowLatest erectile dysfunction News THURSDAY, Sept. 16, 2021 (HealthDay News) The cost of providing hospital care for unvaccinated Americans has reached $5.7 billion in just three months, CBS News reported.

Between June and August, about 287,000 people who were not vaccinated were hospitalized for erectile dysfunction treatment in the United States, according to data from the Kaiser Family Foundation (KFF) and the Peterson Center on Healthcare, which collaborated to track health care costs and quality. Most adults in the United States have had access to treatments since the spring, so these hospital stays could likely have been avoided, the study authors noted. In the new report, the KFF-Peterson team used data from the U.S. Centers for Medicare and Medicaid Services to estimate the average cost of hospitalization with erectile dysfunction treatment at $20,000 per person. They then calculated the overall expense at $5.7 billion.

"This ballpark figure is likely an understatement of the cost burden from preventable treatment of erectile dysfunction treatment among unvaccinated adults," the authors wrote, noting that the study doesn't account for outpatient costs. According to the U.S. Centers for Disease Control and Prevention, compared to fully vaccinated people, those who are unvaccinated are 11 times more likely to die from erectile dysfunction treatment. This study factored in that treatments are effective in preventing severe illness and hospitalization, and the occurrence of breakthrough s in fully vaccinated people. The expense of health care for people with erectile dysfunction treatment is "borne not only by patients but also by society more broadly, including taxpayer-funded public programs and private insurance premiums paid by workers, businesses and individual purchasers," according to the authors of the report.

These shared costs – for copays, coinsurance or payments toward a deductible – have not always been passed on to the patient, but they soon could be. As of November 2020, nearly 90% of insured individuals would have had their out-of-pocket costs waived if they were hospitalized for erectile dysfunction treatment, according to the report. Now, more than 70% of the largest insurers are not waiving treatment costs. Another 10% will phase out cost-sharing by the end of next month, CBS News reported. More information The U.S.

Centers for Disease Control and Prevention has more on erectile dysfunction treatment. SOURCE.

16, 2021 (HealthDay News) Multiple sclerosis (MS) patients undergoing a euromed top order levitra online treatment that depletes a type of purchase levitra canada immune cell that fuels MS attacks still have a strong response to mRNA erectile dysfunction treatments, a new study finds. "The message from this study is clear — it is worthwhile for patients with MS receiving [anti-CD20] treatment to get a erectile dysfunction treatment, which will prevent severe illness," said researcher E. John Wherry, director of the Penn Institute for Immunology, in Philadelphia.

Anti-CD20 treatment depletes the B-cells that contribute to the MS euromed top order levitra online attacks. B-cells and T-cells are types of white blood cells that make immune system antibodies. For the study, Wherry's team measured antibody and T-cell responses in 20 patients with MS who were getting anti-CD20 treatment.

They compared euromed top order levitra online those patients with a group of healthy people. All of the healthy participants had antibodies following the first dose of an mRNA treatment (such as Moderna or Pfizer), and the level of antibody increased after the second dose. In patients with MS, however, the antibody response was more varied.

A month after their second treatment dose, between 50% and 85% had developed protective responses to euromed top order levitra online erectile dysfunction. For those without detectable antibodies, the size of the response was lower and delayed, the researchers found. "This data not only reveal that patients undergoing anti-CD20 infusions are still able to mount important erectile dysfunction treatment responses which are likely to protect from severe illness, but also informs our clinical practices in how we advise patients with MS and other autoimmune disorders on such therapies," said researcher Dr.

Amit Bar-Or, chief of the division of MS euromed top order levitra online and related disorders at Penn's Perelman School of Medicine. "For example, knowing that responses are weakest immediately following an anti-CD20 infusion, we can now advise patients to wait a number of months after their therapy to get a erectile dysfunction treatment," Bar-Or added in a university news release. Because of the limited antibody responses among patients receiving anti-CD20 treatment, they might not be able to kill the levitra as quickly before it infects other cells, the researchers said.

As a result, they could euromed top order levitra online be carriers of the levitra for a longer period of time. The findings were published online Sept. 14 in the journal Nature Medicine.

More information For answers to your questions euromed top order levitra online about erectile dysfunction treatments, visit the U.S. Centers for Disease Control and Prevention. SOURCE.

University of Pennsylvania euromed top order levitra online Perelman School of Medicine, news release, Sept. 14, 2021 Steven Reinberg Copyright © 2021 HealthDay. All rights reserved.

SLIDESHOW What euromed top order levitra online Is Multiple Sclerosis?. MS Symptoms, Causes, Diagnosis See SlideshowLatest erectile dysfunction News THURSDAY, Sept. 16, 2021 (HealthDay News) If you're making your own face mask to protect against erectile dysfunction treatment, three layers of cotton towel fabric are best, researchers from India report.

That recommendation comes after euromed top order levitra online testing how best to block cough droplets moving at different rates, from mild to severe. "Our results show cotton, towel-based fabrics were most effective among the considered fabrics and must be stitched together as multiple layers for making homemade face masks," said researcher Saptarshi Basu, from the Indian Institute of Science in Bengaluru. "A three- or more-layered homemade mask is recommended since it can suppress aerosolization significantly," Basu said in a news release from the American Institute of Physics.

The report was euromed top order levitra online published online Sept. 14 in the institute's journal Physics of Fluids. Such masks remain effective even after 70 washings, the researchers said.

For the study, the team sprayed single euromed top order levitra online layers of summer stole, handkerchief, cotton towel and surgical masks. They used high-speed imaging to quantify the threshold for penetration and amount of droplet penetration at different velocities. Overall, the researchers confirmed that N95 and surgical masks are most effective.

But when those euromed top order levitra online aren't available, cotton towel fabric can be layered and stitched into an effective makeshift face mask, they said. More information For more on face masks, see the U.S. Centers for Disease Control and Prevention.

SOURCE. American Institute of Physics, news release, Sept. 14, 2021 Steven Reinberg Copyright © 2021 HealthDay.

All rights reserved.Latest Pregnancy News THURSDAY, Sept. 16, 2021 (HealthDay News) The erectile dysfunction treatment levitra has many women thinking twice about having more kids. In a survey of close to 1,200 New York City women with young children, one-third of respondents who had been thinking about having another baby before the levitra but hadn't started trying said they were no longer considering it.

For women who stopped trying to become pregnant when the levitra began, fewer than half were certain they would continue trying once the levitra ended, a new study shows. "Our findings show that the initial erectile dysfunction treatment outbreak appears to have made women think twice about expanding their families and, in some cases, reduce the number of children they ultimately intend to have," said lead author Linda Kahn, an assistant professor of pediatrics and population health at NYU Langone Health in New York City. "This is yet another example of the potential long-lasting consequences of the levitra beyond the more obvious health and economic effects," Kahn said in an NYU news release.

Researchers asked nearly 1,200 women to recall their pre-levitra pregnancy plans and whether they still planned to go forward with them. The survey was administered from April 20 to Aug. 31, 2020.

Women who had higher stress levels and greater financial insecurity were more likely to postpone or abandon plans for another child. Researchers suspect that child care challenges that parents experienced during the first wave of erectile dysfunction treatment and lockdown may have contributed to these choices. Early evidence had already pointed to drop in the U.S.

Birth rate, with 300,000 fewer births in 2020 than forecast by fertility trends. The last two months of 2020 were particularly low, dovetailing with the levitra's start early in the year. "These results emphasize the toll the erectile dysfunction has taken not only on individual parents, but perhaps on fertility rates overall," said senior author Melanie Jacobson, of Division of Environmental Pediatrics at NYU Langone.

The study did not account for unplanned pregnancies. Researchers said the findings suggest that additional financial support may be necessary to address the nation's ongoing fertility decline. The study was published online Sept.

15 in JAMA Network Open. The researchers plan to repeat the survey with the same women and explore the potential impact of vaccination, which wasn't available at the time of this poll. More information The Brookings Institution has more on fertility decline in the United States.

SOURCE. NYU Langone, news release, Sept. 15, 2021 Cara Murez Copyright © 2021 HealthDay.

All rights reserved. QUESTION The first sign of pregnancy is most often. See AnswerLatest Cancer News THURSDAY, Sept.

16, 2021 (HealthDay News) Multiple sclerosis (MS) patients diagnosed with colon cancer may have a greater risk of dying from cancer or other causes in the next six months to year than colon cancer patients without MS, a Canadian study finds. "These results warrant further investigation to determine what factors may lead to shorter survival times," said study author Dr. Ruth Ann Marrie, a professor of neurology at the University of Manitoba in Winnipeg, Canada.

Among many questions that she said need to be investigated are these. Are people with MS less likely to receive cancer treatment?. Or are they less able to tolerate the effects of chemotherapy?.

Are factors specific to MS involved?. How accommodating is the cancer care system for people with disabilities?. For the new study, Marrie's team looked at health records for 338 people in Canada with MS and colon cancer.

These patients were compared with more than 1,300 people who had colon cancer but not MS. On average, they were diagnosed with cancer at 65 years of age. The researchers found that people with MS were 45% more likely to die of any cause six months after their cancer diagnosis than people without MS.

They were also 34% more likely to die of any cause in a year. After that, the risk of death was the same for both groups. Also, people with MS were more likely to die of cancer than people without MS only at six months after diagnosis, when their risk was 29% higher.

"Understanding more about the factors involved in treating cancer in people with MS and their outcomes will be helpful for people with MS and their doctors as they balance the benefits of cancer treatment with the potential adverse effects and consider life expectancy and quality of life," Marrie said in a news release from the American Academy of Neurology. The findings were published online Sept. 15 in the journal Neurology.

More information To learn more about MS, visit the National Multiple Sclerosis Society. SOURCE. American Academy of Neurology, news release, Sept.

15, 2021 Steven Reinberg Copyright © 2021 HealthDay. All rights reserved. SLIDESHOW What Is Multiple Sclerosis?.

MS Symptoms, Causes, Diagnosis See SlideshowLatest erectile dysfunction News THURSDAY, Sept. 16, 2021 (HealthDay News) The cost of providing hospital care for unvaccinated Americans has reached $5.7 billion in just three months, CBS News reported. Between June and August, about 287,000 people who were not vaccinated were hospitalized for erectile dysfunction treatment in the United States, according to data from the Kaiser Family Foundation (KFF) and the Peterson Center on Healthcare, which collaborated to track health care costs and quality.

Most adults in the United States have had access to treatments since the spring, so these hospital stays could likely have been avoided, the study authors noted. In the new report, the KFF-Peterson team used data from the U.S. Centers for Medicare and Medicaid Services to estimate the average cost of hospitalization with erectile dysfunction treatment at $20,000 per person.

They then calculated the overall expense at $5.7 billion. "This ballpark figure is likely an understatement of the cost burden from preventable treatment of erectile dysfunction treatment among unvaccinated adults," the authors wrote, noting that the study doesn't account for outpatient costs. According to the U.S.

Centers for Disease Control and Prevention, compared to fully vaccinated people, those who are unvaccinated are 11 times more likely to die from erectile dysfunction treatment. This study factored in that treatments are effective in preventing severe illness and hospitalization, and the occurrence of breakthrough s in fully vaccinated people. The expense of health care for people with erectile dysfunction treatment is "borne not only by patients but also by society more broadly, including taxpayer-funded public programs and private insurance premiums paid by workers, businesses and individual purchasers," according to the authors of the report.

These shared costs – for copays, coinsurance or payments toward a deductible – have not always been passed on to the patient, but they soon could be. As of November 2020, nearly 90% of insured individuals would have had their out-of-pocket costs waived if they were hospitalized for erectile dysfunction treatment, according to the report. Now, more than 70% of the largest insurers are not waiving treatment costs.

Another 10% will phase out cost-sharing by the end of next month, CBS News reported. More information The U.S. Centers for Disease Control and Prevention has more on erectile dysfunction treatment.

Where can I keep Levitra?

Keep out of the reach of children. Store at room temperature between 15 and 30 degrees C (59 and 86 degrees F). Throw away any unused medicine after the expiration date.

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NCHS Data levitra cena https://www.nikolausschule.de/amoxil-online-usa/ Brief No. 286, September 2017PDF Versionpdf icon (374 KB)Anjel Vahratian, Ph.D.Key findingsData from the National Health Interview Survey, 2015Among those aged 40–59, perimenopausal women (56.0%) were more likely than postmenopausal (40.5%) and premenopausal (32.5%) women to sleep less than 7 hours, on average, in a 24-hour period.Postmenopausal women aged 40–59 were more likely than premenopausal women aged 40–59 to have trouble falling asleep (27.1% compared with 16.8%, respectively), and staying asleep (35.9% compared with 23.7%), four times or more in the past week.Postmenopausal women aged 40–59 (55.1%) were more likely than premenopausal women aged 40–59 (47.0%) to not wake up feeling well rested 4 days or more in the past week.Sleep duration and quality are important contributors to health and wellness. Insufficient sleep is associated with an increased risk for chronic conditions such as cardiovascular levitra cena disease (1) and diabetes (2). Women may be particularly vulnerable to sleep problems during times of reproductive hormonal change, such as after the menopausal transition. Menopause is “the permanent levitra cena cessation of menstruation that occurs after the loss of ovarian activity” (3).

This data brief describes sleep duration and sleep quality among nonpregnant women aged 40–59 by menopausal status. The age range selected for this analysis reflects the focus on midlife sleep health. In this analysis, 74.2% of women are premenopausal, 3.7% are perimenopausal, and levitra cena 22.1% are postmenopausal. Keywords. Insufficient sleep, menopause, National Health Interview Survey Perimenopausal women were more likely than premenopausal and postmenopausal women to sleep less than 7 hours, on average, in a 24-hour period.More than one in three nonpregnant women aged 40–59 slept less than 7 hours, on average, in a 24-hour period (35.1%) levitra cena (Figure 1).

Perimenopausal women were most likely to sleep less than 7 hours, on average, in a 24-hour period (56.0%), compared with 32.5% of premenopausal and 40.5% of postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to sleep less than 7 hours, on average, in a 24-hour period. Figure 1 levitra cena. Percentage of nonpregnant women aged 40–59 who slept less than 7 hours, on average, in a 24-hour period, by menopausal status. United States, 2015image levitra cena icon1Significant quadratic trend by menopausal status (p <.

0.05).NOTES. Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they no longer had a menstrual cycle and their last menstrual cycle was 1 year ago or levitra cena less. Women were premenopausal if they still had a menstrual cycle. Access data table levitra cena for Figure 1pdf icon.SOURCE.

NCHS, National Health Interview Survey, 2015. The percentage of women aged 40–59 who had trouble falling asleep four times or more in the past week varied by menopausal status.Nearly one in five nonpregnant women aged 40–59 levitra cena had trouble falling asleep four times or more in the past week (19.4%) (Figure 2). The percentage of women in this age group who had trouble falling asleep four times or more in the past week increased from 16.8% among premenopausal women to 24.7% among perimenopausal and 27.1% among postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to have trouble falling asleep four times or more in the past week. Figure 2 levitra cena.

Percentage of nonpregnant women aged 40–59 who had trouble falling asleep four times or more in the past week, by menopausal status. United States, 2015image icon1Significant linear trend by menopausal status (p < levitra cena. 0.05).NOTES. Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they levitra cena no longer had a menstrual cycle and their last menstrual cycle was 1 year ago or less.

Women were premenopausal if they still had a menstrual cycle. Access data table for levitra cena Figure 2pdf icon.SOURCE. NCHS, National Health Interview Survey, 2015. The percentage of women aged levitra cena 40–59 who had trouble staying asleep four times or more in the past week varied by menopausal status.More than one in four nonpregnant women aged 40–59 had trouble staying asleep four times or more in the past week (26.7%) (Figure 3). The percentage of women aged 40–59 who had trouble staying asleep four times or more in the past week increased from 23.7% among premenopausal, to 30.8% among perimenopausal, and to 35.9% among postmenopausal women.

Postmenopausal women were significantly more likely than premenopausal women to have trouble staying asleep four times or more in the past week. Figure 3 levitra cena. Percentage of nonpregnant women aged 40–59 who had trouble staying asleep four times or more in the past week, by menopausal status. United States, 2015image icon1Significant linear trend by menopausal status levitra cena (p <. 0.05).NOTES.

Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they no longer had a menstrual levitra cena cycle and their last menstrual cycle was 1 year ago or less. Women were premenopausal if they still had a menstrual cycle. Access data table for Figure 3pdf icon.SOURCE levitra cena. NCHS, National Health Interview Survey, 2015.

The percentage of women aged 40–59 who did not wake up feeling well rested 4 days or more in the past week varied by menopausal status.Nearly one in two nonpregnant women aged 40–59 did not wake up feeling well rested 4 days or more in the past week (48.9%) (Figure 4). The percentage of women in this age group who did not wake up feeling well levitra cena rested 4 days or more in the past week increased from 47.0% among premenopausal women to 49.9% among perimenopausal and 55.1% among postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to not wake up feeling well rested 4 days or more in the past week. Figure 4 levitra cena. Percentage of nonpregnant women aged 40–59 who did not wake up feeling well rested 4 days or more in the past week, by menopausal status.

United States, 2015image icon1Significant linear trend by menopausal status (p <. 0.05).NOTES. Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they no longer had a menstrual cycle and their last menstrual cycle was 1 year ago or less. Women were premenopausal if they still had a menstrual cycle.

Access data table for Figure 4pdf icon.SOURCE. NCHS, National Health Interview Survey, 2015. SummaryThis report describes sleep duration and sleep quality among U.S. Nonpregnant women aged 40–59 by menopausal status. Perimenopausal women were most likely to sleep less than 7 hours, on average, in a 24-hour period compared with premenopausal and postmenopausal women.

In contrast, postmenopausal women were most likely to have poor-quality sleep. A greater percentage of postmenopausal women had frequent trouble falling asleep, staying asleep, and not waking well rested compared with premenopausal women. The percentage of perimenopausal women with poor-quality sleep was between the percentages for the other two groups in all three categories. Sleep duration changes with advancing age (4), but sleep duration and quality are also influenced by concurrent changes in women’s reproductive hormone levels (5). Because sleep is critical for optimal health and well-being (6), the findings in this report highlight areas for further research and targeted health promotion.

DefinitionsMenopausal status. A three-level categorical variable was created from a series of questions that asked women. 1) “How old were you when your periods or menstrual cycles started?. €. 2) “Do you still have periods or menstrual cycles?.

€. 3) “When did you have your last period or menstrual cycle?. €. And 4) “Have you ever had both ovaries removed, either as part of a hysterectomy or as one or more separate surgeries?. € Women were postmenopausal if they a) had gone without a menstrual cycle for more than 1 year or b) were in surgical menopause after the removal of their ovaries.

Women were perimenopausal if they a) no longer had a menstrual cycle and b) their last menstrual cycle was 1 year ago or less. Premenopausal women still had a menstrual cycle.Not waking feeling well rested. Determined by respondents who answered 3 days or less on the questionnaire item asking, “In the past week, on how many days did you wake up feeling well rested?. €Short sleep duration. Determined by respondents who answered 6 hours or less on the questionnaire item asking, “On average, how many hours of sleep do you get in a 24-hour period?.

€Trouble falling asleep. Determined by respondents who answered four times or more on the questionnaire item asking, “In the past week, how many times did you have trouble falling asleep?. €Trouble staying asleep. Determined by respondents who answered four times or more on the questionnaire item asking, “In the past week, how many times did you have trouble staying asleep?. € Data source and methodsData from the 2015 National Health Interview Survey (NHIS) were used for this analysis.

NHIS is a multipurpose health survey conducted continuously throughout the year by the National Center for Health Statistics. Interviews are conducted in person in respondents’ homes, but follow-ups to complete interviews may be conducted over the telephone. Data for this analysis came from the Sample Adult core and cancer supplement sections of the 2015 NHIS. For more information about NHIS, including the questionnaire, visit the NHIS website.All analyses used weights to produce national estimates. Estimates on sleep duration and quality in this report are nationally representative of the civilian, noninstitutionalized nonpregnant female population aged 40–59 living in households across the United States.

The sample design is described in more detail elsewhere (7). Point estimates and their estimated variances were calculated using SUDAAN software (8) to account for the complex sample design of NHIS. Linear and quadratic trend tests of the estimated proportions across menopausal status were tested in SUDAAN via PROC DESCRIPT using the POLY option. Differences between percentages were evaluated using two-sided significance tests at the 0.05 level. About the authorAnjel Vahratian is with the National Center for Health Statistics, Division of Health Interview Statistics.

The author gratefully acknowledges the assistance of Lindsey Black in the preparation of this report. ReferencesFord ES. Habitual sleep duration and predicted 10-year cardiovascular risk using the pooled cohort risk equations among US adults. J Am Heart Assoc 3(6):e001454. 2014.Ford ES, Wheaton AG, Chapman DP, Li C, Perry GS, Croft JB.

Associations between self-reported sleep duration and sleeping disorder with concentrations of fasting and 2-h glucose, insulin, and glycosylated hemoglobin among adults without diagnosed diabetes. J Diabetes 6(4):338–50. 2014.American College of Obstetrics and Gynecology. ACOG Practice Bulletin No. 141.

Management of menopausal symptoms. Obstet Gynecol 123(1):202–16. 2014.Black LI, Nugent CN, Adams PF. Tables of adult health behaviors, sleep. National Health Interview Survey, 2011–2014pdf icon.

2016.Santoro N. Perimenopause. From research to practice. J Women’s Health (Larchmt) 25(4):332–9. 2016.Watson NF, Badr MS, Belenky G, Bliwise DL, Buxton OM, Buysse D, et al.

Recommended amount of sleep for a healthy adult. A joint consensus statement of the American Academy of Sleep Medicine and Sleep Research Society. J Clin Sleep Med 11(6):591–2. 2015.Parsons VL, Moriarity C, Jonas K, et al. Design and estimation for the National Health Interview Survey, 2006–2015.

National Center for Health Statistics. Vital Health Stat 2(165). 2014.RTI International. SUDAAN (Release 11.0.0) [computer software]. 2012.

Suggested citationVahratian A. Sleep duration and quality among women aged 40–59, by menopausal status. NCHS data brief, no 286. Hyattsville, MD. National Center for Health Statistics.

2017.Copyright informationAll material appearing in this report is in the public domain and may be reproduced or copied without permission. Citation as to source, however, is appreciated.National Center for Health StatisticsCharles J. Rothwell, M.S., M.B.A., DirectorJennifer H. Madans, Ph.D., Associate Director for ScienceDivision of Health Interview StatisticsMarcie L. Cynamon, DirectorStephen J.

Blumberg, Ph.D., Associate Director for Science.

NCHS Data euromed top order levitra online Brief No. 286, September 2017PDF Versionpdf icon (374 KB)Anjel Vahratian, Ph.D.Key findingsData from the National Health Interview Survey, 2015Among those aged 40–59, perimenopausal women (56.0%) were more likely than postmenopausal (40.5%) and premenopausal (32.5%) women to sleep less than 7 hours, on average, in a 24-hour period.Postmenopausal women aged 40–59 were more likely than premenopausal women aged 40–59 to have trouble falling asleep (27.1% compared with 16.8%, respectively), and staying asleep (35.9% compared with 23.7%), four times or more in the past week.Postmenopausal women aged 40–59 (55.1%) were more likely than premenopausal women aged 40–59 (47.0%) to not wake up feeling well rested 4 days or more in the past week.Sleep duration and quality are important contributors to health and wellness. Insufficient sleep is associated with an increased euromed top order levitra online risk for chronic conditions such as cardiovascular disease (1) and diabetes (2). Women may be particularly vulnerable to sleep problems during times of reproductive hormonal change, such as after the menopausal transition.

Menopause is “the permanent cessation of menstruation that euromed top order levitra online occurs after the loss of ovarian activity” (3). This data brief describes sleep duration and sleep quality among nonpregnant women aged 40–59 by menopausal status. The age range selected for this analysis reflects the focus on midlife sleep health. In this analysis, 74.2% of euromed top order levitra online women are premenopausal, 3.7% are perimenopausal, and 22.1% are postmenopausal.

Keywords. Insufficient sleep, menopause, National Health Interview Survey Perimenopausal women were more likely than premenopausal and postmenopausal women euromed top order levitra online to sleep less than 7 hours, on average, in a 24-hour period.More than one in three nonpregnant women aged 40–59 slept less than 7 hours, on average, in a 24-hour period (35.1%) (Figure 1). Perimenopausal women were most likely to sleep less than 7 hours, on average, in a 24-hour period (56.0%), compared with 32.5% of premenopausal and 40.5% of postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to sleep less than 7 hours, on average, in a 24-hour period.

Figure 1 euromed top order levitra online. Percentage of nonpregnant women aged 40–59 who slept less than 7 hours, on average, in a 24-hour period, by menopausal status. United States, 2015image icon1Significant quadratic trend by euromed top order levitra online menopausal status (p <. 0.05).NOTES.

Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they no longer had a menstrual cycle and their euromed top order levitra online last menstrual cycle was 1 year ago or less. Women were premenopausal if they still had a menstrual cycle. Access data euromed top order levitra online table for Figure 1pdf icon.SOURCE.

NCHS, National Health Interview Survey, 2015. The percentage of women aged 40–59 who had trouble falling asleep four times or more in the past week varied by menopausal status.Nearly one in five nonpregnant women aged 40–59 had trouble falling asleep four times or more in the past euromed top order levitra online week (19.4%) (Figure 2). The percentage of women in this age group who had trouble falling asleep four times or more in the past week increased from 16.8% among premenopausal women to 24.7% among perimenopausal and 27.1% among postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to have trouble falling asleep four times or more in the past week.

Figure 2 euromed top order levitra online. Percentage of nonpregnant women aged 40–59 who had trouble falling asleep four times or more in the past week, by menopausal status. United States, 2015image icon1Significant linear trend by menopausal status (p < euromed top order levitra online. 0.05).NOTES.

Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they no longer had a menstrual cycle and their last menstrual cycle was 1 year ago euromed top order levitra online or less. Women were premenopausal if they still had a menstrual cycle. Access data table euromed top order levitra online for Figure 2pdf icon.SOURCE.

NCHS, National Health Interview Survey, 2015. The percentage of women aged 40–59 who had trouble staying asleep four times or more in the past week varied by menopausal status.More than one in four nonpregnant women aged 40–59 had trouble euromed top order levitra online staying asleep four times or more in the past week (26.7%) (Figure 3). The percentage of women aged 40–59 who had trouble staying asleep four times or more in the past week increased from 23.7% among premenopausal, to 30.8% among perimenopausal, and to 35.9% among postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to have trouble staying asleep four times or more in the past week.

Figure 3 euromed top order levitra online. Percentage of nonpregnant women aged 40–59 who had trouble staying asleep four times or more in the past week, by menopausal status. United States, 2015image icon1Significant linear trend euromed top order levitra online by menopausal status (p <. 0.05).NOTES.

Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they no longer had a menstrual cycle and their last menstrual cycle was 1 year euromed top order levitra online ago or less. Women were premenopausal if they still had a menstrual cycle. Access data table for Figure 3pdf icon.SOURCE euromed top order levitra online.

NCHS, National Health Interview Survey, 2015. The percentage of women aged 40–59 who did not wake up feeling well rested 4 days or more in the past week varied by menopausal status.Nearly one in two nonpregnant women aged 40–59 did not wake up feeling well rested 4 days or more in the past week (48.9%) (Figure 4). The percentage of women in this age group who did not wake up feeling well rested 4 days or more euromed top order levitra online in the past week increased from 47.0% among premenopausal women to 49.9% among perimenopausal and 55.1% among postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to not wake up feeling well rested 4 days or more in the past week.

Figure 4 euromed top order levitra online. Percentage of nonpregnant women aged 40–59 who did not wake up feeling well rested 4 days or more in the past week, by menopausal status. United States, 2015image icon1Significant linear trend by menopausal status (p <. 0.05).NOTES.

Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they no longer had a menstrual cycle and their last menstrual cycle was 1 year ago or less. Women were premenopausal if they still had a menstrual cycle. Access data table for Figure 4pdf icon.SOURCE.

NCHS, National Health Interview Survey, 2015. SummaryThis report describes sleep duration and sleep quality among U.S. Nonpregnant women aged 40–59 by menopausal status. Perimenopausal women were most likely to sleep less than 7 hours, on average, in a 24-hour period compared with premenopausal and postmenopausal women.

In contrast, postmenopausal women were most likely to have poor-quality sleep. A greater percentage of postmenopausal women had frequent trouble falling asleep, staying asleep, and not waking well rested compared with premenopausal women. The percentage of perimenopausal women with poor-quality sleep was between the percentages for the other two groups in all three categories. Sleep duration changes with advancing age (4), but sleep duration and quality are also influenced by concurrent changes in women’s reproductive hormone levels (5).

Because sleep is critical for optimal health and well-being (6), the findings in this report highlight areas for further research and targeted health promotion. DefinitionsMenopausal status. A three-level categorical variable was created from a series of questions that asked women. 1) “How old were you when your periods or menstrual cycles started?.

€. 2) “Do you still have periods or menstrual cycles?. €. 3) “When did you have your last period or menstrual cycle?.

€. And 4) “Have you ever had both ovaries removed, either as part of a hysterectomy or as one or more separate surgeries?. € Women were postmenopausal if they a) had gone without a menstrual cycle for more than 1 year or b) were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they a) no longer had a menstrual cycle and b) their last menstrual cycle was 1 year ago or less.

Premenopausal women still had a menstrual cycle.Not waking feeling well rested. Determined by respondents who answered 3 days or less on the questionnaire item asking, “In the past week, on how many days did you wake up feeling well rested?. €Short sleep duration. Determined by respondents who answered 6 hours or less on the questionnaire item asking, “On average, how many hours of sleep do you get in a 24-hour period?.

€Trouble falling asleep. Determined by respondents who answered four times or more on the questionnaire item asking, “In the past week, how many times did you have trouble falling asleep?. €Trouble staying asleep. Determined by respondents who answered four times or more on the questionnaire item asking, “In the past week, how many times did you have trouble staying asleep?.

€ Data source and methodsData from the 2015 National Health Interview Survey (NHIS) were used for this analysis. NHIS is a multipurpose health survey conducted continuously throughout the year by the National Center for Health Statistics. Interviews are conducted in person in respondents’ homes, but follow-ups to complete interviews may be conducted over the telephone. Data for this analysis came from the Sample Adult core and cancer supplement sections of the 2015 NHIS.

For more information about NHIS, including the questionnaire, visit the NHIS website.All analyses used weights to produce national estimates. Estimates on sleep duration and quality in this report are nationally representative of the civilian, noninstitutionalized nonpregnant female population aged 40–59 living in households across the United States. The sample design is described in more detail elsewhere (7). Point estimates and their estimated variances were calculated using SUDAAN software (8) to account for the complex sample design of NHIS.

Linear and quadratic trend tests of the estimated proportions across menopausal status were tested in SUDAAN via PROC DESCRIPT using the POLY option. Differences between percentages were evaluated using two-sided significance tests at the 0.05 level. About the authorAnjel Vahratian is with the National Center for Health Statistics, Division of Health Interview Statistics. The author gratefully acknowledges the assistance of Lindsey Black in the preparation of this report.

ReferencesFord ES. Habitual sleep duration and predicted 10-year cardiovascular risk using the pooled cohort risk equations among US adults. J Am Heart Assoc 3(6):e001454. 2014.Ford ES, Wheaton AG, Chapman DP, Li C, Perry GS, Croft JB.

Associations between self-reported sleep duration and sleeping disorder with concentrations of fasting and 2-h glucose, insulin, and glycosylated hemoglobin among adults without diagnosed diabetes. J Diabetes 6(4):338–50. 2014.American College of Obstetrics and Gynecology. ACOG Practice Bulletin No.

141. Management of menopausal symptoms. Obstet Gynecol 123(1):202–16. 2014.Black LI, Nugent CN, Adams PF.

Tables of adult health behaviors, sleep. National Health Interview Survey, 2011–2014pdf icon. 2016.Santoro N. Perimenopause.

From research to practice. J Women’s Health (Larchmt) 25(4):332–9. 2016.Watson NF, Badr MS, Belenky G, Bliwise DL, Buxton OM, Buysse D, et al. Recommended amount of sleep for a healthy adult.

A joint consensus statement of the American Academy of Sleep Medicine and Sleep Research Society. J Clin Sleep Med 11(6):591–2. 2015.Parsons VL, Moriarity C, Jonas K, et al. Design and estimation for the National Health Interview Survey, 2006–2015.

National Center for Health Statistics. Vital Health Stat 2(165). 2014.RTI International. SUDAAN (Release 11.0.0) [computer software].

2012. Suggested citationVahratian A. Sleep duration and quality among women aged 40–59, by menopausal status. NCHS data brief, no 286.

Hyattsville, MD. National Center for Health Statistics. 2017.Copyright informationAll material appearing in this report is in the public domain and may be reproduced or copied without permission. Citation as to source, however, is appreciated.National Center for Health StatisticsCharles J.

Rothwell, M.S., M.B.A., DirectorJennifer H. Madans, Ph.D., Associate Director for ScienceDivision of Health Interview StatisticsMarcie L. Cynamon, DirectorStephen J. Blumberg, Ph.D., Associate Director for Science.

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This is especially true for the more than 340,000 people 65 and older who break a hip and the nearly 700,000 who develop a spinal fracture each year.Unlike lightning, which almost never strikes the same place twice, “the person at highest risk of a fracture is the one who’s just had a fracture,” Dr. Ethel S. Siris, endocrinologist and director of the Toni Stabile Osteoporosis Center at the Columbia University Medical Center, told me.These second fractures can result in life-limiting disability and a permanent loss of independence. One in five patients dies within a year of surgery for a hip fracture.Yet those at risk of a repeat fracture often fall between the cracks. After their broken bones have healed, far too few patients are referred for treatment that could stave off another costly, debilitating and sometimes deadly fracture.Neither patients nor most physicians realize that if the fracture is not the result of a major trauma, like a car accident, older people who fall and break a hip or who lift something heavy and fracture their spine should be treated to diminish the risk of further fractures.

Even if a bone density test suggests otherwise, by definition, older people who have broken a bone this way have osteoporosis and are at high risk of breaking more bones.“We’ve become so wedded to the concept of bone density that we ignore the simple fact that fracture is itself the definition of the disease,” Dr. Sundeep Khosla, endocrinologist at the Mayo Clinic in Rochester, Minn., said in an interview.In a 2015 study of about two million Medicare patients hospitalized after a fracture, 307,000 had a second fracture during the following two to three years at an additional cost of $6.3 billion.Yet within six months of the first fracture, only 9 percent had been tested for bone loss and, if needed, offered bone-protecting drugs that could have prevented at least 20 percent of the second fractures and saved more than a billion dollars as well as immeasurable pain and suffering among those afflicted.“No one says to the patient ‘you just broke your hip, you’ve got osteoporosis, and it should be treated’,” Dr. Siris said. €œThe problem is that the fracture fixers — the orthopedic surgeons whose job is to get patients back on their feet — are not the fracture preventers who can avert the next fracture. There’s no one connecting the dots between the orthopedic surgeons, who are really good at what they do, and the medical service that can prescribe preventive treatment.”She outlined three critical measures that too often are not taken:1.

Assuring that patients’ blood levels of calcium and vitamin D are adequate, because “if they’re deficient, it sets off mechanisms that are bad for bones.”2. Prescribing medication that can strengthen bones so that they’re less likely to break when a person falls from a standing height or picks up something heavy or even turns the wrong way in bed.3. Taking various steps to prevent falls, like exercises to strengthen supporting muscles and improve balance and mobility, and eliminating fall risks in and around the home.At the very least, following a hip or vertebral fracture, experts say patients should be referred to a physical or occupational therapist or a physiatrist (a specialist in rehabilitation medicine) for advice and exercises to help prevent more broken bones.Last year, a very large group of experts assembled by the American Society for Bone and Mineral Research published a consensus statement recommending steps clinical medicine should take to prevent second fractures among people aged 65 and older with a hip or vertebral fracture.These are people, the experts from diverse fields of medicine and several countries wrote, for whom “the benefits of treatment almost always outweighed the risk.”Dr. Khosla of the Mayo Clinic, who was a member of this illustrious task force, said the current disconnect is “puzzling, a head scratcher. For some diseases we do everything we can to prevent the next event.

If a patient comes in with a heart attack, it’s malpractice if the person is not put on a full preventive program. But the effort to prevent second fractures is dismal. The majority of patients leave the hospital without any preventive measures.”In other countries, and within some medical networks in the United States, including the Kaiser Permanente system in California, there are coordinated services to assure appropriate post-fracture follow-up. In 2013, the International Osteoporosis Foundation introduced a campaign called Capture the Fracture to assure that “fragility fracture sufferers receive appropriate assessment and intervention to reduce future fracture risk,” but such organized preventive measures have remained rare in the United States.Establishing fracture liaison services, as they are called, faces a major stumbling block in this country. There’s no mechanism to pay the person who coordinates care between the orthopedic surgeon and the practicing physician.

Medicare doesn’t cover the cost of a coordinator, Dr. Siris said, “so there’s no incentive to get a post-fracture patient into medical hands. Many primary care doctors don’t even know that their patients broke a hip.”Given the astronomical costs to Medicare of hip fractures, Dr. Khosla called the failure to cover the cost of coordinating services to prevent a second fracture “penny-wise and pound-foolish.” (Of course, this is but one of many economically questionable limitations of Medicare. Consider, for example, its failure to cover hearing aids, the lack of which increases the risk of dementia, falls and a host of other expensive medical problems that Medicare does pay for.)The consensus group’s 13 recommendations for preventing fractures include advice to not smoke or use tobacco, to limit alcohol consumption to two drinks a day for men and one for women, and to exercise regularly, at least three times a week, including weight-bearing, muscle-strengthening and balance and postural exercises.

Doctors are urged to discuss both the benefits and possible risks of medications that can help prevent fractures.Many patients have been unduly frightened, Dr. Khosla said, by the amount of attention given to the rare risks of an atypical femur fracture or jaw decay when taking bisphosphonates like Fosamax that can help maintain bone strength.“When the drugs are used correctly for three to five years, followed by a drug holiday, and attention is paid to warning symptoms like leg or dental pain, the benefits of treatment way outweigh the risks,” he said..

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Screaming and cheering increases the amount of viral particles that a person emits, so skip the big game or at least wear a mask while you’re watching it.Don’t share serving utensils and other itemsGuests should have separate serving spoons and avoid sharing and passing serving dishes or utensils. Be mindful about euromed top order levitra online touching water pitchers, wine bottles and drinking glasses handled by others. Wash hands frequently. Place disposable paper towels in the bathroom so euromed top order levitra online your guests aren’t sharing the same hand towel.

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Eastern on Tuesday, Nov. 10.Older adults who break a bone face a serious yet potentially preventable risk of breaking another, often within the next two years. This is especially true for the more than 340,000 people 65 and older who break a hip and the nearly 700,000 who develop a spinal fracture each year.Unlike lightning, which almost never strikes the same place twice, “the person at highest risk of a fracture is the one who’s just had a fracture,” Dr. Ethel S.

Siris, endocrinologist and director of the Toni Stabile Osteoporosis Center at the Columbia University Medical Center, told me.These second fractures can result in life-limiting disability and a permanent loss of independence. One in five patients dies within a year of surgery for a hip fracture.Yet those at risk of a repeat fracture often fall between the cracks. After their broken bones have healed, far too few patients are referred for treatment that could stave off another costly, debilitating and sometimes deadly fracture.Neither patients nor most physicians realize that if the fracture is not the result of a major trauma, like a car accident, older people who fall and break a hip or who lift something heavy and fracture their spine should be treated to diminish the risk of further fractures. Even if a bone density test suggests otherwise, by definition, older people who have broken a bone this way have osteoporosis and are at high risk of breaking more bones.“We’ve become so wedded to the concept of bone density that we ignore the simple fact that fracture is itself the definition of the disease,” Dr.

Sundeep Khosla, endocrinologist at the Mayo Clinic in Rochester, Minn., said in an interview.In a 2015 study of about two million Medicare patients hospitalized after a fracture, 307,000 had a second fracture during the following two to three years at an additional cost of $6.3 billion.Yet within six months of the first fracture, only 9 percent had been tested for bone loss and, if needed, offered bone-protecting drugs that could have prevented at least 20 percent of the second fractures and saved more than a billion dollars as well as immeasurable pain and suffering among those afflicted.“No one says to the patient ‘you just broke your hip, you’ve got osteoporosis, and it should be treated’,” Dr. Siris said. €œThe problem is that the fracture fixers — the orthopedic surgeons whose job is to get patients back on their feet — are not the fracture preventers who can avert the next fracture. There’s no one connecting the dots between the orthopedic surgeons, who are really good at what they do, and the medical service that can prescribe preventive treatment.”She outlined three critical measures that too often are not taken:1.

Assuring that patients’ blood levels of calcium and vitamin D are adequate, because “if they’re deficient, it sets off mechanisms that are bad for bones.”2. Prescribing medication that can strengthen bones so that they’re less likely to break when a person falls from a standing height or picks up something heavy or even turns the wrong way in bed.3. Taking various steps to prevent falls, like exercises to strengthen supporting muscles and improve balance and mobility, and eliminating fall risks in and around the home.At the very least, following a hip or vertebral fracture, experts say patients should be referred to a physical or occupational therapist or a physiatrist (a specialist in rehabilitation medicine) for advice and exercises to help prevent more broken bones.Last year, a very large group of experts assembled by the American Society for Bone and Mineral Research published a consensus statement recommending steps clinical medicine should take to prevent second fractures among people aged 65 and older with a hip or vertebral fracture.These are people, the experts from diverse fields of medicine and several countries wrote, for whom “the benefits of treatment almost always outweighed the risk.”Dr. Khosla of the Mayo Clinic, who was a member of this illustrious task force, said the current disconnect is “puzzling, a head scratcher.

For some diseases we do everything we can to prevent the next event. If a patient comes in with a heart attack, it’s malpractice if the person is not put on a full preventive program. But the effort to prevent second fractures is dismal. The majority of patients leave the hospital without any preventive measures.”In other countries, and within some medical networks in the United States, including the Kaiser Permanente system in California, there are coordinated services to assure appropriate post-fracture follow-up.

In 2013, the International Osteoporosis Foundation introduced a campaign called Capture the Fracture to assure that “fragility fracture sufferers receive appropriate assessment and intervention to reduce future fracture risk,” but such organized preventive measures have remained rare in the United States.Establishing fracture liaison services, as they are called, faces a major stumbling block in this country. There’s no mechanism to pay the person who coordinates care between the orthopedic surgeon and the practicing physician. Medicare doesn’t cover the cost of a coordinator, Dr. Siris said, “so there’s no incentive to get a post-fracture patient into medical hands.

Many primary care doctors don’t even know that their patients broke a hip.”Given the astronomical costs to Medicare of hip fractures, Dr. Khosla called the failure to cover the cost of coordinating services to prevent a second fracture “penny-wise and pound-foolish.” (Of course, this is but one of many economically questionable limitations of Medicare. Consider, for example, its failure to cover hearing aids, the lack of which increases the risk of dementia, falls and a host of other expensive medical problems that Medicare does pay for.)The consensus group’s 13 recommendations for preventing fractures include advice to not smoke or use tobacco, to limit alcohol consumption to two drinks a day for men and one for women, and to exercise regularly, at least three times a week, including weight-bearing, muscle-strengthening and balance and postural exercises. Doctors are urged to discuss both the benefits and possible risks of medications that can help prevent fractures.Many patients have been unduly frightened, Dr.

Khosla said, by the amount of attention given to the rare risks of an atypical femur fracture or jaw decay when taking bisphosphonates like Fosamax that can help maintain bone strength.“When the drugs are used correctly for three to five years, followed by a drug holiday, and attention is paid to warning symptoms like leg or dental pain, the benefits of treatment way outweigh the risks,” he said..

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