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Shaving rash(also expect 100 photos from this location from misc buy real propecia online influencers the @mondayswimwear party today. It’s peak lighting and there’s literally a line rn),” she wrote.Despite the fact that yes – that lighting is 10/10 – we love that Abbie’s keeping it real with us.“PSA. The new trend buy real propecia online is shaving rash!.

!. € she added in the comments.Like what you see?. Sign up to our bodyandsoul.com.au newsletter for more stories like this.Her followers were quick to praise the influencer for steering away from the airbrushed f*ckery we’re bombarded with online these days.“It’s nice to see some normality in a photo,” one follower wrote.“It’s the shaving rash for me.

Love my relatable queen,” another said.Chatfield also posted a series of other snaps, including a video of her twerking, and a few hair related photos of her new bangs getting swept by the wind, culminating in an ‘alfalfa’ look ala The Little Rascals.Any products featured in this article are selected by our editors, who don’t play favourites. If you buy something, we may get a cut of the sale. Learn more..

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For immediate propecia prices walmart Can i buy cipro over the counter release. October 19, 2020Boston, MA – Air pollution was significantly associated with an increased risk of hospital admissions for several neurological disorders, including Parkinson’s disease, Alzheimer’s disease, and other dementias, in a long-term study of more than propecia prices walmart 63 million older U.S. Adults, led by researchers at Harvard T.H. Chan School of Public Health.The study, conducted propecia prices walmart with colleagues at Emory University’s Rollins School of Public Health and Columbia University’s Mailman School of Public Health, is the first nationwide analysis of the link between fine particulate (PM2.5) pollution and neurodegenerative diseases in the U.S. The researchers leveraged an unparalleled amount of data compared to any previous study of air pollution and neurological disorders.The study was published online October 19, 2020 in The Lancet Planetary Health.“The 2020 report of the Lancet Commission on dementia prevention, intervention, and care has added air pollution as one of the modifiable risk factors for these outcomes,” said Xiao Wu, doctoral student in biostatistics at Harvard Chan School and co-lead author of the study.

€œOur study builds on the small but emerging evidence base indicating that long-term PM2.5 exposures propecia prices walmart are linked to an increased risk of neurological health deterioration, even at PM2.5 concentrations well below the current national standards.”Researchers looked at 17 years’ worth (2000–2016) of hospital admissions data from 63,038,019 Medicare recipients in the U.S. And linked these with estimated PM2.5 concentrations propecia prices walmart by zip code. Taking into account potential confounding factors like socioeconomic status, they found that, for each 5 microgram per cubic meter of air (μg/m3) increase in annual PM2.5 concentrations, there was a 13% increased risk for first-time hospital admissions both for Parkinson’s disease and for Alzheimer’s disease and related dementias. This risk remained elevated even below supposedly safe levels of propecia prices walmart PM2.5 exposure, which, according to current U.S. Environmental Protection Agency standards, is an annual average of 12 μg/m3 or less.Women, white people, and urban populations were particularly susceptible, the study found.

The highest risk for first-time Parkinson’s disease hospital admissions was among older adults in propecia prices walmart the northeastern U.S. For first-time Alzheimer’s disease and related dementias hospital admissions, older adults in the Midwest faced the highest risk.“Our U.S.-wide study shows that the current standards are not protecting the aging American population enough, highlighting the need for stricter standards and policies that help further reduce PM2.5 concentrations and improve air quality overall,” said Antonella Zanobetti, principal research scientist in Harvard Chan School’s Department of Environmental Health and co-senior author of the study.Liuhua Shi, research assistant professor at Emory’s Rollins School of Public Health, was a co-lead author and Marianthi-Anna Kioumourtzoglou, assistant professor in environmental health sciences at Columbia’s Mailman School of Public Health, was a co-senior author.Other Harvard Chan School authors included Mahdieh Danesh Yazdi, Danielle Braun, Yaguang Wei, Yun Wang, Joel Schwartz, and Francesca Dominici.This study was supported by the Health Effects Institute (4953-RFA14-3/16-4), the National Institute of Environmental Health Sciences (NIEHS R01 ES024332, R01 ES028805, R21 ES028472, P30 ES009089, P30 ES000002), the National Institute on Aging (NIA/NIH R01 AG066793-01, P50 AG025688), and the HERCULES Center (P30ES019776). Research described in this article was done under contract to the Health Effects Institute, an organization jointly funded by the U.S propecia prices walmart. Environmental Protection Agency (assistance award number R-83467701) and some motor vehicle propecia prices walmart and engine manufacturers.“Long-term effects of PM2.5 on neurological disorders in the American Medicare population. A longitudinal cohort study,” Liuhua Shi, Xiao Wu, Mahdieh Danesh Yazdi, Danielle Braun, Yara Abu Awad, Yaguang Wei, Pengfei Liu, Qian Di, Yun Wang, Joel Schwartz, Francesca Dominici, Marianthi-Anna Kioumourtzoglou, Antonella Zanobetti, The Lancet Planetary Health, online October 19, 2020, doi.

Https://doi.org/10.1016/S2542-5196(20)30227-8Photo. IStock/hapabapaVisit the Harvard Chan School website for the latest news, press releases, and multimedia offerings.Nicole Rura617.221.4241nrura@hsph.harvard.edu###Harvard T.H. Chan School of Public Health brings together dedicated experts from many disciplines to educate new generations of global health leaders and produce powerful ideas that improve the lives and health of people everywhere. As a community of leading scientists, educators, and students, we work together to take innovative ideas from the laboratory to people’s lives—not only making scientific breakthroughs, but also working to change individual behaviors, public policies, and health care practices. Each year, more than 400 faculty members at Harvard Chan School teach 1,000-plus full-time students from around the world and train thousands more through online and executive education courses.

Founded in 1913 as the Harvard-MIT School of Health Officers, the School is recognized as America’s oldest professional training program in public health.CORVALLIS, Ore. €“ Oregon State University scientists have developed a method that could potentially predict the cancer-causing potential of chemicals released into the air during wildfires and fossil fuel combustion. The research, which was recently published in the journal Toxicology in Vitro, was conducted as a part of the OSU Superfund Research Program. The findings are important for agencies that regulate air pollution caused by these chemicals, known as polycyclic aromatic hydrocarbons (PAHs). It also could help medical researchers who study patients with conditions such as asthma.

PAHs are a class of chemicals that occur naturally in coal, crude oil and gasoline. They also are produced when coal, oil, gas, wood, garbage and tobacco are burned. At high levels, as was the case during recent wildfires in the western United States, when PAHs are inhaled they can be harmful to human health. Despite PAHs being the first class of chemicals identified as cancer-causing, little is known about the carcinogenic potential of the more than 1,500 PAHs. Part of the challenge is that PAHs usually occur as a mixture of chemicals, making it difficult to tease apart roles of individual chemicals in the mixture.

The OSU researchers, led by Susan Tilton, an associate professor in the Department of Environmental and Molecular Toxicology in the College of Agricultural Sciences, have been studying PAHs for over six years. They previously developed a system to predict whether tumors formed in mice exposed to certain PAHs. The current research translates that approach using human bronchial cells. The researchers treated the cells with individual PAHs and then used computational analysis to look at changes across thousands of genes simultaneously to identify gene signatures. They then looked for gene signatures consistent across the different chemicals with similar carcinogenic potential.

€œThose with similar carcinogenic potential are the ones we can focus on,” Tilton said. €œPotentially, in the future we wouldn’t need to look at thousands and thousands of genes. Once we tested enough chemicals and felt very confident about this we could drill down and look at a select handful of genes in order to make these types of predictions.” In the future, the researchers plan to expand the number of chemicals that they test, particularly chemicals whose carcinogenic potential is not well understood. They also want to study lung cells from people with pre-existing conditions, such as asthma and chronic obstructive pulmonary disease, to see if they are particularly sensitive to certain chemicals. Co-authors of the paper were Yvonne Chang, Celine Thanh Thu Huynh, Kelley M.

Bastin, Brianna N. Rivera, Lisbeth K. Siddens, all of Oregon State..

For immediate release buy real propecia online. October 19, 2020Boston, MA – Air pollution was significantly associated with an increased risk of hospital admissions for several neurological disorders, including Parkinson’s disease, Alzheimer’s disease, and other dementias, in a long-term buy real propecia online study of more than 63 million older U.S. Adults, led by researchers at Harvard T.H.

Chan School of Public Health.The study, conducted with colleagues at Emory University’s Rollins School of Public Health and Columbia University’s Mailman School of Public Health, is the first nationwide analysis of the link between fine particulate buy real propecia online (PM2.5) pollution and neurodegenerative diseases in the U.S. The researchers leveraged an unparalleled amount of data compared to any previous study of air pollution and neurological disorders.The study was published online October 19, 2020 in The Lancet Planetary Health.“The 2020 report of the Lancet Commission on dementia prevention, intervention, and care has added air pollution as one of the modifiable risk factors for these outcomes,” said Xiao Wu, doctoral student in biostatistics at Harvard Chan School and co-lead author of the study. €œOur study builds on the small but emerging evidence base indicating that long-term PM2.5 exposures are linked to an increased risk of neurological health deterioration, even at PM2.5 concentrations well below the current national standards.”Researchers looked at 17 buy real propecia online years’ worth (2000–2016) of hospital admissions data from 63,038,019 Medicare recipients in the U.S.

And linked these with estimated PM2.5 concentrations by zip buy real propecia online code. Taking into account potential confounding factors like socioeconomic status, they found that, for each 5 microgram per cubic meter of air (μg/m3) increase in annual PM2.5 concentrations, there was a 13% increased risk for first-time hospital admissions both for Parkinson’s disease and for Alzheimer’s disease and related dementias. This risk remained elevated even below supposedly safe levels of PM2.5 buy real propecia online exposure, which, according to current U.S.

Environmental Protection Agency standards, is an annual average of 12 μg/m3 or less.Women, white people, and urban populations were particularly susceptible, the study found. The highest risk for first-time Parkinson’s disease hospital admissions buy real propecia online was among older adults in the northeastern U.S. For first-time Alzheimer’s disease and related dementias hospital admissions, older adults in the Midwest faced the highest risk.“Our U.S.-wide study shows that the current standards are not protecting the aging American population enough, highlighting the need for stricter standards and policies that help further reduce PM2.5 concentrations and improve air quality overall,” said Antonella Zanobetti, principal research scientist in Harvard Chan School’s Department of Environmental Health and co-senior author of the study.Liuhua Shi, research assistant professor at Emory’s Rollins School of Public Health, was a co-lead author and Marianthi-Anna Kioumourtzoglou, assistant professor in environmental health sciences at Columbia’s Mailman School of Public Health, was a co-senior author.Other Harvard Chan School authors included Mahdieh Danesh Yazdi, Danielle Braun, Yaguang Wei, Yun Wang, Joel Schwartz, and Francesca Dominici.This study was supported by the Health Effects Institute (4953-RFA14-3/16-4), the National Institute of Environmental Health Sciences (NIEHS R01 ES024332, R01 ES028805, R21 ES028472, P30 ES009089, P30 ES000002), the National Institute on Aging (NIA/NIH R01 AG066793-01, P50 AG025688), and the HERCULES Center (P30ES019776).

Research described in this article was buy real propecia online done under contract to the Health Effects Institute, an organization jointly funded by the U.S. Environmental Protection buy real propecia online Agency (assistance award number R-83467701) and some motor vehicle and engine manufacturers.“Long-term effects of PM2.5 on neurological disorders in the American Medicare population. A longitudinal cohort study,” Liuhua Shi, Xiao Wu, Mahdieh Danesh Yazdi, Danielle Braun, Yara Abu Awad, Yaguang Wei, Pengfei Liu, Qian Di, Yun Wang, Joel Schwartz, Francesca Dominici, Marianthi-Anna Kioumourtzoglou, Antonella Zanobetti, The Lancet Planetary Health, online October 19, 2020, doi.

Https://doi.org/10.1016/S2542-5196(20)30227-8Photo. IStock/hapabapaVisit the Harvard Chan School website for the latest news, press releases, and multimedia offerings.Nicole Rura617.221.4241nrura@hsph.harvard.edu###Harvard T.H. Chan School of Public Health brings together dedicated experts from many disciplines to educate new generations of global health leaders and produce powerful ideas that improve the lives and health of people everywhere.

As a community of leading scientists, educators, and students, we work together to take innovative ideas from the laboratory to people’s lives—not only making scientific breakthroughs, but also working to change individual behaviors, public policies, and health care practices. Each year, more than 400 faculty members at Harvard Chan School teach 1,000-plus full-time students from around the world and train thousands more through online and executive education courses. Founded in 1913 as the Harvard-MIT School of Health Officers, the School is recognized as America’s oldest professional training program in public health.CORVALLIS, Ore.

€“ Oregon State University scientists have developed a method that could potentially predict the cancer-causing potential of chemicals released into the air during wildfires and fossil fuel combustion. The research, which was recently published in the journal Toxicology in Vitro, was conducted as a part of the OSU Superfund Research Program. The findings are important for agencies that regulate air pollution caused by these chemicals, known as polycyclic aromatic hydrocarbons (PAHs).

It also could help medical researchers who study patients with conditions such as asthma. PAHs are a class of chemicals that occur naturally in coal, crude oil and gasoline. They also are produced when coal, oil, gas, wood, garbage and tobacco are burned.

At high levels, as was the case during recent wildfires in the western United States, when PAHs are inhaled they can be harmful to human health. Despite PAHs being the first class of chemicals identified as cancer-causing, little is known about the carcinogenic potential of the more than 1,500 PAHs. Part of the challenge is that PAHs usually occur as a mixture of chemicals, making it difficult to tease apart roles of individual chemicals in the mixture.

The OSU researchers, led by Susan Tilton, an associate professor in the Department of Environmental and Molecular Toxicology in the College of Agricultural Sciences, have been studying PAHs for over six years. They previously developed a system to predict whether tumors formed in mice exposed to certain PAHs. The current research translates that approach using human bronchial cells.

The researchers treated the cells with individual PAHs and then used computational analysis to look at changes across thousands of genes simultaneously to identify gene signatures. They then looked for gene signatures consistent across the different chemicals with similar carcinogenic potential. €œThose with similar carcinogenic potential are the ones we can focus on,” Tilton said.

€œPotentially, in the future we wouldn’t need to look at thousands and thousands of genes. Once we tested enough chemicals and felt very confident about this we could drill down and look at a select handful of genes in order to make these types of predictions.” In the future, the researchers plan to expand the number of chemicals that they test, particularly chemicals whose carcinogenic potential is not well understood. They also want to study lung cells from people with pre-existing conditions, such as asthma and chronic obstructive pulmonary disease, to see if they are particularly sensitive to certain chemicals.

Co-authors of the paper were Yvonne Chang, Celine Thanh Thu Huynh, Kelley M. Bastin, Brianna N. Rivera, Lisbeth K.

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Credit. IStock Share Fast Facts New @HopkinsMedicine study finds African-American women with common form of hair loss at increased risk of uterine fibroids - Click to Tweet New study in @JAMADerm shows most common form of alopecia (hair loss) in African-American women associated with higher risks of uterine fibroids - Click to Tweet In a study of medical records gathered on hundreds of thousands of African-American women, Johns Hopkins researchers say they have evidence that women with a common form of hair loss have an increased chance of developing uterine leiomyomas, or fibroids.In a report on the research, published in the December 27 issue of JAMA Dermatology, the researchers call on physicians who treat women with central centrifugal cicatricial alopecia (CCCA) to make patients aware that they may be at increased risk for fibroids and should be screened for the condition, particularly if they have symptoms such as heavy bleeding and pain. CCCA predominantly affects black women and is the most common form of permanent alopecia in this population. The excess scar tissue that forms as a result of this type of hair loss may also explain the higher risk for uterine fibroids, which are characterized by fibrous growths in the lining of the womb.

Crystal Aguh, M.D., assistant professor of dermatology at the Johns Hopkins University School of Medicine, says the scarring associated with CCCA is similar to the scarring associated with excess fibrous tissue elsewhere in the body, a situation that may explain why women with this type of hair loss are at a higher risk for fibroids.People of African descent, she notes, are more prone to develop other disorders of abnormal scarring, termed fibroproliferative disorders, such as keloids (a type of raised scar after trauma), scleroderma (an autoimmune disorder marked by thickening of the skin as well as internal organs), some types of lupus and clogged arteries. During a four-year period from 2013-2017, the researchers analyzed patient data from the Johns Hopkins electronic medical record system (Epic) of 487,104 black women ages 18 and over. The prevalence of those with fibroids was compared in patients with and without CCCA. Overall, the researchers found that 13.9 percent of women with CCCA also had a history of uterine fibroids compared to only 3.3 percent of black women without the condition.

In absolute numbers, out of the 486,000 women who were reviewed, 16,212 had fibroids.Within that population, 447 had CCCA, of which 62 had fibroids. The findings translate to a fivefold increased risk of uterine fibroids in women with CCCA, compared to age, sex and race matched controls. Aguh cautions that their study does not suggest any cause and effect relationship, or prove a common cause for both conditions. €œThe cause of the link between the two conditions remains unclear,” she says.

However, the association was strong enough, she adds, to recommend that physicians and patients be made aware of it. Women with this type of scarring alopecia should be screened not only for fibroids, but also for other disorders associated with excess fibrous tissue, Aguh says. An estimated 70 percent of white women and between 80 and 90 percent of African-American women will develop fibroids by age 50, according to the NIH, and while CCCA is likely underdiagnosed, some estimates report a prevalence of rates as high as 17 percent of black women having this condition. The other authors on this paper were Ginette A.

Okoye, M.D. Of Johns Hopkins and Yemisi Dina of Meharry Medical College.Credit. The New England Journal of Medicine Share Fast Facts This study clears up how big an effect the mutational burden has on outcomes to immune checkpoint inhibitors across many different cancer types. - Click to Tweet The number of mutations in a tumor’s DNA is a good predictor of whether it will respond to a class of cancer immunotherapy drugs known as checkpoint inhibitors.

- Click to Tweet The “mutational burden,” or the number of mutations present in a tumor’s DNA, is a good predictor of whether that cancer type will respond to a class of cancer immunotherapy drugs known as checkpoint inhibitors, a new study led by Johns Hopkins Kimmel Cancer Center researchers shows. The finding, published in the Dec. 21 New England Journal of Medicine, could be used to guide future clinical trials for these drugs. Checkpoint inhibitors are a relatively new class of drug that helps the immune system recognize cancer by interfering with mechanisms cancer cells use to hide from immune cells.

As a result, the drugs cause the immune system to fight cancer in the same way that it would fight an . These medicines have had remarkable success in treating some types of cancers that historically have had poor prognoses, such as advanced melanoma and lung cancer. However, these therapies have had little effect on other deadly cancer types, such as pancreatic cancer and glioblastoma. The mutational burden of certain tumor types has previously been proposed as an explanation for why certain cancers respond better than others to immune checkpoint inhibitors says study leader Mark Yarchoan, M.D., chief medical oncology fellow.

Work by Dung Le, M.D., associate professor of oncology, and other researchers at the Johns Hopkins Kimmel Cancer Center and its Bloomberg~Kimmel Cancer Institute for Cancer Immunotherapy showed that colon cancers that carry a high number of mutations are more likely to respond to checkpoint inhibitors than those that have fewer mutations. However, exactly how big an effect the mutational burden has on outcomes to immune checkpoint inhibitors across many different cancer types was unclear. To investigate this question, Yarchoan and colleagues Alexander Hopkins, Ph.D., research fellow, and Elizabeth Jaffee, M.D., co-director of the Skip Viragh Center for Pancreas Cancer Clinical Research and Patient Care and associate director of the Bloomberg~Kimmel Institute, combed the medical literature for the results of clinical trials using checkpoint inhibitors on various different types of cancer. They combined these findings with data on the mutational burden of thousands of tumor samples from patients with different tumor types.

Analyzing 27 different cancer types for which both pieces of information were available, the researchers found a strong correlation. The higher a cancer type’s mutational burden tends to be, the more likely it is to respond to checkpoint inhibitors. More than half of the differences in how well cancers responded to immune checkpoint inhibitors could be explained by the mutational burden of that cancer. €œThe idea that a tumor type with more mutations might be easier to treat than one with fewer sounds a little counterintuitive.

It’s one of those things that doesn’t sound right when you hear it,” says Hopkins. €œBut with immunotherapy, the more mutations you have, the more chances the immune system has to recognize the tumor.” Although this finding held true for the vast majority of cancer types they studied, there were some outliers in their analysis, says Yarchoan. For example, Merkel cell cancer, a rare and highly aggressive skin cancer, tends to have a moderate number of mutations yet responds extremely well to checkpoint inhibitors. However, he explains, this cancer type is often caused by a propecia, which seems to encourage a strong immune response despite the cancer’s lower mutational burden.

In contrast, the most common type of colorectal cancer has moderate mutational burden, yet responds poorly to checkpoint inhibitors for reasons that are still unclear. Yarchoan notes that these findings could help guide clinical trials to test checkpoint inhibitors on cancer types for which these drugs haven’t yet been tried. Future studies might also focus on finding ways to prompt cancers with low mutational burdens to behave like those with higher mutational burdens so that they will respond better to these therapies. He and his colleagues plan to extend this line of research by investigating whether mutational burden might be a good predictor of whether cancers in individual patients might respond well to this class of immunotherapy drugs.

€œThe end goal is precision medicine—moving beyond what’s true for big groups of patients to see whether we can use this information to help any given patient,” he says. Yarchoan receives funding from the Norman &. Ruth Rales Foundation and the Conquer Cancer Foundation. Through a licensing agreement with Aduro Biotech, Jaffee has the potential to receive royalties in the future..

Credit finasteride propecia price buy real propecia online. IStock Share Fast Facts New @HopkinsMedicine study finds African-American women with common form of hair loss at increased risk of uterine fibroids - Click to Tweet New study in @JAMADerm shows most common form of alopecia (hair loss) in African-American women associated with higher risks of uterine fibroids - Click to Tweet In a study of medical records gathered on hundreds of thousands of African-American women, Johns Hopkins researchers say they have evidence that women with a common form of hair loss have an increased chance of developing uterine leiomyomas, or fibroids.In a report on the research, published in the December 27 issue of JAMA Dermatology, the researchers call on physicians who treat women with central centrifugal cicatricial alopecia (CCCA) to make patients aware that they may be at increased risk for fibroids and should be screened for the condition, particularly if they have symptoms such as heavy bleeding and pain. CCCA predominantly affects black women and is the most buy real propecia online common form of permanent alopecia in this population. The excess scar tissue that forms as a result of this type of hair loss may also explain the higher risk for uterine fibroids, which are characterized by fibrous growths in the lining of the womb. Crystal Aguh, M.D., assistant professor of dermatology at the Johns Hopkins University School of Medicine, says the scarring associated with CCCA is similar to the scarring associated with excess fibrous tissue elsewhere in the body, a situation that may explain why women with this type of hair loss are at a higher risk for fibroids.People of African descent, she notes, are more prone to develop other disorders of abnormal scarring, termed fibroproliferative disorders, such as keloids (a type buy real propecia online of raised scar after trauma), scleroderma (an autoimmune disorder marked by thickening of the skin as well as internal organs), some types of lupus and clogged arteries.

During a four-year period from 2013-2017, the researchers analyzed patient data from the Johns Hopkins electronic medical record system (Epic) of 487,104 black women ages 18 and over. The prevalence of those with fibroids was compared in patients with and without buy real propecia online CCCA. Overall, the researchers found that 13.9 percent of women with CCCA also had a history of uterine fibroids compared to only 3.3 percent of black women without the condition. In absolute numbers, out of the 486,000 women who were reviewed, 16,212 had fibroids.Within that population, 447 had CCCA, of which 62 had fibroids. The findings translate to a fivefold increased risk of uterine fibroids in women with CCCA, compared to age, buy real propecia online sex and race matched controls.

Aguh cautions that their study does not suggest any cause and effect relationship, or prove a common cause for both conditions. €œThe cause of the link between the buy real propecia online two conditions remains unclear,” she says. However, the association was strong enough, she adds, to recommend that physicians and patients be made aware of it. Women with buy real propecia online this type of scarring alopecia should be screened not only for fibroids, but also for other disorders associated with excess fibrous tissue, Aguh says. An estimated 70 percent of white women and between 80 and 90 percent of African-American women will develop fibroids by age 50, according to the NIH, and while CCCA is likely underdiagnosed, some estimates report a prevalence of rates as high as 17 percent of black women having this condition.

The other authors on this paper were Ginette buy real propecia online A. Okoye, M.D. Of Johns Hopkins and Yemisi Dina of Meharry Medical College.Credit. The New England Journal of Medicine Share Fast Facts This study buy real propecia online clears up how big an effect the mutational burden has on outcomes to immune checkpoint inhibitors across many different cancer types. - Click to Tweet The number of mutations in a tumor’s DNA is a good predictor of whether it will respond to a class of cancer immunotherapy drugs known as checkpoint inhibitors.

- Click to Tweet The “mutational burden,” or the number of mutations present in a tumor’s DNA, is a good predictor of whether that cancer type will respond to a class of cancer immunotherapy drugs known as checkpoint inhibitors, a new study led by Johns Hopkins Kimmel Cancer buy real propecia online Center researchers shows. The finding, published in the Dec. 21 New England Journal of Medicine, could be used to guide future clinical trials buy real propecia online for these drugs. Checkpoint inhibitors are a relatively new class of drug that helps the immune system recognize cancer by interfering with mechanisms cancer cells use to hide from immune cells. As a result, the drugs cause the immune system to fight cancer in the same way that it would fight an .

These medicines have had remarkable success in treating some types of cancers that historically have had poor prognoses, such as advanced melanoma and lung buy real propecia online cancer. However, these therapies have had little effect on other deadly cancer types, such as pancreatic cancer and glioblastoma. The mutational burden of certain tumor types has previously been proposed as an explanation for why certain cancers respond buy real propecia online better than others to immune checkpoint inhibitors says study leader Mark Yarchoan, M.D., chief medical oncology fellow. Work by Dung Le, M.D., associate professor of oncology, and other researchers at the Johns Hopkins Kimmel Cancer Center and its Bloomberg~Kimmel Cancer Institute for Cancer Immunotherapy showed that colon cancers that carry a high number of mutations are more likely to respond to checkpoint inhibitors than those that have fewer mutations. However, exactly how big an effect the mutational burden has on buy real propecia online outcomes to immune checkpoint inhibitors across many different cancer types was unclear.

To investigate this question, Yarchoan and colleagues Alexander Hopkins, Ph.D., research fellow, and Elizabeth Jaffee, M.D., co-director of the Skip Viragh Center for Pancreas Cancer Clinical Research and Patient Care and associate director of the Bloomberg~Kimmel Institute, combed the medical literature for the results of clinical trials using checkpoint inhibitors on various different types of cancer. They combined these findings with data on the mutational burden of buy real propecia online thousands of tumor samples from patients with different tumor types. Analyzing 27 different cancer types for which both pieces of information were available, the researchers found a strong correlation. The higher a cancer type’s mutational burden tends to be, the more likely it is to respond to checkpoint inhibitors. More than half of the differences buy real propecia online in how well cancers responded to immune checkpoint inhibitors could be explained by the mutational burden of that cancer.

€œThe idea that a tumor type with more mutations might be easier to treat than one with fewer sounds a little counterintuitive. It’s one of those things that doesn’t sound buy real propecia online right when you hear it,” says Hopkins. €œBut with immunotherapy, the more mutations you have, the more chances the immune system has to recognize the tumor.” Although this finding held true for the vast majority of cancer types they studied, there were some outliers in their analysis, says Yarchoan. For example, Merkel cell cancer, a rare and highly aggressive skin cancer, tends to have buy real propecia online a moderate number of mutations yet responds extremely well to checkpoint inhibitors. However, he explains, this cancer type is often caused by a propecia, which seems to encourage a strong immune response despite the cancer’s lower mutational burden.

In contrast, the most common type of colorectal cancer has moderate mutational burden, yet responds poorly to checkpoint inhibitors for reasons that are still unclear. Yarchoan notes that these findings could help guide clinical trials to test checkpoint inhibitors on cancer types for buy real propecia online which these drugs haven’t yet been tried. Future studies might also focus on finding ways to prompt cancers with low mutational burdens to behave like those with higher mutational burdens so that they will respond better to these therapies. He and his colleagues plan to extend this line of research by investigating buy real propecia online whether mutational burden might be a good predictor of whether cancers in individual patients might respond well to this class of immunotherapy drugs. €œThe end goal is precision medicine—moving beyond what’s true for big groups of patients to see whether we can use this information to help any given patient,” he says.

Yarchoan receives funding from the Norman buy real propecia online &. Ruth Rales Foundation and the Conquer Cancer Foundation. Through a licensing agreement with Aduro Biotech, Jaffee has the potential to receive royalties in the future..

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A study led by researchers at the UCLA Jonsson Comprehensive Cancer Center has found that magnetic resonance imaging, or MRI, frequently underestimates the size of prostate tumors, potentially leading to undertreatment.The study authors found that such underestimation occurs most often when the MRI-measured tumor size is small and the PI-RADS score, which is used to classify lesions in prostate MRI analysis, is low.For what i should buy with propecia prostate tumor generic propecia online for sale treatments to be successful, both the MRI size measurement and PI-RADS score must be accurate because they allow physicians to determine precisely where tumors end and where the normal, healthy tissue surrounding them begins.MRI is frequently used to diagnose and manage prostate cancer. It is also increasingly used as a means to map and guide delivery of new, highly focused therapies that use freezing (cryotherapy), ultrasound (HIFU) and heat (laser ablation) to destroy cancerous tissue in the prostate gland while sparing healthy tissue.Researchers compared MRI-measured tumor size with actual tumor size after prostate removal in 441 men treated for prostate cancer.Improving the ability to better predict ablation margins will allow for more successful treatments for men with prostate cancer and can help reduce the morbidity of prostate cancer treatment. Story Source what i should buy with propecia. Materials provided by University of California - Los Angeles http://www.em-gliesberg-strasbourg.ac-strasbourg.fr/?page_id=173 Health Sciences.

Note. Content may be edited for style and length..

A study led Click Here by researchers at the UCLA buy real propecia online Jonsson Comprehensive Cancer Center has found that magnetic resonance imaging, or MRI, frequently underestimates the size of prostate tumors, potentially leading to undertreatment.The study authors found that such underestimation occurs most often when the MRI-measured tumor size is small and the PI-RADS score, which is used to classify lesions in prostate MRI analysis, is low.For prostate tumor treatments to be successful, both the MRI size measurement and PI-RADS score must be accurate because they allow physicians to determine precisely where tumors end and where the normal, healthy tissue surrounding them begins.MRI is frequently used to diagnose and manage prostate cancer. It is also increasingly used as a means to map and guide delivery of new, highly focused therapies that use freezing (cryotherapy), ultrasound (HIFU) and heat (laser ablation) to destroy cancerous tissue in the prostate gland while sparing healthy tissue.Researchers compared MRI-measured tumor size with actual tumor size after prostate removal in 441 men treated for prostate cancer.Improving the ability to better predict ablation margins will allow for more successful treatments for men with prostate cancer and can help reduce the morbidity of prostate cancer treatment. Story Source buy real propecia online. Materials provided by University of California - Los Angeles Health Sciences.

Note. Content may be edited for style and length..

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Post-Authorization Activity Table (PAAT) for Post-Authorization Activity Table (PAAT) RowNum Activity/submission type, control number Date propecia withdrawal submitted Decision and http://matthewmusser.com/can-i-buy-cialis-online/ date Summary of activities Summary Basis of Decision (SBD) for Date SBD issued. The following information relates to the new drug submission for. Drug Identification Number (DIN). 1 propecia withdrawal What was approved?.

2 Why was approved?. 3 What steps led to the approval of ?. Submission Milestones. Submission Milestone Date 4 What follow-up measures will the company take?.

5 What post-authorization activity has taken place for ?. 6 What other information is available about drugs?. Summary Basis of Decision (SBD) documents provide information related to the original authorization of a product. The SBD for is located below.

Recent Activity for SBDs written for eligible drugs approved after September 1, 2012 will be updated to include post-authorization information. This information will be compiled in a Post-Authorization Activity Table (PAAT). The PAAT will include brief summaries of activities such as submissions for new uses of the product, and whether Health Canada's decisions were negative or positive.

Can i buy cialis online 1 What buy real propecia online was approved?. 2 Why was approved?. 3 What steps led to the approval of ?.

Submission Milestones. Submission Milestone Date 4 What follow-up measures will the company take?. 5 What post-authorization activity has taken place for ?.

6 What other information is available about drugs?. Summary Basis of Decision (SBD) documents provide information related to the original authorization of a product. The SBD for is located below.

Recent Activity for SBDs written for eligible drugs approved after September 1, 2012 will be updated to include post-authorization information. This information will be compiled in a Post-Authorization Activity Table (PAAT). The PAAT will include brief summaries of activities such as submissions for new uses of the product, and whether Health Canada's decisions were negative or positive.

PAATs will be updated regularly with post-authorization activity throughout the product's life cycle. Post-Authorization Activity Table (PAAT) for Post-Authorization Activity Table (PAAT) RowNum Activity/submission type, control number Date submitted Decision and date Summary of activities Summary Basis of Decision (SBD) for Date SBD issued. The following information relates to the new drug submission for.

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Over the past 20 years, a large body of research has documented a relationship between higher nurse-to-patient staffing ratios and better patient outcomes, including shorter hospital stays, lower rates of failure to prevent mortality after an in-hospital complication, inpatient mortality for multiple types of patients, hospital-acquired pneumonia, unplanned extubation, respiratory failure and cardiac arrest.1–5 In addition, patients report higher satisfaction when they are cared for in hospitals with higher staffing levels.6 7To date, most studies have not identified where can i buy propecia over the counter usa an ‘optimal’ nurse staffing ratio,8 which creates a challenge for determining appropriate staffing levels. If increasing nurse staffing always produces at least some improvement in the quality of care, how does one determine what staffing level is best?. This decision where can i buy propecia over the counter usa is ultimately an economic one, balancing the benefits of nurse staffing with the other options for which those resources could be used. It is in this context that hospitals develop staffing plans, generally based on historical patterns of patient acuity.Practical challenges of nurse staffingHospital staffing plans provide the structure necessary for determining hiring and scheduling, but fall short for a number of reasons. First, there are multiple ways in which where can i buy propecia over the counter usa patient acuity can be measured, which can have measurable effects on the staffing levels resulting from acuity models.9 Second, patient volume and acuity can shift rapidly with changes in the volume of admissions, discharges and transfers between units.

Third, staffing plans provide little guidance regarding the optimal mix of permanent staff, variable staff and externally contracted staff.The paper by Saville and colleagues10 in this issue of BMJ Quality &. Safety addresses the latter where can i buy propecia over the counter usa two issues by applying a simulation model to identify the optimal target for baseline nurse staffing in order to minimise periods of understaffing. Included in this model is consideration of the extent to which hospitals should leverage temporary personnel (typically obtained through an external agency) to fill gaps. The model acknowledges the likelihood that a where can i buy propecia over the counter usa hospital cannot realistically prevent all shifts from having a shortfall of nurses at all times, as well as the reality that hospital managers lack information about the best balance between permanent and temporary staff. In addition, the analysis includes a calculation of the costs of each staffing approach, drawing from the records of 81 inpatient wards in four hospital organisations.The application of sophisticated simulation models and other advanced analyticl approaches to analysis of nurse staffing has been limited to date, and this paper is an exemplar of the value of such research.

Recent studies have used machine learning methods to forecast hospital discharge volume,11 a discrete event simulation model to determine nursing staff needs in a neonatal intensive care unit,12 and a prediction model using machine learning and hierarchical linear regression to link variation in nurse staffing with patient outcomes.13 This new study applied a unique Monte Carlo simulation model to estimate demand for nursing care where can i buy propecia over the counter usa and test different strategies to meet demand.The results of the analysis are not surprising in that hospitals are much less likely to experience understaffed patient shifts if they aim to have higher baseline staffing. The data demonstrate a notable leftward skew, indicating that hospitals are more likely to have large unanticipated increases in patient volume and acuity than to have unanticipated decreases. This results in hospitals being more likely to have shifts that are understaffed than shifts that are overstaffed, which inevitably places pressure on where can i buy propecia over the counter usa hospitals to staff at a higher level and/or have access to a larger pool of temporary nurses. It also is not surprising that hospitals will need to spend more money per patient day if they aim to reduce the percent of shifts that are understaffed. What is surprising about the results is that hospitals do not necessarily achieve cost savings by relying on temporary personnel versus setting regular staffing at a higher level.Trade-offs between permanent and temporary staffThe temporary nursing workforce enables healthcare facilities to maintain flexible yet full care teams based on patient care needs.

Hospitals can use temporary nurses to address staffing gaps during leaves where can i buy propecia over the counter usa of absence, turnover or gaps between recruitment of permanent nurses, as well as during high-census periods. Temporary personnel are typically more expensive on an hourly basis than permanent staff. In addition, over-reliance on temporary staff can have detrimental effects on where can i buy propecia over the counter usa permanent nurses’ morale and motivation. Orientations prior to shifts are often limited, which leads to a twofold concern as temporary nurses feel ill-prepared for shifts and permanent staff feel flustered when required to bring the temporary nurse up to speed while being expected to continue normal operations.14 Agency nurses may be assigned to patients and units that are incongruent with their experience and skills—either to unfamiliar units, which affects their ability to confidently deliver care, or to less complex patients where they feel as if their skills are not used adequately.14 15 These issues can create tension between temporary and permanent nursing staff, which can be compounded by the wage disparity. Permanent staff might feel demoralised and expendable when working alongside temporary staff who are not integrated into the social fabric of where can i buy propecia over the counter usa the staff.16Hospital managers also must be cognisant of the potential quality impact of relying heavily on temporary nursing staff.

Research on the impact of contingent nursing employment on costs and quality have often found negative effects on quality, including mortality, and higher costs.17 18 However, other studies have found that the association between temporary nursing staff and low quality result from general shortages of nursing staff, which make a hospital more likely to employ temporary staff, and not directly from the contingent staff.19–21 Thus, temporary nurses play an important role in alleviating staffing shortages that would otherwise lead to lower quality of care.22Charting a path forward in hospital management and healthcare researchThe maturation of electronic health records and expansion of computerised healthcare management systems provide opportunities both for improved decision making about workforce deployment and for advanced workforce research. In the area of workforce management, nursing and where can i buy propecia over the counter usa other leaders have a growing array of workforce planning tools available to them. Such tools are most effective when they display clear information about predicted patient needs and staff availability, but managers still must rely on their on-the-ground understanding of their staff and their context of patient care.23 Integration of human resources data with patient outcomes data has revealed that individual nurses and their characteristics have important discrete effects on the quality of care.24 25 Future development of workforce planning tools should translate this evidence to practice. In addition, new technology platforms are emerging to facilitate direct matching between temporary healthcare personnel and healthcare where can i buy propecia over the counter usa organisations. One recent study tested a smartphone-based application that allowed for direct matching of locum tenens physicians with a hospital in the English National Health Service, finding that the platform generated benefits including greater transparency and lower cost.26 Similar technologies for registered nurses could facilitate better matching between hospital needs and temporary nurses’ preparedness to meet those needs.Analytical methods that fully leverage the large datasets compiled through electronic health records, human resources systems and other sources can be applied to advance research on the composition of nursing teams to improve quality of care.

As noted above, prior research has applied machine learning and where can i buy propecia over the counter usa discrete event simulation to analyses of healthcare staffing. Other recent studies have leveraged natural language processing of nursing notes to identify fall risk factors27 and applied data mining of human resources records to understand the job titles held by nurses.28 Linking these rapidly advancing analytical approaches that assess the outcomes and costs of nurse staffing strategies, such as the work by Saville and colleagues published in this issue, to data on the impact of nurse staffing on the long-term costs of patient care will further advance the capacity of hospital leaders to design cost-effective policies for workforce deployment.Guidelines aim to align clinical care with best practice. However, simply publishing a guideline rarely triggers behavioural changes to match guideline recommendations.1–3 We thus transform guideline recommendations into actionable tasks by introducing interventions that promote behavioural changes meant to produce guideline-concordant care. Unfortunately, not much has changed in the 25 years since Oxman and colleagues concluded that we have no ‘magic bullets’ when it comes to changing clinician behaviour.4 In fact, far from magic bullets, interventions aimed at increasing the degree to which patients receive care recommended in guidelines (eg, educational interventions, reminders, audit and feedback, financial incentives, computerised decision support) typically produce disappointingly small improvements in care.5–10Much improvement work aims to ‘make the right thing to do the easy thing to do.’ Yet, design solutions which where can i buy propecia over the counter usa hardwire the desired actions remain few and far between. Further, improvement interventions which ‘softwire’ such actions—not guaranteeing that they occur, but at least increasing the likelihood that clinicians will deliver the care recommended in guidelines—mostly produce small improvements.5–9 Until this situation changes, we need to acknowledge the persistent reality that guidelines themselves represent a main strategy for promoting care consistent with current evidence, which means their design should promote the desired actions.11 12In this respect, guidelines constitute a type of clinical decision support.

And, like all decision where can i buy propecia over the counter usa support interventions, guidelines require. (1) user testing to assess if the content is understood as intended and (2) empirical testing to assess if the decision support provided by the guideline does in fact promote the desired behaviours. While the processes for developing guidelines have received substantial attention over the years,13–18 surprisingly little attention has been paid to empirically answering basic questions about the where can i buy propecia over the counter usa finished product. Do users understand guidelines as intended?. And, what version of a given guideline engenders the desired behaviours by where can i buy propecia over the counter usa clinicians?.

In this issue of BMJ Quality and Safety, Jones et al19 address this gap by using simulation to compare the frequency of medication errors when clinicians administer an intravenous medication using an existing guideline in the UK’s National Health Service (NHS) versus a revised and user-tested version of the guideline that more clearly promotes the desired actions. Their findings demonstrate that changes to guideline design (through addition of actionable decision supports) based on user feedback does in fact trigger changes in behaviour that can improve where can i buy propecia over the counter usa safety. This is an exciting use of simulation, which we believe should encourage further studies in this vein.Ensuring end users understand and use guidelines as intendedJones and colleagues’ approach affords an opportunity to reflect on the benefits of user testing and simulation of guidelines. The design and evaluation of their revised guidelines provides an excellent example of a where can i buy propecia over the counter usa careful stepwise progression in the development and evaluation of a guideline as a type of decision support for clinicians. First, in a prior study,20 they user tested the original NHS guidelines to improve retrieval and comprehension of information.

The authors produced a revised guideline, which included reformatted sections as well as increased support for key calculations, such as for infusion rates. The authors again user tested the revised guideline, successfully showing where can i buy propecia over the counter usa higher rates of comprehension. Note that user testing refers to a specific approach focused on comprehension rather than behaviour21 and is distinct from usability testing. Second, in the current study, Jones et al evaluated whether nurse where can i buy propecia over the counter usa and midwife end users exhibited the desired behavioural changes when given the revised guidelines (with addition of actionable decision supports), compared with a control group working with the current version of the guidelines used in practice. As a result, Jones and colleagues verify that end users (1) understand the content in the guideline and (2) actually change their behaviour in response to using it.Simulation can play a particularly useful role in this context, as it can help identify problems with users’ comprehension of the guideline and also empirically assess what behavioural changes occur in response to design changes in the guidelines.

The level of methodological control and qualitative detail that simulation provides is difficult where can i buy propecia over the counter usa to feasibly replicate with real-world pilot studies, and therefore simulation fills a critical gap.Jones et al report successful changes in behaviour due to the revised guidelines in which they added actionable decision supports. For example, their earlier user testing found that participants using the initial guidelines did not account for displacement volume when reconstituting the powdered drug, leading to dosing errors. A second error with the initial guidelines involved participants using the shortest infusion rate provided (eg, guidelines state ‘1 to 3 hours’), without realising that the shortest rate is not appropriate for certain doses (eg, 1 hour is appropriate for smaller doses, but larger doses should not be infused over 1 hour because the drug where can i buy propecia over the counter usa would then be administered faster than the maximum allowable infusion rate of 3 mg/kg/hour). These two issues were addressed in the revised guidelines by providing key determinants for ‘action’ such as calculation formulas that account for displacement volume and infusion duration, thereby more carefully guiding end users to avoid these dose and rate errors. These changes to the guideline triggered specific behaviours (eg, where can i buy propecia over the counter usa calculations that account for all variables) that did not occur with the initial guidelines.

Therefore, the simulation testing demonstrated the value of providing determinants for action, such as specific calculation formulas to support end users, by showing a clear reduction in dose and rate errors when using the revised guidelines compared with the initial guidelines.The authors also report that other types of medication-specific errors remained unaffected by the revised guidelines (eg, incorrect technique and flush errors)—the changes made did not facilitate the desired actions. The initial where can i buy propecia over the counter usa guidelines indicate ‘DO NOT SHAKE’ in capital letters, and there is a section specific to ‘Flushing’. In contrast, the revised guidelines do not capitalise the warning about shaking the vial, but embed the warning with a numbered sequence in the medication preparation section, aiming to increase the likelihood of reading it at the appropriate time. The revised guidelines do not have a section specific to flushing, but embed the flushing instructions as an unnumbered step in the administration section. Thus, the value of embedding technique and flushing information within the context of use was not validated in the simulation testing (ie, no significant differences in the rates of these errors), highlighting precisely the pivotal role that simulation can play in assessing whether attempts to improve usability result in actual behavioural changes.Finally, simulation can where can i buy propecia over the counter usa identify potential unintended consequences of a guideline.

For instance, Jones and colleagues observed an increase in errors (although not statistically significant) that were not medication specific (eg, non-aseptic technique such as hand washing, swabbing vials with an alcohol wipe). Given that the revised guidelines were specific to the medication tested, it is unusual where can i buy propecia over the counter usa that we see a tendency toward a worsening effect on generic medication preparation skills. Again, this finding was not significant, but we highlight this to remind ourselves of the very real possibility that some interventions might introduce new and unexpected errors in response to changing workflow and practice6. Simulations offer an opportunity to spot these where can i buy propecia over the counter usa risks in advance.Now that Jones et al have seen how the revised guidelines change behaviour, they are optimally positioned to move forward. On one hand, they have the option of revising the guidelines further in attempts to address these resistant errors, and on the other, they can consider designing other interventions to be implemented in parallel with their user-tested guidance.

At first glance, the errors that were resistant to change appear to be mechanical tasks that end users might think of as applying uniformly where can i buy propecia over the counter usa to multiple medications (eg, flush errors, non-aseptic technique). Therefore, a second intervention that has a more general scope (rather than drug specific) might be pursued. Regardless of what they decide to pursue, we applaud their measured approach and highlight that the key takeaway is that their next steps are supported with clearer evidence of what to expect when the guidelines are released—certainly a helpful piece of information to guide decisions as to whether broad implementation of guidelines is justified.Caveats and conclusionSimulation is not where can i buy propecia over the counter usa a panacea—it is not able to assess longitudinal adherence, and there are limitations to how realistically clinicians behave when observed for a few sample procedures when under the scrutiny of observers. Further, studies where interventions are implemented to assess whether they move the needle on the outcomes we care about (eg, adverse events, length of stay, patient mortality) are needed and should continue. However, having end users physically perform clinical tasks with the intervention in representative environments represents an important strategy to assess the degree to which guidelines and other decision support interventions in fact promote the desired behaviours and to spot where can i buy propecia over the counter usa problems in advance of implementation.

Such simulation testing is not currently a routine step in intervention design. We hope it becomes a more common phenomenon, with more improvement work following the example of the approach so effectively demonstrated by Jones and colleagues..

Over the past 20 years, a large body of research has documented a relationship between higher nurse-to-patient staffing ratios and better patient outcomes, including shorter hospital stays, lower rates of failure to prevent mortality after an in-hospital complication, inpatient mortality for multiple types of patients, hospital-acquired pneumonia, unplanned extubation, respiratory failure and cardiac arrest.1–5 In addition, patients report higher satisfaction when they are cared for in hospitals with higher staffing levels.6 buy real propecia online 7To date, most studies have not identified an ‘optimal’ nurse staffing ratio,8 which creates a challenge for determining appropriate staffing levels. If increasing nurse staffing always produces at least some improvement in the quality of care, how does one determine what staffing level is best?. This decision is ultimately buy real propecia online an economic one, balancing the benefits of nurse staffing with the other options for which those resources could be used.

It is in this context that hospitals develop staffing plans, generally based on historical patterns of patient acuity.Practical challenges of nurse staffingHospital staffing plans provide the structure necessary for determining hiring and scheduling, but fall short for a number of reasons. First, there are multiple ways in buy real propecia online which patient acuity can be measured, which can have measurable effects on the staffing levels resulting from acuity models.9 Second, patient volume and acuity can shift rapidly with changes in the volume of admissions, discharges and transfers between units. Third, staffing plans provide little guidance regarding the optimal mix of permanent staff, variable staff and externally contracted staff.The paper by Saville and colleagues10 in this issue of BMJ Quality &.

Safety addresses the latter two issues by applying a simulation buy real propecia online model to identify the optimal target for baseline nurse staffing in order to minimise periods of understaffing. Included in this model is consideration of the extent to which hospitals should leverage temporary personnel (typically obtained through an external agency) to fill gaps. The model acknowledges the likelihood that a hospital cannot realistically prevent all shifts from having a shortfall of nurses at all times, buy real propecia online as well as the reality that hospital managers lack information about the best balance between permanent and temporary staff.

In addition, the analysis includes a calculation of the costs of each staffing approach, drawing from the records of 81 inpatient wards in four hospital organisations.The application of sophisticated simulation models and other advanced analyticl approaches to analysis of nurse staffing has been limited to date, and this paper is an exemplar of the value of such research. Recent studies have used machine learning methods to forecast hospital discharge volume,11 a discrete event simulation model to determine nursing staff needs in a neonatal intensive care unit,12 and a prediction model using machine learning and hierarchical linear regression to link variation in nurse staffing with patient outcomes.13 This new study applied a unique Monte Carlo simulation model to estimate buy real propecia online demand for nursing care and test different strategies to meet demand.The results of the analysis are not surprising in that hospitals are much less likely to experience understaffed patient shifts if they aim to have higher baseline staffing. The data demonstrate a notable leftward skew, indicating that hospitals are more likely to have large unanticipated increases in patient volume and acuity than to have unanticipated decreases.

This results in hospitals being more likely to have shifts that are understaffed than shifts that are overstaffed, which inevitably places pressure on hospitals to staff at a higher level and/or have access to buy real propecia online a larger pool of temporary nurses. It also is not surprising that hospitals will need to spend more money per patient day if they aim to reduce the percent of shifts that are understaffed. What is surprising about the results is that hospitals do not necessarily achieve cost savings by relying on temporary personnel versus setting regular staffing at a higher level.Trade-offs between permanent and temporary staffThe temporary nursing workforce enables healthcare facilities to maintain flexible yet full care teams based on patient care needs.

Hospitals can use temporary nurses to address staffing gaps during leaves of absence, turnover or gaps between recruitment of permanent buy real propecia online nurses, as well as during high-census periods. Temporary personnel are typically more expensive on an hourly basis than permanent staff. In addition, buy real propecia online over-reliance on temporary staff can have detrimental effects on permanent nurses’ morale and motivation.

Orientations prior to shifts are often limited, which leads to a twofold concern as temporary nurses feel ill-prepared for shifts and permanent staff feel flustered when required to bring the temporary nurse up to speed while being expected to continue normal operations.14 Agency nurses may be assigned to patients and units that are incongruent with their experience and skills—either to unfamiliar units, which affects their ability to confidently deliver care, or to less complex patients where they feel as if their skills are not used adequately.14 15 These issues can create tension between temporary and permanent nursing staff, which can be compounded by the wage disparity. Permanent staff might feel demoralised and expendable when working alongside temporary buy real propecia online staff who are not integrated into the social fabric of the staff.16Hospital managers also must be cognisant of the potential quality impact of relying heavily on temporary nursing staff. Research on the impact of contingent nursing employment on costs and quality have often found negative effects on quality, including mortality, and higher costs.17 18 However, other studies have found that the association between temporary nursing staff and low quality result from general shortages of nursing staff, which make a hospital more likely to employ temporary staff, and not directly from the contingent staff.19–21 Thus, temporary nurses play an important role in alleviating staffing shortages that would otherwise lead to lower quality of care.22Charting a path forward in hospital management and healthcare researchThe maturation of electronic health records and expansion of computerised healthcare management systems provide opportunities both for improved decision making about workforce deployment and for advanced workforce research.

In the area of workforce management, buy real propecia online nursing and other leaders have a growing array of workforce planning tools available to them. Such tools are most effective when they display clear information about predicted patient needs and staff availability, but managers still must rely on their on-the-ground understanding of their staff and their context of patient care.23 Integration of human resources data with patient outcomes data has revealed that individual nurses and their characteristics have important discrete effects on the quality of care.24 25 Future development of workforce planning tools should translate this evidence to practice. In addition, new technology platforms are emerging buy real propecia online to facilitate direct matching between temporary healthcare personnel and healthcare organisations.

One recent study tested a smartphone-based application that allowed for direct matching of locum tenens physicians with a hospital in the English National Health Service, finding that the platform generated benefits including greater transparency and lower cost.26 Similar technologies for registered nurses could facilitate better matching between hospital needs and temporary nurses’ preparedness to meet those needs.Analytical methods that fully leverage the large datasets compiled through electronic health records, human resources systems and other sources can be applied to advance research on the composition of nursing teams to improve quality of care. As noted above, prior research has applied machine learning and discrete event simulation to buy real propecia online analyses of healthcare staffing. Other recent studies have leveraged natural language processing of nursing notes to identify fall risk factors27 and applied data mining of human resources records to understand the job titles held by nurses.28 Linking these rapidly advancing analytical approaches that assess the outcomes and costs of nurse staffing strategies, such as the work by Saville and colleagues published in this issue, to data on the impact of nurse staffing on the long-term costs of patient care will further advance the capacity of hospital leaders to design cost-effective policies for workforce deployment.Guidelines aim to align clinical care with best practice.

However, simply publishing a guideline rarely triggers behavioural changes to match guideline recommendations.1–3 We thus transform guideline recommendations into actionable tasks by introducing interventions that promote behavioural changes meant to produce guideline-concordant care. Unfortunately, not much has changed in the 25 years since Oxman and colleagues concluded that we have no ‘magic bullets’ when it comes to changing clinician behaviour.4 In fact, far from magic bullets, interventions aimed at increasing the degree to which patients receive care recommended in guidelines (eg, educational interventions, reminders, audit and feedback, financial incentives, computerised buy real propecia online decision support) typically produce disappointingly small improvements in care.5–10Much improvement work aims to ‘make the right thing to do the easy thing to do.’ Yet, design solutions which hardwire the desired actions remain few and far between. Further, improvement interventions which ‘softwire’ such actions—not guaranteeing that they occur, but at least increasing the likelihood that clinicians will deliver the care recommended in guidelines—mostly produce small improvements.5–9 Until this situation changes, we need to acknowledge the persistent reality that guidelines themselves represent a main strategy for promoting care consistent with current evidence, which means their design should promote the desired actions.11 12In this respect, guidelines constitute a type of clinical decision support.

And, like all decision buy real propecia online support interventions, guidelines require. (1) user testing to assess if the content is understood as intended and (2) empirical testing to assess if the decision support provided by the guideline does in fact promote the desired behaviours. While the processes buy real propecia online for developing guidelines have received substantial attention over the years,13–18 surprisingly little attention has been paid to empirically answering basic questions about the finished product.

Do users understand guidelines as intended?. And, what version of a given guideline engenders the desired buy real propecia online behaviours by clinicians?. In this issue of BMJ Quality and Safety, Jones et al19 address this gap by using simulation to compare the frequency of medication errors when clinicians administer an intravenous medication using an existing guideline in the UK’s National Health Service (NHS) versus a revised and user-tested version of the guideline that more clearly promotes the desired actions.

Their findings demonstrate that changes to guideline design buy real propecia online (through addition of actionable decision supports) based on user feedback does in fact trigger changes in behaviour that can improve safety. This is an exciting use of simulation, which we believe should encourage further studies in this vein.Ensuring end users understand and use guidelines as intendedJones and colleagues’ approach affords an opportunity to reflect on the benefits of user testing and simulation of guidelines. The design and evaluation of their revised guidelines provides buy real propecia online an excellent example of a careful stepwise progression in the development and evaluation of a guideline as a type of decision support for clinicians.

First, in a prior study,20 they user tested the original NHS guidelines to improve retrieval and comprehension of information. The authors produced a revised guideline, which included reformatted sections as well as increased support for key calculations, such as for infusion rates. The authors again user tested the revised guideline, successfully showing higher rates of buy real propecia online comprehension.

Note that user testing refers to a specific approach focused on comprehension rather than behaviour21 and is distinct from usability testing. Second, in the current study, Jones et al evaluated whether nurse and midwife end users exhibited the desired behavioural changes when given the buy real propecia online revised guidelines (with addition of actionable decision supports), compared with a control group working with the current version of the guidelines used in practice. As a result, Jones and colleagues verify that end users (1) understand the content in the guideline and (2) actually change their behaviour in response to using it.Simulation can play a particularly useful role in this context, as it can help identify problems with users’ comprehension of the guideline and also empirically assess what behavioural changes occur in response to design changes in the guidelines.

The level of methodological control and qualitative buy real propecia online detail that simulation provides is difficult to feasibly replicate with real-world pilot studies, and therefore simulation fills a critical gap.Jones et al report successful changes in behaviour due to the revised guidelines in which they added actionable decision supports. For example, their earlier user testing found that participants using the initial guidelines did not account for displacement volume when reconstituting the powdered drug, leading to dosing errors. A second error with the initial guidelines involved participants using the shortest infusion rate provided (eg, buy real propecia online guidelines state ‘1 to 3 hours’), without realising that the shortest rate is not appropriate for certain doses (eg, 1 hour is appropriate for smaller doses, but larger doses should not be infused over 1 hour because the drug would then be administered faster than the maximum allowable infusion rate of 3 mg/kg/hour).

These two issues were addressed in the revised guidelines by providing key determinants for ‘action’ such as calculation formulas that account for displacement volume and infusion duration, thereby more carefully guiding end users to avoid these dose and rate errors. These changes to the guideline triggered specific behaviours (eg, calculations that account for all variables) that did not occur with the initial guidelines buy real propecia online. Therefore, the simulation testing demonstrated the value of providing determinants for action, such as specific calculation formulas to support end users, by showing a clear reduction in dose and rate errors when using the revised guidelines compared with the initial guidelines.The authors also report that other types of medication-specific errors remained unaffected by the revised guidelines (eg, incorrect technique and flush errors)—the changes made did not facilitate the desired actions.

The initial guidelines indicate ‘DO NOT SHAKE’ in capital letters, and there is a section buy real propecia online specific to ‘Flushing’. In contrast, the revised guidelines do not capitalise the warning about shaking the vial, but embed the warning with a numbered sequence in the medication preparation section, aiming to increase the likelihood of reading it at the appropriate time. The revised guidelines do not have a section specific to flushing, but embed the flushing instructions as an unnumbered step in the administration section.

Thus, the value of embedding technique and flushing information within the context of use was not validated in the simulation testing (ie, no significant differences in the rates of these errors), highlighting precisely the pivotal role that simulation can play in assessing whether attempts to improve usability result in actual behavioural changes.Finally, simulation can identify potential unintended consequences buy real propecia online of a guideline. For instance, Jones and colleagues observed an increase in errors (although not statistically significant) that were not medication specific (eg, non-aseptic technique such as hand washing, swabbing vials with an alcohol wipe). Given that the revised guidelines were specific to the medication tested, it is unusual that we see buy real propecia online a tendency toward a worsening effect on generic medication preparation skills.

Again, this finding was not significant, but we highlight this to remind ourselves of the very real possibility that some interventions might introduce new and unexpected errors in response to changing workflow and practice6. Simulations offer an opportunity to spot these risks in advance.Now that buy real propecia online Jones et al have seen how the revised guidelines change behaviour, they are optimally positioned to move forward. On one hand, they have the option of revising the guidelines further in attempts to address these resistant errors, and on the other, they can consider designing other interventions to be implemented in parallel with their user-tested guidance.

At first glance, the errors buy real propecia online that were resistant to change appear to be mechanical tasks that end users might think of as applying uniformly to multiple medications (eg, flush errors, non-aseptic technique). Therefore, a second intervention that has a more general scope (rather than drug specific) might be pursued. Regardless of what they decide to pursue, we applaud their measured approach and highlight that the key takeaway is that their next steps are supported with clearer evidence of what to expect when the guidelines are released—certainly a helpful buy real propecia online piece of information to guide decisions as to whether broad implementation of guidelines is justified.Caveats and conclusionSimulation is not a panacea—it is not able to assess longitudinal adherence, and there are limitations to how realistically clinicians behave when observed for a few sample procedures when under the scrutiny of observers.

Further, studies where interventions are implemented to assess whether they move the needle on the outcomes we care about (eg, adverse events, length of stay, patient mortality) are needed and should continue. However, having end users physically perform clinical tasks with the intervention in representative environments represents an important strategy to assess the degree to which guidelines and other decision buy real propecia online support interventions in fact promote the desired behaviours and to spot problems in advance of implementation. Such simulation testing is not currently a routine step in intervention design.

We hope it becomes a more common phenomenon, with more improvement work following the example of the approach so effectively demonstrated by Jones and colleagues..

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