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Declining rates of teenage pregnancies in England are related to local areas experiencing less youth unemployment, growing Black or South Asian teenage populations, more educational attainment, unaffordable housing, and a lack of available social housing, a recent study has found.

All English regions have seen a decline in under-18 conception rates, but there are significant geographical differences in the levels and rates of decline. Northern regions have higher conception rates than southern regions. Inner London had much higher initial conception rates but has seen a faster decline. Areas with more youth unemployment still have higher rates of teenage conception than less deprived regions.

The study was led by Southampton PhD student Katie Heap with Professor Ann Berrington from the ESRC Centre for Population Change and Roger Ingham, Professor of Health and Community Psychology at the University of Southampton. They used England's Local Authority Districts to explore possible geographical reasons for declining teenage conception rates between 1998 and 2017.

Birth rates among under-18s fell by around a quarter between 1998 and 2008 but then halved in the following eight years. This decline was mostly driven by reduced conception rates and, to a lesser extent, higher proportions of conceptions ending in abortion.

Both education and employment for young people changed dramatically during the period studied. There were rising numbers of teenagers entering higher education, as well as the 2008 economic recession. There has also been growing second- and third-generation teenage ethnic minority populations.

Areas with greater proportions of South Asian pupils had lower conception rates throughout 1998-2017. This may be due to later sexual experiences, or that they may have more reasons to avoid pregnancy, being more likely to aspire to higher education. Indeed, young people from ethnic minority groups are now more likely to attend university than in the past. Added to this, in 2003 both Black African and Caribbean teenagers had lower GCSE attainment than their White British counterparts, but by 2013 had closed this gap.

Housing became less affordable throughout the 2000/2010s. At the same time, the age of leaving education rose and other transitions into adulthood happened later. The study found that there were lower conception rates in areas with less affordable housing or a lack of social housing, and increasingly unaffordable housing was associated with a larger fall in teenage pregnancies.

Katie Heap said, "This study found that some of the changes in teenage pregnancy rates at the local level are explained by the characteristics of teenagers living in the area and the wider society changing, so policy-makers need to keep in mind the contextual changes of their area and areas they aim to emulate alongside behavioural changes.

"Overall, the key concern is to improve outcomes for teenagers and children, especially the most vulnerable, and reduce long-term demand on services. It will therefore be vital for policy-makers to consider these geographical and population-level changes, helping local areas to continually adapt their approach to maintaining and reducing under-18 conception rates."

Philadelphia, November 10, 2020 - The causes of autism spectrum disorder (ASD) - including genetic and environmental factors - are not entirely understood. Many studies have already shown that serious maternal infection during pregnancy is associated with increased risk for offspring in both people and animals. New research however, shows that the lowest risk for ASD is associated with mid-levels of an immune marker measured at birth - whereas too much or not enough were linked to increased risk.

The report from researchers at the Karolinska Institute in Sweden appears in Biological Psychiatry, published by Elsevier. The study hinges on the idea that the developing brain may be particularly vulnerable to disturbances in immune signaling and exposure to inflammation.

"We studied a set of molecules called acute phase proteins that are part of the innate immune system, which is our first line of defense against infections and is always monitoring the body for signs of invasion," said lead author Renee Gardner, PhD. "These molecules are circulating in our bloodstream all the time, but they can rise rapidly after exposure to infection."

The researchers examined the proteins from blood samples, taken at birth, of nearly 1,000 children with ASD and over 1,000 healthy controls from the Stockholm Youth Cohort, a Swedish health registry. Babies born with high levels of a classical marker of inflammation, called C-reactive protein (CRP), were at highest risk for ASD.

The thinking based on previous studies was simply that too much inflammation is bad for the developing brain. Surprisingly, however the lowest risk was associated with levels of CRP in the mid-range. "This means that too much inflammation may indeed be a bad thing for the developing brain, but so might too little, Dr. Gardner explained.

"Among newborn babies whose mothers had been hospitalized for an infection during pregnancy, those who were able to make a little more of these acute phase proteins tended to have a lower risk of autism. So it seems as if a greater ability to respond to the immediate environment might translate to a lower risk of autism," she added.

In a second part of the study, the researchers compared the immune protein levels at birth between children with ASD and their siblings without ASD. The unaffected siblings had higher levels of the immune markers than those with ASD. "This is interesting because siblings share about half their DNA, and the environment inside the womb and during the first few days of life are likely similar between siblings," Dr. Gardner said.

Another interesting finding relates to the risk for ASD posed by maternal anemia, or iron deficiency. Among babies whose mothers were anemic, those with the highest levels of the iron-binding protein ferritin in their blood - a proxy for iron levels - were protected from autism. That finding hints at the importance of iron status for the developing brain and may explain the anemia-linked risk of neurodevelopmental disorders.

"The association between markers of activation of the immune system at birth and the subsequent risk for autism could be important," said Biological Psychiatry editor John Krystal, MD. "We have been seeking avenues for prevention for ASD, such as mechanisms that could be targeted by medications before the onset of symptoms. However, we must be cautious as we do not yet know whether immune activation is a contributor or a marker of the risk for autism."

INDIANAPOLIS - Regenstrief Institute and Indiana University School of Medicine research scientists have developed and tested one of the first U.S.-based models to predict personal risk for advanced precancerous polyps and colon cancer in average risk individuals.

Colorectal cancer is the third most common cancer and second most lethal cancer in the U.S.

Especially during the COVID-19 pandemic, when many people are hesitant to visit medical facilities and healthcare resources are stretched, the new risk estimation model could help physicians determine whether an average risk patient's specific risk indicates an at-home stool test would be a good screening option or points to a colonoscopy as the most appropriate option.

"Our model helps to refine where on the average risk continuum an individual falls," said study leader Thomas Imperiale, M.D., of Regenstrief Institute and IU School of Medicine. "This information could be used to guide doctor-patient discussions about screening options, with the potential to increase patient acceptance of screening by giving them a choice correlated to their individual risk - true precision medicine. Studies have shown that giving individuals a choice increases screening uptake as many people look for alternatives to colonoscopy."

Personalized risk-based tailoring of colorectal screening is commonly recommended but not generally used, except for decisions about when to commence screening based on race and family history.

Eight out of 10 individuals who fall within the range for whom colorectal cancer screening is recommended by national guidelines are considered to be at average risk of the disease. The new predictive model for average risk individuals considers age, sex, lifestyle, diet, smoking history and eight other factors.

The study deriving and validating the tool evaluated 4,500 individuals ages 50 to 80 who had not had a previous colonoscopy and identified sizeable lower risk and higher risk groups among average risk individuals. About a quarter of average risk individuals in the study were found to be at 2 percent risk, which is considered low risk. Approximately 60 percent were found to be medium risk, reflective of truer "average risk." About 10 percent were deemed high risk for which a screening colonoscopy is appropriate.

"The importance of colorectal cancer screening cannot be overstated," said Dr. Imperiale. "A home annual FIT [fecal immunochemical test] testing, which looks for blood in the stool and is inexpensive, or stool DNA and blood testing every three years, are efficient ways to screen those at the low-risk end of the average risk population. "Particularly during the COVID-19 pandemic, as we see people less willing to consider screening colonoscopies, having an accurate risk assessment tool to determine for whom other options are perfectly good and letting them know which options are suitable is essential. It also has the added benefits of enabling us to prioritize those who are in greatest need of colonoscopy while conserving potentially scare resources -- from masks and other PPE (personal protective equipment) to the ancillary costs of anesthesia."

"Derivation and validation of a predictive model for advanced colorectal neoplasia in asymptomatic adults" is published in Gut, an official journal of the British Society of Gastroenterology, published by BMJ. Authors of the study, in addition to Dr. Imperiale are Patrick Monahan, PhD and Timothy Stump, M.A. of IU School of Medicine's Department of Biostatistics and David Ransohoff, M.D. of the University of North Carolina at Chapel Hill.

BOSTON - Menopause that occurs before a woman is 40 years old accelerates aging and is a risk factor for cardiovascular disease. New research led by investigators at Massachusetts General Hospital (MGH) reveals women with such premature menopause often exhibit certain blood cell changes that elevate their risk of developing coronary artery disease. The findings, which were published in Circulation to coincide with the American Heart Association's Scientific Sessions 2020, uncover the mechanisms behind premature menopause's link to cardiovascular disease and point to a potential blood marker for identifying women at especially high risk.

"We recently found that the presence of chronological-age-associated mutations in blood cells--called clonal hematopoiesis--without overt cancer is a new risk factor for coronary artery disease," says senior author Pradeep Natarajan, MD, who is an investigator in Preventive Cardiology at MGH and an assistant professor of Medicine at Harvard Medical School. "We wondered whether earlier age at menopause independently was associated with clonal hematopoiesis."

To investigate, the team analyzed blood samples from 11,495 postmenopausal women aged 40-70 years from the UK Biobank and 8,111 postmenopausal women aged 50-79 years from the U.S.'s Women's Health Initiative (WHI). A total of 418 women (2.1 percent) had natural premature menopause and 887 (4.5 percent) had surgical premature menopause. Over a median follow-up of 10.0 and 13.1 years in the UK Biobank and the WHI, respectively, there were 473 and 1,146 new cases of coronary artery disease. The team used DNA sequencing of blood cells to identify the presence of clonal hematopoiesis. (Its presence was not detectable by routine clinical laboratory tests, including complete blood counts or C-reactive protein.)

Premature menopause was associated with a 36 percent higher likelihood of exhibiting clonal hematopoiesis in the blood, with a larger association for women with natural premature menopause. Clonal hematopoiesis was in turn associated with a 36 percent higher likelihood of developing coronary artery disease. When there were high levels of clonal hematopoiesis, the risk was 48 percent higher.

Previous research has shown that coronary artery disease that arises following clonal hematopoiesis may involve key inflammatory pathways that are less relevant in the context of other cardiovascular risk factors. Therefore, women with premature menopause and signs of clonal hematopoiesis may benefit from prevention strategies targeting these pathways.

"Our work suggests that women with premature menopause are enriched for clonal hematopoiesis, and screening may facilitate novel precision medicine strategies for coronary artery disease in affected women," says Natarajan.

(Boston)--Despite being theoretically at an increased risk for AL amyloidosis, underrepresented minorities make up only a small percentage of patients seen at specialized treatment centers for this disease.

AL amyloidosis is caused when a person's antibody-producing white blood cells (i.e. plasma cells) do not function properly and generate abnormal protein fibers made of components of antibodies called light chains, which then deposit in various organs of the body. This severe illness is closely related to, and occasionally overlaps with, multiple myeloma--a cancer of plasma cells. Multiple myeloma is known to be most common hematologic cancer among Black Americans with an incidence rate that is more than two times higher than that observed among White Americans.

To better understand how AL amyloidosis may affect various groups of patients differently, researchers from Boston University School of Medicine (BUSM) examined disease characteristics, treatments, and outcomes according to the self-reported race/ethnicity of patients referred to the Amyloidosis Center from 1990-2020. Among over 2,400 patients with AL amyloidosis seen during this 30-year period, only 14 percent were underrepresented minorities--considerably lower than in the general population. "Systematic underdetection among minorities, along with access barriers to referral centers, may be at the root of this discrepancy," says lead author Andrew Staron, MD, a hematology/oncology fellow at Boston Medical Center.

Despite similarities in disease manifestation, the researchers observed younger age and more severe illness among racial/ethnic minorities. Proportionately, fewer minority patients underwent aggressive treatment with stem cell transplantation as compared to non-Hispanic White patients. The researchers learned that this treatment difference was largely explained by lower educational level and more advanced heart disease among minorities, rather than race/ethnicity itself.

"These findings indicate that, in order to mitigate disparities, earlier disease detection and efforts to reduce economic and/or language barriers are key. After controlling for disease severity and treatment, race/ethnicity did not independently impact survival," explained corresponding senior author Vaishali Sanchorawala, MD, professor of medicine and director of the Amyloidosis Center at BUSM and Boston Medical Center.

According to the researchers, diagnosing AL amyloidosis can be perplexing and requires awareness by healthcare providers to pursue tissue biopsy. Its manifestations such as structural heart changes, nephrosis (kidney disease), and neuropathy (disease of the peripheral nerves) can mimic common disorders like hypertension and diabetes mellitus. "Because these conditions are more prevalent among certain racial/ethnic minority groups, there is an even greater need for awareness of AL amyloidosis in marginalized communities so that the diagnosis is not missed or delayed," adds Sanchorawala.

For the first time, researchers have attributed an understudied adverse fetal outcome to the strenuousness of an expectant mother's job.

The researchers matched data on maternal and fetal health, as well as job data, from the New Jersey Department of Health with an objective measurement of job strenuousness. They found that women in relatively strenuous jobs have a 17% increase in the likelihood of having a baby with fetal macrosomia. Fetal macrosomia?having a birth weight of over 4,000 grams or 8.8 pounds?is associated with a higher risk of being overweight as an adolescent. The condition is also associated with a higher risk of breast cancer for the mother.

The study, "Maternal and fetal health effects of working during pregnancy" is authored by Muzhe Yang, professor of economics at Lehigh University and Dhaval Dave, professor of economics at Bentley University, and has been published in the Review of Economics of the Household.

Previous research in this area has relied on self-reporting of physical activities, which may be biased (and a conflation of work-related and leisure-time activities), and only looked at certain activities in isolation rather than the overall level of physical activity demanded by a job. Demanding job-related activities include heavy lifting, prolonged standing or repeated bending. To determine the job strenuousness of the mothers represented in the New Jersey Department of Health data, Yang and Dave used an objective measuring tool provided by the federal Census Occupational Classification System called the Metabolic Equivalent of Task, which rates the level of physical activity associated with various jobs.

"Our findings also indicate an understudied link between gestational diabetes, which is a known risk factor for fetal macrosomia, and intensive physical activities at work during pregnancy," said Yang.

Specifically, compared with light-intensity activity, Yang and Dave found that moderate-intensity activity at work during pregnancy is associated with an increase in the likelihood of fetal macrosomia of about 1.5 percentage points or 17%. One possible mechanism underlying this finding, they say, is sleep-deprivation-induced diabetes developed during pregnancy leading to fetal macrosomia. There is some evidence suggesting an adverse effect of strenuous activities at work on sleep quality?and sleep deprivation has been found to correlate with diabetes.

According to data from the Current Population Survey (CPS), a primary source of labor force statistics for the population of the U.S., the share of women working while pregnant grew from 44% in 1967 to 68% in 2018.

"Expectant mothers are also working longer hours and further into their pregnancy, making it particularly important to understand how job attributes are affecting pregnancy outcomes," says Yang.

Working during pregnancy is generally considered safe for most women with uncomplicated pregnancies, although special guidelines have been issued by the Centers for Disease Control and Prevention (CDC) and the American College of Obstetricians and Gynecologists with respect to jobs that have particular physical demands.

The study, says Yang, sheds light on the possible inadequacy of existing accommodations laws, through the detection of an adverse birth outcome of pregnant women in strenuous jobs who are supposed to have access to reasonable accommodations. As of September 2020, only 30 states, plus D.C. and four cities (Central Falls, RI; New York, NY; Philadelphia, PA; Providence, RI), had passed laws requiring employers to provide reasonable accommodations to women affected by pregnancy, according to Yang. Even in states where accommodation laws are in place, adverse birth outcomes may still occur because of how much variation there is in the interpretation of "reasonable accommodations."

"Focusing on New Jersey, which requires reasonable accommodations for pregnant women at the workplace if requested, our study points to the potential deficiencies of such laws by detecting adverse birth outcomes among pregnant women in strenuous jobs," says Yang. "The adverse health effect we found could only be an underestimate of the true effect for the entire nation, and our finding reveals a need for establishing universal access to accommodations for pregnant women in strenuous jobs."

The researchers urge lawmakers to consider the impact of strenuous work activities on maternal and fetal health when developing policies around employer requirements to provide reasonable accommodations for workers during pregnancy.

Patients with cancer have multiple treatment options available to them today, but each has its drawbacks. Chemotherapy kills rapidly dividing cancer cells, but it also damages healthy cells in the body and often does not effectively prevent tumor metastasis or disease recurrence. Immunotherapies avoid those problems by acting on a patient's immune system to generate a sustained anti-cancer response, but frequently have trouble accessing tumors due to the immunosuppressive local environment that tumors create.

Now, a new, best-of-both-worlds approach packages the cancer-killing power of chemotherapy and the long-term efficacy of immunotherapy into a biomaterial-based cancer vaccine that can be injected adjacent to a tumor site. When mice with aggressive triple-negative breast cancer (TNBC) were given the vaccine, 100% of them survived a subsequent injection of cancer cells without relapsing. This research is reported in Nature Communications.

"Triple-negative breast cancer does not stimulate strong responses from the immune system, and existing immunotherapies have failed to treat it. In our system, the immunotherapy attracts numerous immune cells to the tumor while the chemotherapy produces a large number of dead cancer cell fragments that the immune cells can pick up and use to generate an effective tumor-specific response," said co-first author Hua Wang, Ph.D., a former Postdoc and Technology Development Fellow at Harvard's Wyss Institute for Biologically Inspired Engineering and John A. Paulson School for Engineering and Applied Sciences (SEAS) who is now an Assistant Professor in the Department of Materials Science and Engineering at University of Illinois, Urbana-Champaign.

Personalized vaccines without the wait

First developed in 2009, the injectable cancer vaccine has shown great promise in treating multiple types of cancer in mice, and has been explored in clinical trials for treating melanoma at Dana Farber Cancer Institute. In the original formulation of the vaccine, molecules found in cancerous cells called tumor-associated antigens (TAAs) were incorporated together with adjuvants inside the aspirin-sized scaffold so that arriving dendritic cells could recognize them as "foreign" and mount an immune response targeted against the tumor. These TAAs can be isolated from harvested tumors or identified by sequencing the genome of cancerous cells and subsequently manufactured, but both of these processes to create personalized cancer vaccines can be long, tedious, and expensive.

"One of the critical limiting factors in the development of cancer vaccines is the selection of TAAs, because currently we only have a very small library of known antigens for a few specific tumor cell lines, and it's difficult to predict which can mount an effective immune response," said co-first author Alex Najibi, a graduate student in the lab of Wyss Core Faculty member David Mooney. "Implanting chemotherapy drugs inside the vaccine scaffold creates a burst of cancer cell death that releases TAAs directly from the tumor to the dendritic cells, bypassing the long and costly antigen development process."

Wang, Najibi, and their colleagues set out to apply this new cancer vaccine tactic to TNBC, a disease in which the tumors aggressively suppress immune activity in their local area, limiting the efficacy of immunotherapy. The team first loaded their alginate hydrogel scaffold with a protein molecule called Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF). GM-CSF stimulates the development and concentration of dendritic cells, which take up antigens from tumors and other invaders and present them to T cells in the lymph nodes and spleen to initiate an immune response. They also added the chemotherapy drug doxorubicin (Dox) attached to a peptide called iRGD. iRGD is known to penetrate tumors, and helps target the Dox to tumors upon release.

When mice with TNBC tumors were injected with the new vaccine, those that received a scaffold loaded with GM-CSF and the Dox-iRGD conjugate showed significantly better penetration of the drug into tumors, increased cancer cell death, and fewer metastatic tumors in the lungs than those that received gels containing Dox conjugated to a scrambled peptide molecule, unmodified Dox, or were untreated. Analysis of the scaffolds showed that they had accumulated a large number of dendritic cells, indicating that both the immunotherapy and chemotherapy components of the vaccine were active.

Encouraged by these results, the team then experimented with adding a third component to the vaccine called CpG, a synthetic bacterial DNA sequence that is known to enhance immune responses. Mice that received vaccines with this addition displayed significantly slower tumor growth and longer survival times than mice that received vaccines without it. To evaluate the strength and specificity of the immune response generated by this three-part vaccine, the researchers extracted and analyzed cells from the animals' lymph nodes and spleens. Strikingly, 14% of the T cells taken from lymph nodes reacted against the tumor cells, indicating that they had been "trained" by the dendritic cells to target the cancer, compared with only 5.3% of the mice that received the two-part vaccine and 2.4% of the T cells from untreated mice. In addition, giving a "booster" dose of the vaccine 12 days post-injection increased their survival time even further.

Localized action, long-term protection

While these results revealed the vaccine's effect on activating the immune system, the team also wanted to understand how it affected the local tumor microenvironment. Analysis of the vaccines and their nearby tumors revealed that cells in tumors treated with gels containing GM-CSF, Dox-iRGD, and CpG had an increased amount of the protein calreticulin on their surfaces, which is an indicator of cell death. Mice that received the three-part vaccine also displayed higher numbers of pro-inflammatory macrophages: white blood cells that are associated with improved anticancer activity and longer survival.

The researchers also discovered that their treatment caused an increase in the expression of the cell-surface protein PD-L1 on tumor cells, which is used by cancer to evade immune detection. They had a hunch that co-administering an anti-PD-1 checkpoint inhibitor treatment that blocks this immune evasion with their vaccine would increase its effectiveness. They implanted the three-part vaccine into mice, then injected anti-PD-1 separately. Mice treated with the combination of gel vaccine and anti-PD-1 showed significantly reduced tumor size and number, and survived for a median of 40 days compared to 27 days for untreated mice and 28 days for mice that received anti-PD-1 alone. This synergy suggested that the vaccine might best be used in combination with checkpoint inhibitor therapies.

To imitate how the cancer vaccine might be administered to human patients, the team tested its ability to prevent cancer recurrence after a primary tumor is removed. They surgically excised TNBC tumors from mice, then injected either their three-part hydrogel vaccine or a liquid vaccine containing all the components in a suspension near the original tumor site. Both treated groups had significantly lower tumor recurrence, but the gel vaccine produced significantly slower tumor growth and improved survival. Mice were then re-challenged with an injection of cancer cells and, strikingly, 100% of the mice that had received the gel vaccine survived with no metastasis, while all of the untreated mice succumbed to the disease.

"The ability of this vaccine to elicit potent immune responses without requiring the identification of patient-specific antigens is a major advantage, as is the ability of local chemotherapy delivery to bypass the severe side effects of systemic chemotherapy, the only treatment currently available for the disease," said corresponding author Mooney, Ph.D., who leads the Immuno-Materials platform at the Wyss Institute and is also the Robert P. Pinkas Family Professor of Bioengineering at SEAS. "Not only does this vaccine activate dendritic cells with tumor-specific TAAs in situ, it also reshapes the tumor microenvironment to allow the immune system greater access to the tumor, and creates an immune memory that prevents further recurrences."

The team is continuing to explore the combination of chemotherapy with cancer vaccines, and hopes to improve their antitumor efficacy for other difficult-to-treat tumor models. The team hopes that future studies to better understand and optimize the system will allow it to move into preclinical trials and, eventually, human patients.

"The team's newest version of their cancer vaccine is a novel multifunctional anticancer therapy that offers new hope for the treatment of a wide range of cancers. It is essentially an entirely new form of combination chemotherapy that can be administered through a single injection and potentially offer greater efficacy with much lower toxicity than conventional treatments used today," said Wyss Institute Founding Director Don Ingber, M.D., Ph.D. Ingber is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Vascular Biology Program at Boston Children's Hospital, as well as Professor of Bioengineering at SEAS.

Scientists have developed an optical elastography technique that could revolutionise the accuracy and ease to which health professionals can detect biomechanical alterations of cells and tissues.

A study derived by an international collaboration between the University of Exeter, Gloucestershire Hospitals NHS Foundation Trust, the University of Perugia (Italy) and the Institute of Materials of the National Research Council of Italy (IOM-CNR) applied an innovative biophotonic approach to highlight how the microscopic processes drive mechanical modification in biological tissues.

The team of experts, coordinated by Dr Francesca Palombo from the University of Exeter and Prof. Daniele Fioretto from the University of Perugia, Italy, analysed the great potential of the technique in the investigation of tissue on the microscale.

While the mechanical properties of both cells and tissues play a fundamental role in the function of cells and how disease develops, the traditional methods to study these properties can be limited and invasive.

Scientists have recently utilised Brillouin microscopy - a form of imaging that uses light to create an acoustic measurement of the cells and tissue - as a way of carrying out non-invasive studies of these biomechanical properties.

However, a complicating factor in these measurements is the contribution of water both to tissue and cell biomechanics, as well as the Brillouin spectrum itself.

Now, for the new study, the team utilised natural biopolymer hydrogels to mimic human tissue and to compare results against measurements taken in human tissue samples.

They found that this new technique allows investigations of tissue functional properties (and alterations) to a subcellular scale - meaning professionals can gain information from analysing a new spatiotemporal region of biological processes.

The results of this study demonstrate that, whilst water plays a major role in determining mechanical properties, the effect of the solute including proteins, lipids and other components is apparent especially on viscosity, which is relevant for the transport of metabolites and active molecules.

The research was published in Science Advances.

Dr Palombo, an Associate Professor in Biomedical Spectroscopy at the University of Exeter, said: "We set out to understand the bases of Brillouin signals in biomedical samples.

"While taking a step back to analyse the fundamentals of this light scattering process, we made a substantial advancement in that we now understand the distinctive contribution of interfacial dynamics, beyond bulk water, to the viscoelastic response of biological tissues.

"This has wide-ranging implications in that phase changes, as well as acoustic anisotropy, are ideal scenarios where Brillouin imaging provide unique information. We are still working on establishing the relevance of this technique in medical sciences, however it is undisputable that it offers an invaluable contrast mechanism to detect physiological and disease states."

Treating Opioid Addiction in Primary Care Benefits Both Patients and Cash-Strapped Medical Practices

Buprenorphine-based treatment for opioid addiction is in short supply in many areas of the United States. And while many physicians want to offer it, clinics are unsure how to offer buprenorphine therapy in a financially sustainable way. A team of researchers at Harvard Medical School conducted financial cost and revenue analysis for four different approaches to delivering buprenorphine-based treatment in primary care practices. The approaches differed based on who in the clinic delivered the majority of face-to-face care, the presence of nurse care managers, and whether care was delivered in traditional one-on-one or group settings.

Microsimulation modelling found that all four approaches to care produced positive net revenue after the first year, and net revenues were consistently highest for rural practices. Physician-led treatment and shared medical visits, both of which relied on nurse care managers, consistently produced the greatest net revenue gains. Additionally, net revenues were positive for all primary care practices that had at least nine patients in buprenorphine treatment per provider at any given time and no-show rates less than 34 percent. The findings suggest that in the current fee-for-service-dominated environment, offering office-based therapy for opioid addiction with buprenorphine can be a financially sustainable choice for cash-strapped primary care practices, despite hurdles.

Financing Buprenorphine Treatment in Primary Care: A Microsimulation Model
Sanjay Basu, MD, PhD, et al
Harvard Medical School, Center for Primary Care, Boston, Massachusetts
https://www.annfammed.org/content/18/6/535

The EAR-PC Study Findings Encourages Screening for Hearing Loss in Older Adults

Hearing loss is the second most common disability in the United States and comes with it a higher risk for being diagnosed with significant health conditions, such as hypertension, diabetes, dementia and depression, as well as higher health care cost and use. The Early Auditory Referral-Primary Care (EAR-PC) study was designed to address the lack of data about hearing loss screening. Implemented in real-world, community-based clinics, it evaluated the effect of a tailored electronic clinical alert appearing at all visits of patients 55 and older, to encourage clinicians to ask, "Do you have difficulty with your hearing?" The study's lead author is Philip Zazove, M.D., who is hearing impaired. He and his team of researchers evaluated a screening paradigm for identifying patients 55 years and older at risk of hearing loss from 10 family medicine clinics in two health systems for formal hearing evaluation and treatment. An electronic prompt alerted clinicians to screen for hearing loss during visits. About 25 percent of the patients had signs of hearing loss with the primary care screener (Hearing Handicap Inventory for the Elderly). Referral rates to audiology specialists increased from baseline rates of 3.2 percent to 14.4 percent at one health system and 0.7 percent to 4.7 percent at the other. Considering the high prevalence of hearing loss and the impact on quality of life, increasing referral rates for audiology testing may improve health outcomes.

Effective Hearing Loss Screening in Primary Care: The Early Auditory Referral-Primary Care Study
Philip Zazove, MD, MM, et al
University of Michigan, School of Medicine, Ann Arbor, Michigan
https://www.annfammed.org/content/18/6/520

Six Ways Primary Care "Medical Homes" Are Lowering Health Care Spending

New analysis of 394 U.S. primary care practices identifies the aspects of care delivery that are associated with lower health care spending and lower utilization of emergency care and hospital admissions. Researchers from the Urban Institute and RTI International analyzed health care cost data from a large group of Medicare patients and their primary care practices. Each practice previously took part in a 2011-2014 Centers for Medicare and Medicaid Services initiative to establish advanced primary care "medical homes," with improved and centralized care coordination.

What worked to reduce overall health care cost and utilization? At the top of the list: primary care practices that used patient clinical data to identify and remind patients due for preventive services saved, on average, about $70 per patient per month, lowered acute care hospital spending, and reduced hospitalizations and emergency department visits in their patient population.. Additionally, using their patient clinical records to initiate pre-visit planning, clinician reminders, targeted patient outreach, and population health monitoring were also linked to lower total Medicare spending. In short, practices that were able to leverage their patient data registry to anticipate need and target effective preventive services saved money.

Additional activities that were associated with fewer emergency department visits, reduced acute care spending and/or reduced hospital admissions include: offering targeted consultations for patients with chronic conditions to set health goals; following patients during hospital stays and supporting other specialists in patient care; establishing a protocol for sharing information in medical referrals; and adopting systematic approaches to quality improvement. Surprisingly, expanding access to care, such as expanded night and weekend hours, was not associated with lowered health care spending, utilization of emergency departments, nor reduced hospital readmissions.

Patient-Centered Medical Home Activities Associated With Low Medicare Spending and Utilization
Rachel A. Burton, MPP, et al
The Urban Institute, Washington, D.C.
https://www.annfammed.org/content/18/6/503

Improving Affordable Care and Quality of Life for Seniors

Nitin Budhwar, MD, a geriatrician, and Soraya Gollop, PhD, a medical ethicist, find the U.S. medical system at a crucial juncture where we should aim to both reduce per capita health care costs, but also provide health care to facilitate the best possible quality of life. Their editorial highlights two studies in this issue, Burton et al. and Zazove et al., that present strategies for progressing toward these goals while improving the quality of life for seniors. While underlining the value of both studies, Drs. Budhwar and Gollop remind us how much work remains to be done: "The issue here is not that primary care clinics fail to implement best practices, but rather that policy has not made it rational for primary care clinics to implement these proven practices."

Editorial: Can You Hear Me Now? Refining the PCMH Model and an Overlooked Disability Affecting Seniors
Nitin Budhwar, MD, FAAFP and Soraya Gollop, PhD
University of New Mexico, Albuquerque
https://www.annfammed.org/content/18/6/482

Older Americans Who Are Black, Hispanic, or Medicaid-Eligible Are More Likely to Experience Preventable Hospitalizations

When complications due to diabetes, asthma, urinary tract infections, high blood pressure and other common conditions lead patients to visit the ER, researchers and health care quality administrators may label these visits as "potentially preventable hospitalizations." That is, with good outpatient care, these visits could have been potentially avoided. Potentially preventable hospitalizations are costly and can negatively impact the health and well-being of individuals, particularly if they are older. Researchers examined national trends in PPH to see differences across racial and socioeconomic subpopulations, as well as county-level differences, using 2010-2014 Medicare claims data. Overall, PPH rates consistently declined across all subpopulations. However, they found that Black and Hispanic Americans had higher PPH rates compared to Whites. Additionally, those who also had Medicaid insurance had higher rates than those with only Medicare coverage.

This examination of county-level potentially preventable hospitalization trends can inform health and social policies to support groups identified to be at-risk of PPH. The primary care system needs to be accessible and affordable, particularly for populations who are at higher risk of PPH. Policies with financial incentives to increase the number of primary care physicians, especially in rural and low-income areas, can potentially improve health care access and reduce PPH among vulnerable populations.

Potentially Preventable Hospitalizations Among Older Adults: 2010-2014
Elham Mahmoudi, PhD, et al
University of Michigan, School of Medicine, Ann Arbor, Michigan

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Primary Care Teams Test New Tool to Prescribe Referrals for Community Health and Social Services

Family physicians provide the majority of health care for underserved rural and urban populations in the U.S. and treat a more diverse population of patients than any other medical specialty. They have an important role to play in helping to mitigate health inequities by connecting patients to community-based wellness and self-care resources such as food and nutrition supports, weight management and smoking cessation to support them in preventing and managing cardiovascular disease.

CommunityRx-H3 is a practice-level, customizable community resource referral system that uses evidence-based algorithms to auto-generate a list of community resources to address such needs. This study evaluated the implementation of CommunityRx-H3 through the perspective of primary care practice facilitators.

This study found that practice facilitators can play a key role in implementing quality improvement initiatives like CommunityRx-H3. However, it also underscores the importance of support from an engaged practice leadership to address such barriers as: limited time, lack of staff, staff apathy, material resources (e.g., printers and paper) and lack of integration between a community resource referral system and the practice's EMR system.

Implementation of Community-Based Resource Referrals for Cardiovascular Disease Self-Management
Emily Abramsohn, MPH, et al
The University of Chicago, Chicago, Illinois
https://www.annfammed.org/content/18/6/511

Under-Insured Transgender Americans Turn to Riskier, Non-Licensed Sources for Gender-Affirming Hormones

Transgender people who lack access to insurance coverage for gender-affirming hormone therapy are more likely to use hormones from sources other than a licensed prescriber, compared to those with insurance coverage. Analysis of the most recent United States Transgender Survey shows that about 9 percent of transgender adults - which comes to about 170,000 transgender adults in the U.S. today - access hormones from non-licensed sources like friends or online. The study found an association between the use of non-prescribed hormones and lack of health insurance or denial of insurance coverage for gender-affirming medical care. Survey respondents also identified insurance coverage as a prevailing barrier; it was ranked as a top issue affecting transgender people in the United States, ranked second only to direct violence.

The authors note that hormones accessed from an unlicensed source may pose health and safety risks, as medications may be unmonitored for content, quality, formulation and dosing. Additionally, use of non-prescription hormones likely entails decreased monitoring of hormone levels and less opportunity for mitigating risks or other forms of harm reduction and preventive care.

Insurance Coverage and Use of Hormones Among Transgender Respondents to a National Survey
Daphna Stroumsa, MD, MPH, et al
University of Michigan, Ann Arbor, Michigan
https://www.annfammed.org/content/18/6/528

New Analysis Finds Lung Cancer Screening Reduces Rates of Lung Cancer-Specific Death

Low-dose CT screening methods may prevent one death per 250 at-risk adults screened, according to a meta-analysis of eight randomized controlled clinical trials of lung cancer screening. Researchers at the University of Georgia analyzed the health outcomes of 90,275 patients, comparing those who were screened versus those who received usual medical care or chest x-rays. Their analysis found a clinically and statistically significant 0.4 percent reduction in lung cancer-caused death long term, which translates into one preventable death per 250 at-risk adults screened. The authors recognize the important potential harm of overdiagnosis in cancer screening programs, and there was some evidence of overdiagnosis due to increased incidence in the screened group. However, based on the reduction in all-cause mortality being in the same direction and magnitude as lung cancer mortality, the authors interpret that the associated harms "do not appear to increase other causes of mortality," and the results of the study align with the U.S. Preventive Services Task Force recommendations for CT-based lung cancer screenings for adults age 55 to 80 who have a history of regular smoking.

Cancer-Specific Mortality, All-Cause Mortality, and Overdiagnosis in Lung Cancer Screening Trials: A Meta-Analysis
Mark H. Ebell MD, MS, et al
University of Georgia, College of Public Health, Athens, Georgia
https://www.annfammed.org/content/18/6/545

My Mother's Brave Choice of Medical Aid in Dying

Epidemiologist Margaret Handley, PhD, MPH, presents a narrative about her mother's decision to use the End of Life Act to request aid-in-dying drugs after being diagnosed with atypical lymphoma. The End of Life Act became law in California in 2015 and has been in effect since 2016. The law allows an adult diagnosed with a terminal disease, who meets certain qualifications, to request aid-in-dying drugs from their attending physician.

Handley's mother went through three painful months of surgery, radiation and a single horrific round of chemotherapy near the end of her life. While her mother was recovering in the hospital after chemo, three doctors left an important impression: the palliative care doctor, who established a deep connection which helped Handley's mother see the trajectory of her life, the doctor from the end of life options group who gave her information without expectation, and the oncologist who helped her understand her choices in context.

Handley writes that what was vital for her mom's decision to feel right for her and to bring her comfort was the oncologist's engagement with her. "The clarity the oncologist gave her through his honesty and explanation was essential to her peace of mind in her decision making, and as a result she gained her life back. She was able to 'die well,' feeling content in her resolve because she could see that she had the option to live, but it was one she could reject... " Handley writes.

In a corresponding editorial, palliative care doctor Lou Lukas, MD, worries about altering rules the medical establishment has put in place about participating in a patient's hastened death. She also has concerns that if the choice of a quick, controlled death is made too easy for patients, that we as a society may forsake what she calls "vital lessons" that come at the end of life--namely the opportunity to practice compassionate presence and the acquisition of deep wisdom and courage when the ego "lets go" of the fear of death. Lukas cites emerging research that patients with terminal cancer have been helped by brief supportive counseling and one monitored session of high-dose psilocybin, the active ingredient in magic mushrooms. The classic psychedelic drug, however, is inaccessible to doctors to prescribe to their patients. Lukas finds it ironic that while there is movement to allow physicians to prescribe legally available medications specifically intended to end a patient's life, they have no legal access to a drug that could restore a patient's ability to live comfortably through a terminal diagnosis.

The "Foresty Way": My Mother's Brave Choice of Medical Aid in Dying
Margaret A. Handley, PhD, MPH
University of California, San Francisco; Zuckerberg San Francisco General Hospital and Trauma
Center, San Francisco, California
https://www.annfammed.org/content/18/6/553

Editorial: Nonlinear Dynamics and Navigating the End of Life

Lou Lukas, MD
Veterans Administration; University of Nebraska Medical Center, Omaha
https://www.annfammed.org/content/18/6/484

Essay Calls for Physician Mindfulness When Caring for Patients With Dementia

In medical school, Rebecca MacDonell-Yilmaz delayed her neurology rotation as a way to avoid acknowledging her mother's developing symptoms of dementia. As her mother's cognitive and functional abilities declined further, Dr. MacDonell-Yilmaz had no option but to confront this reality. While her training in palliative care gave her effective clinical tools for assessing dementia, her own experience taught her how important it is for physicians and other health professionals to be mindful of the deeply personal side of caring for a loved one with dementia. She recognizes that while personal markers of decline such as her mother's inability to follow the plot of a television program, "cannot indicate eligibility for a clinical trial or hospice services and will vary between families, they offer vivid illustrations of who patients were prior to their illness, how drastically their cognitive or functional status has changed, and how this evolution impacts both patient and family."

Counting Backward by Seven
Rebecca E. MacDonell-Yilmaz, MD, MPH
Brown University, The Warren Alpert School of Medicine; Hasbro Children's Hospital, Providence, Rhode Island
https://www.annfammed.org/content/18/6/561

Standing in the Breach with Patients and their Families

Timothy P. Daaleman, DO, MPH, shares in an essay about his value as a doctor beyond the performance data he accesses on a daily basis, which quantifies the number of patients who received his services and his response time in answering their questions, among other services he renders. Dr. Daaleman explores the philosophic question of value and the difference between intrinsic and extrinsic value. Data has extrinsic value, he writes, but what about his doctoring has intrinsic value, that makes him unique in the clinical setting? Though it took him time and self-insight, Dr. Daaleman realized that as a doctor, he literally "stands in the breach" with patients and their families during a medical crisis that brings about challenging emotions for each person involved, whether they are the patients themselves or family members. "I can see now that determining the value of what I do is not important," Dr. Daaleman writes. "What is of greater importance is my identity as a physician, and the humdrum work which places me in the midst of the height and depth and width of the human condition." In other words, his weekly performance reviews blinded him to his lived experience. This realization has led him to make it a daily practice of reflecting on his day with gratitude; an attention to his own emotions; the recognition of any minor or major "gifts" he has received, such as a co-worker asking him how his day is going or delivering the news to a patient that all evidence of his or her cancer is gone; and a request for grace to move forward the next day.

What Is My Value as a Doctor?
Timothy P. Daaleman, DO, MPH
University of North Carolina at Chapel Hill
https://www.annfammed.org/content/18/6/558

I Found Myself Hating the Words "Metastatic Breast Cancer": How a Nursing Professor Shared Her Own Cancer Story

After a 40-year career as a nurse, professor, and Dean of the Fay W. Whitney School of Nursing at the University of Wyoming, Mary E. Burman shares a personal account of her diagnosis of metastatic breast cancer. In the essay, she follows the information trail of her own terminal illness diagnosis. Starting from a pain in her chest that signaled conversations with her primary care clinician, to CT scan information shared between clinicians that led to a diagnosis delivered first digitally--through her patient portal--and in-person at her nurse practitioner's office. Post-diagnosis, she wrestles with how to disclose her diagnosis of metastatic breast cancer to friends, family and her professional community. In sharing her personal experience, Burman challenges readers to focus attention and primary care practice improvements on three pivotal relationships in one's cancer journey: the patient and primary care clinician and sharing bad news; the patient and their support community and the stress of sharing a diagnosis; and the online patient portal linking individuals to the health care environment.

How Giving and Receiving Information Has Shaped My Cancer Journey
Mary E. Burman, PhD, BSN, RN
University of Wyoming, Fay W. Whitney School of Nursing, Laramie, Wyoming
https://www.annfammed.org/content/18/6/555

Representation of Female Authors in Family Medicine Academic Journals is Trending Upward

After decades of underrepresentation in medicine, women are now entering many specialties in the United States, including family medicine, at higher rates than men. Despite the rising proportion of female physicians in family medicine, they continue to be underrepresented in the highest levels of professional attainment, particularly in academic settings. This study from the Robert Graham Center examines female authorship of research published in three leading U.S. family medicine journals over time. They found a statistically significant increase in female authorship of published research over time, with a 13-point jump in original research with female senior authors, from 29 percent in 2008 to 42 percent by 2017. In that same time period, the gender composition of the journals' editorial boards remained roughly the same. Published research was more likely to be male led if it did not have grant funding or if there were no other co-authors. This study's authors discuss the importance of increasing female representation in peer-reviewed publications, closing the gender gaps in the highest levels of academic medicine, and ensuring appropriate representation of thoughts and ideas in the field of family medicine.

Has Female Authorship Distribution in Family Medicine Research Evolved Over Time?
Yalda Jabbarpour, MD, et al
Robert Graham Center, Washington, D.C.
https://www.annfammed.org/content/18/6/496

Innovations in Primary Care

Innovations in Primary Care are brief one-page articles that describe novel innovations from health care's front lines. In this issue:

A Staff- and Protocol-Driven System to Apply Urine Drug Testing in Primary Care
Family physicians in a rural, resource-limited setting developed a scalable clinic-wide system to facilitate routine urine drug testing of chronic pain patients prescribed opioids.
https://www.annfammed.org/content/18/6/563

An In-Clinic Food Pharmacy Addresses Very Low Food Security
In partnership with a local food pantry, a primary care clinic in Charlotte, North Carolina, successfully piloted a food pharmacy that provided a nutritionally balanced two-day supply of shelf-stable foods to patients at risk of food insecurity.
https://www.annfammed.org/content/18/6/564

The Xavante, one of the indigenous communities most vulnerable to SARS-CoV-2 in Brazil, are suffering from an epidemic of diabetes, a “silent” disease considered a risk factor for severe COVID-19.

A group of researchers affiliated with the Federal University of São Paulo’s Medical School (EPM-UNIFESP) and the University of São Paulo’s Ribeirão Preto Medical School (FMRP-USP) examined the retinas of 157 individuals before the COVID-19 pandemic and found a high prevalence of type 2 diabetes and eye disorders caused by the disease.

The study was supported by FAPESP, and the results are published in Diabetes Research and Clinical Practice, the official journal of the International Diabetes Federation.

“Ninety-five of the 157 Xavante we examined [60.5%] were diagnosed with diabetes,” Fernando Korn Malerbi, a postdoctoral researcher in the Ophthalmology Department of EPM-UNIFESP and first author of the article published on the study.

According to Malerbi, diabetes can cause ocular problems such as retinopathy. Diabetic retinopathy develops when high blood sugar levels damage blood vessels in the retina, leading to vision loss if left untreated.

To diagnose cases of diabetic retinopathy and other possible eye disorders, the researchers examined members of the Xavante community on the Volta Grande and São Marcos Reservations in the state of Mato Grosso in Brazil’s Center-West region. They used a smartphone-controlled retinal photography system developed by Phelcom Technologies via a project supported by FAPESP’s Innovative Research in Small Business Program (PIPE).

Called the Eyer, the handheld retinograph is an optical device that produces precise images of the retina to detect back-of-the-eye (fundus) disease at a far lower cost than conventional methods. In addition, it has the advantage of being usable for remote diagnosis by an ophthalmologist via telemedicine.

The optical device is connected to a smartphone. It lights up and images the retina, and a specially written software application sends the images over the internet to Eyer Cloud, which stores and manages patient files.

In the absence of Wi-Fi or a 3G or 4G network, the images are stored in the smartphone and sent to the cloud when a broadband internet connection becomes available (read more at: agencia.fapesp.br/30784).

Malerbi personally examined the Xavante volunteers and promptly gave them his diagnosis. “When retinal damage suggesting a risk of blindness was observed via the handheld retinograph, we informed the subjects via an interpreter and referred them to the local indigenous health service for follow-up and treatment,” he said.

Of the 95 individuals with diabetes who underwent the complete ocular imaging protocol, 23 (24.2%) had ungradable images owing to cataract-caused media opacities that precluded evaluation of retinopathy in at least one eye.

Images from the remaining 72 subjects (75.8%) were good enough for diabetic retinopathy to be detected. The researchers found that 16 had the disease, and it was severe enough to be sight-threatening in seven.

“We proved that screening for diabetic retinopathy with a portable retinograph is feasible and economically viable because the technology is inexpensive and can be used in remote communities such as Indian reservations, where the population is usually dispersed in several villages,” Malerbi said.

Deteriorating health

A previous study of eye problems among the Xavante reported diabetic retinopathy prevalence of 19.3% in the same locations. The higher level of prevalence found in this latest study may be due to the superior quality of the retinal camera images compared with the indirect ophthalmoscopy method used in the earlier study.

Another hypothesis is that the health of this indigenous population – one of the largest in Brazil, comprising some 17,000 Indians living on nine reservations – has deteriorated in the intervening years, the researchers surmised.

A previous study showed that 66.1% of 932 members of the Xavante community had metabolic syndrome, defined as a condition in which risk factors for cardiovascular disease and diabetes mellitus occur in the same individual.

For the researchers, the situation reflected changes in health profile and diet in recent decades, especially the consumption of industrialized foods and sedentary living (read more at: agencia.fapesp.br/22624).

“The Xavante were traditionally hunter-gatherers but have become more sedentary. They’ve also changed their diet in recent decades, consuming new foodstuffs with high sugar content,” Malerbi said.

Besides the Xavante, the researchers also examined the retinas of 33 Bororo – another community endangered by both COVID-19 and the bush fires that destroyed much of the Pantanal this year. Seven Bororo were found to have diabetes. One of these was diagnosed with severe diabetic retinopathy and referred to a health service for treatment.

Buprenorphine-based treatment for opioid addiction is in short supply in many areas of the United States. And while many physicians want to offer it, clinics are unsure how to offer buprenorphine therapy in a financially sustainable way. A team of researchers at Harvard Medical School conducted financial cost and revenue analysis for four different approaches to delivering buprenorphine-based treatment in primary care practices. The approaches differed based on who in the clinic delivered the majority of face-to-face care, the presence of nurse care managers, and whether care was delivered in traditional one-on-one or group settings.

Microsimulation modelling found that all four approaches to care produced positive net revenue after the first year, and net revenues were consistently highest for rural practices. Physician-led treatment and shared medical visits, both of which relied on nurse care managers, consistently produced the greatest net revenue gains. Additionally, net revenues were positive for all primary care practices that had at least nine patients in buprenorphine treatment per provider at any given time and no-show rates less than 34 percent. The findings suggest that in the current fee-for-service-dominated environment, offering office-based therapy for opioid addiction with buprenorphine can be a financially sustainable choice for cash-strapped primary care practices, despite hurdles.

Peer-reviewed / 1 Observational study + 1 Systematic review and meta-analysis / People

An observational study finds risk of heart attack and cardiovascular disease is highest in people aged 70 and over with elevated levels of LDL cholesterol, compared to younger age groups, and estimates the number needed to treat with statins to prevent one heart attack in five years is lowest in people aged 70 to 100 years.

A separate systematic review and meta-analysis including data from more than 21,000 people aged 75 years and older finds LDL cholesterol-lowering therapies (including statins) are as effective at reducing cardiovascular events (including stroke and heart attack) in this age group as they are in younger people.

Two studies published today in The Lancet provide fresh evidence on the issue of whether LDL cholesterol-lowering therapies, including statins, can reduce the rate of major cardiovascular events in older people.

An observational study suggests that among people who have not had a previous cardiovascular event, those aged 70 to 100 years may gain the most benefit from taking medications that lower cholesterol compared to younger age groups, in terms of the number of heart attacks and cardiovascular events that could potentially be prevented per person treated. The study, involving more than 90,000 people living in Copenhagen, Denmark, including 13,779 people aged between 70 and 100 years, concluded that people aged over 70 years had the highest incidence of heart attack and cardiovascular disease of any age group (heart attacks per 1,000 people per year irrespective of LDL cholesterol levels: Age 80-100, 8.5; age 70-79, 5.2; age 60-69, 2.5; age 50-59, 1.8; age 20-49, 0.8 - ie, in people aged 80-100 years, there were 8.5 heart attacks per 1,000 people each year).The study also estimates that the number of older people who need to receive a moderate-intensity statin therapy to prevent one heart attack in five years is fewer than for younger age groups. One heart attack will be prevented for every 80 people aged 80 to 100 years treated. In people aged 50 to 59 years, 439 need to be treated to prevent one incidence of heart attack, the researchers estimate.

In a separate systematic review and meta-analysis, researchers show that cholesterol-lowering therapies are as effective at reducing cardiovascular events in people aged 75 years or older as they are in younger people. The study, which included data from more than 21,000 people aged 75 years or older from 29 randomised controlled trials, found that cholesterol-lowering medications reduced the relative risk of major vascular events in older patients by 26% per 1mmol/L reduction in LDL cholesterol, which is comparable to the risk reduction in patients younger than 75 years (15% per 1mmol/L reduction in LDL cholesterol).

Together, the findings strengthen evidence that cholesterol-lowering medications can benefit older adults, who have historically been underrepresented in clinical trials of these therapies, and could help reduce the burden of cardiovascular disease in an aging population.

Having high levels of LDL cholesterol can lead to narrowing of blood vessels, making it more likely that a person will have a heart attack or stroke. People aged over 70 years have been underrepresented in cardiovascular studies, so the evidence around cholesterol lowering therapies and the benefits of primary prevention in this age group have been less certain. These studies provide more up to date evidence.

Primary prevention study

The first study is an observational study designed to assess primary prevention of cardiovascular events - meaning that participants did not already have clinical signs of heart disease when they joined the study. Researchers analysed data from 91,131 people aged 20 to 100 years who were not taking statins or other cholesterol-lowering medication, and were enrolled in the Copenhagen General Population Study between 2003 and 2015. Of those, 10,592 participants were aged 70 to 79 years, and 3,188 participants were aged 80 to 100 years.

Participants were followed for an average of 7.7 years, and the number of first-time heart attacks and cases of cardiovascular diseases, along with the LDL cholesterol levels, were recorded for each individual. To evaluate the potential benefit of statins for each age group, the authors estimated the number of people who would need to be treated with a moderate-intensity statin therapy to prevent one incidence of heart attack in five years.

There was a total of 1,515 incidences of a first-time heart attack and 3,389 cases of cardiovascular disease in the study.

The risk of heart attack in the overall population was increased by 34% for every 1mmol/L rise in LDL cholesterol. The effect was amplified with increasing age, such that people aged 80 to 100 years with elevated LDL cholesterol levels had the highest absolute risk of heart attack (at the highest LDL cholesterol levels, >5mmol/L, the rates of heart attacks in 1,000 people per year for each age group were: age 80-100, 13.2, age 70-79, 6.6; age 60-69, 3.1; age 50 to 59, 3.1; age 20-49, 3.3 - ie, in people aged 80-100 years with the highest levels of LDL cholesterol, there were 13.2 heart attacks per 1,000 people each year).

The incidence of cardiovascular disease also increased with age and rising LDL cholesterol levels and was highest in people aged 80 to 100 (at the highest LDL cholesterol levels, >5mmol/L, the rates of cardiovascular disease in 1,000 people per year for each age group were: age 80-100, 37.1, age 70-79, 14.6; age 60-69, 6.4; age 50 to 59, 5.4; age 20-49, 4.6 - ie, in people aged 80-100 years with the highest levels of LDL cholesterol, there were 37.1 cases of cardiovascular disease per 1,000 people each year).

The researchers found that older people were likely to gain the greatest benefits from treatment of moderate-intensity statin therapy, compared to younger people. To prevent one cardiovascular disease event of any type, 42 people aged 80 to 100 would need to be treated with a moderate-intensity statin to prevent one cardiovascular disease event. The figures were 88 for those aged 70 to 79 years, 164 for those aged 60 to 69 years, 345 for those aged 50 to 59 years, and 769 for those aged 20 to 49 years.

To prevent one heart attack, 80 individuals aged 80 to 100 would need to be treated with a moderate-intensity statin for 5 years. The figures were 145 for people aged 70 to 79, 261 for those aged 60 to 69, 439 for those aged 50 to 59, and 1,107 for those aged 20 to 49.

The findings show that LDL cholesterol levels are an important risk factor for heart attack and cardiovascular disease in older people, contrary to historical reports. Previous evidence suggested there was no association, leading people to believe that those who had not had a heart attack before 70 years of age were healthier and at a lower risk. However, the lack of representation of this age group in trials, changing clinical practices, and increasing life expectancies for older populations means evidence was out of date. The two latest studies provide new evidence for this age group on both accounts.

Professor Børge Nordestgaard, joint author of the first study, of the Copenhagen University Hospital, Denmark, said: "Our study provides further evidence for the cumulative burden of LDL cholesterol over a person's lifetime and the progressive increase in risk for heart attack and cardiovascular disease with age. With the proportion of people living beyond 70 years of age worldwide rapidly increasing, these data point to the huge potential for primary prevention strategies aimed at lowering LDL cholesterol levels to reduce the population burden of heart disease. The findings should guide decision making about whether older individuals will benefit from statin therapy." [2]

A strength of the first study is that the data originate from a large, present-day group of people. In addition, because all individuals in Denmark are assigned a personal identification number at birth or immigration with which they can be traced in national registries, not a single participant was lost during the follow up process.

However, a limitation of the first study is that it only included people of white European origin living in a high-income country, so it is not clear if the results would apply to other ethnic groups or people living in low-income settings. A second limitation is that the estimations for the number needed to treat in five years to prevent one incidence of heart attack and cardiovascular disease are based on modelling analyses with assumptions about the efficacy of LDL cholesterol-lowering drugs. However, the authors say that these estimates are reliable as the underlying event rates in different age groups and LDL cholesterol levels are based on actual data from the cohort study.

Meta-analysis on LDL lowering treatments

A previous meta-analysis from the Cholesterol Treatment Trialists' Collaboration suggested that statin treatment reduced the number of major cardiovascular events in people aged 75 years and older, but ultimately concluded that the evidence of potential benefit was less strong than for younger people [2].

In the second study published today, researchers carried out a meta-analysis and systematic review of data from the Cholesterol Treatment Trialists' Collaboration meta-analysis of 24 trials and five individual randomised-controlled trials. The trials included in the analysis included both primary prevention studies, where participants did not have clinical signs of cardiovascular disease before joining the trial, and secondary prevention studies, where participants had already shown clinical signs of cardiovascular disease.

Data from a total of 244,090 participants were included in the analysis, including 21,492 people aged at least 75 years. Just over half of participants aged 75 years or older were from trials of statin therapies (54.7%, 11,750/21,482), 28.9% were from trials of the cholesterol-lowering drug ezetimibe (6,209/21,482) and the remaining 16.4% were from trials of PCSK9 inhibitors (3,533/21,482), which are another class of drugs prescribed to lower cholesterol. The average time of study follow-up ranged from 2.2 to 6 years.

The analysis found that cholesterol-lowering therapies were associated with a reduction in the incidence of all cardiovascular events, including death, heart attack and stroke. The reduction in risk of major cardiovascular events for people aged over 75 years was statistically comparable to younger age groups - 26% per 1mmol/L reduction in LDL cholesterol in people aged over 75 years, compared to a 15% risk reduction in patients younger than 75 years.

The authors warn that their findings do not mean that patients should wait to initiate treatment until they are older and stress the importance of keeping LDL cholesterol well controlled as early as possible in individuals to prevent the build-up of cholesterol in the arteries.

Deaths from all cardiovascular disease outcomes in people aged over 75 years were reduced by 15% per 1mmol/L reduction in LDL cholesterol (treatment group 723 deaths; control group 799 deaths). The incidence of heart attacks in this age group was reduced by 20% for every 1mmol/L reduction in cholesterol (treatment group 813 events, control group 971 events) and the occurrence of any type of stroke was reduced by 27% (treatment group 401 events; control group 486 events).

There was no difference in the magnitude of the risk reduction in major vascular events between statins and other cholesterol-lowering medications in the older age group.

Older individuals have higher rates of major cardiovascular events than younger people overall, and in this study, rates were almost 40% higher in those aged 75 years and older. The authors say this means it is expected that treating people aged over 75 years with cholesterol-lowering therapies is likely to particularly prevent large numbers of cardiovascular events.

Professor Marc Sabatine, lead author of the study, from Brigham and Women's Hospital, Boston, Mass., USA, said: "Cholesterol-lowering medications are affordable drugs that have reduced risk of heart disease for millions of people worldwide, but until now their benefits for older people have remained less certain. Our analysis indicates that these therapies are as effective in reducing cardiovascular events and deaths in people aged 75 years and over as they are in younger people. We found no offsetting safety concerns and together, these results should strengthen guideline recommendations for the use of cholesterol-lowering medications, including statin and non-statin therapy, in elderly people." [2]

The authors acknowledge some limitations to their study. The definitions of cardiovascular events differed slightly between trials. However, the authors say these minor differences are unlikely to affect the clinical implications of their findings. Additionally, older patients who are included in clinical trials might not be representative of everyday practice, because people who already have multiple medical conditions or are unable to attend follow-up visits would not typically be enrolled in a clinical trial.

Writing in a linked Comment, Professor Frederick Raal, University of the Witwatersrand, South Africa, who was not involved in the study, said: "As the authors acknowledge, although lipid-lowering therapy was efficacious in older patients, we should not lose sight of the benefit of treating individuals when they are younger. The average age of patients in all the trials analysed was older than 60 years, an age when atherosclerotic cardiovascular disease is already well established. Lipid-lowering therapy should be initiated at a younger age, preferably before age 40 years, in those at risk to delay the onset of atherosclerosis rather than try to manage the condition once fully established or advanced."

Kanazawa, Japan - The relationship between dietary habits and the occurrence of chronic kidney disease (CKD) is not fully known. In a new study, researchers from Kanazawa University found out that skipping breakfast and late dinner might be associated with a higher risk of proteinuria which is a key prognostic factor of CKD.

CKD is defined as either a structural and/or functional abnormality of the kidney or a reduced glomerular filtration. CKD is a risk factor for end-stage renal disease and cardiovascular disease, which is a major health problem in several countries. The most common causes of CKD are diabetes, high blood pressure and obesity. Although these diseases can be treated individually with drug treatment, in recent years, treatment with behavior change such as diet and exercise have attracted attention.

"CKD is associated with a higher risk of cardiovascular-related death," says corresponding author of the study Professor Takashi Wada. "It is therefore important to understand what behavior may facilitate the development of this deadly disease. The goal of our study was to investigate the relationship between dietary habits and CKD."

The researchers focused on proteinuria which is a key prognostic factor of CKD. Proteinuria is generally defined as dipstick urinary protein excretion ?1+ . Proteinuria is an early sign of kidney disease. Therefore, preventing its occurrence is important for our health. The researchers planed a study using the questionnaire used in annual medical check-ups with the cooperation of the Kanazawa Medical Association.

The researchers conducted a retrospective study, in which they investigated over 26,000 patients aged >40 years who underwent annual medical check-ups in Kanazawa between 1998 and 2014. Unhealthy dietary habits were defined as follows: late dinner (eating dinner within 2 h of going to bed at a frequency of three or more times a week); skipping breakfast (three or more times a week); quick eating (eating faster than people of the same age group); and late evening snack (eating snacks after dinner three or more times a week).

Quick eating (29%) was the most common unhealthy dietary habit in the whole patient population, followed by late dinner (19%), late evening snack (16%), and skipping breakfast (9%). During an average follow-up period of over 3 years, 10% of patients developed proteinuria. Of these dietary habits, skipping breakfast and late dinner were associated with an increased risk of developing proteinuria. Surprisingly, unhealthy dietary habits were not associated with changes in body weight.

"This result indicates that unhealthy dietary habits might be associated with risk factor for CKD irrespective of changes in body weight. Our findings are of behavioral changes to prevent the development of CKD. It may help develop new approaches to this, "says Professor Wada.

Researchers from Tokyo Medical and Dental University (TMDU) report a case of frosted branch angiitis in a woman presenting years after being treated for leukemia-lymphoma with allogeneic human stem cell transplant.

Tokyo, Japan - Leukemias and lymphomas are life-threatening malignancies affecting white blood cells and the immune system; fortunately, radiotherapy and chemotherapy, combined with stem cell therapy, can improve survival significantly. Now, Japanese researchers report one such patient who presented with an intriguing and rare delayed ocular complication descriptively named frosted branch angiitis.

A Japanese woman in her early fifties was diagnosed with acute-type adult T-cell leukemia-lymphoma associated with human T-cell lymphotropic virus type 1 (HTLV-1). She was managed with whole body irradiation and anti-cancer drugs, followed by allogeneic (donor) human stem cell transplant (HSCT). HSCT allows physicians to use higher doses of chemoradiotherapy as the patient gets an infusion (transplant) of blood-forming stem cells to restore collaterally damaged bone marrow. The patient went into remission and had no complications for several years.

Over four years after HSCT, she developed blurred vision and was referred for further examination. A slit-lamp biomicroscope, which shines a thin sheet of light into the eye for inspection, revealed cellular infiltrates in both segments. Associate Professor Koju Kamoi, lead / corresponding author, describes the remarkably picturesque fundoscopy findings. "Along the retinal blood vessels, a translucent sheath was visible resembling the icy branches of a tree in winter. We recognized this as frosted branch angiitis (Figure A), a rare presentation of florid retinal vasculitis."

The medical team ran a battery of tests to rule out recurrence, other autoimmune disease, and bacterial, viral or fungal infections. Therefore, the physicians concluded that the frosted branch angiitis resulted from immune activation following HSCT. First described in the Japanese literature by Ito in 1976 occurring in a six-year-old child, frosted branch angiitis is very rare, with most cases reported from Japan and sporadically from other countries.

The patient was treated with corticosteroids to suppress inflammation. After six months the lesion regressed but steroids were continued for over a year. Surprisingly, a month after stopping systemic steroids, the patient developed a skin rash (Figure B) and dryness of both eyes. "This sequence of events suggests that frosted branch angiitis was likely the first sign of systemic inflammation," explains Dr Kamoi. "Steroids could have suppressed the slower skin and eye-surface changes that were expressed following discontinuation."

"Though HSCT is beneficial in many situations, it may activate the immune system adversely," warns Professor Kyoko Ohno-Matsui, senior author. "Frosted branch angiitis could serve as early warning sign of inflammation elsewhere in the body. Therefore, intraocular monitoring is warranted in these patients."

Working in farming or the wood industry while suffering from asthma is not a good combination. This is because it increases the risk of being hospitalised again with asthma. This is shown by a new study from Aarhus University.

Farmers and people who process wood should preferably not suffer from asthma. If they do, they are even more vulnerable while at work. For the first time, a new study from Aarhus University has examined whether working in farming and the wood industry - in occupations with dust exposure - increases the risk of renewed contact with the hospital system if the person has asthma or the lung disease COPD.

This is clearly the case for asthma, while it is uncertain whether the same is true for COPD, explains Vivi Schlünssen, who is one of the researchers behind the study. The risk of renewed contact with a hospital is more than doubled for people with asthma and is most marked for people working in farming, where the risk is more than tripled.

In the study, the researchers examined the correlation between readmission for asthma and dust exposure for 769 asthmatics working in farming or the wood industry in the years 1997-2007.

More readmissions

There were a total of 94 readmissions (4.9 per 100 person-years) for asthma among those who were exposed, while there were only 24 (1.3 per 100 person-years) among those who were not exposed. Hospitalisation could be either admittance to a hospital ward or a visit to a hospital outpatient clinic.

The results have been published in the scientific journal Scandinavian Journal of Work, Environment & Health.

According to Vivi Schlünssen, the study should be followed by studies stretching over a longer period of time and with information about the severity of the diseases, as the risk of hospitalisation will depend on the severity of the asthma and COPD.

"The results of the study confirm previous studies: That asthmatics more often report that they cannot control their asthma if they work in industries with high dust exposure, compared to asthmatics who do not work in dusty environments. And work in dust is associated with a poorer prognosis for people with asthma," explains the researcher.