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HIV patients can suffer from a range of ailments. However, the prevalence of specific diseases may be depended on geographical or demographic factors. A team of researchers from the University of Fort Hare in South Africa, led by Olufunso O. Sogbanmu have studied the incidence of diabetes mellitus in HIV patients Buffalo City, East London. The team's research has shown the need to screen older individuals diagnosed with HIV as crucial in offering a timely point of care and interventions to enable prompt diagnosis of diabetes mellitus in this cohort of patient and prevent possible comorbidities that may result from delayed diagnosis.

The study examined the prevalence of diabetes mellitus in newly diagnosed HIV-positive patients in Buffalo City Municipality, East London, South Africa. The majority of the participants were female (75%) and the prevalence of diabetes mellitus was 6% amongst newly diagnosed HIV positive patient using the definition based on the Society for Endocrinology, Metabolism and Diabetes of South Africa (SEMDSA) 2017 guideline of HbA1c of above 6.5%. The multivariate analysis indicates only age (p=0.031) and race (0.019) significantly shows a correlation to increase the risk of development of diabetes mellitus in newly diagnosed HIV positive patients. The binary logistic regression analysis shows that age (above 46 years) (p=0.001; AOR (6.60); CI (2.08-20.9) was directly related to the development of diabetes mellitus.

Passing on dangerous naked explosives: the state of multiple antibiotic resistant Enterobacteriaceae in Cape Coast, Ghana.

The dynamisms involved in bacterial drug resistance, emergence and spread of multiple antibiotic resistant Enterobacteriaceae in Ghana are poorly understood. The current state of antibiotic resistance is gradually becoming alarming. To make matters worse, the factors that drive the transmission of antibiotic resistance among organisms in Ghana are still poorly understood. The isolation of multi-antibiotic resistant Enterobacteriaceae to ß-lactams, the first, second and third generation cephalosporins from circulating coin currencies and meat sources in Cape Coast, Ghana, is a major concern as it poses a serious threat to the entire healthcare system. E. coli, Enterobacter spp, Shigella spp, Klebsiellaspp, Pseudomonas spp, and Proteus spp showed resistance to second and third generation cephalosporins, an effective antibiotic against Enterobacteriaceae species. There is a possibility that this extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae in circulation will spread rapidly with limited timely treatment to curb the infections. These microbes cause a range of infections including acute diarrhoea, respiratory infection, urinary tract infections (UTI), bacteremia, sepsis, pneumonia, cystitis, pyelonephritis, and lung abscess. The easy spread of this multi-antibiotic resistant Enterobacteriaceae through contact with contaminated surfaces and by person-to-person contact makes it major public health concern as it has a high implication on the health facilities of the region which have limited resources. The isolation of MDR Enterobacteriaceae from circulating coin currencies and meat sources gives an indication of an individual's multiple points of contact with these pathogens during daily routines, risk of infection and possible transmission to another person. The impending danger of possible outbreak of multiple ESBL-E resistant strains requires immediate public health measures to circumvent an epidemic outbreak in Ghana. Understanding the underlying mechanisms of ESBL-E transmission would be essential in providing permanent control measures to deal with drug resistance in Ghana. Personal hygiene and proper handling of currencies are encouraged to mitigate the spread of drug-resistant pathogens.

A drug with three active ingredients that are released in sequence at specific times: Thanks to the work of a team at the Technical University of Munich (TUM), what was once a pharmacologist's dream is now much closer to reality. With a combination of hydrogels and artificial DNA, nanoparticles can be released in sequence under conditions similar to those in the human body.

It is becoming much more common for patients to be treated with several different medications. It is often necessary for the patient to take them at fixed intervals - a limitation that makes everyday life difficult and increases the risk of doses being skipped or forgotten.

Oliver Lieleg, a professor of biomechanics and a member of the Munich School of BioEngineering at TUM, and doctoral candidate Ceren Kimna have now developed a process that could serve as the basis for medications containing several active ingredients that would reliably release them in the body in a pre-defined sequence at specified times. "For example, an ointment applied to a surgical incision could release pain medication first, followed by an anti-inflammatory drug and then a drug to reduce swelling," explains Oliver Lieleg.

One active ingredient after the other

"Ointments or creams releasing their active ingredients with a time delay are not new in themselves," says Oliver Lieleg. With the drugs currently in use, however, there is no guarantee that two or more active ingredients will not be released into the organism simultaneously.

To test the principle behind their idea, Oliver Lieleg and Ceren Kimna used nanometer-sized silver, iron oxide and gold particles embedded in a special gel-like substance known as a hydrogel. They then used a spectroscopic method to track the exit of the particles from the gel. The particles selected by the researchers have similar motion characteristics within the gel to the particles used to transport real active ingredients, but are easier and cheaper to make.

The special ingredient controlling the nanoparticles is artificial DNA. In nature, DNA is above all the carrier of genetic information. However, researchers are increasingly exploiting another property: The ability of DNA fragments to be combined with great accuracy, both in terms of the types of bonds and their strength, for example to build machines on a nanometer scale.

The DNA cascade: compress and then release at the right instant

The silver particles were released first. In the initial state, the particles were bound together by DNA fragments designed by Lieleg and Kimna using special software. The resulting particle clusters are so large that they are unable to move in the hydrogel. However, when a saline solution is added, they separate from the DNA. They can now move in the gel and drift to the surface. "Because the saline solution has approximately the same salinity as the human body, we were able to simulate conditions where the active ingredients would not be released until the medication is applied," explains Ceren Kimna.

The mesh-like DNA structure surrounding the iron oxide particles consists of two types of DNA: The first has one end attached to the iron oxide particles. The second type is attached to the loose ends of the first type. These structures are not affected by the saline solution. The iron oxide particles can only be released when the first clusters have dissolved. This event releases not only the silver nanoparticles, but also DNA, which eliminates the "connection DNA" of the second cluster without forming connections itself. As a result, the iron oxide particles can separate. This releases DNA fragments which in turn act as the key to the third DNA-nanoparticle combination.

"The consistency of ointments makes them the most obvious solution for a hydrogel-based approach. However, this principle also has the potential to be used in tablets that could release several effective ingredients in the body in a specific order," explains Prof. Lieleg.

ANN ARBOR--Dozens of counties in the Midwest and South are at the highest risk for opioid deaths in the United States, say University of Michigan researchers.

In a study of more than 3,000 counties across the U.S., the researchers found that residents of 412 counties are at least twice as likely to be at high risk for opioid overdose deaths and to lack providers who can deliver medications to treat opioid use disorder.

States with among the most high-risk counties include: North Carolina, Ohio, Virginia, Kentucky, Michigan, Tennessee, Illinois, Indiana, Georgia, Oklahoma, West Virginia, South Carolina, Wisconsin and Florida.

The study, published in the June 28 issue of JAMA Network Open, suggests strategies for increasing treatment for opioid addiction, including by increasing the number of primary care clinicians capable of providing medications as well as improving employment opportunities in those communities.

"We hope policymakers can use this information to funnel additional money and resources to specific counties within their states," said lead author Rebecca Haffajee, assistant professor of health management and policy at the U-M School of Public Health. "We need more strategies to augment and increase the primary care provider workforce in those high-risk counties, people who are willing and able to provide opioid use disorder treatments."

The U-M researchers looked at opioid overdose mortality rates in 3,142 U.S. counties between January 2015 and December 2017. They defined an opioid high-risk county as one with opioid overdose mortality above the national rate and with the availability of providers to deliver opioid use disorder medications below the national rate.

The study, they say, is the first to include data from all three opioid use disorder medications on the market, including methadone, buprenorphine and naltrexone. Their analysis included publicly listed providers of methadone (1,517 opioid treatment programs), buprenorphine (24,851 clinicians approved to prescribe the medication) and the extended-release naltrexone product Vivitrol (5,222 health care providers, as compiled by the drug manufacturer).

In their cross-sectional study, the researchers also looked at demographics, workforce, access to health care insurance, road density, urbanicity and opioid prescriptions.

Among counties analyzed, they found that:

412 counties (13%) are classified as high-risk, having both high opioid overdose mortality and low treatment capacity.

751 counties (24%) had a high rate of opioid overdose mortality.

1,457 (46%) counties lacked a publicly available provider of opioid use disorder medication.

946 out of 1,328 rural counties (71%) lacked a publicly available provider of opioid use disorder medication.

The study found that certain factors--such as a younger population, lower rates of unemployment and higher density of primary care physicians--are associated with a lower risk of opioid overdose death and lack of capacity to treat opioid use disorder.

Haffajee, also a member of the U-M Institute for Healthcare Policy and Innovation, said it's important to understand the differences of the opioid epidemic at the local level.

"In rural areas, the opioid crisis is often still a prescription opioid issue. But in metropolitan counties, highly potent illicit fentanyl and other synthetic opioids are more prevalent and are killing people," she said. "That's likely why we identified metropolitan areas as higher-risk, despite the fact that these counties typically have some (just not enough) treatment providers.

"Understanding these differences at the sub-state level and coming up with strategies that target specific county needs can allow us to more efficiently channel the limited amount of resources we have to combat this crisis."

Taking medical 'selfies' and sharing them with a doctor empowers and reassures healthcare consumers, and can improve doctor-patient relationships, a two-part study led by Queensland University of Technology (QUT) in Brisbane, Australia has found.

The findings have been published in the Journal of Medical Internet Research.

Former medical photographer Dr Kara Burns conducted the research as part of her PhD through the QUT Business School.

To gauge experiences with and attitudes to consumer-generated health photographs, Dr Burns first interviewed 30 patients, clinicians, and carers.

The second study was a pilot trial with parents taking photos of their children's surgical wounds after they had undergone laparoscopic appendectomy at the Queensland Children's Hospital. 26 parents completed the study, receiving training and then taking photos every two days and emailing the photos to the hospital so that surgeons could review healing.

Parents said it improved their confidence in and satisfaction with the medical service, and taking the photos was a useful reminder for them to check how the surgical sites were healing.

Dr Burns said the findings from the photographic trial supported conclusions drawn from the interview study.

"The first study asked a range of people what they think about the role of this kind of consumer-generated data, and the second study was to see how people engage with it, as there can be a difference between what people say they will do and what they will do," she said.

"But these two studies largely confirmed each other. Consumers feel this data is valuable, it helps them have a sense of autonomy in their care, improves their view of the service they are being provided, and it enhances the relationship between doctor and patient because there is a sense of mutual respect and communication.

"The parents who took part in the trial said they felt reassured and that the service was going above and beyond. They said normally the door feels shut when you leave a hospital, and providing the photos was a way to stay connected and contact the surgeon afterwards."

Dr Burns said while for clinicians it may be difficult to integrate patient-generated data, such as photographs, video, or information from apps or body monitoring devices, into clinical records, medical professionals should consider it.

"This study adds to a body of research that shows there are benefits for clinicians and also for patients in engaging with this kind of patient or carer-generated information," she said.

"If doctors ignore it and don't engage, this research shows that it impacts the service experience and that some patients will switch doctors.

"In one case, a mum had a six-week-old baby who was constantly vomiting, and she felt no one was listening to her concerns. She was so unimpressed by the doctor's responses to her that she changed providers. When she took a video to the next doctor, they assessed that something was wrong and that her daughter needed surgery.

"My Health Record should also consider ways to integrate patient-generated health data. People have expressed concerns about privacy and accessibility but giving them an option to upload their own information may give them a reason to use the portal, to be less fearful of it."

Health care institutions and providers face mounting pressure to wring more value out of every dollar spent on caring for their patients.

A new review shows that most efforts to decrease low-value care have based their measurement of success on how much they reduced the overall use of certain tests and treatments. Far fewer looked at whether these efforts actually ensured that patients got more appropriate care and avoided unintended negative consequences.

The review, published in the Journal of General Internal Medicine, looks at 117 different efforts aimed at reducing low-value care and how they measured the effects of these efforts.

"Low-value" can mean many things, including care that doesn't benefit patients and could even harm them, wastes limited health care resources or leads to unnecessary costs.

Hundreds of studies over the past two decades have revealed many services that lack value for all patients, or just certain patients. Patients and clinicians now have easy-to-follow guidance on what those are, thanks to the Choosing Wisely campaign from the the American Board of Internal Medicine Foundation.

The new review focuses on what happens when teams act on this evidence and guidance, and researchers try to study the effects.

The bottom line? Those trying to reduce low-value care should take a bigger-picture view.

The authors, led by health care researchers from the University of Michigan Institute for Healthcare Policy and Innovation, VA Ann Arbor Center for Clinical Management Research and the University of Toronto, performed the review at the request of AcademyHealth, a non-profit professional society focused on improving health and health care by moving researchers' evidence into action. The study was funded by the Patient-Centered Outcomes Research Institute.

"Reducing use of low-value services is important, but in doing so, we need to also make sure we are assessing things that are clinically relevant, like whether appropriate care is being delivered to patients rather than only whether use of a given service is being reduced," says Jennifer Maratt, M.D., clinical lecturer in the U-M Department of Internal Medicine and the VA Ann Arbor Healthcare System who led the study with Sameer Saini, M.D. and Eve Kerr, M.D.

More about the findings

The researchers looked at 101 papers published between 2010 to 2016 about specific efforts to reduce low-value care. They also examined 16 studies that are still under way through ClinicalTrials.gov.

In all, 68% of the already-published efforts focused on measuring and changing the use of a particular test or treatment, but only 41% measured an outcome -- that is, what happened when they changed that use. About half tried to gauge whether a particular test or treatment was appropriate for patients -- arguably the most clinically meaningful measure.

But only one-third of these studies had looked for unintended consequences of their effort to wring low-value care out of their care environment.

Such consequences - such as missing when an individual patient needs a particular treatment or test- can occasionally happen when an across-the-board cut in a particular medical service results in some patients not getting something that could have helped them specifically.

For instance, an effort to reduce overuse of antibiotics in hospitalized patients could unintentionally lead to more of them ending up at the emergency department later if an infection flares up.

"The Choosing Wisely campaign has dramatically increased the number of studies done to reduce low-value care, which is great," says Kerr, a professor at U-M and director of the VA CCMR. "However, we found that the majority of these studies do not assess outcomes that are truly meaningful to patients."

A patient's perspective

Not only did most studies not look for this kind of 'backfiring' -- very few involved a patient perspective. In all, only 8% asked patients about the impact that the change had on them -- what researchers call a "patient-reported outcome."

The 16 studies still in progress were a little better at aiming to take a big-picture view than the published studies.

Of these ongoing studies, 75% aim to measure a specific outcome of the effort, and 63% are looking for unintended consequences. And half include plans to measure patient-reported outcomes.

The researchers also found that ongoing studies are much more likely to use methods that meet the 'gold standard' of research, including randomizing patients to a particular care group, or including a control group to compare with.

Newer studies are also more likely to involve patients directly in efforts to reduce low-value care, mainly by educating them about whether a particular test or treatment is likely to benefit them.

Says Saini, "By focusing on simple utilization, the vast majority of studies provide an incomplete picture of the impact of these often powerful and complex interventions. For example, we often do not know how interventions to reduce use of low-value care affect the patient-provider relationship or to what extent they unintentionally lead to fewer tests or prescriptions in patients who need them."

Saini is an associate professor of medicine at U-M and research scientist at the VA CCMR.

Next steps

In general, the team says, researchers and evaluators should work to incorporate more clinically meaningful and patient-centered measures into studies, to provide a more comprehensive understanding of the impact of these interventions.

They call for more standardization for how health care providers evaluate their efforts to reduce low-value care.

They also say more of these studies need to evaluate that the right services are being reduced in the right patients, that patient/provider relationships are assessed, and that downstream outcomes improve.

Examples of interventions to reduce low-value care:

Cost sharing and value-based purchasing

Patient education and decision-making

Quality indicators and reporting

Physician performance incentives

Utilization management

Financial risk sharing/physician reimbursement

Clinical decision support

Provider education

Provider feedback and peer reporting

Bottom Line: In utero exposure to opioids was associated with higher risks for short- and long-term adverse outcomes including preterm birth and neurodevelopmental and physical health disorders in children. This observational study analyzed clinical and epidemiological data for a group of 8,509 mother-child pairs collected at birth starting in 1998, and 3,153 children who continued to be followed after birth up to age 21 years old. Of the 8,509 children, 454 (5.3%) had in utero opioid exposure, which was defined as maternal self-reported opioid use or a clinical diagnosis of neonatal abstinence syndrome for a child. The study reports that in utero exposure to opioids was associated with a higher likelihood of being small for gestational age and preterm birth. In utero exposure to opioids also was associated with postnatal neurodevelopmental and physical disorders, including a higher likelihood of conduct disorder or emotional disturbance diagnoses, as well as lack of normal physiological development in children before age 6 years old, and later on, a higher likelihood of attention-deficit/hyperactivity disorder. Study limitations to consider include that mothers may have used other substances, such as alcohol, cigarettes, marijuana and stimulants, which could have influenced the outcomes.

Bottom Line: A survey study based on 25 years of data from more than 5.4 million people in the Centers for Disease Control and Prevention's Behavioral Risk Factor Surveillance System suggests more work is needed on health equity in the United States. The study assessed health equity for healthy days and self-reported health, using a novel measure of health equity as well as the disparities gap between black and white individuals, income disparities and health justice (a measure of how health outcomes correlate with income, race/ethnicity and sex). National estimates of change from 1993 to 2017 suggest downward movement in average health; improvement in the disparities gap between black and white individuals; a decline in other measures of health equity and health justice; and worsening income disparities. The study has limitations in its data. Study authors suggest more or different approaches are needed to improve health equity.

Glioblastoma is an aggressive brain tumour that usually occurs in late adulthood. Just two years after diagnosis, only 13.6% of patients are still alive. Standard treatment consists of surgery, followed by radiation and chemotherapy. In addition, tumour treating fields (TTF), a new treatment method based on electrostimulation, has recently become available. The German Institute for Quality and Efficiency in Health Care (IQWiG) has therefore examined whether TTF offers advantages to newly diagnosed patients if it is used in addition to standard treatment. As the results of a recently published study show, this is in fact the case: patients survive longer, and although TTF is burdensome, it does not impair quality of life.

New study compares TTF with chemotherapy alone

The Federal Joint Committee (G-BA) commissioned the Institute to carry out the benefit assessment in an accelerated procedure (rapid report) after the results of a study had been published in December 2017. This was a randomized controlled trial that included a total of 695 patients newly diagnosed with glioblastoma and conducted at 83 centres worldwide (EF-14 study).

After surgery or biopsy, all patients received radiotherapy plus chemotherapy with the chemotherapeutic agent temozolomide. All patients then received temozolomide again and two thirds of them (466) were additionally treated with TTF. The study lasted 24 months, but there was an interim analysis for the outcome of mortality after 18 months. Due to positive results in this analysis, participants in the control group were then free to switch to the TTF study arm.

Patients should apply TTF by themselves 18 hours daily

TTF is a non-invasive treatment method that uses alternating electric fields to inhibit tumour growth. TTF is conducted via ceramic gel pads on the head. For direct skin contact to be possible, the scalp must be shaved. The electricity comes from a portable field generator. Patients can apply TTF themselves, preferably 18 hours a day.

Clear advantage for survival time

The mortality data from this one study show that the patients additionally treated with TTF lived on average (median) almost five months longer than without TTF.

As far as symptoms are concerned (morbidity), itching of the skin was more frequent in the TTF group. In contrast, the results for "cognitive performance" and "daily activities" were better than in patients who had not additionally received TTF.

No differences in quality of life and social function

According to the study, TTF showed neither advantages nor disadvantages with regard to the outcomes "health-related quality of life" and "social function". This is remarkable, because TTF itself can be burdensome for patients; for the longest time of the day, they must wear a conspicuous hood on their head connected to a wiring harness, while carrying a bag or rucksack for the generator.

However, the positive results of this one study cannot be applied to all patients with glioblastoma. The participants were in a comparatively good physical condition, which enabled them to manage their daily lives without major restrictions. In addition, best possible tolerance of chemotherapy was ensured for all patients.

Overall, the Institute sees an indication of a greater benefit of TTF compared with standard treatment.

Process of report production

In November 2018, the Federal Joint Committee (G-BA) commissioned IQWiG to prepare the report in an accelerated procedure as a so-called rapid report. Interim products were therefore not published or made available for a hearing. This rapid report was sent to the contracting agency, the G-BA, in May 2019.

A new study from City, University of London suggests that effective communication from eye health professionals may help reduce patient fears after they are diagnosed with the 'dry' form of age-related macular degeneration (AMD).

Dry AMD is a currently incurable, progressive disease of the macular, the central part of the retina through which we see the world directly in front of us.

AMD is responsible for 50% of severe sight impairment registrations in England and Wales1, and there are currently an estimated 1.5m people in the UK with sight loss caused by some form of macular disease, with dry AMD the most common form2.

The number of people with AMD is set to rise as the world's population both increases and ages; 196 million people worldwide are predicted to be affected by 2020 and 288 million by 20403.

Whilst the progressive sight loss from dry AMD does not generally lead to complete blindness, it can make recognising faces and everyday activities like reading, watching television, and driving difficult. Symptoms may begin as a blurring or distortion of the central vision, and lead to a complete blind spot (scotoma) of the central vision.

The onset of dry AMD may not be accompanied by symptoms, and may be diagnosed as part of a routine eye check by an optometrist or other health professional.

The new study involved 27 participants at various stages of dry AMD progression, who received an eye examination and then took part in a semi-structured interview to gauge the impact their diagnosis and symptoms had on their lives in the short and longer term. A 'framework' analysis was used to capture key themes, and issues from participants to inform recommendations.

These patients reported a range of responses, including how they reacted to being diagnosed with dry AMD as an incurable condition.

One patient reported:

"At the end of the day he just said you've got dry macular degeneration, end of story and that's how he put it; end of story. So I said to him, what do you mean end of story? He said well that's it, there's nothing we can do, there's no cure for it so there's nothing we can recommend you do, which is quite a big shock."

With another commenting:

"I don't hold out a lot of hope, although I do have a little spark that maybe something can be done eventually about it."

Other recommendations made by the study include standardising the rehabilitation pathways across the eye care sector, which could include referral to an Eye Clinic Liaison Officer (ECLO) to discuss information about dry AMD, and to refer patients to other relevant support services.

David Crabb, Professor of Statistics and Vision Research at City, University of London, who led the research team, said:

"What I learned from the research is that there are many people diagnosed with dry AMD who perceive the impact of the condition on their daily life as considerable, whilst their measurable visual function remains reasonable. Many fear going blind, and suffer a great deal of anxiety, particularly with the current lack of a treatment for the condition.

"Much of this distress might be allayed through more supportive conversations with their eye health professionals, and receiving timely information about the disease and outcomes, and referral to any further necessary support."

Researchers at the University of Cambridge have criticised a recent study calling into question guidelines on genetic testing for hereditary breast cancer.

In an article published in the Journal of Clinical Oncology in December 2018 entitled "Underdiagnosis of Hereditary Breast Cancer: Are Genetic Testing Guidelines a Tool or an Obstacle?", 27 US researchers argued for expanded genetic testing in all patients with a diagnosis of breast cancer. Their argument rested on the finding that of patients who met National Comprehensive Cancer Network (NCCN) guidelines, 9.39% had a pathogenic/likely pathogenic variant, whilst of patients who did not meet guidelines, 7.9% had one of these variants.

In a letter published today in the same journal, Dr Marc Tischkowitz from the Department of Medical Genetics at the University of Cambridge and Dr Amy Taylor from Cambridge University Hospitals, claim that the study is flawed and point out that a third of the authors have potential conflicts of interest.

Drs Tischkowitz and Taylor point out that the US researchers have included in their calculations many variants in genes that have no definite proven association with an increased risk of breast cancer. Reanalysing the data including only variants in genes with definitive evidence for breast cancer susceptibility brings the figures of patients with a pathogenic/likely pathogenic variant down to 6.47% for those who met NCCN guidelines and 3.75% for those who did not.

"Not surprisingly, since the guidelines are intended to identify patients at high risk, the majority of variants identified in patients who did not meet guidelines were in [moderate risk genes], which do not impact on surgical management," they write.

In addition, the Cambridge researchers say that in expanded genetic testing, an "unacceptably high" number of patients (54%) will test positive for variants of uncertain significance (VUS).

"These results take time to interpret and explain to patients, and may require follow-up, further testing, or review in case of reclassification. Of even greater concern, they are frequently misinterpreted, leading to inappropriate clinical management."

Dr Taylor adds: "Indiscriminate expanded panel testing not only has financial implications, but can lead of results that are difficult to interpret even for healthcare professionals, and may result in unnecessary surgery. Until we understand more about the genetics of breast cancer, we think it is unnecessary - and even unwise - to expand genetic testing."

Finally, Drs Tischkowitz and Taylor note that at least a third of the 27 authors are employees of, or receive honoraria, research funding or indirect support from diagnostic laboratories that are heavily involved in marketing gene panels, which "could result in a significant conflict of interest when interpreting of the results of the study".

Guiding chemotherapy to a tumour by attaching it to the antibody-based target drug Herceptin (trastuzumab) is effective at treating women with breast cancer who have no other treatment options, a new clinical trial shows.

The two-in-one treatment kept breast cancer at bay in women with a type of the disease called HER2-positive breast cancer who had stopped responding to existing drugs.

As well as being effective in women with high HER2 levels in their tumour, it was also active in a subset of women with lower levels of the HER2 protein who currently have no treatment options.

The new study, led by researchers at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, assessed the new treatment in patients for the first time, linking together the chemotherapy agent duocarmazine with trastuzumab - also known as Herceptin - which recognises the HER2 protein.

Women with HER2-positive breast cancer lived for 7.6 months after starting the treatment with no disease progression, whilst those with lower HER2 levels had progression-free survival of 4.9 months, showing that the drug extended life for patients who have run out of other treatment options.

The study was published today (Thursday) in The Lancet Oncology and funded by Synthon Biopharmaceuticals.

25 per cent of all breast cancers have higher than normal levels of HER2, which is a protein that plays a key role in the development of breast cancer. HER2-positive breast cancers are more aggressive and grow faster than some other subtypes.

HER2-positive breast cancer patients eventually develop resistance to standard therapies, leaving them with a poor prognosis and few further treatment options.

Therefore, scientists began exploring other approaches to deliver anti-cancer drugs to the tumours by linking chemotherapy drugs to an antibody.

The antibody acts as a guide for the attached drug, detecting the HER2 protein on the surface of the cancer cells. Once these two drugs - attached by a 'linker' to form the antibody drug conjugate - are internalised into the cancer cell, the linker is broken by enzymes within the cell to release the cytotoxic drug, resulting in DNA damage to the cancer cell. This approach allows the drug to be delivered directly to the target cancer cells.

As this method selectively targets the cancer cells, it minimises the damage done to the surrounding healthy cells, reducing toxicity and side effects in the patient.

The well-known breast cancer treatment Kadcyla is an example of this approach. Kadcyla is made up of the antibody trastuzumab linked to the chemotherapy drug emtansine.

However, HER2-positive cancers that are resistant both to trastuzumab alone and also to the trastuzumab-emtansine conjugate are becoming more common, again leaving these patients without further treatment options.

In this study, scientists linked trastuzumab with another chemotherapy drug, duocarmycin. When treated with this antibody-drug conjugate, on average breast cancer patients with high levels of HER2 in their tumour survived with no disease progression for more than seven extra months.

This indicates that by linking trastuzumab with a different chemotherapy drug - duocarmycin instead of emtansine - it was possible to overcome previous resistance to treatment.

Also, patients with breast cancer who had low levels of HER2 lived for nearly 5 months longer with no disease progression when treated with trastuzumab duocarmazine than they would have without the treatment.

This is an important finding as there are currently no approved HER2-targeting drugs or antibody-drug conjugate for low-HER2 breast cancer patients. This high unmet need could be met by the duocarmazine conjugate, potentially giving these patients life-extending options.

The researchers are hopeful that this approach could not only be used to treat breast cancer with high and low HER2 levels, but also to other cancer types with varying HER2 levels such as endometrial, urothelial and oesophageal cancer which have limited treatment options due to drug resistance and poor prognosis - although further studies are required to confirm this.

The late-phase TULIP trial is currently recruiting patients to looking into whether trastuzumab duocarmazine is more effective than the standard chemotherapy for women with HER2-postivie breast cancer.

First author Professor Udai Banerji, Deputy Director of the Drug Development Unit at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, said:

"The approach used in this study of combining the antibody and drug is a highly successful way of targeting tumours. With the antibody acting as a guide to find and target the cancer, the duocarmazine drug can be released directly to the tumour cells, destroying them whilst minimising the damage to surrounding healthy cells."

"Trastuzumab duocarmazine has shown promising anti-tumour activity in breast cancer patients with varying levels of the cancer-driving HER2 protein. As these cancers often develop resistance to the current standard of care, this treatment could be extend the lives of patients who have otherwise run out of options."

Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said:

"This trial shows that the innovative approach of linking antibodies to specifically target cancer cells with chemotherapy drugs to kill them is effective in patients who have developed resistance to other treatments.

"Drug resistance is a major challenge we face in getting cancer treatments to work. By adapting the technique of antibody-drug conjugates to overcome resistance to current treatments, the lives of patients can be extended to give them valuable time with friends and family.

"This research is part of the ICR's ambitious strategy to understand cancer's complexity and evolution - and to overcome evolution and drug resistance through the world's first 'Darwinian' drug programme."

The most comprehensive study to measure the impact of the Mexico City policy between 1995 and 2014 finds that abortion rates rose substantially among women in sub-Saharan African countries with high exposure to the policy relative to countries less exposed. In addition, the use of modern contraception declined and pregnancies increased. This pattern of more frequent abortions and lower contraceptive use was reversed after the policy was rescinded, suggesting a causal effect, according to an observational study published in The Lancet Global Health.

The Mexico City Policy, also known as the Global Gag Rule, is a US government policy that prevents federal funding from being used overseas to support any organisation that performs or provides counselling on abortion. As the world's biggest donor of development assistance, the US government has instated and rescinded the policy along partisan lines within the first week of a new administration since its creation by the Republican Reagan administration in 1984.

It was rescinded by Democratic President Bill Clinton on Jan 22, 1993, reinstated by Republican President George W Bush on Jan 22, 2001, rescinded again by Democratic President Barack Obama on Jan 23, 2009, and reinstated again and extended by Republican President Donald J Trump on Jan 23, 2017.

This study looked at induced abortion, contraception use and pregnancy rates. It used data from 26 sub-Saharan African countries and over two policy transitions - from Clinton to Bush, then from Bush to Obama (1995-2014) - and compares rates in countries that had high or low exposure to the Mexico City Policy [1]. It used the Demographic and Health Surveys (nationally representative household surveys) to estimate abortion and pregnancy rates for 743,691 women, and used the UN Population Division's World Contraceptive Use dataset to estimate use of modern contraceptive methods.

The authors used a "difference-in-difference" approach to determine if any changes seen in rates of abortion, contraceptive use, and pregnancy over time were due to the policy: this would be the case if the difference between the rates in high-exposure countries versus low-exposure countries was significantly greater when the policy was active than when it was not active.

The difference-in-difference in abortion rates between high-exposure and low-exposure countries was on average of 4.8 per 10,000 --a statistically significant 40% increase relative to when the policy was not in effect. The corresponding difference-in-difference was 3.2 percentage points lower for contraceptives and 3.2 percentage points higher for pregnancies--a relative decrease of 13.5% and a relative increase of 12.0%, respectively.

The authors note that while the policy's restriction on funding to abortion-giving organisations implies its intention is to reduce abortions by reducing their availability, many of the organisations affected by the restrictions in funding are also distributors of modern contraception. Therefore, they suggest that the increase in abortions when the policy is in effect could be due to a reduction in the availability of modern contraception and a subsequent increase in pregnancies.

Dr Eran Bendavid from Stanford University, USA, author on the study, comments on the possible impacts of the policy outside of the scope of this study , "The full consequences of the policy include additional potential harms to maternal health that we do not capture. Because abortions are an important cause of maternal mortality, the increase in abortion uptake that we find might also increase maternal deaths--and possibly disproportionately given that abortions under the policy could be less safe if they were less likely to be performed or guided by experienced organisations and providers. Our estimates of excess abortion under the policy therefore provide only a partial estimate of the policy's harm to maternal health." [2]

Nina Brooks from Stanford University, USA, comments on their findings, "The health of mothers is a global priority. Our findings suggest how a US policy that aims to restrict federal funding for abortion services can lead, unintentionally to more - and probably riskier - abortions in poor countries." [1]

The authors note some limitations of their study. Firstly, abortions are under-reported in the survey,; however, the authors point out that this is unlikely to undermine their main findings, as this bias is unlikely to apply to periods when the Mexico City Policy was and was not in effect and across countries with high and low exposure to the policy. The authors also simulated various forms of under-reporting, and their main results were statistically unchanged, suggesting that underreporting does not undermine the results.

Secondly, to measure exposure to the Mexico City Policy, they use country level numbers on US foreign aid funding. How this affects individual family planning organisations' funding at a regional level is unknown, as this data is not available; however, it is likely to be proportionate to the measure the authors used.

Finally, the authors note that there may also be alternative factors influencing the abortion, contraception and pregnancy rates. However, this is unlikely as the authors accounted for country differences, common changes over time, individual-level characteristics (such as age and education) and country-level characteristics (such as per capita GDP and population) to minimise this concern.

In a linked commentary on the study, Dr Joseph Zulu from School of Public Health, University of Zambia, Zambia, stressed the importance of considering the findings within local sub-Saharan political and social contexts, "Brooks and colleagues provide much needed documentation of the wide-ranging effects of the Mexico City Policy that allow us some insight into the sometimes subtle mechanisms of global reproductive governance. We would like, however, to encourage readers to situate these global mechanisms in the specific contexts where they take effect. Our examples from Zambia describe a complex web of socially, morally, and politically embedded factors that along with the Mexico City Policy have implications for contraceptive use and abortions. We urge readers to keep these factors in mind in further discussions about the consequences of the policy in sub-Saharan Africa. Only by situating the policy in the contexts it is implemented in and considering the wide range of relevant factors can we get a better understanding of what conditions unwanted pregnancies and unsafe abortions."

ATLANTA--Small molecules found in fecal matter could provide clues to the early inflammation found in chronic gut conditions, such as inflammatory bowel disease (IBD), and serve as new biomarkers for diagnosis, according to a study led by the Institute for Biomedical Sciences at Georgia State University.

The researchers found that fecal miRNA, small nucleic acid sequences, could be used as a tool to assess the healthiness of gut microbiota, the microorganisms living in our gastrointestinal tract, and provide early clues to intestinal inflammation in mice.

Studies have shown that some microbiotas can play a role in the development of intestinal inflammation. Since disruption of the symbiosis between the microbiota and the intestine is associated with various inflammatory diseases, such as IBD and metabolic syndrome, it is essential to identify new biomarkers of microbiota healthiness. The findings, published in the journal Theranostics, are some of the first to show connections between fecal miRNAs and gut microbiota. Earlier studies to find biomarkers for IBD or inflammation have mostly been done from tissue and blood.

"We found that miRNA from feces are indicative of inflammation level as well as microbiota function," said Dr. Emilie Viennois, first author of the study and assistant professor in the Institute for Biomedical Sciences. "It can indeed indicate if the microbiota is more prone to induce inflammation or is more protective against inflammation, and it could also determine the ability of patients to respond to therapeutics."

The researchers used germ-free mice, or animals that have no microorganisms living in their bodies, and colonized them with various microbiotas. Mice with microbiotas that were associated with the development of intestinal inflammation had distinctly altered fecal miRNA profiles compared to mice that received a "healthy" microbiota.

Next, Viennois plans to study human feces samples, which are relatively easy to obtain because clinicians routinely collect feces specimens from patients to test for gastrointestinal conditions.

"Further study will need to be done in humans, but we think that fecal miRNA can also be a way to indicate the status of the microbiota in IBD patients," Viennois said. "We know that some microbiotas are more prone to induce inflammation than others, and using miRNA as a tool to determine that would be extremely useful."

London, June 27, 2019 - Researchers have found no evidence of elevated cardiac risk in runners who completed a 24-hour ultramarathon (24UM), despite the transient elevation of blood biomarkers that measure cardiac health. According to the study in the journal Heliyon, published by Elsevier, trained runners were more likely than their novice counterparts to experience raised levels, reflecting the greater cardiac load and pituitary-adrenocortical response to extremely strenuous exercise.

"Experienced runners performed with greater intensity and speed, which placed strains on their hearts. Novice runners ran with less intensity, which resulted in lower cardiac biomarker levels," explained co-lead investigator, Rodrigo Hohl, PhD, Department of Physiology, Institute of Biological Sciences, Federal University of Juiz de Fora, Juiz de Fora, Brazil. Prof. Hohl also noted that 24UM participants self-pace for a set time and towards an established endpoint. Runners with differences in training experience and competitive performances present variations in running speeds and, therefore, cardiac biomarker responses.

"The good news is that while experienced runners pushed their heart limits during the ultramarathon, they did not show evidence of cardiac risk assessed through elevated biomarkers," Prof. Hohl noted. "Novice runners appear to pace themselves well below their cardiac limit, self-selecting a safe pacing strategy for their hearts.

The study examined the relationship between self-selected exercise intensity with cardiac biomarkers comparing experienced and novice runners able to finish a 24UM. Biomarkers that measure necrosis, inflammation, cardiac function/injury, and ischemia were used to understand the impact of acute exercise on the cardiac health of runners with different training levels and performance, including cortisol, total creatine kinase, C-reactive protein, and leukocyte levels. The findings showed higher levels of cortisol in the experienced group and confirmed previous research that cortisol is a good predictor of speed during a 24UM.

Although the study did not show clear evidence of cardiac risk when comparing cardiac biomarker levels with clinical cut-off values, it did establish that prolonged heart overload varies according to running speed. The wide range of ultramarathon distances and durations makes it challenging to generalize about cardiac risks and biomarkers response. Moreover, competitors modulate running intensity according to individual exercise tolerance and motivations to push themselves to increase levels of physical endurance, and little is known about the effect of extreme environmental conditions. Therefore, experienced ultramarathon runners should not consider themselves free of risk.

"Our study provides evidence for caution and self-monitoring especially for experienced runners. After participating in an ultramarathon, runners should recover for at least two days before running any significant distance. This time is needed to normalize cardiac markers and allow the heart time to recover after such a challenge," cautioned Prof. Hohl.

A total of 25 runners participated in the study, which involved observation of a 24UM and blood tests before and after the event. Eleven runners in the experienced group had trained a distance of more than 100 km a week over a five-year period. Fourteen novices had previously run at least one regular marathon but had not participated in an ultramarathon. Exclusion criteria eliminated smokers, steroid users, as well as anyone with cardiovascular or metabolic disease or musculoskeletal injury from the study group.