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Munich, Germany, 20 October 2018 - Social vulnerability showed to be a major limitation to participation in cancer screening for four tumors types - breast, cervical, colorectal and lung - according to the French nationwide observational survey, EDIFICE 6. Also, a disbelief in cancer test efficacy among target populations was highlighted as new indicator of the non-uptake of screening, according to results to be presented at the ESMO 2018 Congress. (1, 2, 3, 4)

The EDIFICE programme has been conducted every three years since 2005 with the aim to provide a better understanding of population adherence to cancer screening in France. The latest round of the survey was conducted from 26 June to 28 July 2017 by using an online questionnaire (rather than phone calls as in previous editions) and involved a representative sample of 12,046 individuals between 18 and 69 years old.

Analysing results on breast cancer, Professor Jean-Francois Morere of Hopital Paul Brousse of Villejeuif said: "Participation rates for breast cancer screening, which is freely accessible to all women aged 50-74 in France, are generally higher than for other types of cancer. In our survey, only 6% of participants declared they had never had a mammogram." He continued: "On the last two rounds we started to observe an impact of social vulnerability on screening reluctance. We can only suppose that for persons with low social conditions prevention is not a priority".

Higher reluctance was reported for colorectal cancer (CRC) screening, with 38% of individuals involved in the analysis who had never undergone a fecal immunochemical test (FIT) in their lifetime. Professor Francois Eisinger of Institute Paoli-Calmettes of Marseille, France, said: "They were more likely to be younger, current smokers or socially vulnerable. Fear of the examination or of results was a barrier for 29% of survey participants. We cannot make a reliable comparison with past surveys due to a change in methodology, but ten years ago very few persons declared this motivation." He continued: "Attendance rates in both breast and CRC cancer screening have now reached a plateau in the country and new strategies are needed to move beyond it. What is not clear is why the plateau is only 50-60% for colorectal cancer. We have to understand if it is due to CRC screening test in itself, organisation of screening or poor risk or benefit perception."

Targeting who is out of reach of cancer screening is still a major issue for long-standing practices like cervical cancer (CC) screening, according to Dr Thibault De La Motte Rouge of the Centre Eugene Marquis in Rennes, France. He reminded that incidence of cervical cancer is higher among socially marginalised women who are generally more exposed to HPV infections, due to several factors, including early age at first sexual practice, poor diet, tobacco and alcohol consumption. "However, our survey showed that major items associated with reluctance to undergo tests are, living alone or socio-economic deprivation," he said. "We are now trying to implement a screening programme at a national level in France, and identifying social patterns can help us improving the organisation of the programme."

Researchers agree that one key question is to understand why some unscreened groups do not trust preventive measures offered by healthcare systems. Morere said: "A sort of negative attitude towards the efficacy of how cancer care is organised emerged. We reported disbelief in progress of clinical research and efficacy of protection given by screening programmes as relevant items of poor adherence to breast and colorectal cancer screenings. It is the first time that we have tried to address medical skepticism; the investigation approach is still not accurate enough but we will refine this type of questions for the next round."

Commenting for ESMO, Prof. Martin-Moreno of the Medical School and Clinical Hospital of the University of Valencia, Spain, stated that addressing inequalities in uptake must remain a priority for screening programmes and a combined approach is required. He said: "Stratifying screening through correlation with anamnestic, clinical, radiological and genomic data has proved to be useful in other studies. Furthermore, exploiting new information and communication technologies such as smartphone applications or personalised text messages should also be increasingly used. Strategies to improve uptake typically produce only incremental increases: we need to be consistent and resilient if we are to succeed in achieving coverage rates that are high enough for screening programmes to be truly effective."

Differently from programmes for other types of cancer, implementation of lung cancer screening is still under debate in Europe. "In France it is not routinely proposed to individuals, although it has the potential to early detect lung cancer, which is typically diagnosed when it is has spread (stage IIIb or IV)", said Prof. Sebastien Couraud of Hospices Civils de Lyon, Lyon. He continued: "In our survey, current smoking was associated with intention of being screened, which is good news: we want to screen smokers. We also found that 15% of samples had already been tested although we did not investigate which type of exam was or whether the proper exam was ordered by the physician."

Martin-Moreno commented that despite smokers' attitude towards lung cancer tests, low-dose CT screening is a major cause for hesitation due to false-positive rates and the possibility of complications from invasive follow-up. "We need to build evidence-based prevention which is trustworthy and worthwhile for the people to whom it is offered. One drawback of screening is that some smokers may think that it does not matter to continue smoking as long as there is a test on hand that tells them if something is wrong with their lungs in time".

He said: "Screening can provide an educational opportunity to reach the target population and promote preventive measures, but evidence is still poor. At the moment, I believe that it is best to focus priority efforts from the very beginning on quitting smoking".

Despite the many challenges in the implementation of cancer screening programmes in Europe, detection of pre-cancer conditions or early disease has been recognised to play a key role in cancer management. The ESMO Clinical Practice Guidelines (5,6,7,8) recommend screening for breast cancer in all women aged 50-69 years with regular mammography after discussion of the benefits and risks with expert oncologists. Also, primary prevention of cervical cancer is recommended via immunisation with highly efficacious HPV vaccines; and HPD DNA testing or Pap test has proven to be effective for screening female population. For early detection of colorectal cancer, ESMO dedicated guidelines encourage the use of faecal occult blood test for regularly screening of average-risk populations aged 50-74 years. While important questions on who to screen for lung cancer, how often and for how long, are still under evaluation, recent recommendations support that screening with low dose CT scan can reduce lung cancer-related mortality provided it is offered within a dedicated programme with quality control in current or former heavy smokers aged 55-74 years.

Martin-Moreno concluded: "It is clear that oncology has shifted from being merely reactive to being proactive and cancer screening is fully in line with this idea. (9) It has the potential to make a major contribution to effective early diagnosis, if wide coverage, informed choice and equitable distribution of screening services are ensured."

Munich, Germany, 20 October 2018 - Immunotherapy has been a major breakthrough in oncology, with registered drugs now approved for use in an increasing number of tumour types - but little is known about its safety for HIV-positive cancer patients. A study (1) to be presented at the ESMO 2018 Congress in Munich has now provided data to suggest that treatment with PD-1/PD-L-1 immune checkpoint inhibitors, which target the very system affected by the HIV virus, is feasible in this patient population for whom cancer is currently one of the principal cause of mortality.

According to study author Dr. Aurelien Gobert of Groupe Hospitalier Pitie Salpetrire in Paris, France, there are about two million people living with HIV in Europe today. "These patients are at higher risk for a number of cancers: AIDS-defining forms, the diagnosis of which results in the categorisation of a person as suffering from AIDS, but also various other types that they are two to three times more likely to develop than in the general population, such as anal, skin, head and neck, and lung cancer," he explained. HIV-positive cancer patients are not represented in clinical drug trials, which select candidates with the lowest probability of suffering complications, so their responses to new therapies are not immediately known.

"The point of this study was to look at an HIV-positive patient cohort treated with immunotherapy in conjunction with a close monitoring of their viral load and CD4 lymphocyte count," said Gobert. "Viral load is the quantity of virus found in the bloodstream, and CD4 lymphocytes are the cells of the immune system that HIV targets. Both measures are indicators of the extent to which a person is affected by the virus: patients treated properly with antiretroviral therapy typically have a lymphocyte count of 350-500/mm3 and a viral load that is undetectable."

To assess the effects of the PD-1 inhibitor nivolumab in this population, cases presented in the multidisciplinary meetings of the national Cancer VIH network (2) were evaluated. In addition to CD4 lymphocyte count and viral load, tolerance and efficacy information was retrospectively collected from patients treated with this drug, along with demographic data. "Our study population was demographically homogenous, most patients being males around 60 years old," Gobert reported.

Out of the 20 patients evaluated, one (5%) had metastatic melanoma - the remaining 95% were treated for metastatic non small-cell lung cancer. Median lymphocyte count at diagnosis was 338.5/mm3. Viral load was undetectable in 17 patients, low in two cases and unknown in one person. At the time of the cut-off analysis, median follow-up was almost 11 months, and the median number of nivolumab infusions received was six (ranging from three to 53).

"We didn't see any toxic deaths or immune-related adverse events," Gobert reported. "One patient did experience a rising HIV viral load and decreasing CD4 lymphocyte count, indicating a reactivation of the virus, but this occurred following the interruption of his antiretroviral therapy." Of the 17 individuals in whom response could be assessed, a partial response was observed in four patients, while two had stable disease and the majority (eleven) had disease progression at the first evaluation.

"Although the response data is fairly consistent with results obtained with the same drug among other cancer patients, the size of our sample and the length of follow-up do not allow us to draw any conclusions regarding efficacy," Gobert cautioned. "We know that few patients respond to immunotherapy, but those who do respond for long periods of time and thus have significantly improved survival. This seems to have been the case for the melanoma patient in our cohort, but the study is too recent for us to quantify survival rates at this time."

"Our key insight then, is that the treatment appears to be well tolerated by HIV-positive cancer patients - so long as antiretroviral therapy is continued in parallel," Gobert concluded. "It speaks to the feasibility of immunotherapy in this patient population, which represents a significant proportion of cancer diagnoses, and among whom malignancies accounted for more than a third of deaths in 2010. (3) Going forward, this will need to be confirmed for various tumour types."

Commenting on this study for ESMO, Prof. John Haanen from the Netherlands Cancer Institute in Amsterdam, said: "This is a retrospective analysis of a relatively small cohort, which is nevertheless one of the largest so far presented, of HIV patients on antiretrovirals treated with immunotherapy for metastatic cancer. The results confirm those of other, smaller cohorts in showing that while on antiretroviral therapy, cancer patients living with HIV can safely receive anti-PD-1 treatment. The efficacy data also suggests that the overall response rate of HIV-positive patients seems to be similar to that of other cancer patients. These promising results need to be confirmed in larger studies - ideally, in a prospective clinical trial."

Munich, Germany, 20 October 2018 - Most people with lung cancer are unaware of the benefits of regular exercise, yet new data show it can significantly reduce fatigue and improve well being. Results of two studies to be presented at the ESMO 2018 Congress in Munich (1,2) underline the value of exercise, including in patients with advanced or metastatic lung cancer.

Over half (54%) of patients with advanced cancer who completed an exercise survey at a cancer centre in Queensland, Australia, were unaware of the benefits of exercise and only 22% achieved healthy activity levels, as recommended by the World Health Organisation. (1)

"Exercise benefits everyone, not just those who are well, and too few people are aware that gentle aerobic exercise and strength training should be as much a part of treating advanced lung cancer as anti-tumour therapy," said Dr. Quan Tran, Medical Oncologist at the Cancer Care Centre, St Stephen's Hospital, Urraween, Australia.

Nearly nine out of 10 patients in the survey had advanced lung cancer, and at least six out of 10 respondents said they did not exercise because of fatigue or shortness of breath. Over half named low mood, lack of motivation, pain and side effects of treatment as barriers to exercising.

"We need to break down the barriers that are stopping patients from exercising, for example by treating the anaemia that may be causing their fatigue," added Tran.

The Australian research also showed that patients who were less active had significantly less social support than those who were more active. Asked what type of activity programme would be most helpful, respondents voted for education, group exercise classes, and other support at the same place they were receiving their cancer treatment.

"Patients preferred to get information and support and become more active in a buddy or group programme than through web-based initiatives. They weren't interested in competitions and incentives, but they did feel that being with others in a similar situation would motivate them to overcome their barriers to exercise," Tran explained.

In a second study of 227 patients with advanced or metastatic lung cancer, those who did regular easy aerobic and muscle strengthening exercises improved their symptom scores by approximately 10% during chemotherapy. (2)

"This is the first time that patients undergoing palliative care for lung cancer have been shown to benefit from exercise. Patients who exercised also felt more independent and needed less help with daily activities, and our research suggested that they may be able to have more and longer chemotherapy which, in turn, may result in better tumour control," explained Dr. Joachim Wiskemann, Exercise Physiologist and Sports Psychologist, National Center for Tumor Diseases (NCT) and Heidelberg University Hospital, Heidelberg, Germany.

In the study, patients were randomly assigned to 24 weeks of partly-supervised combined resistance and aerobic training, for up to 45 minutes, three times a week, and weekly care management phone calls (CMPC) or CMPC alone. Although there were no significant effects of exercise on physical well-being and general fatigue at week 12, patients who completed at least 70% of exercise sessions did achieve significant benefits. Fatigue scores improved by 10% with combined exercise and CMPC compared to 2% with CMPC alone (p=0.01), functional well-being by 11% vs 3% (p=0.03) and overall physical and functional well-being (Trial Outcome Index) by 8% vs 4% (p=0.04).

Wiskemann estimated that 50-60% of patients with advanced lung cancer are willing and able to exercise and recommends adapting the nature and setting for exercise to individual needs. He also stressed the importance of coordinated care with good commitment from oncologists and cancer nurses and a specific individual responsible for counselling and delivery of tailored exercise programmes for patients.

"In the past, we have assumed that only the healthiest and fittest patients with cancer could exercise, but our study has shown this is not true and that those with advanced disease can benefit too. We must now be flexible in the way we offer exercise, so patients can do it wherever they are most comfortable - at home, in a class at the hospital or in a gym," said Wiskemann.

Commenting on the results of the two studies for ESMO, Dr. Martijn Stuiver, Associate Professor of Functional Recovery from Cancer and its Treatment at the Amsterdam University of Applied Sciences, the Netherlands, pointed out that the Clinical Oncology Society of Australia already recommends that exercise should be part of standard cancer care and he stresses the importance of greater awareness of the benefits of exercise, including in advanced cancer.

"We must now find out which exercise programmes work best for patients with different forms and stages of cancer and how to achieve different outcomes, such as reducing fatigue or improving fitness, so that benefits can be optimised," said Stuiver.

He explained that previous exercise studies have shown mixed results for improvement of fatigue in patients with advanced cancer, while most have shown beneficial effects on physical fitness.

"Scientifically, we need to understand how exercise is having these effects and, clinically, we need to develop ways to triage patients to the type of exercise most likely to help them, based on what they feel will have the greatest impact on their quality of life," added Stuiver.

Like Wiskemann, he drew attention to the potential of exercise to enable patients to remain on chemotherapy, with previous data from a breast cancer study suggesting that patients who follow a supervised exercise programme are three times less likely to need a change of therapy than those who do not exercise. (3)

"Physical fitness is a key factor in determining whether patients can start treatment and maintain dosing. Exercise may therefore become a primary adjuvant therapy to improve fitness so that patients are in the best possible shape to start or continue treatment and tolerate toxicities of other therapies," he concluded.

Munich, Germany, 19 October 2018 - Some European countries take more than twice as long as others to reach health technology assessment (HTA) decisions to reimburse new cancer drugs following their approval by the European Medicines Agency (EMA). The average decision time is longer than one year in some countries, according to a study to be reported at ESMO 2018 Congress (1).

Once the EMA has approved a new treatment, many countries evaluate its benefit and cost-effectiveness through a systematic health technology assessment process as part of making a decision on whether to reimburse use of the treatment for routine patient care.

Researchers identified all new cancer drugs approved for solid tumours by the EMA between January 2007 and December 2016. They then tracked the time between EMA approval for each of the drugs and HTA decisions being taken by health authorities in four European countries: England, France, Germany and Scotland.

Results for 47 drugs approved for 77 solid tumour indications revealed that the median time from EMA approval to HTA decisions was two to three times longer in England (405 days) and Scotland (384 days) compared to Germany (209 days) and France (118 days).

"In contrast to the centralised approval of anticancer drugs by the EMA, the time to HTA decisions remains a national responsibility," explained study co-author Dr Kerstin Vokinger, senior research scientist at the University Hospital of Zurich, Switzerland, and affiliated researcher at Harvard Medical School, Boston, USA. She added: "Among other things, the different amount of resources invested in such assessments and different national regulations regarding HTA systems may lead to variation in the time from EMA approval to HTA decisions in different countries."

Commenting on the findings, Dr Bettina Ryll, founder of Melanoma Patient Network Europe (2) and Chair of the ESMO Patient Advocacy Working Group, (3) said: "We in melanoma still mourn the lives we lost due to the tardy and inconsistent introduction of approved innovative therapies. It is a country's responsibility to ensure sufficient administrative capacity so that processes like HTA that were put in place for the benefit of society do not start harming citizens. And we need more pragmatic approaches to reducing uncertainty- simply letting patients die while waiting for data to mature is not a civilised option."

The study found that health authorities generally made decisions much more quickly for drugs ranked as being of "highest benefit" on the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS) (4) compared to those with less clinical benefit. However, the variation in time from EMA approval to HTA decisions remained between different countries for these "highest benefit" drugs.

The ESMO Magnitude of Clinical Benefit Scale uses a rational, structured and consistent approach to grade the magnitude of clinical benefit that can be expected from anti-cancer treatments. "Lowest benefit" refers, for example, to drugs increasing median progression-free survival by a few weeks, whereas the category of "highest benefit" is given to drugs improving long-term survival in the neo/adjuvant setting (5,6).

In France, the median time to an HTA decision on "highest benefit" drugs was 154 days compared to 198 days for drugs of less benefit. Faster HTA decisions for "highest benefit" cancer drugs were also made in Germany and England but the time to HTA decisions was much longer in England (median 302 days) than in France or Germany (203 days).

Further analysis showed that nearly all cancer drugs ranked as being of "highest benefit" on the ESMO-MCBS were approved for reimbursement by all four countries: Germany (100%), Scotland (95%), England (92%) and France (90%)... In addition, the researchers found high concordance between ESMO-MCBS and scores health regulators gave in HTA procedures for cancer drugs of "highest benefit".

"Our study shows that there is a high concordance between ESMO Magnitude of Clinical Benefit Scale and HTA scores for the categorisation of "highest benefit". Therefore, the ESMO Magnitude of Clinical Benefit Scale could serve different countries as a helpful tool to assess the clinical value of anticancer drugs," suggested Vokinger.

Commenting on the findings for ESMO, Prof. Elisabeth de Vries, Medical Oncologist at the University Medical Center Groningen, Groningen, The Netherlands, Chair of the ESMO-MCBS Working Group, said: "It is reassuring that in the countries studied, anticancer drugs with greatest clinical benefit on ESMO-MCBS (version 1.1) are associated with faster times to HTA decisions and nearly all are approved for reimbursement."

Noting the variation in times to final decisions, she suggested, "Hopefully, this information can be helpful to raise the interest of HTA agencies in their performance and timeframes."

de Vries added, "Data were analysed only for England, France, Germany and Scotland. This means data for HTA procedures and reimbursement decisions were reported for only part of Europe, with no countries included from Southern or Eastern Europe. Insights into these procedures in other European countries might be of interest."

Vokinger said the research group now plans to expand research in this area. "Among other things, we plan to include more countries for assessing HTA decisions and to explore access to new cancer medicines by individual patients," she said.

Munich, Germany, 20 October 2018 - Including exercise or sport as part of cancer care can significantly improve symptom management, quality of life and fitness during and after treatment, French researchers have concluded in two presentations to be reported at the ESMO 2018 Congress in Munich. Even among patients at highest risk of poor quality of life, exercise can make a difference.

More than 3,500 patients with cancer already participate in exercise programmes each year at over 80 cancer centres in France, at a cost of approximately €400 per patient, and the number continues to rise, explained Dr. Thierry Bouillet, Medical Oncologist, Ile de France, American Hospital of Paris, Neuilly Sur Seine, France, and author of one of the new studies. (1) Classes are run by trainers with specialist knowledge of cancer and its treatment who can adapt exercise programmes to individual needs.

"We have found that patients get the greatest benefit if they exercise two or three times a week for at least an hour during the six months of their chemotherapy or radiotherapy and then for a further six months so that physical activity becomes a part of their life," said Bouillet.

"With 20 years' experience, we have also seen that patients find it easier to exercise in on-site classes and feel more secure than if we give them exercise information and leave them to do it themselves or go to classes away from the hospital with trainers who do not know about the special needs of patients with cancer," added Bouillet.

In one of the French studies to be presented at ESMO, (1) twice-weekly, 60-minute strength training and aerobic exercise classes significantly reduced pain and fatigue scores at 3 and 6 months in 114 patients undergoing cancer treatment, 83% for breast cancer and 21% with metastatic disease. Fatigue scores fell from 3.3 at baseline to 2.8 (p

There were also significant reductions in body fat, while lean body mass remained stable. In the overall group, fat mass fell from 33.9% at baseline to 33.2% at 3 months (p

"Patients are often fatigued and have started to lose muscle before they are diagnosed with cancer, so it is essential to start exercise as soon as possible after the first consultation. We should see it as 'emergency treatment' for their initial symptoms and later to help with the side effects of treatment," said Bouillet.

In a second study to be presented at ESMO 2018, (2) researchers not only reported the value of exercise for patients with cancer, but also demonstrated that it is possible to identify patients at greatest risk of poor quality of life during treatment so they can receive extra help.

In the study of 2525 patients with stage I-III breast cancer undergoing adjuvant chemotherapy, those who took 75 minutes of vigorous or 150 minutes of moderate exercise per week had significantly better overall quality of life at six and 12 months after treatment than those who were inactive (Table 1). They also had significantly better physical well-being and less fatigue, pain and breathlessness. Vigorous exercise included activities such as aerobic dance, heavy gardening or fast swimming, while moderate exercise included brisk walking, water aerobics or volleyball.

"Around 60% of patients were physically active before and after chemotherapy and, although their quality of life was adversely affected by chemotherapy, they scored consistently better on a variety of physical, emotional and symptom scales than those who were inactive," explained Dr. Antonio Di Meglio, study author and Medical Oncologist, Institut Gustave Roussy, Villejuif, France.

The study showed that patients who had a mastectomy or additional illnesses, smoked or had a low income were particularly at risk of poor quality of life following chemotherapy for breast cancer, but they too benefited from exercise.

"Using a novel approach, we showed that it is possible to identify breast cancer patients whose quality of life will be worst affected by chemotherapy so we can now target those patients for dedicated interventions including those aimed at increasing physical activity to WHO-recommended levels," (3) added Di Meglio.

Commenting from ESMO, Dr. Gabe Sonke, Medical Oncologist, Netherlands Cancer Institute, Amsterdam, the Netherlands, underlined the importance of the French studies in demonstrating the value of physical therapy in everyday clinical practice, previously seen in clinical trials and supported by current ESMO recommendations for exercise as part of standard care for all cancer survivors. (4)

"The insights from the new studies in patients with metastatic breast cancer are particularly timely as a large study is getting underway from the international PREFERABLE Consortium to further explore the value of exercise in this group of patients," he said.

Sonke pointed out that this and other studies are endeavouring to confirm early signs that physical activity programmes may improve adherence to chemotherapy and radiotherapy and thus improve treatment outcomes so that insurance companies are more encouraged to pay for exercise initiatives.

"Insurers may ask why they should pay for exercise for patients with cancer when they don't pay for it in the general population. But if we can show that there is improved treatment adherence and an added survival benefit for patients with cancer, this will strengthen our case for payment," said Sonke.

He also wants to see more patients routinely asked to participate in exercise programmes, including those who do not normally exercise: "We know that patients who are already active are getting into these exercise programmes, but those who are not active are missing out, particularly those with low income and less healthy lifestyle. The new results must encourage us to focus on how to be more inclusive so that all patients can benefit from exercise in improving quality of life during chemotherapy," he concluded.

Munich, Germany, 19 October 2018 - Nearly one in six premenopausal women being treated for early stage breast cancer do not adhere adequately to tamoxifen therapy after one year of treatment, potentially putting themselves at increased risk of recurrence and reduced survival, a French prospective study reports at ESMO 2018 (1).

Hormonal therapy such as tamoxifen is recommended for five to ten years in all patients with hormone receptor-positive breast cancer (2) but previous research has shown that many discontinue long-term therapy (3).

"This issue is important because non-adherence with hormonal therapy - meaning taking less than 80% of prescribed treatment - can be associated with higher risk of mortality and shorter time to recurrence of breast cancer," said lead author Dr. Barbara Pistilli, a medical oncologist at Institut Gustave Roussy, Villejuif, France.

The French study is the first to assess adherence by measuring serum levels of tamoxifen rather than simply asking patients about how they take their treatment; there has previously been limited information on adherence to hormonal therapy in younger women.

"I was surprised at the high rate of non-adherence, which was considerably higher than reported previously," said Pistilli. "Women with breast cancer should be encouraged to discuss their treatment and any side-effects they experience with their doctor to obtain help to take their therapy."

The study included patients recently diagnosed with early (stage I-III) breast cancer in the CANTO cohort, which is a French prospective study investigating the long-term impact of side-effects with breast cancer treatments in around 12,000 participants. The researchers focused on the sub-group of 1799 (16%) premenopausal women prescribed adjuvant hormonal therapy, assessing their adherence to tamoxifen by measuring serum levels at one, three and five years and comparing this with patients' self-reports of adherence.

The study is also exploring clinical and social characteristics that could impact on adherence to endocrine therapy with the aim of identifying patients most at risk of not taking endocrine therapy as recommended.

Results showed that nearly one in five (16.0%; 188/1177) of the premenopausal women prescribed tamoxifen were not adequately adherent at one year based on serum assessment of tamoxifen (defined as

Just over one in ten (10.7%) were non-adherent, with undetectable levels of tamoxifen. A further 5.3% of patients were poorly adherent, with serum levels of tamoxifen below the steady-state concentration expected after 3 months of treatment.

Analysis of patients' self-reports showed that at least 50% of patients with undetectable/low tamoxifen levels did not declare they were not taking their tamoxifen as prescribed.

Pistilli commented, "We should take time to explore with patients if they are experiencing side-effects that can affect their adherence, and support them to be open about non-adherence so that we can discuss options to help." She added, "We need to understand the patients most at risk of being non-adherent early in their treatment and provide targeted interventions aiming to improve their self-efficacy and self-management of side-effects."

Based on their findings, the researchers now plan to develop an intervention to support improved adherence to hormonal therapy in premenopausal women.

Commenting on the study for ESMO, Prof. Giuseppe Curigliano, Head of the Early Drug Development Division at the European Institute of Oncology, University of Milan, Italy, said: "The fact that 16% of patients appeared not adequately adherent to tamoxifen should, in my opinion, suggest strategies to increase adherence." He warned: "Non-compliance with adjuvant hormonal treatment is an under-appreciated and under-reported problem and places patients at risk of inadequate clinical benefit. Taking into account that many high-risk premenopausal women worldwide are receiving aromatase inhibitors plus ovarian suppression, both inducing more side-effects than tamoxifen, we are under-reporting the non-adherence rate in real life."

Curigliano suggested, "We need also to identify factors that are associated with poor adherence." He noted that patients' beliefs about cancer and their treatment have been shown to be predictive factors for adherence, with fear of recurrence supporting adherence to therapy.

"It is important for physicians to have a good relationship with their patients and get a feel for the patient's personality to be able to orient discussions positively and potentially counteract any misunderstandings in order to reduce poor compliance with treatment," he said.

Pistilli acknowledged that limitations of the study included the fact that it was based on a French cohort, so may not necessarily apply elsewhere. It was not designed to investigate patients' fertility concerns and these are going to be investigated in the future. In addition, serum tamoxifen was measured at only one timepoint, reflecting levels over the previous month, and not across the whole year.

The study will continue to measure serum tamoxifen after three and five years of treatment and the impact of non-adherence on mortality and breast cancer recurrence in long-term follow-up.

Scientists at the University of York have found a way of distinguishing between fatal prostate cancer and manageable cancer, which could reduce unnecessary surgeries and radiotherapy.

A recent study showed that more than 25 men were being unnecessarily treated with surgery or radiotherapy, for every single life saved. It is believed that success rates could be hindered as a result of treating all prostate cancers in the same way.

A team at the University of York and the University of British Columbia, Canada, however, have designed a test that can pick out life-threatening prostate cancers, with up to 92% accuracy.

Professor Norman Maitland, from the University of York's Department of Biology, said: "Unnecessary prostate treatment has both physical consequences for patients and their families, but is also a substantial financial burden on the NHS, where each operation will cost around £10,000.

"Cancers that are contained in the prostate, however, have the potential to be 'actively monitored' which is not only cheaper, but has far fewer negative side-effects in patients with non-life threatening cancer."

It is now understood that to find the different levels of cancer, scientists have to identify genes that have been altered in different cancer types. The team analysed more than 500 cancer tissue samples and compared them with non-cancer tissue to search for patterns of a chemical group that is added to part of the DNA molecule, altering gene expression.

A person's age, what they eat and how they sleep, for example, impacts on chemical alterations to genes and which ones are turned on and off. This is part of the normal functioning of the human body and can tell individuals apart, but the process can sometimes go wrong, resulting in various diseases.

Professor Maitland said: "In some diseases, such as cancer, genes can be switched to an opposite state, causing major health issues and threat to life.

"The challenge in prostate cancer is how to look at all of these patterns within a cell, but hone in on the gene activity that suggests cancer, and not only this, what type of cancer - dangerous or manageable?

"To put it another way: how to do we distinguish the tiger cancer cells from the pussycat cancer cells, when there are millions of patterns of chemical alterations going on, many of which will be perfectly healthy?"

The team needed to eliminate the 'noise' of the genetic patterns that make individuals unique, to leave them with the patterns that indicate cancer. They were able to do this using a computer algorithm, which left the team with 17 possible genetic markers for prostate cancer.

Dr Davide Pellacani, who began these studies in York, before moving to the University of British Columbia, said: "Using this computer analysis, not only could we see which tissue samples had cancer and which didn't, but also which cancers were dangerous and which ones less so.

"Out of almost a million markers studied, we were able to use our new tools to single out differences in cancer potency."

To take this method out of the laboratory, the team are now investigating a further trial with new cancer samples, and hope to involve a commercial partner to allow this to be used for patients being treated in the NHS.

Munich, Germany, 19 October 2018 - Men and women may need to be treated differently - at least when it comes to some types of cancer. In an analysis (1) to be presented at the ESMO 2018 Congress in Munich, data was pooled from four UK randomised controlled clinical trials (RCTs) of first line chemotherapy in oesophagogastric (OG) cancer, finding significant differences in a number of important side-effects experienced by male and female patients.

Study author Dr. Michael Davidson, Royal Marsden Hospital NHS Foundation Trust, London, said: "We have known for a long time in oncology that there are differences between males and females in the incidence and prognosis of many non gender-specific cancers. We are now also beginning to understand some of the complex cellular, molecular and metabolic differences between the two sexes which influence both cancer development and response to treatment. The clinical question we wanted to answer was whether sex influences the toxicity and efficacy of common chemotherapies administered in oesophageal and gastric cancer. It's the first time that gender-differentiated data has been collected on such a large scale for this tumour type."

The trials selected for this pooled analysis were all evaluating first line chemotherapy regimens for patients with advanced OG cancer. "The four trials we included were large international trials conducted in the UK and Australasia with comparable patient populations and treatments being used," Davidson said. "This allowed us to collate and compare the data." In total 1654 patients were included: 80% were male and 20% were female. A greater proportion of gastric as opposed to junctional or oesophageal cancers were seen in female patients. "These findings are consistent with the incidence and distribution of OG cancers in Western populations," Davidson observed.

Based on the toxicities captured commonly in all four trials, the analysis showed no significant difference between the overall rates of toxicity experienced by men and women. "The data get more interesting once we look at individual toxicity results," Davidson explained. Indeed, women were found to have experienced significantly higher rates of nausea and vomiting, with 89.3% of women versus 78.3% of men experiencing this common toxicity. "This tendency was confirmed on the more serious end of the spectrum, too, with 16.7% of female patients experiencing it at a severity grade 3 or above, compared to 9.5% of males," said Davidson.

Women were also more prone to diarrhoea (53.8% of females compared to 46.9% of males), mouth ulceration (49.5% versus 40.7%) and hair loss (81.4% versus 74.3%) at all grades of severity. By contrast, 49.3% of male patients suffered from peripheral neuropathy - damage to peripheral nerves resulting in loss of sensation - compared to 42.6% of females.

In terms of treatment efficacy, no significant difference was seen in survival between male and female patients. The overall response rate - namely the number of patients achieving a reduction in tumour size on chemotherapy - was higher in males to an extent that approached but did not reach statistical significance.

"Our key finding, therefore, is that men and women treated with similar chemotherapy combinations for OG cancer were affected by a number of different toxicities to varying degrees," Davidson said. "The clinical relevance of this remains to be established. Whilst there is not enough data here to support alternative chemotherapy dosing strategies for men and women, it is useful for clinicians to be aware of such findings in order to refine their treatment in other ways. For example, knowing that women are more likely to experience gastrointestinal side-effects such as nausea and vomiting or diarrhoea may allow for more tailored education to be given to patients, empowering them to report problems early and allowing doctors to introduce supportive measures more proactively and intensively."

Commenting on the results, Prof. Michel Ducreux, from the Institut Gustave Roussy in Villejuif, France, said: "Dissimilarities in men and women's reactions to treatment had already been observed in a number of past clinical trials. Until recently though, because no one could explain why such differences might exist, they tended to be written off as a statistical artefact and remained absent from the discussion. In the clinic, meanwhile, the trends highlighted in this study would have been imperceptible to physicians. Thanks to the large number of patients included, this analysis was able to show statistically significant gender differences in the frequency of several side-effects of chemotherapy. Now, not only must we discuss their implications, we also need to understand the underlying reasons."

Ducreux added: "Going forward, we might consider stratifying patients according to their gender in clinical trials, so as to evaluate the efficacy and tolerance of treatments in each sex from the beginning of drug development. If further studies systematically confirm that women are more prone than men to a wider range of side-effects, then we will also need to think about entirely different prevention and support strategies for female patients."

Innovative cardioprotective strategies are of imminent demand. Nonfatal myocardial ischemia (MI) poses a significant risk to patients undergoing major non-cardiac surgery and these non-cardiac surgeries account for around 8 million myocardial injuries per year. Considering perioperative MI is the most common major cardiovascular complication, identifying factors that lead to cardiac disease onset and finding solutions to prevent potential cardiac damage are of critical importance. Previous work revealed that anesthetics used in the perioperative setting alter cellular circadian biology and furthermore, a critical role for the circadian rhythm protein Period 2 (PER2) was revealed in promoting cardioprotection through metabolic pathway mediation. The current studies intended to answer this question: does anesthetic administration lead to increased susceptibility to MI, and if so, does targeting circadian PER2 provide a cardioprotective effect?

The starting point of the study was a screening test for the effects of frequently administered anesthetics on cardiac PER2. This screening demonstrated that only the benzodiazepine, midazolam, significantly downregulated PER2 levels in the heart tissue. Considering loss of PER2 is known to be detrimental during myocardial ischemia and reperfusion (IR)-injury, the study next addressed whether administration of midazolam prior to the occurrence of an MI would increase severity of such an incident. Using a well-established mouse model of myocardial IR-injury, the study team found that mice exposed to midazolam had an approximate 28.8% increase in infarct size compared to the control group. In agreement, Troponin-I levels were on average 198.9% greater in the mice given midazolam compared to the control mice. Indeed, mice administered midazolam were associated with deleterious consequences upon myocardial IR-injury.

The second part of the study sought to reverse the deleterious effects of midazolam when administered prior to myocardial ischemia. Recently, a large-scale screen identified nobiletin, a flavonoid from citrus peels, as a potent circadian PER2 enhancer. Not only was nobiletin found to increase cardiac PER2 and reduce infarct sizes by 47.4%, but nobiletin also abolished the deleterious effects of midazolam as demonstrated by a 28.9% decrease in infarct sizes and 55.4% decrease in Troponin-I levels in mice given both midazolam and nobiletin compared to mice given solely midazolam prior to myocardial ischemia. Furthermore, nobiletin provided cardioprotection in a PER2 dependent manner during IR-injury. This was demonstrated by nobiletin treatment prior to myocardial ischemia in mice with a genetic deletion of PER2, which revealed no cardioprotection.

This publication reports how midazolam mediated alterations of PER2 expression may have functional consequences during myocardial ischemia and identifies circadian biology as a potential consideration in translational studies and in the perioperative setting to prevent or treat myocardial ischemia.

Columbus, Ohio - A drug first identified 150 years ago and used as a smooth-muscle relaxant might make tumors more sensitive to radiation therapy, according to a recent study led by researchers at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James).

The researchers found that the drug called papaverine, inhibits the respiration of mitochondria, the oxygen-consuming and energy-making components of cells, and sensitizes model tumors to radiation. They found that the drug does not affect the radiation sensitivity of well-oxygenated normal tissues.

Additionally, the researchers showed that modifying the papaverine molecule might improve the safety of the molecule and could represent a new class of radiosensitizing drugs that have fewer side effects.

The researchers report their findings in the Proceedings of the National Academy of Sciences. The journal includes a commentary noting that the study "represents a potential landmark in the six-decade-old quest to eliminate hypoxia as a cause for radiotherapy treatment failure."

"We know that hypoxia limits the effectiveness of radiation therapy, and that's a serious clinical problem because more than half of all people with cancer receive radiation therapy at some point in their care," says principal investigator Nicholas Denko, PhD, MD, professor of radiation oncology at the OSUCCC - James.

"We found that one dose of papaverine prior to radiation therapy reduces mitochondrial respiration, alleviates hypoxia, and greatly enhances the responses of model tumors to radiation," Denko says.

Radiation kills cancer cells in two ways: directly, by damaging DNA, and indirectly, by generating reactive, damage-causing molecules called oxygen radicals. Hypoxic conditions reduce the generation of radiation-induced DNA damage and the effective toxicity of a dose of radiation.

"If malignant cells in hypoxic areas of a tumor survive radiation therapy, they can become a source of tumor recurrence," Denko says. "It's critical that we find ways to overcome this form of treatment resistance."

Tumor hypoxia is a consequence of oxygen demand and supply. Cancer cells require high levels of oxygen to fuel their rapid growth, which can be so great that it outpaces the delivery of oxygen from the blood supply. Poorly formed blood vessels in the tumor are not efficient at delivering oxygen and other nutrients. Insufficient oxygen causes pockets of dead, necrotic cells surrounded by areas of hypoxia. Cancer cells in hypoxic regions at a distance from the blood vessel can also be beyond the reach of chemotherapy and be resistant to radiation.

Strategies to overcome radiation resistance typically focus on delivering more oxygen to the tumor, Denko says. "But these attempts have met with little clinical success because tumors have poorly formed vasculature," he adds. "We took the opposite approach. Rather than attempting to increase oxygen supply, we reduced the oxygen demand, and these findings suggest that papaverine or a derivative is a promising metabolic radiosensitizer."

ANN ARBOR--One question that scientists and fitness experts alike would love to answer is whether exercise or nutrition has a bigger positive impact on bone strength.

University of Michigan researchers looked at mineral supplementation and exercise in mice, and found surprising results--nutrition has a greater impact on bone mass and strength than exercise. Further, even after the exercise training stopped, the mice retained bone strength gains as long as they ate a mineral-supplemented diet.

"The longer-term mineral-supplemented diet leads to not only increases in bone mass and strength, but the ability to maintain those increases even after detraining," said David Kohn, a U-M professor in the schools of dentistry and engineering. "This was done in mice, but if you think about the progression to humans, diet is easier for someone to carry on as they get older and stop exercising, rather than the continuation of exercise itself."

The second important finding is that the diet alone has beneficial effects on bone, even without exercising. This surprised Kohn, who expected exercise with a normal diet to fuel greater gains in bone strength, but that wasn't the case.

"The data suggests the long-term consumption of the mineral-supplemented diet could be beneficial in preventing the loss of bone and strength with age, even if you don't do exercise training," he said.

Combining the two amplifies the effect.

Most other studies look at effects of increasing dietary calcium, Kohn said. The U-M study increased calcium and phosphorous, and found benefits to increasing both.

This isn't to suggest that people run out and buy calcium and phosphorus supplements, Kohn said. The findings don't translate directly from mice to humans, but they do give researchers a conceptual place to start.

It's known that humans achieve peak bone mass in their early 20s, and after that it declines. The question becomes how to maximize the amount of bone when young, so that when declines do begin, people start from a better position, Kohn said.

In addition to testing bone mass and strength, Kohn and colleagues performed a full battery of mechanical assessments on the bone, which is important because the amount of bone doesn't always scale with or predict the mechanical quality of the tissue.

They tested the mice after eight weeks of training and supplemented diet or normal diet, and then after eight weeks of detraining.

-- Study from Australia is the first to evaluate a population-level roll-out of pre-exposure prophylaxis (PrEP) in men who have sex with men.

Rapid, targeted, and high-coverage roll-out of pre-exposure prophylaxis (PrEP) to men who have sex with men was associated with a reduction in HIV diagnoses by 25% in one year across New South Wales (Australia), according to a study published in The Lancet HIV journal.

Diagnoses in men who have sex with men across New South Wales reduced from 295 cases in the year before PrEP roll-out to 221 cases in the year after - the lowest levels recorded since the beginning of HIV surveillance in 1985.

The study, led by the Kirby Institute at UNSW Sydney, followed 3,700 men who had been dispensed PrEP as part of the roll-out and found generally high levels of adherence. In this group, the incidence of HIV infection was less than 1 in 2,000 per year, compared with an expected incidence of 2 per 100 per year or higher in the absence of PrEP.

Randomised controlled trials have previously demonstrated the efficacy of PrEP. In addition, mathematical models have predicted that PrEP can have a large and fast impact if rolled out rapidly and at high coverage for people at risk. However, empirical studies to confirm PrEP's population-level effectiveness have not tested these findings until now.

The study in New South Wales was possible due to the existing surveillance system for recent HIV infection in the area, which allowed researchers to quickly document the population-level effect of PrEP. It illustrates the successes possible with effective roll-out of PrEP.

Although a number of countries, including the USA, France, and England, have approved HIV PrEP, uptake has until recently been slow and geographically patchy.

"Our results support the population-level effectiveness of PrEP one year after rapid PrEP implementation at scale," says Professor Andrew Grulich, from the Kirby Institute at UNSW Sydney. "PrEP is a highly effective preventative approach when implemented alongside high levels of HIV testing and treatment. Roll-out should be prioritised as a crucial component of HIV prevention in epidemics predominantly affecting men who have sex with men." [1]

The study recruited 3,700 participants aged 18 years or older from 21 clinics across New South Wales. All participants in the study were at high risk of HIV infection, and were given PrEP for free. HIV testing was conducted at one and three months after enrolment into the trial, then every three months.

Among the 3,700 participants, 3,645 (99%) were dispensed PrEP or had a HIV test at least once during follow-up. During the year-long study, only two men became infected with HIV and these men were not adherent to PrEP.

The authors found that adherence to PrEP was high (median medication possession ratio of 98%). However, approximately 30% of participants had adherence below 80%, but this could also indicate on-demand PrEP use [2], or stopping using PrEP after a period of high-risk behaviour.

State-wide [3], the authors found that after PrEP roll-out there were 25% fewer HIV diagnoses, compared to the 12 months before PrEP roll-out (295 cases vs 221 cases).

The decline was greatest for recent HIV infections (32% decline, from 149 cases to 102 cases). These declines were greatest in men aged 45 years or older, Australian-born men, and those who lived in the gay neighbourhoods of Sydney.

In comparison with other international settings, PrEP roll-out in New South Wales was more rapid and at higher coverage - meeting the initial target of 3,700 participants on PrEP within eight months. 12 months after, 7,621 participants were taking part. By the end of the study, 9,714 people were taking part.

In the USA, PrEP was approved in 2012 and it was estimated that 492,000 men would benefit from the drug. However, uptake was sluggish before accelerating more recently, and by late 2016 it was estimated that 83,672 men in the US had commenced PrEP.

In England, the NHS announced it would provide PrEP to 10,000 patients through an implementation study in selected clinics from September 2017. Reductions in HIV diagnoses in 2017 in London have been attributed to a combination of increased testing and treatment, as well as PrEP sourced through trials or privately.

In France, 2,805 people (97% MSM) were prescribed PrEP in the first 12 months of roll-out in 2016 with only four new HIV infections in this cohort, but population-based trends in HIV have not yet been reported.

Professor Grulich adds: "This study involved a large-scale and state-wide response to ensure that PrEP was made available to men at high risk of HIV infection. This involved leadership from the NSW Government, advocacy groups working to help improve health literacy, and a network of free, publicly funded and private sexual health services serving men who have sex with men." [1]

The authors note some limitations, including that they cannot rule out that some other factors may be involved in the reduced levels of infection at a state level, and some infections may have been missed if people did not attend the last HIV test at 12 months. They also note that some men may have obtained PrEP privately and the level of coverage may have been higher than described in the study.

Writing in a linked Comment, Professor Sheena McCormack, MRC Clinical Trials Unit, UK, notes that New South Wales was an ideal location to help identify the added benefit of PrEP as it has met the 90-90-90 targets [4] for the proportion of individuals with HIV diagnosed, treated, and virally suppressed, which were surpassed in 2016, but adds that most countries are unlikely to reach these targets by 2020.

She notes: "Now, the EPIC-NSW study has provided robust evidence for the added value of PrEP at the population level, as well as endorsing the biological efficacy in individuals who use PrEP consistently during periods of possible exposure to HIV."

ITHACA, N.Y. - Crohn's disease (CD), a chronic inflammatory condition of the intestinal tract, has emerged as a global disease, with rates steadily increasing over the last 50 years. Experts have long suspected that CD likely represents a collection of related but slightly different disorders, but until now it has not been possible to predict accurately which subtype of CD a patient is likely to develop.

In a study published Oct. 4 in the journal JCI Insight, Cornell University and University of North Carolina researchers report they have pinpointed a single molecule - microRNA-31 (miR-31) - the levels of which predict whether a patient has subtype 1 or subtype 2 of the disease.

This is important because patients with subtype 1, unlike subtype 2, often do not respond well to medications and develop strictures - extreme narrowing of the gut tube, requiring surgery once it develops. Markers like miR-31 could be useful in the future for clinicians to predict whether a patient should pursue pre-emptive surgery before the condition worsens.

"We are not at the point at which we are able to perform personalized medicine on this, but at the very least we think it can lead to better clinical trial designs," said Praveen Sethupathy, associate professor in the Department of Biomedical Sciences at Cornell's College of Veterinary Medicine and a senior co-author of the study, along with Terrence Furey, associate professor of genetics, and Dr. Shehzad Sheikh, associate professor of medicine, both at UNC.

Clinical trials have generally grouped all patients together when testing a new therapy for CD, and that leads to inconsistent results across the group, Sethupathy said. Using miR-31, researchers potentially could separate individuals with CD into subtypes in order to more accurately determine if a particular drug works for one subtype and not the other.

In the study, the researchers also used a state-of-the-art artificial gut, called an intestinal organoid, that allowed them to culture human biopsy samples while retaining the basic physiology that exists inside a human. "This innovative system can serve as a personalized testing platform to screen therapeutic agents before administering them to patients," Sheikh said.

The researchers also used cutting-edge genomic techniques to track the abundance of different molecules in the colon tissue of more than 150 pediatric and adult patients. MicroRNAs control the extent to which a target gene is turned on. They function as negative dials - the greater the abundance of a microRNA, the more a target gene will be suppressed. Data from genomic sequencing technology allowed the researchers to make their miR-31 discovery.

"Our study hints that it's not only that miR-31 could be a predictive indicator of clinical outcome, but also that it could be functionally relevant in driving the disease," Sethupathy said.

Future work will explore exactly what miR-31 does and what role it might play in the integrity of the gut epithelium. "Our long-term goal, extending the work of this study, is to better understand at the molecular level why CD is so different in its presentation across patients, and to use this knowledge to develop more effective therapies," Furey said.

SAN FRANCISCO - Even with concerns about addiction, side effects and the other risks of opioids dominating headlines, a study presented at the ANESTHESIOLOGY® 2018 annual meeting found people expect to be prescribed opioids and perceive them to be the most effective form of pain relief after surgery. Interestingly, other research presented at the meeting found opioids led to complications such as increased pain, poorer quality of life and dependence following back surgery.

While opioids may effectively relieve pain after surgeries and procedures, they may not be the best option in all cases. Opioids can be highly addictive and carry some risks and side effects, such as sleepiness, constipation and nausea, as well as life-threatening shallow breathing and slowed heart rate, which may indicate an overdose.

"Patients often assume they will receive opioids for pain, believing they are superior, and therefore may pressure physicians to prescribe them after surgery," said Nirmal B. Shah, D.O., lead author of the first study and an anesthesia resident at Thomas Jefferson University Hospital, Philadelphia. "But research shows opioids often aren't necessarily more effective. Clearly, we need to provide more education to bridge that gap and help patients understand that there are many options for pain relief after surgery, including other pain medications such as acetaminophen and ibuprofen."

Patients expect opioids after surgery, study finds

In the first study, researchers set out to understand expectations of pain management after surgery. They gave a 13-question survey to 503 adults who were scheduled to have surgery for the back, ear-nose-and-throat, abdomen, or hip or knee replacement.

Everyone responded that they expected to receive pain medication after surgery:

77 percent expected opioids, such as morphine, fentanyl and dilaudid

37 percent expected acetaminophen, such as Tylenol

18 percent expected a non-steroidal anti-inflammatory (NSAID), such as Motrin

The majority of patients believed opioids would be most effective, even if they didn't expect to receive them: 94 percent of those who assumed they would get opioids thought they would be effective, as did 67.5 percent of those who didn't expect to receive them. Only 35.6 percent of patients expecting to receive acetaminophen thought it would be effective and 53.1 percent of those expecting to receive NSAIDs thought they would be effective.

"In previous opioid research, we found only 10 percent of people were worried about respiratory problems and 40 percent were concerned about nausea or constipation," said Dr. Shah. "We believe there is a lack of education and understanding of the dangerous side effects of these drugs, which contributes to the epidemic."

Opioids associated with complications after back surgery, study finds

In the second study, researchers analyzed nine papers that assessed opioid use in managing pain after spinal fusion (back) surgery. Interestingly, many of the findings contradict the assumptions of the patients in the first study. Findings included:

Those whose postsurgical pain was managed with opioids had higher postoperative pain scores and worse quality of life than those who managed their pain through non-medication regimens such as exercise.

Those who used opioids before surgery were six times more likely to use opioids long-term after surgery.

The longer patients used opioids prior to surgery, the longer they needed them after surgery.

Opioid use before surgery was associated with increased risk of opioid dependence 12 months after surgery.

Those who used opioids before surgery were more likely to have surgical site pain after the procedure.

Those who used opioids to manage pain before surgery stayed in the hospital longer after surgery, and were more likely to be readmitted after they had been discharged.

"Our review suggests there hasn't been much clinical emphasis on alternative methods to manage pain after back surgery," said Ramneek Dhillon, M.Sc., lead author of the study and a medical student at the University of Toledo College of Medicine and Life Sciences, Ohio. "While we looked at research on opioid use after spinal surgery, we believe these complications likely occur after other surgeries as well."

Terrorist attacks injure far more people than they kill, leaving victims with lost limbs, hearing loss, respiratory disease, depression and other issues. But little research has measured the impact of that damage beyond the number of people who are hurt.

New research from The University of Texas at Dallas provides a more complete picture of the suffering caused by terrorist attacks. The study, published in the journal Public Choice, estimates the number of years of healthy life -- years free of the injuries or disabilities caused by terrorist attacks -- that victims lost due to injuries.

The study was led by Dr. Daniel G. Arce, Ashbel Smith Professor and program head of economics in the School of Economic, Political and Policy Sciences.

"By examining terrorism through the lens of deaths and injuries, we can better understand the devastating impact terrorist attacks have on survivors," said Arce, who specializes in terrorism and conflict. "This information can help us determine the most effective way to spend our limited resources to confront terrorism."

An average of 8,338 people died and 10,785 people were injured every year in domestic and international terrorist attacks between 1970 and 2016, according to an international terrorism database that Arce used for his analysis.

Arce analyzed the percentage of attacks that were bombings, mass shootings, intentional vehicular assaults or other types of attacks. He also examined the distributions and types of injuries based on hospital admissions.

Using that data, Arce applied a methodology developed by the World Bank and World Health Organization to rank major diseases in terms of lives lost. The methodology allowed him to use one metric to estimate the overall impact of terrorism from deaths plus losses from injuries.

When including the number of healthy years of life that victims lost, Arce's study puts the annual toll at 12,628 years of life lost to terrorism.

The formula assigns different values to reflect the impact of various types of injuries on victims. For example, an individual with profound hearing loss experiences 77 percent of optimal health, while a person with major depressive disorder experiences 35 percent.

When possible, Arce also calculated the years of life lost by those who died in the Oklahoma City bombing in 1995, the Norway mass shootings in 2011 and vehicular assaults in Israel. Data was not available to apply the same analysis to victims in other attacks.

One of the goals of the research was to help decision-makers put the human consequences of terrorism in context when compared to the burden of diseases. The study compared the number of healthy years of life lost due to terrorism to that of various diseases and other causes of death. Heart disease was the top cause of death and years of healthy life lost. By contrast, terrorism ranked in the bottom 10 percent of the list, highlighting the low probability of someone becoming a victim of an attack.

"You want to put these things in context so people fear terrorism less," Arce said.

The research also can help emergency rooms better prepare for the types of likely injuries in the aftermath of different attacks, Arce said. His analysis includes findings about the types of injuries caused by different types of attacks.

"In an emergency situation, you have to know what to be prepared for," Arce said. "The answer is, it depends."