The University of Missouri has settled claims over ‘BioJoint’ knee surgeries for $16.2 million, in what appears to be one of its largest public payouts in recent years.
The surgeries in question used the BioJoint system, a “biological joint restoration” which involves replacing parts of the knee with bones or cartilage from cadavers to treat arthritis or joint damage. This technology was pioneered by James Stannard, MD, and veterinarian James Cook, DVM. The 22 plaintiffs, some of whom were minors, allege that they were not informed about the highly experimental nature of the BioJoint knee surgeries, with a failure rate of as high as 86%. This often required patients to have additional corrective surgeries or knee replacements. Some plaintiffs said that the surgery was pitched to them as a way to avoid a total knee joint replacement. They also allege that Dr Stannard negligently allowed Dr Cook—a veterinarian surgeon—to perform parts of the surgery without supervision.
The University denied wrongdoing, and settled without admission of liability or wrongdoing after claims against the defendants, Dr Stannard, Cook and another employee were dismissed.
“It’s not uncommon to have vets as part of your research team, but it would be uncommon to have them as part of your clinical patient care team,” said Patrick McCulloch, MD, vice chairman of Houston Methodist’s orthopaedic surgery department.
“You have to be licensed as a physician to perform surgery on a human being,” added Jeff Howell, executive vice president of the Missouri State Medical Association.
A key part of the plaintiff’s case involved false advertising, including local airing at the Super Bowl and at Chicago’s O’Hare International Airport, and which they claim led them to the procedure. It was speculated that the false advertising claim made the settlement amount larger than the medical malpractice suit alone.
A recent trial showed that nightly 30mg doses of zuranolone, a new drug to treat major depressive disorder (MDD), are safe and only requires about two courses to achieve clinical improvement.
Zuranolone is one of a new class of neuroactive steroid drugs that positively modulates GABAA receptors. It has high bioavailability, can be taken orally and has a half-life suitable for daily administration.
The SHORELINE Study is a Phase III, open-label, one year longitudinal study to evaluate the safety, tolerability, and need for repeat dosing with zuranolone in adults with MDD. Two cohorts with either zuranolone 30mg or 50mg as a starting dose taken once nightly for 14 days. Need for repeated dosing is assessed every 14 days based on a patient-reported assessment, with a maximum of five courses over a year.
Analysis of the data showed that the study’s primary endpoint of safety and tolerability show that zuranolone was generally well-tolerated in both dosage cohorts, with adverse events being generally consistent with those seen in previous zuranolone trials.
Secondary endpoints included response and remission as evaluated by the 17-item Hamilton Rating Scale for Depression (HAMD-17) and the number of times a patient received retreatment. A mean of 2.2 treatments resulted in patients with a clinical response (baseline HAMD-17 reduction of ≥50%) to the initial course of zuranolone 30mg. Additional data from patients in the 50 mg dose cohort is expected to be reported in late 2021.
“Sage embarked on the LANDSCAPE clinical program to evaluate the safety and efficacy of zuranolone with the ambition of reimagining the treatment for depression with the goal of a rapid-acting, durable, treat-as-needed option in a disease where innovation is lacking and the incidence rate has unfortunately increased exponentially in the last 20 years,” said Barry Greene, Chief Executive Officer at Sage Therapeutics. “Today we are announcing additional positive data from the SHORELINE Study that demonstrate continued strong results from the 30 mg dose and strengthens our confidence in the potential of the 50 mg dose. Designed as a naturalistic study, these data approximate real-world evidence of use of zuranolone at 30 mg and 50 mg doses. We look forward to the results of the WATERFALL and CORAL Phase 3 pivotal data readouts in MDD this year.”
In a new study, lab-made heart valves were shown to grow along with their recipient when implanted into lambs for a year, making a new alternative possible for thousands of paediatric patients who need replacement heart valves.
Researchers from the University of Minnesota Twin Cities’ College of Science and Engineering and the Medical School published the results in Science Translational Medicine. The production procedure for the valves has also been patented and licensed to the University of Minnesota startup company Vascudyne, Inc.
Compared to currently used animal-derived valves, these new valves also showed reduced calcification and improved blood flow when tested in the same growing lamb model. Current solutions for children involve prosthetic valves, but these calcify over time and cannot grow with the patient. This requires up to five open-heart surgeries to replace them as the children grow towards adulthood, involving considerable risk and expense, as well as demanding lifelong anticoagulation therapy.
“This is a huge step forward in paediatric heart research,” commented senior researcher Robert Tranquillo, a University of Minnesota professor in the Departments of Biomedical Engineering and the Department of Chemical Engineering and Materials Science. “This is the first demonstration that a valve implanted into a large animal model, in our case a lamb, can grow with the animal into adulthood. We have a way to go yet, but this puts us much farther down the path to future clinical trials in children. We are excited and optimistic about the possibility of this actually becoming a reality in years to come.”
Using a combination of tissue engineering and regenerative medicine, they were able to grow the heart valves. Implementing a tissue engineering technique they had previously developed, they grew tube-like structures out of skin cells. This involved combining the skin cells in fibrin, and providing nutrients in a bioreactor. After washing the skin cells out with detergent, the researchers were left with a collageneous matrix which would not provoke an immune response when implanted. They then sewed and trimmed three of these tubes together to make a 19mm diameter heart valve-like structure.
“After these initial steps, it looked like a heart valve, but the question then became if it could work like a heart valve and if it could grow,” Tranquillo said. “Our findings confirmed both.”
The valves grew from 19mm to 25mm over a year, and showed little of the calcification or clotting associated with prosthetic valves, while performing better than animal-derived valves.”We knew from previous studies that the engineered tubes have the capacity to regenerate and grow in a growing lamb model, but the biggest challenge was how to maintain leaflet function in a growing valved conduit that goes through 40 million cycles in a year,” said lead researcher Zeeshan Syedain, a University of Minnesota senior research associate in Tranquillo’s lab. “When we saw how well the valves functioned for an entire year from young lamb to adult sheep, it was very exciting.”
The next steps are to implant the valve into the right ventricle of the heart to see how it performs, and apply for FDA approval to proceed to human trials.
Journal information: Zeeshan H. Syedain et al, Pediatric tri-tube valved conduits made from fibroblast-produced extracellular matrix evaluated over 52 weeks in growing lambs, Science Translational Medicine (2021). DOI: 10.1126/scitranslmed.abb7225
French authorities have announced the detection of a variant of SARS-CoV-2 in the northwestern region of Brittany that has escaped detection by standard polymerase chain reaction (PCR) tests.
Real-time PCR tests are considered to be the current gold standard for detection of SARS-CoV-2, and currently take 4-6h to yield a result. PCR tests make millions to billions of copies of a small sample of DNA to create a larger sample for analysis.
Eight carriers of the variant were identified using genomic sequencing among a cluster of 79 cases in the town of Lannion in the Côtes d’Armor on March 13th.
In a statement on Monday, the French health ministry said that according to initial analyses, the new variant did not appear more transmissible or cause more severe disease. However, on Tuesday, authorities said that this variant was able to escape detection in PCR tests is raising concern.
Belgian virologist and interfederal COVID spokesperson Steven Van Gucht clarified the situation, in that about eight individuals presented with standard coronavirus symptoms, “but the tests remained negative.”
The World Health Organization has labelled this new French COVID variant a ‘variant under investigation’ (VUI), of which there are many thousands currently being monitored, as opposed to more serious variants like the South African B.1.351 variant which is more transmissible and is a ‘variant of concern’ (VOC).
However, just because this variant escaped the PCR tests being used in that area does not mean that it necessarily can escape all of them, as laboratories vary in the tests that they perform.
According to Gucht, tests differ in the different parts of the virus they look for, and also test for at least two to three. “Usually, a good test does not depend on detecting one specific part. So, if there is a mutation in one part of the virus, that signal may be lost, but there is usually a second or third signal that will be found,” explained Gucht.
French authorities are setting up systems to monitor the spread of this variant, and are also putting measures in place to contain it.
In a phase Ib/II trial, the AstraZeneca vaccine was ineffective against both the South African SARS-CoV-2 variant or the wild-type virus.
In this South African trial, the vaccine’s overall efficacy versus mild-to-moderate COVID was 21.9% and efficacy against the B.1.351 variant was 10.4%.
Participants’ median age was 30, about 56% were men, and 71% were black. Almost 20% of participants were obese, 42% were smokers, and about 3% of those had underlying hypertension or chronic respiratory conditions. All were HIV negative. The median time between doses was 28 days.
Overall, 19 of 750 in the vaccine group (2.5%) and 23 of 717 in the placebo group (3.2%) developed mild-to-moderate COVID.
In regard to the secondary outcome of testing effectiveness against the B.1.351 variant, the authors note that “the trial was powered for the primary objective of a vaccine efficacy of at least 60% in preventing COVID-19 of any severity, regardless of variants.”
Exploratory analyses found about 33.5% efficacy against COVID of any severity more than 14 days after the first dose. No cases of severe COVID were reported among the participants, but with the groups’ demographics, especially their relatively young age, it was unlikely that severe COVID would be observed in such a small trial.
Professor Shabir Madhi, Executive Director of the Vaccines and Infectious Diseases Analytics Research Unit at Wits, said in a press release that the AstraZeneca results “threw a curveball” after the initial “euphoria” over the effectiveness of the first COVID vaccines. He nevertheless stressed that the AstraZeneca vaccine was still important in preventing hospitals being overrun with COVID patients.
Despite the disappointing results, Prof Madhi said these findings “need to be made in the context of ongoing global spread and community transmission of the B.1.351 variant”.
Journal information: Madhi SA, et al “Efficacy of the ChAdOx1 nCOV-19 Covid-19 vaccine against the B.1.351 variant” N Engl J Med 2021; DOI: 10.1056/NEJM2102214.
Rates of alcoholic liver disease are skyrocketing in young women, doctors in the US have warned. Much of it has to do with added pressures on women in the pandemic.
Alcoholic liver disease — including milder fatty liver and the permanent scarring of cirrhosis, as well as alcoholic hepatitis — are up 30% over the last year at the University of Michigan’s health system, said Dr Jessica Mellinger, a liver specialist there. Severe liver disease and cirrhosis can see survival rates as low as 10%.
The route by which liver disease develops varies according to the individual, although obesity, genetics and underlying health conditions play a role. Moderate consumption of alcohol, a glass or two of wine daily, is unlikely to contribute to it.
However, Dr Mellinger says that along with her colleagues, she has seen alcohol consumption edging upward, to a bottle of wine per day which results in increased risk of serious liver disease.
Since the beginning of the pandemic, no data on overall increases in serious alcoholic liver disease has yet been compiled by The Centers for Disease Control and Prevention. But, Dr Mellinger said, “in my conversations with my colleagues at other institutions, everybody is saying the same thing: ‘Yep, it’s astronomical. It’s just gone off the charts.’ “
The age demographic is also changing. “We’re seeing kids in their late 20s and early 30s with a disease that we previously thought was kind of exclusive to middle age,” she said.
The pressures of the COVID pandemic are partly to blame, and in many cases the extra burden is falling on women – who are already more susceptible to alcoholbecause they have a smaller water volume to distribute alcohol into and their bodies do less ‘first pass’ metabolism of alcohol in the stomach. Popular culture and advertising also encourages women to drink.
Psychological factors such as eating disorders and trauma from sexual abuse also fuel the disease.
“Whether this is early life sexual trauma or they are in a recent or ongoing abusive relationship, we see this link very, very closely,” said psychiatrist Dr Scott Winder, a clinical associate professor at the University of Michigan who treats liver disease patients. “Just the sheer amount of trauma is really, really tragic.”
The lack of overlap between the various fields in this complex relationship results in what he calls a “tragic gap”.
“The cultures of hepatology and the cultures of psychology and psychiatry are very disparate; we see patients very differently,” so physicians aren’t coordinating care, even when they should, he said.
Advanced liver disease may leave no other recourse than a liver transplant. “Unfortunately, transplantation is finite,” said Dr Haripriya Maddur, a hepatologist at Northwestern University. “There aren’t enough organs to go around. What it unfortunately means is that many of these young people may not survive, and die very young — in their 20s and 30s. It’s horrific.”
Some people such as Jessica Duena, a teacher who was diagnosed with alcoholic hepatitis at 34, and was hospitalised several times following the death of her boyfriend from heroin, have managed to turn the disease around and are encouraging others to do the same.
She wrote about her long-held secret in the Louisville Courier-Journal: “I’m Jessica, I’m the 2019 Kentucky State Teacher of the Year, I’m an alcoholic and I’ve been suffering in silence for years.”
She received hundreds of responses, mostly women like herself who were in similar circumstances.
“What I’ve noticed is quite a few of the women, typically, they were either educators, they were moms or they happened to be nurses or attorneys,” Duenas said. They poured their hearts out about the crushing and constant stress of kids, work and home life.
They also complained of the pressures outside the home. “Imagine being a teacher who gets evaluated on how your students do, given the situation today,” Duenas says. “I mean, that makes me want to drink for them, you know — like that’s a terrible pressure to be under.”
Duenas has started writing about the stories of such people who reach out to her on her website, www.bottomlesstosober.com.
Having large numbers of widely cited publications has no bearing on the Twitter popularity of academics in the interventional cardiology community, a new study has found.
The study, by Davide Capodanno, MD, PhD, Azienda Ospedaliero-Universitaria Policlinico “G Rodolico-San Marco” in Catania, Italy, and colleagues, found that academic impact through papers and citations, as calculated by the Hirsch index (or h-index) was found to be unrelated to whether or not academics were in the top quartile of Twitter followers (> 736 followers).
“Indeed, accounts generating a stream of valuable content are more likely to be followed. In addition, some accounts may take advantage of celebrity to amplify their success, in a kind of incremental cycle,” wrote the authors. Rather, Twitter followers were defined by factors mostly related to time and effort spent on the platform.
Having abundant tweets (> 505 tweets, adjusted OR 16.39), along with individual charisma (‘Kardashian index’ >5, adjusted OR 8.66), were the most significant predictors. Large number of accounts user follows (> 309 following), tweet rate (> 2.6 tweets per week), a large cooperation network and being affiliated to the US were also predictive of the heart doctors’ Twitter popularity.
“Indeed, accounts generating a stream of valuable content are more likely to be followed. In addition, some accounts may take advantage of celebrity to amplify their success, in a kind of incremental cycle,” according to the authors.
Individual charisma per the ‘Kardashian index‘, which measures discrepancy between social media reputation and publication record, was not a significant factor in the rate at which someone amassed followers.
“In aggregate, our results suggest that a prediction rule for durable popularity on Twitter is to be active and generate valuable contents rather than relying on individual academic or social reputation,” Capodanno’s team concluded.
An earlier study had shown that the reverse was true; the more Twitter followers, the greater their academic standing. Limitations include not being able to account for anonymous or pseudonym accounts, and the results may not be generalisable to the interventional cardiology community as a whole.
Journal information: D’Arrigo P, et al “Determinants of popularity and natural history of social media accounts in interventional cardiology” JACC Cardiovasc Interv 2021; DOI: 10.1016/j.jcin.2021.01.021.
Commencing chemotherapy several days before the first lumbar puncture for diagnosis and treatment of acute lymphoblastic leukaemia (ALL) may lower the risk of central nervous system (CNS) relapse in children, according to a study from St Jude Children’s Research Hospital and collaborators in China.
“This study identified factors to help us predict and better manage the risk of CNS relapse that will be useful for treating ALL patients worldwide, in both resource-rich and resource-limited countries,” said corresponding author Ching-Hon Pui, MD, chair of the St. Jude Department of Oncology. Dr Pui pioneered paediatric ALL treatment that has achieved 94% long-term survival for St. Jude patients that did not receive brain irradiation.
Using an adapted paediatric protocol from St Jude Hospital, 7640 children and adolescents across 20 Chinese hospitals were enrolled in the trial. However, there was a great disparity across the hospital settings. For example, just three of the hospitals offered total intravenous anaesthesia for children undergoing spinal taps, while only two had flow cytometry for the diagnosis of leukaemia cells in cerebrospinal fluid.
The five-year overall survival rate was 91% for study patients, and the cancer-free survival rate was 80%, which is a dramatic improvement over previous clinical trials in China. But 1.9% of patients relapsed in the CNS alone, and in another 2.7% of patients the relapse involved the CNS. In comparison, a Canadian study reported a 6.6% rate for CNS-involved relapse in paediatric ALL patients followed over 10 years.
According to Dr Piu, in order to increase the survival rate of paediatric ALL patients requires identifying those at risk for CNS relapse, along with increasing their quality of life. Three factors reduced the risk of CNS relapse. First, commencing dexamethasone a few days before the spinal tap, prevents leukaemia cells entering the cerebrospinal fluid (CSF). Second, intravenous anaesthesia reduced bleeding risk during lumbar punctures, and improved intrathecal therapy. Third, flow cytometry enables more accurate diagnosis of leukaemia cells in CSF, and reduced CNS relapse.
Journal information: Jingyan Tang et al. Prognostic Factors for CNS Control in Children with Acute Lymphoblastic Leukemia Treated Without Cranial Irradiation, Blood (2021). DOI: 10.1182/blood.2020010438
Following arthroscopic knee surgery, patients are as satisfied with telemedicine follow-ups as they are with in-person follow-up, according to a new study published in The Journal of Bone & Joint Surgery.
“Patient satisfaction with overall care is equivalent between telemedicine and office-based follow-up after an arthroscopic meniscal surgical procedure in the immediate postoperative period,” wrote Christina P Herrero, MD, and colleagues of NYU Langone Health.
The study recruited 122 patients who underwent arthroscopic surgery on the meniscus in the knee, which is one of the most common orthopaedic surgical procedures. Of these patients, 88% had a removal of the meniscus (meniscectomy), with the rest undergoing meniscal repair procedures. Patients were randomly assigned to either office-based or telemedicine follow-up, scheduled for 5 to 14 days postoperatively. During both types of follow-up visits, the surgeon spoke to the patient about the surgical findings, pain the patient might be experiencing, and the postoperative recovery period, as well as performing a physical examination that included range-of-motion testing.
The telemedicine follow-ups were performed using the patient’s home computer or mobile device via a telemedicine program that was compliant with privacy rules. Surgeons of course were unable to physically feel or touch the knee during telemedicine follow-ups. However they could still conduct a visual assessment of wound healing, drainage, and swelling.
Overall satisfaction ratings were nearly identical between groups. The surveys showed average patient satisfaction scores (on a 0-to-10 scale) were 9.77 in office-based follow-up and 9.79 for telemedicine follow-up. In both groups, only about 20% of patients said they would have preferred the other type of visit. There was also similar improvement observed in pain scores between groups: from about 5 (out of a maximum of 10) on the day of the surgery to 3 at the follow-up visit.
Telemedicine has become all the more crucial in the COVID pandemic to minimise contact, but the levels of satisfaction shown indicate that it may be a promising standard mode of care in the future, especially for cases where access to physical follow-up consultation may be difficult for the patients.
“Telemedicine may be a reasonable alternative to office-based follow-up after knee arthroscopy,” Dr Herrero and coauthors concluded. “[Our] study only evaluated the first postoperative visit, but future studies may benefit from expanding the use of telemedicine to longer-term follow-ups or to additional surgical procedures.”
Journal information: Herrero, C. P., et al. (2021) Patient Satisfaction Is Equivalent Using Telemedicine Versus Office-Based Follow-up After Arthroscopic Meniscal Surgery. The Journal of Bone & Joint Surgery. doi.org/10.2106/JBJS.20.01413.
With the integration of whole genome sequencing in Swedish healthcare, some 1200 individuals with rare diseases have received a diagnosis, with novel disease genes discovered in the process.
“We’ve established a way of working where hospital and university collaborate on sequencing each patients’ entire genome in order to find genetic explanations for different diseases,” said first author Henrik Stranneheim, researcher at the Department of Molecular Medicine and Surgery, Karolinska Institutet. “This is an example of how precision medicine can be used to make diagnoses and tailor treatments to individual patients.”
The technology of large-scale whole genome sequencing to yield a person’s entire DNA, is not yet widely used in hospitals despite the technology becoming much more accessible over the last ten years. Whole genome sequencing has uncovered a great genetic variety among different populations, such as in South Africa, where a pilot study uncovered a high rate of novel variants in African populations.
Karolinska University Laboratory and the Clinical Genomics facility at SciLifeLab launched the Genomic Medicine Centre Karolinska-Rare Diseases (GMCK-RD) five years ago. Since then, the centre has sequenced the genomes of 3219 patients, which led to molecular diagnoses for 40% of them with rare diseases.
In addition to these, the researchers found pathogenic mutations in more than 750 genes and discovered 17 novel disease genes.
“Clinical whole genome sequencing has had huge implications for the area of rare diseases,” explained corresponding author Anna Wedell, professor at the Department of Molecular Medicine and Surgery, Karolinska Institutet. “Used in the right way, targeted at each patient’s specific clinical situation, new groups of patients can receive the right diagnosis and treatment in a way that hasn’t been possible before.”
Whole genome sequencing is challenging in part due to having to manage and interpret the millions of variations that exist within each invidual’s genome. In order to overcome this difficulty, the centre came up with a model that directs the initial analysis to pathogenic variants in genes relevant for that patient’s clinical symptomsIn this way, doctors play an important role in choosing which genetic analyses to run first. Should the first assessment fail, the analyses are then broadened to more gene panels, which has uncovered new disease genes.
“For us to succeed with precision medicine, a multidisciplinary collaboration between health care and academia is essential,” said second corresponding author Anna Lindstrand, professor at the Department of Molecular Medicine and Surgery, Karolinska Institutet and consultant at Karolinska University Hospital’s Department of Clinical Genetics. “Through these initiatives we combine clinical expertise with bioinformatic tools and together deliver accurate diagnoses and individualised treatments.”
Journal information: “Integration of whole genome sequencing into a health care setting: High diagnostic rates across multiple clinical entities in 3219 rare disease patients,” Genome Medicine (2021). DOI: 10.1186/s13073-021-00855-5
