Using a model reproducing a respiratory epithelium, researchers have discovered that a simple film of liquid is sufficient to restore the airways’ seal and reduce the risk of bacterial infection. Their findings, published in the journal Cells, may enable new therapies based on mucus hydration – a promising alternative to current therapies which often lack efficacy.
Despite recent therapeutic advances, people with cystic fibrosis (one in every 2500 births in Europe) have a life expectancy of no more than 46 years and altered quality of life. The disease is caused by one or more mutations in the CFTR gene, which affects the proper functioning of an essential protective barrier. The epithelial cells that line the airways are usually sealed together and thus protect the airways from bacterial colonisation. They are also lined with a fluid, a slippery mucus that traps unwanted germs and carries them away. When the CFTR protein is altered, the junctions between the cells loosen and the dehydrated mucus tends to stagnate, both of which promote the development of respiratory infections.
“While it was already known that mucus hydration and the presence of sufficiently tight junctions preserved the integrity of the airways, the mechanisms involved and the links between these two mechanisms remained mysterious, which hindered the development of new therapies,” explained Professor Marc Chanson, who led the reasearch.
Hydrating to restore tightness
The scientists first developed an in vitro model using human lung cells. This model reproduces airways epithelium of healthy and cystic fibrosis patients in a way that is both accurate and close to clinical reality. The researchers compared the response of epithelial cells invalidated for CFTR to bacterial infection, to which either hydrated, healthy mucus or physiological saline solution had been added.
“We observed a similar response in both cases: the presence of liquid, whatever its composition, restored the airways and protected them from infection,” explained Juliette Simonin, post-doctoral fellow in Prof Chanson’s laboratory and first author of the study. “Surface hydration is sufficient to tighten the junctions between cells and protects the epithelium integrity from bacterial colonisation, even when CFTR is not functioning.”
One treatment for all mutations?
A triple therapy pharmacologically targeting the CFTR protein has recently become available on the market. However, it only targets certain mutations of the CFTR gene and is only prescribed for a specific population of people with cystic fibrosis. More widely effective and safe treatments are still sorely lacking.
“Our results provide evidence that rehydration of the airway surface is beneficial. The challenge now is to find a simple way of doing this in all people with the disease, whatever the mutation involved,” concluded Prof Chanson.
Immune response and the lymphatic system are central to cardiac repair after a heart attack, according to a study published in the Journal of Clinical Investigation. These insights into the basic mechanisms of cardiac repair pave the way towards the development of new treatments to preserve heart function.
“We found that macrophages, or immune cells that rush to the heart after a heart attack to ‘eat’ damaged or dead tissue, also induce vascular endothelial growth factor C (VEGFC) that triggers the formation of new lymphatic vessels and promotes healing,” said co-senior author Edward Thorp, PhD, from the Heart Center at Lurie Children’s and Associate Professor of Pathology and Pediatrics at Northwestern University Feinberg School of Medicine. “Our challenge now is to find a way either to administer VEGFC or to coax these macrophages to induce more VEGFC, in order to speed the heart repair process.”
People who suffer a heart attack are at high risk for heart failure, even with the advances in medications to reduce mortality. This occurs in part because some macrophages that arrive at the site of damage are proinflammatory and do not induce VEGFC.
“It is a Dr. Jekyll and Mr. Hyde scenario, with ‘good’ macrophages that induce VEGFC and the ‘bad’ ones that don’t. We need to prevent the ‘bad’ macrophages from causing further damage,” said co-senior author Guillermo Oliver, PhD, Director of Feinberg Cardiovascular and Renal Research Institute – Center for Vascular and Developmental Biology, and Professor of Medicine at Northwestern University Feinberg School of Medicine. “We are working to understand more about the progression to heart failure after a heart attack, in order to intervene early and reset the course to cardiac repair.”
Young children who grow up with a dog or in a large family appears to confer some protection later on in life from Crohn’s disease, according to a study presented at Digestive Disease Week® (DDW) 2022.
Crohn’s disease is a common type of inflammatory bowel disease that often develops in young adults, smokers, and those with a close family member who has IBD. Symptoms include diarrhoea, abdominal pain and weight loss. Treatments currently aim to prevent symptom flare-ups through diet modification, medication, and surgery.
“Our study seems to add to others that have explored the ‘hygiene hypothesis’ which suggests that the lack of exposure to microbes early in life may lead to lack of immune regulation toward environmental microbes,” said Williams Turpin, PhD, the study’s senior author and a research associate with Mount Sinai Hospital and the University of Toronto.
Researchers used an environmental questionnaire to collect information from nearly 4300 first-degree relatives of people with Crohn’s disease enrolled in the Crohn’s and Colitis Canada Genetic, Environmental, and Microbial (CCC-GEM) project. Using responses to the questionnaire and historical data collected at the time of recruitment, Dr Turpin and his team analysed several environmental factors, including family size, the presence of dogs or cats as household pets, the number of bathrooms in the house, living on a farm, drinking unpasteurised milk and drinking well water. The analysis also included age at the time of exposure.
The study found that exposure to dogs, especially from ages 5 to 15, was associated with healthy gut permeability and balance between the microbes in the gut and the body’s immune response, which may all help protect against Crohn’s disease. Similar effects were observed with exposure to dogs across all age groups.
“We did not see the same results with cats, though we are still trying to determine why,” Dr Turpin said. “It could potentially be because dog owners get outside more often with their pets or live in areas with more green space, which has been shown previously to protect against Crohn’s.”
Another protective factor seemed to be living with three or more family members in the first year of life, which was associated with microbiome composition later in life. The gut microbiome is believed to play a role in a number of health conditions, such as inflammatory bowel disease, colorectal cancer, diabetes, and high blood pressure.
Dr Turpin and his colleagues hope their findings may assist physicians in asking detailed questions of patients to determine who is at highest risk. However, he noted that the early life environmental factors were assessed by questionnaires, so caution is warranted in interpreting these results due to possible recall bias at recruitment. The reasons dog ownership and larger families appear to provide protection from Crohn’s remain unclear.
By Dr Hlombe Makuluma, Clinical Risk Management at EthiQal and JP Ellis, Senior Legal and Claims Manager at EthiQal Medical Risk Protection, a division of Constantia Insurance.
South Africa’s medicolegal problems are well documented. Our healthcare system is vulnerable, with many healthcare workers working under stressful conditions, not to mention the uncertainty in relation to the implementation of National Health Insurance and the adverse consequences of the pandemic.
A public healthcare system which is overburdened and under-resourced finds itself confronted with litigation daily with the result that it has accumulated contingent liabilities (ie, the projected cost of payments for medical litigation claims) in the billions. Whereas in the private sector the burden of professional indemnity insurance cover for certain high-risk specialities has resulted in many private practitioners limiting their scope of practice or reconsidering the viability of continuing to practise. Since many private hospitals are self-insured for medico-legal claims up to a certain level, the price for their litigation defence is ultimately brought back to the consumer. To make matters worse, the South African civil justice system is renowned for its delays, inefficiencies, and the unnecessarily high cost of litigation. All these things make up the perfect recipe for a very lucrative industry which rewards many role-players, who have no hesitation in taking advantage of a vulnerable medicolegal system.
The South African Law Reform Commission (SALRC) was requested by the Ministers of Health and Justice to review the current system and to offer proposals. The SALRC has published their discussion paper 154 in November 2021 on their recommendations based on preliminary research, five years after the publication of their initial working paper on Project 141: Medico-legal Claims. While we should all be happy that progress has been made the real question is whether there is real appetite to improve our system or whether this is all a knee-jerk reaction?
There is an urgent need for meaningful reform. Patients who suffer harm because of negligence by healthcare providers require reasonable compensation quickly, and healthcare providers should be sufficiently protected from abuse and unmeritorious claims. Sadly, our medicolegal system does not adequately provide for this.
The burden of clinical negligence litigation is great as it often takes many years to finalise cases – whether in the form of a resolution or judgment – and the cost of litigation is exorbitant. Overall, the SALRC has taken great care in considering the rights of claimants and the burden of compensation on the State by thoroughly researching the medico-legal landscape in South Africa. Reform is generally classified into three areas, namely reforms that limit access to our courts, reforms that influence court processes, and reforms that limit the amount of compensation awarded.
They have offered recommendations which they believe will make the most difference. Most notably:
Reforms that limit access to our courts
Mediation has been encouraged as a first step to deal with medico-legal disputes before litigation. Most stakeholders appear to have no serious objections to mediation, especially because Uniform Rule 41A was introduced a few years ago, which requires a plaintiff or applicant who initiates litigation proceedings to file a certificate indicating whether they agree to the referral of the matter to mediation and, if not, to state the reasons for that refusal.
A certificate of merit affidavit should be filed on behalf of an accredited and suitably qualified medical practitioner to avoid frivolous, meritless, fraudulent or abandoned claims. This essentially opens the door for a successful defendant to claim the costs of litigation against those parties, and possibly their attorneys, who engage in irresponsible litigation.
A plaintiff is barred from proceeding with a claim after a period of inaction after issuing summons, with the possibility of having the period extended by the court but only on good cause shown. Either our Court rules or Practice manuals should be amended to ensure that once legal action is taken the matter must be finalised within a specified period, depending on the nature and extent of the litigation.
Adopting an administrative compensation system for smaller medical negligence claims.
Introducing a pre-action protocol system for larger medical negligence claims.
Reforms that influence court processes
There seems to be a consensus in the legal fraternity that the rules relating to the way in which experts are used should be reconsidered. The recommendation from the SALRC is that opposing parties to litigation should use joint expert witnesses, and when necessary, a panel of three joint expert witnesses from the discipline concerned, for technical medical evidence. The use of joint experts should be encouraged but naturally there will be situations where it is inappropriate, and a panel of three experts will only increase the costs unnecessarily. Rather the two main areas of concern which ought to be addressed is the accreditation and accountability of expert witnesses for the purposes of court proceedings and the desirability of sanctions for inappropriate or unethical conduct by expert witnesses.
The Superior Courts Act and the Uniform Rules of Court should be amended to provide for the appointment of specialist assessors to assist judges in complex medical negligence matters, rather than the establishment of specialist medical courts. Although the use of specialist assessors will be helpful this won’t necessarily address the issue that a generalist court will misapply the law, confuse rather than clarify the issues, and inadvertently encourage additional litigation rather than a specialist court.
Civil procedures be amended to substantially improve pre-trial procedures, as well as case management to expedite and simplify the finalisation of litigation.
Reforms that limit the amount of compensation awarded
Compensation to be awarded in the form of a structured settlement, with part of the compensation paid in a lump sum, part of the compensation paid as periodic payments, and part of the compensation provided as ‘payments in kind’ by means of the delivery of services – allowing a combination of these methods and determining the ratio of one aspect in comparison to another aspect by considering the circumstances of each case. This ‘payment in kind’ element is arguably the most controversial, given the parlous state of much of South Africa’s public healthcare system.
Periodic payments in the nature of an annuity be awarded for future maintenance, loss of earnings and the portion of future medical care, treatment, rehabilitation and therapy that the state cannot provide.
The underlying principle for the calculation of future loss of income be changed to a structured method based on the average national income or the average income of the area where the claimant lives.
It may be necessary to cap any damages other than special damages such as constitutional damages and general damages (non-pecuniary damages).
It should be possible to adjust periodic payments in exceptional circumstances.
Except for a few controversial recommendations, most will probably carry widespread support from various stakeholders. But the reality is that this is not enough. As the saying goes ‘the proof is in the pudding’. How exactly these recommendations will translate into independent pieces of legislation, amendments to existing legislation, adjustments to Court rules and practices are largely uncertain.
Whether their recommendations will carry through into positive and meaningful change is dependent on the ‘Powers that Be’. At this stage, there are indications that tend to suggest that the SALRC is under political pressure to now finalise this investigation and are more concerned with adopting recommendations which will relieve the most burden on the public sector rather than taking this opportunity to adopt a holistic approach to strengthening the entire South African medico-legal system, which is obviously preferable.
For example, there has been much criticism levelled at the SALRC for their exclusive focus on reform to the public sector. In their own words “(t)he proposals focus mainly on measures to alleviate the financial burden of medico-legal claims against the state on the fiscus, and to provide for alternative procedures for the speedy resolution of medical negligence claims against the state”. What is clear from the proposals offered in chapter 9 of Discussion Paper 154 is that efforts to reform the system can only realistically be done through a process of collaboration between the private and public healthcare system. According to them this was deliberate since the request for the current investigation was initiated at the insistence of the Ministries of Health and Justice. It would be preferable if law reform was not a knee-jerk reaction to the financial burden medical malpractice claims present for the State. Although the public sector exposure is, for various reasons, much greater financially: if not similar, the same risks exist for the private healthcare industry. Many medical malpractice claims and significant awards continue to plague the private sector. Therefore, it would be ideal if law reform was universally applied because there is no reason why the SALRC’s investigation should not include specific law reform initiatives that are helpful to the challenges presented to the private sector. Patients, health establishments and medical practitioners, whether in the private or public sector, are equally deserving of the constitutional imperative of equality before the law and “the right to equal protection and benefit of the law”.
What remains to be seen is how the recommendations in the final report will be implemented. The state has an exceptionally poor track record in following the corrective measures contained in the Public Protector reports, the South African Human Rights Commission reports, the Auditor-General audit reports, the Office of Health Standards Compliance reports, the Presidential Health Summit 2018 Compact and other existing government-initiated reports, plans and studies.
So whereto from here? Only time will tell. The investigative work of the SALRC is ongoing and it will no doubt take some time before we receive a final report. The real issue confronted by the SALRC is that there are a variety of different competing interests in the healthcare ecosystem, and it will be difficult to provide a holistic set of recommendations that will please everyone.
Acknowledging the good work done by SALRC the final report should adopt a balanced approach, one which prioritises interests of the state versus the poor and most vulnerable. Deciding how to compensate someone for harm suffered due to medical negligence is a thorny and complicated question. There is a difficult balancing act here. On the one hand, people have a right to be given fair compensation. On the other hand, the state has only limited funds and there is an understandable impulse to limit how much of those funds go toward compensation payments.
Of course, those mechanisms of compensation must not be unfair and punitive. The work of the SALRC is difficult, necessary, and very important to the sustainability of our healthcare system. The SALRC has noted the contribution of an ailing healthcare system to the significant medicolegal burden the country is facing. Factors contributing to poor healthcare service delivery by the State include maladministration, mismanagement and fraud, number of qualified healthcare workers and access to drugs, technologies and emergency transport.
Unfortunately, legislation and other reforms cannot fix the healthcare system or improve the standards of healthcare. But, overall, care must be taken to ensure that the final recommendations are well balanced and will pass constitutional muster.
A study published in the Journal of the American Geriatrics Society shows that a 12-month home-based supervised exercise programme can help to improve physical performance and functioning after patients undergo hip fracture surgery.
Hip fracture is a major health problem among older people, often resulting in long-term, sometimes persistent, functional impairments such as poor mobility and reduced independence in daily activities. Sedentary behaviour and low level of physical activity are also common among patients recovering from surgical repair of a hip fracture.
Standard care post-discharge care does not seem to meet the requirements of effective rehabilitation, as many patients with hip fractures do not reach their pre-fracture level of functioning. Growing evidence shows that multidisciplinary and well-coordinated rehabilitation started at the hospital and continued after discharge enhances the recovery of patients with hip fractures. Multicomponent rehabilitation in particular, which includes individualised and progressive resistance training, has improved functioning and mobility and decreased dependency in everyday activities. Longer lasting exercise programs of 6 to 12 months duration have reduced or reversed incident disability after hip fractures.
For the study, 121 patients aged 60 years and older were randomised to either an exercise group or a usual care group as a control. Home-based exercise sessions were delivered by physiotherapists twice a week and included strength, balance, mobility, and functional components as well as brief counselling on physical activity and nutrition.
Compared with patients in the usual care group, patients in the exercise group saw more improvements over the course of a year in their physical performance, their handgrip strength, and their ability to complete certain activities of daily living.
“It is worthwhile to invest in rehabilitation exercise for older people after hip fracture. Better functioning benefits the individual and also society,” said lead author Paula K. Soukkio, MSc, of the South Karelia Social and Health Care District (Eksote), in Finland.
