The finding may explain why similar NSAIDs produce a range of clinical outcomes and could inform how the drugs are used in the future. The study was published in the journal Immunity. 

Yale researchers have uncovered a distinct mechanism by which a subset of NSAIDs reduce inflammation.

Until now, the anti-inflammatory effects of NSAIDs were believed to arise solely through the inhibition of certain enzymes. But this mechanism does not account for many clinical outcomes that vary across the family of drugs. For example, some NSAIDs prevent heart disease while others cause it, some NSAIDs have been linked to decreased incidence of colorectal cancer, and various NSAIDs can have a wide range of effects on asthma. 

Now, using cell cultures and mice, Yale researchers have uncovered a distinct mechanism by which a subset of NSAIDs reduce inflammation. And that mechanism may help explain some of these curious effects. 

The research showed that only some NSAIDs – including indomethacin, which is used to treat arthritis and gout, and ibuprofen – also activate a protein called nuclear factor erythroid 2-related factor 2, or NRF2, which, among its many actions, triggers anti-inflammatory processes in the body. 

“It’s interesting and exciting that NSAIDs have a different mode of action than what was known previously,” said Dr Anna Eisenstein, an instructor at the Yale School of Medicine and lead author of the study. “And because people use NSAIDs so frequently, it’s important we know what they’re doing in the body.” 

The research team can’t say for sure that NSAIDs’ unexpected effects are due to NRF2 – that will require more research. “But I think these findings are suggestive of that,” Dr Eisenstein said. 

Eisenstein is now looking into some of the drugs’ dermatological effects – causing rashes, exacerbating hives, and worsening allergies – and whether they are mediated by NRF2. 

This discovery still needs to be confirmed in humans, the researchers note. But if it is, the findings could have impacts on how inflammation is treated and how NSAIDs are used. 

For instance, several clinical trials are evaluating whether NRF2-activating drugs are effective in treating inflammatory diseases like Alzheimer’s disease, asthma, and various cancers; this research could inform the potential and limitations of those drugs. Additionally, NSAIDs might be more effectively prescribed going forward, with NRF2-activating NSAIDs and non-NRF2-activating NSAIDs applied to the diseases they’re most likely to treat. 

The findings may also point to entirely new applications for NSAIDs, said Dr Eisenstein. 

NRF2 controls a large number of genes involved in a wide range of processes, including metabolism, immune response, and inflammation. And the protein has been implicated in aging, longevity, and cellular stress reduction. 

Dr Eisenstein said, “That NRF2 does so much suggests that NSAIDs might have other effects, whether beneficial or adverse, that we

Roche recently announced the launch of the cobas® 5800 System, a new molecular laboratory instrument, in countries accepting the CE mark. Testing is one of the first lines of defence to protect a patient’s general well-being and is vitally important in quickly guiding their treatment.

Testing is vitally important in quickly guiding a patient’ treatment

The cobas® 5800 System helps address laboratory challenges of increased patient testing, reimbursement complexities and the need for a diverse testing, while providing meaningful and timely results.

“The cobas 5800 System is a potential gateway to access where it is needed the most. Patients in Africa face barriers to access throughout their healthcare journey. Among the most pressing barriers are awareness, diagnostics, funding and healthcare capacity, said Alan Yates – Ad-Interim general manager for Roche Diagnostics, Southern Africa (South Africa and SADC). Yates adds,

“We are pleased that we can now offer a compact, fully-automated molecular system to help address the high demands on labs through greater efficiency, optimised workflows and cost savings, enabling them to deliver quality patient care and doing now what patients need next.

FAST FACTS

• Infectious diseases, such as those infections transmitted via respiratory, sexually and transplant, are becoming increasingly difficult to manage and represent an ever-growing medical need for millions of patients worldwide.

• Access to accurate and reliable diagnostic tests help clinicians
improve patient care, limit healthcare spending and contribute to protecting public health.

• The cobas® 5800 System is a compact new addition to the Roche Molecular portfolio, providing efficiency, simplicity, and timely results to laboratories of all sizes so clinicians can quickly determine the best treatment strategies for their patients.

In South Africa, we have three main governing acts regulating labour relations namely, The Basic Conditions of Employment Act 75 of 1997, the Labour Relations Act 66 of 1995 and the Employment Equity Act 55 of 1998. The question is, why do we need these acts? It effectively regulates the relationship between the employer and the employee to implement the ethics of how parties must conduct themselves in the workplace and to give effect to the parties’ rights and responsibilities towards each other.

Practices could have to pay employees a substantive amount of money awarded to them by the CCMA

Although it is not a statutory requirement that an employer and employee engage in a Contract of Employment, it is advisable to do so. The benefit of having a Contract of Employment in place confirms the scope of the basic conditions between the employer and the employee. The employer can decide what the contract’s content should look like, but they must bear in mind the three governing acts. The contract shall be drafted to make provisions for the employer and employees’ details, salary, working hours, leave, overtime, responsibilities, the need to keep the practice and its patient’s personal information confidential, any other unique provisions and how the contract should be terminated.

For further assistance, it is recommended that the employee receive a detailed job description from the employer. This will result in the employee understanding exactly what is expected of them in terms of duties during their contract of employment with the employer.

Policies and procedures are also important in the workplace. It helps to reinforce and clarify the standards expected of employees and helps employers manage staff more effectively as it defines what is acceptable and unacceptable behaviour in the workplace. It is suggested that the practice should have a separate document for Policies and Procedures that can be read together with the Contract of Employment. Further, the practice should draft a Disciplinary Code of Conduct for employees to follow. The document should be an exhaustive list of actions relating to misconduct by the employee and the appropriate sanctions for each type of misconduct.

What do you need to prove if an employee’s action is of such a serious nature that a disciplinary hearing, with the possible outcome of dismissal, is necessary? In other words, when is a dismissal fair? The employer must prove that the dismissal was procedurally and substantively fair. Procedural fairness refers to the process being followed for the specific dismissal, and substantive fairness refers to the merits or the reason for the dismissal.

WHAT ARE THE REQUIREMENTS FOR PROCEDURAL FAIRNESS FOR A DISMISSAL?

1. The employee should have received a notice from the employer 48 hours before the scheduled hearing. In the disciplinary hearing notice, the following needs to be noted:

a. Time, date and place

b. Sufficient details of the alleged charges against the employee

c. The employee’s rights

d. Should the employee fail to attend the hearing, the hearing can proceed without their attendance.

WHAT ARE THE RIGHTS OF THE EMPLOYEE?

• To be represented by a fellow employee

• To state their case

• To have an interpreter present

• To cross-examine witnesses

• To know the outcome of the disciplinary hearing

• To refer the matter to the CCMA within 90 days.

WHAT ARE THE REQUIREMENTS FOR SUBSTANTIVE FAIRNESS OF A DISMISSAL?

Any person who is determining whether a dismissal for misconduct is fair should consider the following:

• Whether or not the employee contravened a rule or standard regulating conduct in the workplace and

– If a rule or standard was contravened, whether

– The rule or standard was a valid or reasonable rule or standard

– The employee was aware or could have been expected to be aware of the rule or standard

– The rule or standard has been consistently applied by the employer

– The dismissal was the appropriate sanction contravening the standard or the rule.

Taking all into account, the practice needs to have contracts of employment, disciplinary codes and policy and procedures in place to avoid having to spend hours at the CCMA losing valuable time that should have been spent on taking care of patients and having to pay an employee a substantive amount of money due to an award given them by the CCMA.

“I had always considered working for Doctors Without Borders (MSF),” says Dr Lindsay Demes, “but I didn’t expect to do more than one assignment.” Now, I’m on my third international assignment. It’s something that I love.” Lindsay’s first MSF assignment was in 2017 in Pakistan. Since then, he’s racked up some serious experience in several exciting projects across the African continent. In 2019, the Cape Town doctor spent seven months working with MSF in Maban county, an isolated area near the South Sudanese border with Sudan. Maban is home to thousands of refugees and internally displaced people who often face additional challenges like severe flooding. The camps they live in were constructed on a natural flood plain.

“In some places, the villages were only accessible using quad bikes, which meant that we had to pack the bikes with the day’s supplies and set out early in the morning and start vaccinating, often under a tree.”

On routine days, Lindsay would review the most critically ill patients with the medical staff, discuss optimisation of prescriptions and engage in bedside teaching related to patients’ conditions. Most afternoons were filled up with further staff training.

He faced more daunting challenges on not-so-ordinary days, like a sudden measles outbreak. “One Friday evening, three patients presented with measles,” Lindsay explains. “Within 30 minutes of the patients arriving, about 12 colleagues arrived from the compound and worked late into the night to set up an isolation ward with a 30-bed capacity. It really shows the amazing teamwork we have at MSF.”

Another highlight was running a crucial measles vaccination campaign to reach 7 000 children between six months and 15 years old. “In some places, the villages were only accessible using quad bikes, which meant that we had to pack the bikes with the day’s supplies and set out early in the morning and start vaccinating, often under a tree.” At the start of 2020, Lindsay was set to head off to his next assignment – a plan quickly derailed by the Covid-19 pandemic. With international borders closed, many South African MSF staff who typically work internationally were reassigned to projects within South Africa as part of the national response to the pandemic. In April, Lindsay joined our teams in Johannesburg, where they were providing primary healthcare at shelters for people experiencing homelessness.

“I appreciated the work in the shelters because it helped me to build a relationship with people that you usually only meet on a transient basis and you don’t usually take the time to get to know,” he says. “Hearing about life from a different perspective was very interesting and humbling.”

In July, he travelled to Kenema in the eastern region of Sierra Leone, where he is working in an MSF-built hospital focused on reducing the mortality of children under five years old and offering quality healthcare to pregnant and lactating women.

Sierra Leone’s two health indicators are among the worst in the world, and there is not enough medical staff to meet demands, partly due to the untimely deaths of 7% of the country’s healthcare workers during the Ebola outbreak from 2014 to 2016.

am, Kang et al (2021) analysed the asthma treatment outcomes, safety, and patient preferences using formoterol/beclomethasone (FORM/BDP), a pMDI with extra-fine particles, compared with formoterol/budesonide (FORM/BUD), another pMDI with non-extra-fine particles. It was independent, double-blind, double-dummy head-to-head randomised controlled trial, funded by the Korean Government. This study aimed to assess the treatment outcomes, safety, and patient preferences.

Inhaled drugs with extra-fine particles are more effectively distributed in the peripheral airway

METHODS

In this parallel group study, 40 adult asthmatics were randomised to FORM/BDP group (n=18; active FORM/BDP and placebo FORM/BUD) or FORM/BUD group (n=22; active FORM/BUD and placebo FORM/BDP). During the two visits (baseline and end of eight-weeks treatment), subjects were asked to answer questionnaires including asthma control test (ACT), asthma control questionnaires (ACQ), and Quality of Life Questionnaire (QoLQ) for adult Korean asthmatics (QLQAKA). Lung function, compliance with inhaler, and inhaler-handling skills were also assessed.

RESULTS

The increase in forced expiratory volume in one second/forced vital capacity and forced expiratory flow at 25% to 75% of the pulmonary volume in the FORM/BDP group was higher than in the FORM/BUD group. Regarding preference, subjects responded that the flume velocity of FORM/BDP was higher, but more adequate than that of FORM/BUD. They also answered that FORM/BDP reached the trachea and bronchus and irritated them significantly more than FORM/BUD.

The study results suggest that FORM/BDP, an ICS/LABA with extra-fine particles, may be intrinsically more effective in terms of lung function because it reaches the distal airways, consequently relieving airway constriction. Inhaled drugs with small particles are more evenly deposited in the lung after inhalation, which may suggest that asthma can be more effectively controlled using these medications.

Moreover, inhaled drugs with extra-fine particles are more effectively distributed, in the peripheral airway, which can contribute to more uniform therapeutic effects on the patient’s lung. In a clinical study, inhaled drugs with extra-fine particles resulted in better asthma treatment outcomes in elderly asthmatics compared with the same dose of drugs with non-extra-fine particles. Furthermore, ICS/LABA with extra-fine particles resulted in less frequent AE than other ICS/LABAs with non-extra-fine particles.  

However, there were no differences in other treatment outcomes, such as ACT, ACQ, QLQAKA, asthma control, AE, FeNO, FVC, or FEV1, during the study.

The relatively short study period and the small number of subjects in this study may have hampered sufficient evaluation of the potential therapeutic benefits of extra-fine formulations. Asthma control using pMDIs with extra-fine particles may relieve smaller airway obstruction more than that those with non-extra-fine particles despite no significant differences in overall treatment outcomes. In addition, asthma patients may prefer specific pMDIs for reasons that may not be consistent with health care providers’ expectations, such as high flume velocity.

CONCLUSION

The study suggests that inhaled drugs with extra-fine particles have better therapeutics advantages in treating inflammation and bronchoconstriction of small airways than those with non-extra-fine particles, despite no significant differences in overall treatment outcomes. This evidence further enriches the dataset regarding the benefits of extra-fine pMDIs in adult asthmatics when compared to non-extra-fine formulations.

REFERENCES: Nam T-H, Kang S-Y et al. Comparison of Two pMDIs in Adult Asthmatics: A Randomized Double-Blind Double-Dummy Clinical Trial. Tuberc Respir Dis 2022;85:25-36. Doi: https://doi.org/10.4046/trd.2021.0093.

Medical malpractice insurance is essential to medical practitioners. Equally as important is a financially secure and trusted medical malpractice (med mal) partner. Genoa Underwriting Managers director Michael John Damant tells Medical Chronicle what makes a good medical malpractice partner.

In the medical environment, we launched five years ago, taking care of the medical malpractice needs of over 7 000 medical practitioners.

Q. WHY IS IT IMPORTANT TO CHECK FINANCIAL BACKING OF YOUR MED-MAL PARTNER?

A: Medical malpractice is a highly specialist line of liability insurance associated with large value claims. As an insured it is essential to engage with an insurance company that has strong underwriting experience (thus avoiding cross-subsidisation of premiums between multiple claimants and non-claimants).

Due to the severe nature of the claims these insurance companies are also generally supported by reinsurance companies to ensure that they have the appropriate balance sheet to withstand the claims.  

Q. WHAT PERCENTAGE OF MEDICAL PRACTITIONERS FACE SOME TYPE OF LITIGATION DURING THEIR CAREERS?

A: It is imperative for a practice to maintain appropriate liability insurance coverage in the event of a medical malpractice event. Whilst claims are not seen frequently, when they do arise, they are often of a severe nature. Our claims team at Genoa

Underwriting Managers will be able to guide you through these difficult times. We will assist with both HPSCA matters as well as briefing top panel attorneys (including Norton Rose Fulbright, Werksmans, Clyde & Co, Mac Roberts and Garlicke and Bousfield) to represent your interests in the event of a valid claim.

Q. IF YOU ARE SUED AND YOUR MED MAL PARTNER HAS GONE INTO LIQUIDATION WHAT DOES THIS MEAN?

A: This could, amongst other things, mean that the Prudential Authority has been consulted and has suggested that the insurer be placed in liquidation. Now a legal process will commence to wind up the insurer. Insured practitioners may not receive the full claims benefit that they may have been previously entitled to.  

Q. HOW LONG HAS GENOA BEEN AROUND?

A: Established in 2005 and previously trading as Multiline Insurance Administrators, Genoa Underwriting Managers has well-established business in the attorney environment where we insure in excess of 650 law firms, including top law firms in South Africa. We have written the professional indemnity policies for business rescues including Ster Kinekor, Comair, Group 5, CNA, and Stefanutti Stocks, all of which require large levels of indemnification.

In the medical environment, we launched five years ago, taking care of the medical malpractice needs of over 7 000
medical practitioners.

Q. WHO BACKS THE GENOA MEDICAL MALPRACTICE PRODUCT?

A: This product is underwritten by Safire Insurance Company Ltd, and further backed by reputable global reinsurers (with whom our senior directors have worked with for numerous years).

These global specialists offer the necessary balance sheet protection when claims arise.  

Q. WHY IS HAVING A STRONG SA-BASED PROVIDER IMPORTANT?

A: Having access to a South African-based insurer is essential as they have first-hand knowledge and experience
of the local market and legislation. Further, should you as the insured be unhappy with a decision taken by the insurer, then youhave access to the ombudsman for short term insurance (OSTI).

The OSTI is essentially the ‘champion of the people’ and has the power to overturn a decision taken by the South African insurer,provided the insurer is a member of the OSTI and the dispute falls within the OSTI’s jurisdiction.  

University of Virginia School of Medicine researchers and their collaborators have solved a decades-old mystery about how E. coli and other bacteria are able to move. 

An international team led by a leader in the field of high-tech cryo-electron microscopy, has cracked the case of how bacteria can move.

Bacteria push themselves forward by coiling long, threadlike appendages into corkscrew shapes that act as makeshift propellers. But how exactly they do this has baffled scientists, because the “propellers” are made of a single protein. 

An international team led by UVA’s Professor Edward Egelman, a leader in the field of high-tech cryo-electron microscopy (cryo-EM), has cracked the case. The researchers used cryo-EM and advanced computer modelling to reveal what no traditional light microscope could see: the strange structure of these propellers at the level of individual atoms. 

“While models have existed for 50 years for how these filaments might form such regular coiled shapes, we have now determined the structure of these filaments in atomic detail,” said Prof Egelman, of UVA’s Department of Biochemistry and Molecular Genetics. “We can show that these models were wrong, and our new understanding will help pave the way for technologies that could be based upon such miniature propellers.” 

BLUEPRINTS FOR BACTERIA’S ‘SUPERCOILS’ 

Different bacteria have one or many appendages known as a flagellum, or, in the plural, flagella. A flagellum is made of thousands of subunits, but all these subunits are exactly the same. You might think that such a tail would be straight, or at best a bit flexible, but that would leave the bacteria unable to move. That’s because such shapes can’t generate thrust. It takes a rotating, corkscrew-like propeller to push a bacterium forward. Scientists call the formation of this shape “supercoiling,” and now, after more than 50 years, they understand how bacteria do it. 

Using cryo-EM, Prof Egelman and his team found that the protein that makes up the flagellum can exist in 11 different states. It is the precise mixture of these states that causes the corkscrew shape to form. 

It has been known that the propeller in bacteria is quite different than similar propellers used by hearty one-celled organisms called archaea. Archaea are found in some of the most extreme environments on Earth, such as in nearly boiling pools of acid, the very bottom of the ocean and in petroleum deposits deep in the ground. 

Prof Egelman and colleagues used cryo-EM to examine the flagella of one form of archaea, Saccharolobus islandicus, and found that the protein forming its flagellum exists in 10 different states. While the details were quite different than what the researchers saw in bacteria, the result was the same, with the filaments forming regular corkscrews. They conclude that this is an example of “convergent evolution” – when nature arrives at similar solutions via very different means. This shows that even though bacteria and archaea’s propellers are similar in form and function, the organisms evolved those traits independently. 

“As with birds, bats and bees, which have all independently evolved wings for flying, the evolution of bacteria and archaea has converged on a similar solution for swimming in both,” said Prof Egelman. “Since these biological structures emerged on Earth billions of years ago, the 50 years that it has taken to understand them may not seem that long.”