Day: February 1, 2022

Categories : COVIDTags :

Nitazoxanide Flops in South African COVID Trial

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Interim analysis of a South African clinical trial has revealed that nitazoxanide, an oral antiparasitic agent with antiviral properties, was ineffective in improving outcomes in ambulatory patients with mild-to-moderate COVID.

Funded by the South African Medical Research Council (SAMRC), the study was performed at four sites in South Africa. The primary goal of the trial was to evaluate the effectiveness of nitazoxanide (1g twice daily for 7 days) in reducing the progression from mild to severe COVID in ambulatory patients. Progression to severe disease was defined as hospitalisation or death. The trial underwent an interim analysis at 67% of the recruitment target (290 participants), and the data was reviewed by an independent data and safety monitoring board (DSMB). Following the interim analysis, the DSMB recommended halting recruitment of the trial on the grounds of futility.

No significant difference was seen in serious adverse events, which included all causes of hospitalisation and death, between the nitazoxanide and the placebo groups [12/144 (8.3%) vs 10/146 (6.8%)]. Hospitalisation and death specifically due to COVID showed the same pattern [7/144 (4.9%) vs 8/146 (5.5%)].

Principal investigator Prof Keertan Dheda from the University of Cape Town (UCT) and the London School of Hygiene and Tropical Medicine, said that the results of the trial, although disappointing, contributes to the growing body of evidence, clarifying what works and what doesn’t for the treatment of COVID. Thus, clarifying what does not work is as important as finding effective therapies so that clinically useful management algorithms can be developed.

Nitazoxanide is a low-cost broad-spectrum antiviral drug with an extensive safety record. Originally developed as antiparasitic, it seemed promising against SARS-CoV-2 in the lab but the real world test did not show any benefit. It is still possible that nitazoxanide may be of benefit at higher doses (greater than the dose used in the trial, which was already twice the normal dose), however this will most likely cause an increase in intolerable gastrointestinal side effects. “The next step will be to focus on formally publishing the data in a peer reviewed journal and to evaluate secondary objectives of the study, including assessing the efficacy of nitazoxanide in reducing the duration of illness, reducing SARS-CoV-2 viral load, and its efficacy, if any, in preventing COVID in close contacts,” said Prof Dheda.

Prof Dheda concluded that nitazoxanide could have a less than 30% benefit which may be detectable in a larger study. However, it is questionable whether such an effect size is clinically relevant given the number needed to treat to prevent disease progression, adverse events, cost and that other therapies have emerged (eg paxlovid) with an efficacy benefit of greater than 80%.

SAMRC President and CEO, Prof Glenda Gray said although the study did not meet its primary endpoint, the results are an important addition into the scientific repository. “COVID and HIV in their very nature are unique and complex viruses which have posed unprecedented challenges for vaccine development, globally – however, the knowledge gained from this trial will help us advance our pursuit of effective therapies and vaccines for both COVID and HIV alike,” said Prof Gray.

Prof Gray, who also has led numerous trials in search of effective HIV and COVID vaccines, said COVID poses substantial challenges for those living with HIV which evades the immune system. “Until an effective vaccine has been found, all people living with HIV should take all recommended preventive measures to minimise their exposure to COVID,” concluded Prof Gray.

Source: South African Medical Research Council

Categories : GastrointestinalTags :

Propofol and Physician Anaesthesiologists Speed Up Endoscopy

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Using a physician anaesthesiologist-led model administering fast-acting propofol increases patient access to care, compared to previous models which used nurse-administered sedation for gastrointestinal (GI) endoscopy procedures, according to work done by the University of Colorado Hospital.

“The Anaesthesia Care Team model allows us to optimise patient flow and utilise faster-acting medications, resulting in shorter total case lengths and reduced post-anaesthesia care unit (PACU) length of stay for upper and lower GI endoscopic procedures, compared to a model where nurses provided sedation,” said Dr Adeel A. Faruki, senior author of the study. “This allows for scheduling more patients in fewer rooms in the GI suite per day and increases patient access to care.”

Most anaesthesia care in the US is delivered either by a physician anaesthesiologist or a non-physician anaesthesia practitioner supervised by a physician anaesthesiologist within the Anaesthesia Care Team model. This model and physician-led anaesthesia care is seen as the gold standard for ensuring patient safety and the best outcomes.

The University of Colorado Hospital previously used a model where GI procedural nurses provided sedation under supervision from gastroenterologists for cases that did not require general anesthesia (called the GI luminal unit). The hospital transitioned to the Anaesthesia Care Team model for all GI cases July 1, 2021.

In the study, researchers compared GI cases performed under the previous nurse-provided sedation model to those performed under the Anaesthesia Care Team model. They found it took less time to start the procedure (sedation start to scope-in time) when deep sedation with propofol (MAC) was provided by the Anaesthesia Care Team than when nurses administered sedation with fentanyl, midazolam and diphenhydramine. That change, along with a redesigned patient flow, provided the opportunity to increase daily GI procedural volume by 25%, while using the same number of procedural suites, Dr Faruki said.

Propofol is a fast-acting and effective medication with a higher-risk-profile, which physician anesthesiologists have the skills and training to deliver and monitor. “Propofol can result in very deep levels of sedation in a short period of time and, therefore, at most institutions, is restricted for use by anesthesia providers,” said Andrew Mariotti, lead author of the study and M.D. candidate at the University of Colorado. “Unlike GI procedural nurses, the Anesthesia Care Team has the training and expertise to perform advanced airway and cardiovascular interventions if an emergency arises.”

The researchers analysed the sedation-to-scope-in time of 5640 endoscopy patients, comparing 4,606 who received nurse-administered sedation for GI procedures, to 1034 who had MAC. The time was reduced by 2 to 2-1/2 minutes per case with MAC. Extrapolating to the typical cases performed at their hospital over a year (more than 2600 cases), the authors said the time savings equates to more than 5300 minutes, or 90 hours.

Sincerecovery also is faster with propofol, there were time savings in the PACU of 7 minutes for upper GI endoscopies and 2 minutes in lower-GI cases. The researchers also found patients reported being less groggy.

GI endoscopies account for about two-thirds of all endoscopies in the US. The time savings for Anesthesia Care Team-administered MAC sedation likely would apply to non-GI procedures as well, the authors noted.

This research is presented at the American Society of Anesthesiologists’ ADVANCE 2022, the Anesthesiology Business Event.

Source: EurekAlert!

Categories : HospitalsTags :

Operating Room Availability Planning Helped Cushion Staff Shortages

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Photo by Jafar Ahmed on Unsplash

Decreasing operating room (OR) availability by 15% helped a hospital address a 30% staff shortage caused by the COVID pandemic, while surgeons were largely satisfied with the arrangements, according to a study by UPMC Presbyterian Hospital.

“The Great Resignation has disproportionately impacted health care to near-crisis levels and we were able to address ongoing staff shortages by methodically decreasing available surgical times,” said Dr Kimberly Cantees, clinical director of anaesthesiology and perioperative services at UPMC Presbyterian Hospital. “By using a phased approach, including daily meetings to address scheduling issues, we were able to prioritise essential surgeries and care for patients with the greatest need.”

UPMC is a comprehensive quaternary care regional and national referral centre for many surgical specialties. The hospital implemented a five-phased approach for the study, which started in May 2021, to ensure that it could maintain provision of essential surgical care when its surgical technologist and OR nurse vacancy rate reached 30%. The phases went as follows:

  • Phase I (May 2021): Restricted OR availability for surgeries that were less time- sensitive and moved some to other hospitals and surgery centers in the UPMC system; decreased OR availability for surgeons with highly elective cases (eg, sports orthopedic procedures, select hand surgery cases, some plastic surgery) and moved a small amount of surgical work to the bedside in the intensive care unit.
  • Phase II (July 2021): Formed a multidisciplinary surgical services capacity committee that met daily to ensure the staffing matched the surgical schedule for the subsequent two weeks. Values for surgical care were identified and cases such as transplant and cancer surgeries were prioritised.
  • Phase III (Oct. 2021): Reduced OR time availability by 15% when surgeries could be scheduled and extended the deadline for standard scheduling guidelines from three days to five days before surgery.
  • Phase IV (Nov. 2021): Instituted additional reduction of OR scheduling to meet continued staff shortages and reduced available OR time for all surgical services by an additional 10%. Surgeons with two ORs had their time reduced for all services, except for the care of trauma patients.
  • Phase V (Jan. 2022): Implemented UPMC system-wide review of surgical case prioritisation and opened more ORs for booking, which allowed greater flexibility for performing surgeries depending on staffing availability.

Over the course of the phased approach, the available ORs were decreased from 36 to 31 (15%). This has been adequate to address the 30% reduction in surgical services staff, Dr Cantees explained. The approach also helped the hospital to cope with staffing shortages during the Omicron surge.

Dr Cantees said there was minimal pushback from surgeons to the phased approach, mostly thanks to clear communication of both the staffing hurdles, as well as established surgical priorities. Communication occurs between members of the multidisciplinary surgical services capacity committee and individual surgeons.

The study was presented at the American Society of Anesthesiologists’ ADVANCE 2022, the Anesthesiology Business Event.

Source: EurekAlert!

Categories : Cardiovascular DiseaseTags :

Uncovering the Mechanical Basis for Abdominal Aortic Aneurysm

On By ModernMedia
Source: Mat Napo on Unsplash

A new study reveals the mechanical basis underlying abdominal aortic aneurysm (AAA), a complex and life-threatening vascular disease with high incidence worldwide.

Known as the ‘silent killer’, most AAAs are asymptomatic, often undetected until rupture, and involve a poorly understood set of mechanical and biochemical events. Studies have shown that AAA is associated with both vascular inflammation and increased stiffness. That the latter happens with ageing partly explains why AAA is almost only ever seen in people over 65.

Evidence suggests that abnormal acclimation of vascular smooth muscle cells (VSMC) to biomechanical disturbances, such as increased circumferential stress in hypertension, can lead to the development of AAA. However, not much is known about the molecular drivers of altered mechanobiological behaviors of VSMC. Understanding these might provide promising targetable signals that could repress AAA progression and limit rupture incidents.

Now, researchers have demonstrated mechanobiological changes in VSMC and identified a key ion channel that is involved in the development of AAA. In a new study, in Nature Communications, they describe how VSMC gradually adopts a solid-like state by upregulating cytoskeleton crosslinker, α-actinin2, which powers the mechanosensitive ion channel Piezo1.

“Our team applied biomechanical engineering to study aneurysm pathology,” explained study leader Professor Weiqiang Chen. “In contrast to the extensive study of aorta wall properties, we explored how a cell’s mechanical sensitivity, or ‘mechanosensation’ to mechanical stimuli presents an innovative perspective in revealing disease pathogenesis and progression mechanisms.”

Measuring misshapen VSMC with a novel ultrasound tweezers system and a single-cell RNA sequencing technique, the researchers identified Piezo1, which critically regulates VSMC mechanical sensitivity. Inhibiting Piezo1 in mice prevented them from developing AAA, by relieving pathological vascular remodeling. The researchers concluded that deviations of mechanosensation behaviours of VSMC is detrimental for AAA, and Piezo1 could be responsible for mechanically fatigued aorta in AAA. This could lead to new mechano-medical approaches to treating this devastating cardiovascular disease.

Source: EurekAlert!

Categories : Cardiovascular DiseaseTags :

Having Better Conversations about Post-stroke Prognosis

On By ModernMedia
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Though conversations with stroke survivors and their loved ones about possible lasting impairment can be traumatic, they might also be therapeutic, according to research from The University of Queensland, published in the American Journal of Speech-Language Pathology.

PhD candidate Bonnie Cheng from UQ’s School of Health and Rehabilitation Sciences said that prognosis conversations can trigger mixed emotions of hope and grief, so knowing  how people would prefer for them to happen is important.

“When stroke is encountered for the first time, it’s hard to know what’s important and relevant to ask about, especially during that time of crisis immediately after such a serious health event,” Ms Cheng said.

“During this time, there’s also an immense sense of gratitude for the survival of their loved one that seems to stop significant others from asking for more information.

“Conversations about prognosis and lasting impairments, like speech difficulties, need to be an ongoing dialogue between health professionals, the patient, and their support network.

“It’s important for these conversations to be based on a mutual understanding of what improvements are personally meaningful to the patient and their significant others.”

Aphasia is a common condition after a stroke, diagnosed in one-in-three people after a stroke.

The researchers interviewed people who identified as a significant other of someone with aphasia between three and 12 months after stroke, including spouses, close friends, adult children and parents of someone with aphasia.

“In the interviews, we talked in-depth about their experience of finding out about the prognosis for aphasia, the impact these experiences had on them, and how they would want to get information about prognosis in a perfect world,” Ms Cheng said.

“What we found was significant others need to be included in prognosis conversations so that they too can be informed and supported, alongside the patient.

“The prognosis of aphasia is a sensitive issue to address because it often involves having to adjust to long-term difficulties and changes.

“Recovery needs to be looked at holistically in terms of everyday activities that affect the individual, rather than just scores on a language impairment test.

“Even though we can’t yet ‘cure’ aphasia, this research brings us one step closer to talking about recovery in a way that’s as informative and as compassionate as possible, so that people living with aphasia can be supported to live successfully with the condition.”

Source: University of Queensland

Categories : Medical Research & TechnologyTags :

A New Understanding of the Fundamental Order of the Abdomen

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Source: Pixabay

In a research paper published in Communications Biology, researchers from the University of Limerick have detailed the development and structure of the mesentery. In doing this, they uncovered a new order by which all contents of the abdomen are organised or arranged – or the “fundamental order of the abdomen”, where organs are in one of two compartments.

Professor Calvin Coffey, Foundation Chair of Surgery at UL’s School of Medicine in Ireland, whose major discovery led to the reclassification of the mesentery as a new organ in 2016, has published new research on the makeup and structure of the abdomen.

The importance of these findings on the mesentery and the impact these have on our understanding of the abdomen have been further explained in a review article just published in the Lancet Gastroenterology and Hepatology.

Prof Coffey explained that his team have been looking at the development and structure of the mesentery since 2016.

“We showed how the mesentery is a single and continuous organ in and on which all abdominal digestive organs develop and then remain connected to throughout life,” he explained.

“These findings revealed a simplicity in the abdomen that was not apparent in conventional descriptions of anatomy.”

The international team of researchers used cutting edge techniques to clarify how the mesentery develops and the shape it has in adults.

Their work revealed that the organisation of the abdomen has a remarkably simple design.

“The abdomen is not the dauntingly complex collection of separate organs it was previously thought to be,” said Prof Coffey.

“Instead, all digestive organs are neatly packaged and arranged by the mesentery into a single digestive engine. That simplicity lay hidden until clarification of the nature of the mesentery.”

The model itself was described by the team in the most recent edition of Gray’s Anatomy. The supportive evidence was published in Communications Biology and the clinical importance was explained in the review in The Lancet Gastroenterology and Hepatology.

“The most important finding here was the discovery of the fundamental order of the abdomen. At the foundation level, all contents of the abdomen are simply organised into one of two compartments,” explained Prof Coffey.

“The fundamental order of any structure is of considerable importance, in particular when it comes to diagnosing patients with illness and treating their disease. The fundamental order is the foundation from which all science launches and clinical practice is based.

“The organisational simplicity of the abdomen now immediately explains the behaviours of viral and bacterial infections, cancer, inflammatory bowel disease, obesity, diabetes and many others,” he added.

Improvements in surgery have been made to surgery by a better understanding of the mesentery and its functions, and the new research builds on those advances. There are also exciting areas for future investigation, according to Prof Coffey.

“Patients are already benefiting from what we now call mesenteric-based approaches to the diagnosis and treatment of most abdominal conditions. The Mesenteric Model of Abdominal Anatomy – or the description of the order of the abdomen – is being incorporated into numerous reference curricula at this moment,” he said.

“Regarding the future, it is being argued that we are seeing a paradigmatic shift from old to new order. Already, intriguing questions are emerging that we can call ‘legitimate or admissible’ in the strictest scientific sense. Science can approach numerous questions in a new light.  Clinicians can design diagnostic and treatment approaches based on a new foundation,” Prof Coffey concluded.

Source: EurekAlert!