Category: Hospitals

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A New Easy-to-Apply Antimicrobial Coating

On By ModernMedia
Image by Quicknews

Researchers have developed an inexpensive, non-toxic coating for almost any fabric that decreases the infectivity of SARS-CoV-2 by up to 90%. It could even be developed to be applied to fabric by almost anyone.

“When you’re walking into a hospital, you want to know that pillow you’re putting your head onto is clean,” said lead author Taylor Wright, a doctoral student at the University of British Columbia. “This coating could take a little bit of the worry off frontline workers to have Personal Protection Equipment with antimicrobial properties.”

Researchers soaked fabric in a solution of an antimicrobial polymer which contains a molecule that releases reactive oxygen species when light shines on it. They then used UV light to turn this solution to a solid, fixing the coating to the fabric. “This coating has both passive and active antimicrobial properties, killing microbes immediately upon contact, which is then amped up when sunlight hits the cloth,” said senior author Professor Michael Wolf.

Both components are safe for human use, and the entire process takes about one hour at room temperature, said Wright. It also makes the fabric hydrophobic, without sacrificing fabric strength. The researchers detailed their study in American Chemical Society Applied Materials & Interfaces.

The coating can also be used on almost any fabric, with applications in hospital fabrics, masks, and activewear. While other such technologies can involve chemical waste, high energy use, or expensive equipment, the UBC method is relatively easy and inexpensive, said Wright. “All we need is a beaker and a light bulb. I’m fairly certain I could do the whole process on a stove.”

To test the coating’s antimicrobial properties, the researchers bathed treated fabric in bacterial soups of Escherichia coli and Methicillin-resistant Staphylococcus aureus (MRSA). They found that 85% of viable E. coli bacteria remained after 30 minutes, which fell to three per cent when the treated cloth was exposed to green light for the same amount of time. Similarly, 95% of viable MRSA bacteria remained, dropping to 35% under green light. No bacteria remained after four hours.

While sunlight or fluorescent lights have a lesser percentage of green in their spectrums, the team expects similar but less intense results for fabric exposed to those light sources, said Wright. “Particularly in the Pacific Northwest, it’s not always a sunny day. So, at all times you’re going to have that layer of passive protection and when you need that extra layer of protection, you can step into a lit room, or place the fabric in a room with a green light bulb – which can be found for about $35 online.”

The researchers also looked into whether the coating reduced the infectivity of SARS-CoV-2 by bathing treated fabric in a solution of the virus particles and then adding that solution to living cells to see if they could infect them. They found the passive properties were ineffective against the virus, but when treated fabric was exposed to green light for two hours, there was up to a 90% drop in the virus’ infectivity. “In other words, only one tenth of the amount of virus signal was detected on cells infected with the UV-fabric and light treated virus”, says co-author Professor François Jean.

The team found they needed an 18cm2 piece of fabric to kill microbes with material containing 7% of the active ingredient by weight, but that increasing this to 23% increased the effectiveness of the fabric at four times less material, said Wright.

Researchers also found that keeping the fabric under green light for more than 24 hours failed to produce the sterilising forms of oxygen, highlighting an area for further study. This is a similar effect to the colour fading on clothing after being exposed to sunlight for too long.

“Biomanufacturing face masks based on this new UBC technology would represent an important addition to our arsenal in the fight against COVID, in particular for highly transmissible SARS-CoV-2 variants of concern such as Omicron”, said Prof Jean. The coating can also be used for activewear, with an ‘anti-stink’ coating applied to areas where people tend to sweat, killing off the bacteria that makes us smell. Indeed, hospital fabric and activewear companies are already interested in applying the technology, and the university has applied for a patent in the United States, said Prof Wolf.

Source: University of British Columbia

Categories : HospitalsTags :

Netcare Seeking a Buyer for Bougainville Hospital

On By ModernMedia
Credit: Netcare

Netcare is looking for a buyer for its 60-bed Netcare Bougainville Hospital in Pretoria West, which first opened its doors in 1997.

Commenting on the development, Johan Smal, regional director of Netcare’s North East region said that unless a suitable buyer was found, the hospital would close its doors on 30 April 2022.

In outlining the reasons for the closure of the facility, Smal said that Netcare’s hospital division continually conducted strategic reviews of its asset portfolio in which Netcare Bougainville Hospital was identified as an under-performing facility for a sustained period.

“The hospital’s under-performance has prevailed from before COVID and this was further exacerbated by the adverse effects of the pandemic, in the past 24 months. These and other circumstances have rendered it uneconomical to retain Netcare Bougainville Hospital in the current business environment.”

“We have been in consultation with staff, doctors and facility management to notify them that the hospital may have to close. In addition the Department of Health, unions and other key stakeholders have been kept firmly updated on developments,” he added.

Sydney Masalla, general manager of Netcare Bougainville Hospital has confirmed that there are at present only three resident specialists on site at the hospital who also work at other facilities.

“In addition we have only 37 active staff members with whom we are in discussion regarding viable alternative employment options.”

Smal concluded by thanking patients, doctors, staff as well as healthcare service providers for their support through the years stating that they were an integral part of the history of Netcare Bougainville Hospital and the greater South African landscape.

“I am confident that we will continue working together, as we have in the past, in other Netcare facilities – this is therefore not farewell,” he concluded.

Categories : COVID HospitalsTags :

Bleeding from Full-dose Anticoagulants in COVID ICU Patients

On By ModernMedia
Photo by Mufid Majnun on Unsplash

COVID patients in intensive care units (ICU) receiving full-dose anticoagulants are significantly more likely to experience heavy bleeding than patients prescribed a smaller yet equally effective dose, according to a recent study.

The research, which compared the safety and effectiveness of blood clot treatment strategies for more than 150 critically ill COVID patients at two hospitals, found that almost all patients who experienced significant bleeding were on mechanically ventilation and receiving full-dose anticoagulants.

The results, published last month in Hospital Pharmacy, may inform treatment guidelines for blood clots in hospitalised COVID patients, who are at an increased risk for both blood clots and severe bleeding. Previous reports have found that 17% of hospitalised COVID patients experience blood clots, said first author Maya Chilbert, PharmD, clinical assistant professor in the UB School of Pharmacy and Pharmaceutical Sciences.

“A wide variety of practice exists when it comes to approaching blood clots in hospitalized patients with COVID, and there is little data to suggest improved outcomes using one strategy versus another,” said Chilbert. “Caution should be used in mechanically ventilated patients with COVID when selecting a regimen to treat blood clots, and the decision to use full-dose blood thinners should be based on a compelling indication rather than lab markers alone.”

The study analysed the outcome of blood clot treatments and the rate of bleeding events for more than 150 patients with COVID-19 who received either of two blood thinner regimens: a full-dose based on patient levels of D-dimer, and the other a smaller but higher-than-standard dosage.

Patients’ average age was 58, and all experienced elevated levels of D-dimer, fibrinogen, and prothrombin time.

Significant bleeding events were experienced by almost 14% of patients receiving full-dose anticoagulants, compared to only 3% of patients who received a higher-than-standard dosage. All patients who experienced bleeding events were on mechanical ventilation. No difference was reported in the regimens’ effectiveness at treating blood clots.
Further investigation is needed to determine the optimal strategy for treating blood clots and bleeding in hospitalised COVID patients, said Asst Prof Chilbert.

Source: University at Buffalo

Categories : HospitalsTags :

Operating Room Availability Planning Helped Cushion Staff Shortages

On By ModernMedia
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 : HospitalsTags :

Solar-powered Oxygen System Saves Lives in Somalia

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A newly installed solar-powered medical oxygen system at a hospital in central Somalia is proving effective in saving lives, Somali and World Health Organization doctors told Voice of America.

The innovative solar oxygen system, the first of its kind in the country, was installed at Hanaano hospital, in the central town of Dhusamareb a year ago. Doctors say the system is having an impact and helping save the lives of very young patients.

“This innovation is giving us promise and hopes,” says Dr Mamunur Rahman Malik, WHO Somalia Representative.

According to Dr Malik, 171 patients received oxygen at the hospital from the solar-powered system from February to October 2021. Of these, only three patients died, and five others were referred to other hospitals.

Every year some 15 000 to 20 000 deaths occur in Somalia among children under five years of age due to pneumonia, said Dr Malik, making it the deadliest disease among under-fives.

The director of Hanaano hospital, Dr Mohamed Abdi, said the innovation is making a difference.

“It has helped a lot, it has saved more than a hundred people who received the service,” he said to VOA Somali.

“It was a problem for the children under one year and the children who are born six months to get enough oxygen. Now we are not worried about oxygen availability if the electricity goes out because there are the oxygen concentrators.”

One patient was Abdiaziz Omar Abdi, admitted to the hospital on January 16 with severe pneumonia and was struggling to breathe normally. The oxygen rate in his body had dropped to 60%, Dr Abdi said. Doctors immediately put him on oxygen along with ampicillin and dexamethasone medications. When discharged three days later, he was breathing normally. His oxygen was up to 90%.

Dr Malik said the oxygen is being used to treat a wide range of medical conditions – asphyxia, pneumonia, injuries, trauma, and road traffic accidents.

“We have seen in other countries that use of solar-powered medical oxygen (if applied in a timely manner) can save up to 35% of deaths from childhood pneumonia,” he said, adding that it could save the lives of at least 7000 children who die “needlessly” due to pneumonia.

The initiative to install solar-powered bio-medical equipment at Hanaano hospital emerged during the height of COVID in 2020, at a time when people were dying due to respiratory problems. Hospitals were unable to keep up with case loads and the cost of a cylinder of oxygen rose to between $400 to $600, and only 20% of health facilities had any kind of access to oxygen, said Dr Malik.

“If you look at the current situation, as of today Somalia needs close to 3000 or 4000 cubic metres of oxygen per day. So, oxygen was the biggest need in all the hospitals.”

Solar power can also be used for medical refrigerators, and their use is becoming widespread in Africa.

Source: Voice of America

Categories : COVID HospitalsTags :

Omicron Not ‘Mild’ for US, Experts Say

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In stark contrast to South Africa’s approach to COVID and the country’s experts characterising Omicron as “mild”, US experts have said that calling it “mild” ignores the harsh situation their country faces: record hospitalisations, sick children, other conditions being worsened by COVID, and staff shortages.

While Omicron’s odds of causing a person’s hospitalisation or death are lower, US numbers suggest that Omicron is, in fact, serious on a population level.

“What’s mild about hospitals at or near the breaking point? What’s mild about hundreds of healthcare workers per hospital out ill with COVID? What’s mild about 1.3 million cases in the U.S. just yesterday? What’s mild about the rising titer of burnout? What’s mild about an unprecedented number of children now ill and hospitalised with COVID?” Clyde Yancy, MD, chief of cardiology at Northwestern University’s Feinberg School of Medicine in Chicago, wrote in an email to MedPage Today.

“I think prudence would suggest that we reframe ‘mild’ and think more about ‘self-limited,'” he added. “We are likely at or near a plateau but how long will it last and how much more agony awaits?”

Americans were hospitalised in record numbers last week. “When there are many more people sick in large numbers – in millions – even if it’s a smaller percentage that’s going to be severely sick, that is going to result in large numbers in the hospitals,” said Biykem Bozkurt, MD, PhD, a cardiologist at Baylor College of Medicine in Houston.

While Omicron is still a threat for those unvaccinated or without previous infection, its high breakthrough rate is a cause for concern, especially in vulnerable people.

“Individuals who have breakthroughs after being vaccinated, including the elderly who have comorbid heart disease, are now flooding our emergency departments with decompensated cardiovascular diagnoses and a positive coronavirus test,” said cardiologist Jim Januzzi, MD, of Massachusetts General Hospital and Harvard Medical School in Boston.

As well as buckling healthcare systems, vulnerable and overlooked populations are being affected by Omicron even more.

Paediatric hospitalisations in the US reached a new peak in mid-January, with 20% of the entire pandemic’s hospitalisations of children happening in just two weeks in January. Over 1000 children have died from COVID by the CDC’s numbers, including 359 under five.

Moreover, patients on immunosuppressive medications may be less protected by the vaccines. “The labelling of the Omicron infection as ‘mild’ overlooks the important features and the messaging to the public,” rheumatologist Vaidehi Chowdhary, MBBS, MD, DM, of Yale School of Medicine in New Haven, Connecticut, wrote in an email to MedPage Today.

“Some patients who are on strong immunosuppressive medications do not have adequate vaccine titers and remain vulnerable,” she said, pointing out that there’s a shortage of monoclonal antibodies and antivirals, which means that this group must take extra precautions to ensure they aren’t infected in the first place.

Omicron’s impact on those who are immunosuppressed or have long COVID is not yet known, Dr Chowdhary noted. “For immunosuppressed patients, to minimise infections, many in-person appointments have been converted to telehealth or elective procedures deferred. The impact of these practices and their impact on overall patient health are not known.”

People living with disabilities and chronic illnesses continue to be faced with worsened infections, delaying consultations and difficulty accessing healthcare.

Then there are those whose infection has exacerbated their condition, whatever it may be. Omicron could be the thing that tips them over the edge, or that keeps them in the hospital for longer, experts have said. Examples seen include patients with blood clots having those clots exacerbated by COVID, and COVID-positive trauma patients having complications and longer recovery times.

Healthcare workers falling ill due to Omicron has seriously stressed US healthcare, with staff shortages have been reported in almost 20% of the country’s hospitals, leaving their already overworked colleagues to work extra.

Dr Januzzi’s hospital has been “completely full, with a huge number of individuals with COVID. So, we’re really at a breaking point where staff are getting sick. Patients and physicians alike are exhausted … the hope would be that we can get through this time and get to the other side of this.”

Source: MedPage Today

Categories : COVID HospitalsTags :

Little COVID Viral Contamination Risk in Hospital Rooms

On By ModernMedia
Source: Martha Dominguez de Gouveia on Unsplash

A study found that hospital rooms where COVID patients were treated had little to no active virus contaminations on surfaces. The finding, published in Clinical Infectious Diseases, concluded that contaminated surfaces in the hospital environment are unlikely to be a source of indirect transmission of the virus, contrary to earlier views.

“Early on in the pandemic, there were studies that found that SARS-CoV-2 could be detected on surfaces for many days,” said the study’s senior author, Professor Deverick Anderson. “But this doesn’t mean the virus is viable. We found there is almost no live, infectious virus on the surfaces we tested.”

The researchers tested a variety of surfaces in the hospital rooms of 20 COVID patients at Duke University Hospital over several days of hospitalisation, including on days 1, 3, 6, 10 and 14.

Samples were collected from the patients’ bedrail, sink, medical prep area, room computer and exit door handle. A final sample was collected at the nursing station computer outside the patient room.

PCR testing found that 19 of 347 samples gathered were positive for the virus, including nine from bedrails, four from sinks, four from room computers, one from the medical prep area and one from the exit door handle. All nursing station computer samples were negative.

Of the 19 positive samples, most (16) were from the first or third day of hospitalisation.

All 19 positive samples were screened for infectious virus via cell culture with only one sample, obtained on day three from the bedrails of a symptomatic patient with diarrhoea and a fever, demonstrating the potential to be infectious.

“While hospital rooms are routinely cleaned, we know that there is no such thing as a sterile environment,” Prof Anderson said. “The question is whether small amounts of viral particles detected on surfaces are capable of causing infections. Our study shows that this is not a high-risk mode of transmission.”

Prof Anderson said the findings reinforce the understanding that SARS-CoV-2 primarily spreads through person-to-person encounters via respiratory droplets in the air. He noted that people should concentrate on known anti-infection strategies such as masking and socially distancing to mitigate exposures to airborne particles.

Source: Duke University

Categories : HospitalsTags :

Standard Saline as Effective as Specialised Intravenous Fluids in ICU

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New research on intravenous fluids used in intensive care shows that commonly used saline is as effective at keeping people alive and their organs functioning as more expensive balanced solutions.

The results not only provide doctors with greater certainty about the safety and benefits of saline solution, but also have broader implications for treatment availability and costs around the world.

“Just about every patient admitted to the Intensive Care Unit (ICU) will receive intravenous fluids for resuscitation or as part of standard treatment,” said Professor Simon Finfer AO, an ICU physician and senior researcher at The George Institute.

“However, the best choice of fluid has been a longstanding issue of debate as some fluids were approved and licensed for use based on trials in small numbers of patients looking only at short term outcomes.”

Plasma-Lyte 148® is a type of intravenous fluid that more closely matches the body’s normal levels of certain minerals, known as balanced multi-electrolyte solutions, or BMES. Use of BMES has risen since concerns were raised about increased rates of kidney injury and death associated with saline, although this had not been proven in clinical trials.

To address this issue, the Plasma-Lyte 148® versUs Saline (PLUS) study recruited over 5000 patients across 53 sites in Australia and New Zealand.

Participants were adult patients admitted to ICUs in need of intravenous fluid resuscitation for their underlying medical condition. The patients were followed for a period of 90 days after treatment as previous research had shown around one in four would be at risk of dying within this timeframe.

At 90 days after the treatment, the same number of patients who had received BMES or saline had died.

Other outcomes including days of mechanical ventilation, kidney dialysis, patient survival time in the ICU and in hospital, as well as major measures of healthcare costs were similar between the groups.

“We found no evidence that using a balanced multi-electrolyte solution in the ICU, compared to saline, reduced risk of death or acute kidney injury in critically ill adults,” said Prof Finfer.

ICU is one of the most expensive aspects of healthcare and ICU resources are in high demand. Even a small difference in outcomes may result in important clinical and economic effects at the population level.

In the early 1990s, up to one in seven people were dying in ICUs across Australia and New Zealand, prompting George Institute researchers to start investigating intravenous fluid resuscitation – one of the most commonly used treatments in intensive care settings.

This started a program of fluid resuscitation research conducted in ICUs that no-one previously thought possible which has resulted in major changes to clinical treatment guidelines worldwide, preventing harmful practices and saving many lives.

The results from this study were published in the New England Journal of Medicine.

Source: EurekAlert!

Categories : Hospitals PaediatricsTags :

One-sixth of Patients in PICUs Harmed by Medications

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One-sixth of children in paediatric intensive care units (PICUs) were harmed by medications, of which most cases were preventable, according to a new study published in the British Journal of Clinical Pharmacology.

Researchers conducted an observational study across three PICUs in England over a three-month period in 2019.

The study included 302 patients and 62 adverse drug events were confirmed. The estimated incidence of adverse drug events were 20.5 per 100 patients, and most were preventable as judged by the expert panel. ADEs were commonly involved with medicines prescribing (46.8%) and caused temporary patient harm (67.7%). 

Medications for the central nervous system (22.6%), infections (20.9%), and the cardiovascular system (19.4%) were commonly implicated with adverse drug events. Analysis revealed that patients who stayed in PICU for seven or more days were more likely to experience an adverse event compared to patients with a shorter stay. 

“This multicentre study is the first of its kind in the UK hospitals, and its findings can guide future remedial interventions to reduce avoidable medication-related harm in this vulnerable patient population,” said lead author Anwar A. Alghamdi, PhD, of the University of Manchester.

Source: Wiley

Categories : COVID HospitalsTags : 1 Comment

Netcare Reports Less Severe COVID in Fourth Wave

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In a news release by Netcare, the company’s CEO Dr Richard Friedland said that more than three weeks after the discovery of the new Omicron variant in South Africa, data across its hospitals and primary healthcare facilities are demonstrating important early trends.

“Having personally seen many of our patients across our Gauteng hospitals, their symptoms are far milder than anything we experienced during the first three waves,” commented Dr Friedland.

“Approximately 90% of COVID patients currently in our hospitals require no form of oxygen therapy and are considered incidental cases. While we fully recognise that it is still early days, if this trend continues, it would appear that with a few exceptions of those requiring tertiary care, the fourth wave can be adequately treated at a primary care level.”

Rates of community transmission and hospital admission possibly decoupled
During the first three waves, the rate of hospital admissions rose in tandem with the rate of community transmission (the number of people testing positive). Dr Friedland noted that, in the first three waves of the pandemic, Netcare treated 126 000 COVID patients across its 49 acute hospitals, of which 55 000 (44%) patients required admission and 26% of these patients were treated in High Care and Intensive Care (ICU). Significantly, all COVID patients admitted were sick and required some form of oxygen therapy. The high admission rate, as well as the high percentage of patients requiring ICU or High Care indicates the severity of cases during the first three waves.

“As of today we have 337 COVID positive patients admitted (72% in the Gauteng area and 18% in KwaZulu-Natal). Of these patients approximately 10% (33 patients) are on some form of oxygenation versus 100% in the first three waves. Eight of these patients (2%) are being ventilated and of these, two are primary trauma cases that are also COVID positive.”

Netcare’s policy is to test all patients for COVID before or on admission. Patients admitted for other primary diagnoses or surgical procedures who test positive for COVID] but do not require any form of oxygenation are considered to be incidental COVID cases, which currently accounts for 90% of COVID cases now in Netcare hospitals.

“During the first three waves, when the overall community positivity rate breached 26% across South Africa, we were inundated with COVID admissions to hospital. Within Netcare we had over 2000 COVID patients in hospitals during the first wave, over 2 250 patients in hospital during the second wave and over 3000 patients in hospital during the third wave. At present the 337 patients represent a fraction compared to previous waves,” said Dr Friedland.

“The very rapid rise in community transmission as compared to previous waves may partially explain this relatively low hospital admission rate. However, there does appear to be a decoupling in terms of the rate of hospital admissions at this early stage in the evolution of the fourth wave,” suggested Dr Friedland.

Majority of patients unvaccinated
Dr Friedland added that of a total of 800 COVID positive patients that were admitted since 15 November, 75% of patients were unvaccinated. Netcare has seen seven deaths over this period in this group of patients, of which four may be ascribed to COVID. These four patients were 58 to 91 years of age and had significant co-morbidities. Of these patients, three were not vaccinated.

Dr Friedland observed that COVID patients admitted since 15 November are on average younger than those seen during the first three waves. Over 71% are under 50, with an average age of 38.5. This compares to only 40% below 50 in the first three waves, with an average age of 54.

Virtually all patients have presented with mild to moderate flu-like symptoms, including a blocked or runny nose, headache and a scratchy or sore throat and have been treated symptomatically.

Dr Friedland reiterated that the best way to support South Africa remains to take COVID extremely seriously and to be as cautious as ever.