Author: admin

  • Overwatch 2 developer Blizzard sees Marvel Rivals as competition but insists recent changes aren’t in response to its popularity

    Overwatch 2 developer Blizzard sees Marvel Rivals as competition but insists recent changes aren’t in response to its popularity

    Overwatch 2 director explained that “competition is healthy” during a recent stream but says new features were planned long before Marvel Rivals came along.

    There was a time when Overwatch was the top dog in the world of team shooters, but that feels like a lifetime ago now. Since it launched late in 2024, Marvel Rivals has been the new hotness in the genre, with Overwatch 2 feeling almost neglected by fans in the months that have passed. Now, a host of new features for Overwatch 2 are coming out, but the game’s director insists that it isn’t in response to the new competition from Marvel Rivals.

    During a stream with Overwatch streamer Jay3, Overwatch 2 director Aaron Keller was asked if Blizzard was feeling pressure to push itself and innovate in response to the success of Marvel Rivals. “I think that competition is healthy,” Keller explained. “It does force people to innovate more and to always be putting your best foot forward, but I don’t think what you’re seeing in Overwatch right now is a response to Marvel Rivals. So much of what we were doing this year – from perks to Stadium to map voting, we did full hero bans – so much of what we’re doing here and all the heroes we’re releasing has been in the works for over a year as part of a new strategy for the game to have a big annual kick-off to the year.”

    To be fair, Blizzard has probably been looking to innovate with Overwatch in recent years after a lack of story content for the game left fans feeling like the characters they fell in love with weren’t getting much love from the developer, so the idea that 2025 was always going to be a big innovative period for Overwatch 2 feels likely. However, we’d also imagine that sudden competition from Marvel Rivals has given the developer a bit more of a push to get the game back on track.


    You don’t need to beat the game to prepare for the next one—here are all the major new and upcoming games coming our way.

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  • 18 awesome images from the 2025 Astronomy Photographer of the Year awards

    18 awesome images from the 2025 Astronomy Photographer of the Year awards

    Astrophotography can make you feel two very different things: tiny and insignificant in a vast universe or absolutely and complete amazed at our vast universe. We wouldn’t fault you for feeling either way. We’re a tiny occupier of a medium-sized planet in a universe made of billions of galaxies. That universe is stunning to behold.

    For the photographers honored at the 2025 Astronomy Photographer of the Year awards, the universe is their muse. From our fiery sun to dazzling aurorae, and a sparkling Milky Way to captivating nebulae, the images capture our celestial neighborhood in beautiful detail.

    500,000-km Solar Prominence Eruption
    Credit: PengFei Chou / ZWO Astronomy Photographer of the Year

    time-lapse photo of total solar eclipse

    Total Solar Eclipse
    Credit: Louis Egan / ZWO Astronomy Photographer of the Year

    “The ZWO Astronomy Photographer of the Year competition is now in its seventeenth year and returns with an expert panel of judges from the worlds of art and astronomy,” a statement about the honorees says. “The winners of the competition’s nine categories, two special prizes and the overall winner will be announced on Thursday 11 September.”

    a green and purple aurora make a bursting shape above mountains

    The Arctic Flower
    Credit: Vincent Beudez / ZWO Astronomy Photographer of the Year

    a swirling galaxy

    NGC 2997 The Antlia Cabbage Galaxy
    Credit: Xinran Li / ZWO Astronomy Photographer of the Year

    half of the pink moon above an ancient city

    Moonrise Over Villebois-Lavalette
    Credit: Flavien Beauvais / ZWO Astronomy Photographer of the Year LRTimelapse 7.1.0 (Windows) – UNLICENSED, no commercial use allowed!

    saturn passes behind the moon in a time-lapse

    Lunar Occultation of Saturn
    Credit: Chayaphon Phanitloet / ZWO Astronomy Photographer of the Year

    the milky way over a rural area and observatory

    Looking Beyond
    Credit: Chester Hall-Fernandez / ZWO Astronomy Photographer of the Year

    the milky way arches over a desert landscape

    Into the Past
    Credit: Jim Hildreth / ZWO Astronomy Photographer of the Year Jim Hildreth

    a nebula surrounded by stars

    Radiant Canopy The Lustrous Realms of the Running Chicken Nebula
    Credit: Rod Prazeres / ZWO Astronomy Photographer of the Year

    a small fishing village with a cloudy milky way above

    Galactic Catch Salt and Vinegar With Your Cosmos
    Credit: Paul Joels / ZWO Astronomy Photographer of the Year

    swirling stars and galaxies

    Fireworks
    Credit: Bence Tóth, Péter Feltóti, Bertalan Kecskés / ZWO Astronomy Photographer of the Year

    a time-lapse of a space craft passing in front of the sun

    Encounter Within One Second
    Credit: Zhang Yanguang / ZWO Astronomy Photographer of the Year

    a comet streaks above city

    Comet Over Waikiki
    Credit: Ran Shen / ZWO Astronomy Photographer of the Year SHEN_RAN

    a deep red moon rises behind skyscrapers

    Blood Moon Rising Behind the City Skyscrapers
    Credit: Tianyao Yang / ZWO Astronomy Photographer of the Year

    a red and green aurora bursts from the horizon in a watery, rocky area

    Aurora Over Mono Lake A Rare Dance of Light
    Credit: Daniel Zafra / ZWO Astronomy Photographer of the Year Daniel Zafra Portill

    a white comet streaks across a dark sky

    Close-up of a Comet
    Credit: Gerald Rhemann and Michael Jäger / ZWO Astronomy Photographer of the Year

    two colorful nebulae swirl near each other

    A Rainbow Mosaic of the Rosette and the Christmas Tree Nebulae
    Credit: Shaoyu Zhang / ZWO Astronomy Photographer of the Year

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  • Orla Lee-Fisher heads to Warner Music to lead ‘game-changing’ dual catalogue strategy | Labels

    Orla Lee-Fisher heads to Warner Music to lead ‘game-changing’ dual catalogue strategy | Labels

    Universal Music veteran Orla Lee-Fisher has been appointed to the new role of head of dual catalogue strategy at Warner Music Group.

    She will be tasked with crafting and leading campaigns for the major’s off-roster catalogue where it has both recorded music and publishing rights

    Lee-Fisher will be based in London, reporting jointly to Kevin Gore, president, global catalogue, Recorded Music, Warner Music, and Carianne Marshall & Guy Moot, co-chairs of Warner Chappell Music.

    “She will work with WMG’s recorded music and music publishing teams to drive prioritisation, strategy, and alignment on key artists and songwriters, with a focus on creative storytelling and IP development,” said a statement. “Lee-Fisher will create impactful campaigns that drive cultural conversations, promoting some of the world’s greatest catalogues to both new and longstanding fans, while identifying and growing new revenue sources for artists, songwriters, and their estates.”

    She will also support WMG’s M&A team in purchasing catalogues and attracting estate management opportunities, as the company steps up its acquisitions activity. 

    This has the potential to be a game-changer for the way we drive engagement and convert new audiences into fans

    Orla Lee-Fisher

    Lee-Fisher has joined WMG from Universal Music Group, where she worked for more than 20 years, serving in a variety of roles, including general manager of Polydor Records and managing director of A&M Records. 

    She was most recently EVP, global marketing and worked across campaigns for leading artists including The Beatles, The Rolling Stones and Elton John.

    Kevin Gore said: “Orla is a hugely respected figure, and has led inventive, ambitious projects for some of the world’s biggest acts, connecting their music to new audiences. In this unique role, she’ll help deliver meaningful opportunities for our artists and songwriters and unlock new value for the world-class catalogs in our care.” 

    In a joint statement, Carianne Marshall & Guy Moot added: “We’re delighted that Orla is joining WMG at this pivotal time in the evolution of our catalogue offering. She’s renowned for her innovative campaigns and committed to our vision of a dynamic service for our artists and songwriters who trust us with both their publishing and recorded music rights.”

    Orla Lee-Fisher said: “Where recorded music and publishing rights overlap, Warner Music Group has made the strategic decision to manage its artists and songwriters’ catalogues more holistically. This has the potential to be a game changer for the way we drive engagement in their music and convert new audiences into fans. I can’t wait to get started.”

     

    For more stories like this, and to keep up to date with all our market leading news, features and analysis, sign up to receive our daily Morning Briefing newsletter

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  • UK launched secret scheme to relocate Afghans after data leak, documents show

    UK launched secret scheme to relocate Afghans after data leak, documents show


    London
    Reuters
     — 

    Britain set up a secret scheme to relocate thousands of Afghans to the UK after a soldier accidentally disclosed the personal details of more than 33,000 people, putting them at risk of reprisals from the Taliban, court documents showed on Tuesday.

    A judge at London’s High Court said in a May 2024 judgment first made public on Tuesday that about 20,000 people may have to be offered relocation to Britain, a move that would likely cost “several billion pounds.”

    Britain’s current defense minister John Healey said that around 4,500 affected people “are in Britain or in transit … at a cost of around 400 million pounds.”

    The government is also facing lawsuits from those affected by the breach, further adding to the ultimate cost of the incident.

    A Ministry of Defence-commissioned review of the data breach, a summary of which was also published on Tuesday, said more than 16,000 people affected by it had been relocated to the UK as of May this year.

    The British government was forced to act after the breach revealed the names of Afghans who had helped British forces in Afghanistan before they withdrew from the country in chaotic circumstances in 2021.

    The details emerged on Tuesday after a legal ruling known as a superinjunction was lifted. The injunction had been granted in 2023 after the MoD argued that a public disclosure of the breach could put people at risk of extra-judicial killing or serious violence by the Taliban.

    The dataset contained personal information of nearly 19,000 Afghans who had applied to be relocated to Britain and their families.

    It was released in error in early 2022, before the MoD spotted the breach in August 2023, when part of the dataset was published on Facebook.

    The former Conservative government obtained the injunction the following month.

    Prime Minister Keir Starmer’s center-left government, which was elected last July, launched a review into the injunction, the breach and the relocation scheme, which found that although Afghanistan remains dangerous, there was little evidence of intent by the Taliban to conduct a campaign of retribution.

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  • Underwater salty brine deposits may cause surface earthquakes

    Underwater salty brine deposits may cause surface earthquakes

    Nearly three miles beneath the eastern Pacific, researchers found pockets of super-salty water trapped in the crust along the Gofar transform fault, one of the planet’s most active undersea plate boundaries. The find promises fresh insight into why this fault delivers magnitude‑6 earthquakes with clock‑like discipline.

    The survey, led by Christine Chesley of Woods Hole Oceanographic Institution (WHOI), used controlled‑source electromagnetic (CSEM) instruments to map how easily electricity moves through the rocks, a trick that exposes hidden fluids better than standard seismic imaging.


    Chesley’s team saw bright conductive blobs only on the Nazca Plate side of the fault, hinting at a one‑sided heat engine below.

    Why transform faults matter

    Unlike familiar subduction zones where one plate dives or mid‑ocean ridges where plates split, a transform fault lets plates slide past each other sideways, often producing shallow quakes.

    Because these faults slice across spreading centers, they form a global zig‑zag seam on the seafloor. USGS

    Gofar is exceptional because its segments race by at about 140 millimeters per year, among the fastest on Earth. That speed shortens the stress‑loading cycle so scientists can watch several full earthquake rounds during a single research career.

    Instrument records show magnitude‑6 events striking Gofar every three to five years, a regularity rarely seen in tectonics. The new brine discovery offers a missing piece to that tidy schedule.

    The San Andreas in California is the archetype on land, yet its slip rate of 35 millimeters per year is a quarter of Gofar’s, underscoring how quickly energy accumulates offshore.

    Fast offshore faults therefore serve as natural laboratories for testing earthquake theories in compressed time.

    Electric clues beneath the seabed

    CSEM works by towing an energized dipole behind a ship and measuring how its signal diffuses through the crust; saltwater streaks light up because salt ions carry current far better than basalt or peridotite.

    Seafloor receivers record the returning fields, and computer inversion turns those data into a resistivity map.

    Before the cruise, models suggested a modest conductivity contrast near the fault plane caused by scattered seawater in cracks. Instead, data revealed zones thousands of feet across with conductivities orders of magnitude higher than expected.

    Seismologists later overlaid the resistivity map on existing velocity data and found little change in seismic speeds where conductivity spiked, a mismatch that further ruled out molten rock as the culprit.

    That contrast nudged the team toward a fluid explanation because brines raise conductivity dramatically without slowing seismic waves.

    The surprise hidden in brine

    “It was shocking to see such a stark contrast across the fault,” said Chesley at WHOI. One side looked almost metallic while the other stayed electrically dull.

    Laboratory work shows dense brine more than twenty times saltier than seawater can reach conductivities of 10⁻¹ ohm‑meters, explaining the signal without requiring molten rock.

    The team suggests seawater sinks deep through shattered rock, heats near magma, then separates into a heavy salt‑rich layer that pools beneath the crust.

    Phase‑separated brines have been sampled at ridge‑crest vents after eruptions, supporting the idea that hidden salt reservoirs build up in the crust until tectonics or heat flushes them upward.

    Fluids can weaken a fault by lubricating grain contacts and changing pore pressure. Concentrated brines are even more potent because their density keeps them locked at depth, ready to migrate when stress ruptures the fault.

    The Gofar pattern suggests each quake may drain a portion of the brine layer, lowering pressure and letting the fault heal until seawater refills the damage zone and the cycle restarts.

    Regular recharge could explain the three‑to‑five‑year rhythm better than friction models alone.

    Computer models that couple fluid pressure to fault friction reproduce the observed recurrence when they inject a few percent by volume of pressurized brine into the shear zone.

    Removing that fluid in simulations makes earthquakes irregular, matching the real‑world symmetry between brine and predictability.

    Brines and transform faults

    Transform faults were once thought too cool for magma, yet the asymmetric brine points to a lurking heat source on the Nazca side.

    These may be fed by melt migrating from the East Pacific Rise ridge 25 miles away. Hydrothermal models show that such off‑axis melt can drive vigorous circulation far from the ridge axis.

    Brine pockets also matter for biology. The salt‑laden fluids carry metals and energy‑rich chemicals that can feed chemosynthetic microbes when they eventually leak to the seabed, expanding habitable niches in the deep ocean.

    Schematic interpretation of electrical resistivity models in the context of the Gofar transform fault. 1) Results indicate that there is intensified fracturing along the fault plane of the transform valley. 2) Enhanced permeability from the fracturing along with a heat source in the uppermost mantle have driven deep fluid flow. 3) Melt may migrate into the transform domain or be injected into the uppermost lithosphere from the main branch of the EPR south of Gofar. 4) Hydrothermal circulation leads to phase separation and condensation of brines in the crust. Credit: Science Advances (2025)
    Schematic interpretation of electrical resistivity models in the context of the Gofar transform fault. 1) Results indicate that there is intensified fracturing along the fault plane of the transform valley. 2) Enhanced permeability from the fracturing along with a heat source in the uppermost mantle have driven deep fluid flow. 3) Melt may migrate into the transform domain or be injected into the uppermost lithosphere from the main branch of the EPR south of Gofar. 4) Hydrothermal circulation leads to phase separation and condensation of brines in the crust. Click image to enlarge. Credit: Science Advances (2025)

    Understanding their formation helps refine global heat and chemical budgets. Explorers have mapped similar conductivity anomalies beneath continental faults like the Dead Sea, implying that deep salty fluids might be a common but under‑appreciated actor in earthquake physics.

    CSEM surveys at other fast‑slipping oceanic faults could test that idea, revealing whether Gofar is unique or part of a broader pattern.

    Future research on transform faults

    “Whenever we go out and make these kinds of EM measurements, we see the seafloor through a different lens, and it almost always changes our views on the processes that shape the earth,” said Rob Evans, senior scientist at WHOI.

    The team hopes to extend lines toward the East Pacific Rise to trace the brine’s connection to melt.

    Better resolution instruments, denser receiver arrays, and joint seismic‑EM inversions could soon produce 3‑D images, turning these first snapshots into time‑lapse movies of the oceanic crust in action.

    Such movies would not only illuminate earthquake cycles but also guide mineral and microbial resource studies.

    If brines do prove to modulate fault behavior, deep‑sea monitoring could one day feed early‑warning systems, though practical sensors able to survive miles‑down pressures still lie in the future.

    The study is published in Science Advances.

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  • Pokémon Go ‘Water Festival’ 2025 event guide

    Pokémon Go ‘Water Festival’ 2025 event guide

    Pokémon Go’s “Water Festival” event for 2025 has kicked off, running from July 15-20. Obviously this event focuses on water-type Pokémon, but there’s also a few notable bonuses, including the debut of Tatsugiri, the sushi-like Pokémon from Paldea. You will need to raid for Tatsugiri if you want one of these little fishies — though note that the different forms of Tatsugiri are locked to specific regions.

    There’s a few other bonuses, such as Rainy Lure Modules lasting for two hours rather than 30 minutes and increased candy for nice throws or better. Staryu and Tirtouga also have an increased chance to be found shiny and catching the scarf-wearing Lapras from raids can yield a special seasonal background if you’re lucky.

    Below we list all the perks for Pokémon Go’s “Water Festival” 2025 event, including the premium Timed Research, Collection Challenges, and boosted spawns.

    Pokémon Go ‘Water Festival’ 2025 premium Timed Research and reward

    As part of the event, there’s a premium research for $4.99 that gives you a bunch of encounters, as well as a special pose that makes your character eat ice cream.

    Is the “Happiness in Every Scoop” premium research worth buying? It’s only worth buying if you want the pose. The rest of the rewards are pretty meh.

    ‘Happiness in Every Scoop’ step 1 of 1

    • Catch 5 water-type Pokémon (Staryu encounter)
    • Catch 10 water-type Pokémon (Feebas encounter)
    • Catch 15 water-type Pokémon (1 Premium Battle Pass)
    • Evolve a Pokémon (Clamperl encounter)
    • Evolve 3 Pokémon (1 Rainy Lure Module)
    • Send a gift with a sticker (Azumarill encounter)
    • Explore 1 km (Kingler encounter)
    • Spin 5 PokéStops or gyms (Gyarados encounter)

    Rewards: Ice Cream Pose cosmetic, Lapras (scarf) encounter, 3,000 Stardust

    Pokémon Go ‘Water Festival’ 2025 event Collection Challenges

    The following Collection Challenges will be live throughout the duration of the event:

    ‘Water Festival: Fishin’ Mission’ Collection Challenge

    • Catch a Magikarp
    • Catch a Barboach
    • Catch a Finneon
    • Catch a Gyarados

    Rewards: 5,000 XP, 2,500 Stardust, Lapras (scarf) encounter

    ‘Water Festival: She Sells Seashells’ Collection Challenge

    • Catch a Staryu
    • Catch a Krabby
    • Catch a Clamperl
    • Catch a Kingler

    Rewards: 5,000 XP, 2,500 Stardust, Lapras (scarf) encounter

    ‘Water Festival: Fishin’ Mission’ Collection Challenge

    • Catch a Slowpoke
    • Catch a Marill
    • Catch a Buizel
    • Catch a Azumarill

    Rewards: 5,000 XP, 2,500 Stardust, Lapras (scarf) encounter

    Pokémon Go ‘Water Festival’ 2025 event Field Research and rewards

    Spinning a PokéStop during the event period may yield one of these tasks:

    • Catch 5 Pokémon (Slowpoke, Staryu, or Magikarp encounter)
    • Catch 10 Pokémon (Squirtle, Buizel, or Finneon encounter)
    • Catch 10 water-type Pokémon (20 Mega Blastoise Energy or 20 Mega Gyarados Energy)
    • Catch 15 Pokémon (Lantern, Palpitoad, or Tirtouga encounter)
    • Evolve 2 water-type Pokémon (Wimpod encounter)
    • Win a raid (Lapras [scarf] encounter)

    Pokémon Go ‘Water Festival’ 2025 event boosted spawns

    These Pokémon will spawn more frequently during the event period:

    • Squirtle
    • Slowpoke
    • Krabby
    • Staryu*
    • Magikarp
    • Lanturn
    • Marill
    • Barboach
    • Feebas
    • Clamperl
    • Buizel
    • Finneon
    • Palpitoad
    • Tirtouga*
    • Wimpod

    *There is an “increased chance” of finding this shiny in the wild as part of the event.

    Pokémon Go ‘Water Festival’ 2025 event raid targets

    The following changes to the raid schedule will take place as part of the event:

    ‘Water Festival’ 2025 raid line-up

    One-star raids

    Three-star raids

    Shellder Kingler
    Ducklett Gyarados
    Tatsugiri Lapras (scarf)
    Azumarill

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  • Finerenone and the Future of Diabetes-Related Kidney Care

    Finerenone and the Future of Diabetes-Related Kidney Care

    Background

    Diabetes continues to be a growing health care concern worldwide. González-Juanatey (2023) has estimated its prevalence among adults across the globe to rise from 540 million in 2021 to 780 million in 2045.1 Diabetes is also one of the leading causes of chronic kidney disease (CKD), which further exacerbates the negative health effects associated with diabetes. Approximately 40% of individuals with diabetes have stage 1 to 4 CKD, and sequentially, approximately 40% of end-stage CKD cases can be attributed to diabetes.2 Both diabetes and CKD independently result in an increased mortality risk; however, when present concomitantly, the risk of death and development of cardiovascular disease increases 3-fold.3

    Image Credit: © ilusmedical – stock.adobe.com

    Typically, CKD management in patients with diabetes has revolved around the control of hypertension and hyperglycemia through angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and, more recently, sodium-glucose cotransporter 2 (SGLT2) inhibitors.4 Although ACEIs and ARBs are mainstay therapies for renal protection in patients with diabetes, many patients continue to present with cardiovascular and renal complications after initiation of ACEI or ARB therapy. However, SGLT2 inhibitors have recently shown promise in reducing the progression of kidney disease and cardiovascular events.1 Despite the renal protective effects of ACEIs, ARBs, and SGLT2 inhibitors, the risk of CKD progression remains among patients with diabetes, calling for new therapeutic options to be explored.

    This narrative review aims to examine the efficacy of finerenone (Kerendia; Bayer HealthCare Pharmaceuticals Inc), a selective nonsteroidal mineralocorticoid antagonist that was recently approved to treat patients with
    concomitant CKD and type 2 diabetes (T2D). This review will also compare finerenone with previously existing treatment options on the market and discuss the clinical implications of finerenone within daily practice.

    Abstract

    Précis

    Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, has shown benefit in cardiovascular and renal outcomes with lower incidence of hyperkalemia compared with steroidal mineralocorticoid receptor antagonists.

    Objectives

    This review examines the efficacy and safety of finerenone (Kerendia; Bayer HealthCare Pharmaceuticals Inc) based on the FIDELIO-DKD trial (NCT02540993), FIGARO-DKD trial (NCT02545049), and FIDELITY, a pooled analysis of FIDELIO-DKD and FIGARO-DKD. This review also discusses finerenone’s mechanism of action, pharmacokinetics, dosing, and potential for combination therapy with other standard treatments.

    Study Design

    This text is a structured literature review conducted in July 2024.

    Results

    Compared with placebo, finerenone significantly lowered the risk of kidney failure, preserved renal function, and improved cardiovascular outcomes such as heart failure, hospitalization, and cardiovascular death. Although finerenone was associated with an increased risk of hyperkalemia, adverse events were generally manageable.

    Conclusions

    FIDELIO-DKD, FIGARO-DKD, and FIDELITY collectively demonstrated finerenone’s ability to reduce the progression of chronic kidney disease (CKD) and the incidence of cardiovascular events in patients with CKD and type 2 diabetes (T2D). Finerenone fills a critical gap in CKD management and offers a promising option for improving outcomes in patients with CKD and T2D, supporting its integration into clinical practice.

    Data Collection

    A literature search was conducted on the PubMed database using medical evidence subject heading terms with the keywords finerenone, diabetes, and chronic kidney disease, accompanied by the conjunction
    and. Articles were restricted to the English language. References within articles were also reviewed to provide supporting information. The drug monograph for finerenone was accessed through Wolters Kluwer’s Lexicomp to gather basic information regarding the drug. Additionally, the package insert for finerenone was obtained through a search on the National Institutes of Health’s National Library of Medicine package insert database DailyMed.

    Mechanism of Action

    The mineralocorticoid receptor (MR) is activated by aldosterone and serves a central role in sustaining homeostasis of Na+ and K+, maintaining extracellular fluid volume, and dictating blood pressure.5 Overactivation of this receptor contributes to fibrosis and inflammation within the kidneys, which leads to a decreased estimated glomerular filtration rate (eGFR) and increased albuminuria among patients, ultimately resulting in rapid CKD progression.1,6 Finerenone, a nonsteroidal selective mineralocorticoid receptor antagonist (MRA), acts by inhibiting MR-mediated sodium reabsorption and MR overactivation in both epithelial and nonepithelial tissues of the kidney. Finerenone is highly selective for the MR and has no relevant affinity for androgen, progesterone, estrogen, and glucocorticoid receptors.6 This selectivity is attributed to its nonsteroidal properties, translating into a reduced risk for hyperkalemia compared with steroidal MRAs such as spironolactone (Aldactone; Pfizer Inc) or eplerenone (Inspra; Pfizer).5

    Pharmacokinetics

    According to the FDA package insert, finerenone reaches steady-state concentration 2 days after administration of a 20-mg dose.6 Following oral administration, it has an absolute bioavailability of 44% after metabolism.
    Finerenone has a plasma protein binding of 92%, primarily binding to serum albumin in vitro. The terminal half-life of finerenone is also relatively short, lasting approximately 2 to 3 hours. Finerenone is primarily metabolized by CYP3A4 (90%) and to a lesser extent by CYP2C8 (10%) into inactive metabolites. Approximately 80% of the administered dose is excreted in urine, and 20% is excreted in feces. No clinically significant differences were observed in patients with renal or mild hepatic impairment (Child-Pugh A). However, in patients with moderate hepatic impairment (Child-Pugh B), the mean area under the curve of finerenone was increased by 38%, indicating a decreased clearance of the drug.6

    FIDELIO-DKD Trial

    FIDELIO-DKD (NCT02540993) was a phase 3, randomized, double-blind, placebo-controlled, parallel-group, event-driven trial performed in 48 countries and territories in Africa, Asia, Australia, Europe, Latin America, and North America.7 This study aimed to evaluate the effect of finerenone on kidney and cardiovascular outcomes in patients 18 years or older diagnosed with T2D and CKD. CKD was defined as either moderately elevated albuminuria (urine albumin-to-creatinine ratio [UACR] ≥ 30 to < 300 mg/g), an eGFR of 25 or greater to less than 60 mL/min/1.73 m2 and a history of diabetic retinopathy, or severely elevated albuminuria (UACR ≥ 300 to ≤ 5000 mg/g) and an eGFR of 25 or greater to less than 75 mL/min/1.73 m2. Additionally, all patients were required to have a serum potassium level of 4.8 mEq/L or less and to have been on stable treatment with a maximum tolerated dose of an ACEI or an ARB for at least 4 weeks prior to screening.7 Exclusion criteria included patients with known nondiabetic kidney disease, chronic symptomatic heart failure with reduced ejection fraction (HFrEF), a recent history of dialysis for acute kidney failure or a kidney transplant, or uncontrolled hypertension.7

    There were 5674 patients who were analyzed in the study (n = 5674), with a 1:1 random assignment to receive finerenone or the placebo. Almost half (n = 2605, 45.9%) of these patients had a history of cardiovascular disease at baseline.7 Randomization was conducted by a computer-generated schedule based on geographical region (North America, Latin America, Europe, Asia, and other), eGFR (25 to < 45, 45 to < 60, or ≥ 60 mL/min/1.73 m2), and albuminuria categories (UACR 30 to < 300 or ≥ 300 mg/g).7 The primary composite outcome included time to first onset of kidney failure, a sustained 40% or greater decrease in eGFR from baseline over at least 4 weeks, or renal death.7 Secondary outcomes included a composite cardiovascular outcome of time to first onset of cardiovascular death, nonfatal myocardial infarction (MI), nonfatal stroke, or hospitalization for heart failure (HF).7 At baseline, 34.2%, 65.7%, and 4.6% of patients were on an ACEI, ARB, and SGLT2 inhibitor, respectively.

    Finerenone decreased the incidence of the primary composite outcome in comparison with placebo (HR, 0.82; 95% CI, 0.73-0.93). Additionally, the composite cardiovascular outcome decreased compared with the placebo (HR, 0.86; 95% CI, 0.75-0.99).7 Any adverse event (AE) occurred at similar rates between the finerenone and placebo groups (87.3% vs 87.5%, respectively). It was found that investigator-reported hyperkalemia occurred at almost double the rate with finerenone vs placebo (18.3% vs 9%, respectively), and discontinuation due to hyperkalemia occurred in 2.3% and 0.9% of patients in the finerenone and placebo arms, respectively.

    Original and Prespecified Analysis of the FIGARO-DKD Trial Evaluating Heart Failure Outcomes

    The FIGARO-DKD study (NCT02545049) was an international, randomized, double-blind, placebo-controlled, multicenter, phase 3 trial. FIGARO-DKD aimed to determine the effect of finerenone in reducing cardiovascular morbidity and mortality, in addition to standard of care, in patients with albuminuric CKD (stage 2-4 with moderately elevated albuminuria or stage 1-2 with severely increased albuminuria) and T2D.8 Eligibility criteria included patients 18 years or older, diagnosed with T2D and albuminuric CKD, treated with a maximum tolerated dose of ACEI or ARB prior to screening, and a serum potassium level of 4.8 mEq/L or less at screening. According to the supplemental document with the FIGARO-DKD trial, patients were excluded if they had chronic symptomatic HFrEF, significant nondiabetic kidney disease, stroke, transient ischemic cerebral attack, acute coronary syndrome, recent history of dialysis for acute kidney failure, a kidney transplant, or uncontrolled hypertension.8

    The original study found the primary outcome of a time-to-event analysis of composite death from cardiovascular causes, nonfatal MI, nonfatal stroke, or HF hospitalization occurred at a lower rate in the finerenone group compared with the placebo group (12.4%-14.2%; HR, 0.87; 95% CI,
    0.76-0.98).8

    In addition to the original analysis mentioned above, there was a prespecified analysis for the FIGARO-DKD trial with separate outcomes. The prespecified analysis used a 1:1 random assignment to receive finerenone or placebo, with 7352 patients included. Of this total, 571 patients had a history of HF at baseline.9 The prespecified outcomes for the analyses were time to new-onset HF, a composite of time to HF-related death or first hypertensive heart failure (HHF), a composite of time to cardiovascular death or HHF, time to first HHF, a composite of time to cardiovascular death or total HHF, a composite of time to HF-related death to total HHF, and time to total HHF. New-onset HF was defined as first HHF in patients without a history of HF at baseline.9

    The prespecified analysis of the FIGARO-DKD study found that finerenone significantly decreased new-onset HF compared with placebo (1.9% vs 2.8%; HR, 0.68; 95% CI, 0.50-0.93).9 In the overall population, the incidence of all HF outcomes was significantly lower with finerenone than placebo, including an 18% decreased risk of cardiovascular death or first HHF (HR, 0.82; 95% CI, 0.70-0.95; P = .011), a 29% decreased risk of first HHF (HR, 0.71; 95% CI, 0.56-0.90), and a 30% decreased rate of total HHF (rate ratio, 0.70 [95% CI, 0.52-0.94]).9 Finerenone’s effects were also shown not to be affected by a previous history of HF.

    FIDELITY Pooled Analysis

    FIDELITY was a pooled analysis of FIDELIO-DKD and FIGARO-DKD, combining the data from 2 phase 3, randomized, double-blind, placebo-controlled, multicenter clinical trials (Table 1).4,8-10 The purpose of the FIDELITY analysis was to perform an individual patient-level prespecified pooled efficacy and safety analysis across a broad spectrum of CKD to provide more robust estimates of safety and efficacy of finerenone compared with placebo (HR, 0.86; 95% CI, 0.78-0.95).10 The composite kidney outcome occurred in 360 (5.5%) patients receiving finerenone and 465 (7.1%) receiving the placebo (HR, 0.77; 95% CI, 0.67-0.88).10 The outcomes regarding safety were relatively similar among treatment arms; however, hyperkalemia leading to permanent treatment discontinuation occurred more often in patients receiving finerenone (1.7%) compared with placebo (0.6%).10

    FIDELIO-DKD, FIGARO-DKD, and FIDELITY Study Limitations

    These studies were well designed and reliable overall but had limitations worth mentioning. The FIDELIO-DKD study had a limited follow-up time, which, although practical in study design, may not reflect the slow and gradual progression of CKD.7 Additionally, the event rates estimated while calculating power occurred less, which may reduce the power to detect statistical difference in the sample. Further, Black patients were underenrolled in the study (3.5%) in contrast to the overenrollment of White (71.8%) and Asian (19.8%) patients, which is inconsistent with CKD and diabetes mellitus prevalence.11,12 Additionally, some populations of interest (eg, patients with advanced CKD, elevated potassium, or nonalbuminuric CKD) were excluded from enrollment, which limits
    generalizability.

    The FIGARO-DKD study shared similar concerns about limited follow-up time, exclusions of populations of interest, and reduced event rate.8 Although the FIDELITY pooled analysis provides a larger sample to detect the impact of finerenone on cardiovascular outcomes, there are limitations with this analysis.10 The FIDELITY pooled analysis contains the same concerns as its primary literature data sources (FIDELIO-DKD and FIGARO-DKD). Additionally, the pooled analysis design uses studies with different trial designs, which causes some variability in the subjects selected.

    AEs and Precautions

    As previously mentioned, nonsteroidal MRAs such as finerenone are associated with a lower risk of hyperkalemia than steroidal MRAs such as spironolactone and eplerenone.5 However, this does not translate to a complete risk elimination, as hyperkalemia may still occur in some patients taking finerenone. The FDA package insert states that 1% or more of patients on finerenone may experience hyperkalemia, hypotension, and hyponatremia.6

    In the FIDELITY study, AEs associated with a higher frequency of hyperkalemia with finerenone (14%) vs placebo (6.9%) were more frequent; however, none of these events were fatal, and the hyperkalemia resolved upon discontinuation. Wanner et al’s secondary analysis of FIDELIO-DKD and FIGARO-DKD recommends dose reduction and treatment interruption rather than phosphate binders for kidney protection.13 A small proportion of these events led to permanent treatment discontinuation (1.7% for finerenone [incidence rate, 0.66 per 100 patient-years] and 0.6% for the placebo [incidence rate, 0.22 per 100 patient-years], respectively) or hospitalization (finerenone, 0.9%; placebo, 0.2%).10 Although the risk for AEs is relatively low, patients with diminished kidney function should have their potassium levels routinely monitored throughout treatment.

    Dosing and Administration

    As depicted in Table 2, the starting dose of finerenone is 10 mg to 20 mg once daily, depending on eGFR and serum potassium thresholds. A starting dose of 20 mg once daily is initiated if the patient’s eGFR is 60 mL/min/1.73 m2 or greater; 10 mg once daily for an eGFR of 25 or greater to less than 60 mL/min/1.73 m2; and initiation of therapy is not recommended if the patient’s eGFR is less than 25 mL/min/1.73 m2.6 The target maintenance dose of finerenone is 20 mg once daily. Additionally, if the patient is started on the 10-mg once-daily dose, the dose can be increased to 20 mg once daily if the patient’s serum potassium is 4.8 mEq/L or less.6 If the patient’s serum potassium is greater than 4.8 to 5.5 mEq/L, it is recommended to maintain the patient on the 10-mg once daily dose. However, if the patient has a serum potassium level greater than 5.5, regardless of the initiation dose, withhold finerenone until potassium levels are at 5.0 mEq/L or less.6 According to the package insert, no dose adjustment is necessary for hepatic impairment.6,14

    Cost

    As of June 2024, the average wholesale price (AWP) of finerenone was $26.36 per tablet for either the 10- or 20-mg strength.14 The AWP is a reference price that estimates the average price to purchase the medication from the manufacturer.14 Further information regarding insurance coverage and pharmaceutical manufacturer patient assistance programs is yet to be released.

    Relevance to Patient Care and Clinical Practice

    Treatment for patients with diabetes and CKD includes ACEIs, ARBs, and SGLT2 inhibitors, which provide benefit by acting on hemodynamic factors and improving glycemic control; however, these drug classes do not act on the MR.2 Overactivation of the MR receptor in the context of diabetes plays a key role in developing CKD, and this pathway must be targeted to prevent further inflammation and fibrosis of renal tissue.5 Furthermore, research is currently being conducted to examine the potential synergistic relationship among these drug classes of
    treatment options.

    The CONFIDENCE trial (NCT05254002) is an ongoing study that explores the combination effect of finerenone and empagliflozin (Jardiance; Boehringer Ingelheim and Eli Lilly and Company) in patients with concomitant CKD and T2D, as it aims to investigate whether dual therapy is superior to monotherapy of either agent alone in reducing cardiovascular events.15 The findings of this study are yet to be determined; however, the results may pave the way for the possibility of dual-therapy or even triple-therapy options in the future. Additionally, a study analyzing the effect of finerenone and dapagliflozin (Farxiga; AstraZeneca and Bristol Myers Squibb) in patients with nondiabetic CKD showed that the combination was safe and reduced albuminuria compared with finerenone alone by 24% (P < .001) over 8 weeks.16

    These studies also have potential implications for finerenone’s place in therapy for patients with CKD and T2D. Per the 2024 Kidney Disease: Improving Global Outcomes guideline for CKD, finerenone is listed as an add-on therapy for patients already optimized on ACEI or ARB therapy.17 Finerenone has a reduced risk of hyperkalemia compared with spironolactone and may be preferred in patients at particularly high risk, but excluding these patients from the enrollment makes this assertion difficult without further study.7,8 FIDELITY supports the data from both studies regarding cardiovascular outcomes as primary therapy; however, use in combination with an SGLT2 inhibitor is still under investigation in the CONFIDENCE trial.10

    Conclusion

    Despite the current standard of treatment involving ACEIs, ARBs, and SGLT2 inhibitors, a significant risk of cardiovascular events remains among patients with CKD and T2D. Finerenone, a novel nonsteroidal MRA, demonstrates that it could significantly reduce the risk of cardiovascular and renal outcomes. For example, finerenone was capable of reducing the time to first onset of cardiovascular death, nonfatal MI, nonfatal stroke, and hospitalization due to HF, while also minimizing the risk of AEs such as hyperkalemia.7 With its proven efficacy and relative safety, the future of its application toward clinical use is promising and expected to grow within the coming years.

    REFERENCES
    1. González-Juanatey JR, Górriz JL, Ortiz A, Valle A, Soler MJ, Facila L. Cardiorenal benefits of finerenone: protecting kidney and heart. Ann Med. 2023;55(1):502- 513. doi:10.1080/07853890.2023.2171110
    2. Chaudhuri A, Ghanim H, Arora P. Improving the residual risk of renal and cardiovascular outcomes in diabetic kidney disease: a review of pathophysiology, mechanisms, and evidence from recent trials. Diabetes Obes Metab. 2022;24(3):365-376. doi:10.1111/dom.14601
    3. Wen CP, Chang CH, Tsai MK, et al. Diabetes with early kidney involvement may shorten life expectancy by 16 years. Kidney Int. 2017;92(2):388-396. doi:10.1016/j.kint.2017.01.03
    4. Bakris GL, Agarwal R, Anker SD, et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med. 2020;383(23):2219-2229. doi:10.1056/NEJMoa2025845
    5. Barrera-Chimal J, Lima-Posada I, Bakris GL, Jaisser F. Mineralocorticoid receptor antagonists in diabetic kidney disease – mechanistic and therapeutic effects. Nat Rev Nephrol. 2022;18(1):56-70. doi:10.1038/s41581-021-00490-8
    6. Kerendia. Prescribing information. Bayer HealthCare Pharmaceuticals; 2021. Accessed May 29, 2024. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fc726765-5d5a-4d6e-b037-b847bda9fb7c
    7. Filippatos G, Anker SD, Agarwal R, et al. Finerenone and cardiovascular outcomes in patients with chronic kidney disease and type 2 diabetes. Circulation. 2021;143(6):540-552. doi:10.1161/CIRCULATIONAHA.120.051898
    8. Pitt B, Filippatos G, Agarwal R, et al. Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N Engl J Med. 2021;385(24):2252-2263. doi:10.1056/NEJMoa2110956
    9. Filippatos G, Anker SD, Agarwal R, et al. Finerenone reduces risk of incident heart failure in patients with chronic kidney disease and type 2 diabetes: analyses from the FIGARO-DKD trial. Circulation. 2022;145(6):437-447. doi:10.1161/CIRCULATIONAHA.121.057983
    10. Agarwal R, Filippatos G, Pitt B, et al. Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis. Eur Heart J. 2022;43(6):474-484. doi:10.1093/eurheartj/ehab777
    11. Kidney disease surveillance system. CDC. Accessed May 28, 2025. https://nccd.cdc.gov/ckd/FactorsOfInterest.aspx?type=Race/Ethnicity
    12. Hassan S, Gujral UP, Quarells RC, et al. Disparities in diabetes prevalence and management by race and ethnicity in the USA: defining a path forward. Lancet Diabetes Endocrinol. 2023;11(7):509-524. doi:10.1016/S2213-8587(23)00129-8
    13. Wanner C, Fioretto P, Kovesdy CP, et al. Potassium management with finerenone: practical aspects. Endocrinol Diabetes Metab. 2022;5(6):e360. doi:10.1002/edm2.360
    14. Lexi-Comp. Finerenone. Wolters Kluwer Publishing, Inc. 2024. Accessed June 6, 2024. https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/7121026
    15. Green JB, Mottl AK, Bakris G, et al. Design of the combination effect of finerenone and empagliflozin in participants with chronic kidney disease and type 2 diabetes using a UACR endpoint study (CONFIDENCE). Nephrol Dial Transplant. 2023;38(4):894-903. doi:10.1093/ndt/gfac198
    16. Mårup FH, Thomsen MB, Birn H. Additive effects of dapagliflozin and finerenone on albuminuria in nondiabetic CKD: an open-label randomized clinical trial. Clin Kidney J. 2024;17(1):sfad249. doi:10.1093/ckj/sfad249
    17. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024;105(4):S117-S314. doi:10.1016/j.kint.2023.10.018

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  • Major Storm on the Horizon: NCDs and mental health conditions to cost South America trillions by 2050 – PAHO/WHO

    Major Storm on the Horizon: NCDs and mental health conditions to cost South America trillions by 2050 – PAHO/WHO

    Washington D.C., 15 July 2025 (PAHO) – Noncommunicable diseases (NCDs) and mental health conditions will cost South America over US$ 7.3 trillion in lost productivity and healthcare spending between 2020 and 2050, according to estimations in a new Pan American Health Organization (PAHO) report launched today. This figure—equivalent to the entire annual GDP of Latin America and the Caribbean—underscores an urgent economic and health emergency, and the need to act now to prevent disease and protect development.

    “These aren’t just health statistics, they are fiscal alarm bells,” said PAHO Director, Dr. Jarbas Barbosa. “The escalating burden of NCDs and mental health conditions has become an economic emergency – perhaps the worst economic disaster in health.”

    The report – Major storm on the horizon: Health and macroeconomic burdens of noncommunicable diseases and mental health conditions in South America – was commissioned by PAHO and developed with the analytical support of the Harvard T.H. Chan School of Public Health. It presents detailed macroeconomic projections of NCDs and mental health for ten countries: Argentina, Bolivia, Brazil, Chile, Colombia, Ecuador, Paraguay, Peru, Uruguay, and Venezuela.

    NCDs are already the leading cause of death in the Americas, claiming 6 million lives in 2021, with nearly 40% of these occurring prematurely in people under 70. Cardiovascular diseases and cancer alone account for over half of these deaths. Diabetes is also rapidly increasing, with an estimated 43 million people unable to access treatment. Mental health conditions are increasing as well, further straining already stretched health systems and productivity.

    NCDs: A growing economic and health threat

    The combined economic losses from NCDs and mental health across South America are primarily driven by premature deaths, long-term disability, and lower workforce productivity. Individual country losses projected for 2020-2050 range from US$88 billion in Uruguay to US$ 3.7 trillion in Brazil, representing up to 4.5% of GDP in some countries.

    “For decades, policymakers in the Americas and beyond have tended to undervalue health. But the world is increasingly recognizing that health has not only intrinsic, but also instrumental value,” said Dr. David E Bloom, Professor of Economics and Demography at the Harvard T.H. Chan School of Public Health and lead author of the report. “A key goal of this report is to equip PAHO and South American decision-makers with evidence to advance the needle on the priority given to large, transformative increases to health sector budgets.”

    The rise in these conditions is attributed to aging populations, as well as to increased exposure to preventable risk factors such as tobacco use, unhealthy diets, sedentary behavior, harmful alcohol use, and air pollution.

    Since 2000, obesity among adults in the region has surged by 67.5%, diabetes by 53.6%, and physical inactivity by 24.1%. Notably, about 67.5% of adults in the Americas are overweight — far above the global average of 43.5%, and the region has the highest levels of physical inactivity globally at 35.6%. These trends, if left unaddressed, will lead to further economic stagnation, inequality, and healthcare system overload.

    Progress made – but action must be stepped up

    Despite the grim projections, significant progress has been made, with cardiovascular and cancer mortality declining since 2000 due to policy and intervention. PAHO’s HEARTS initiative, implemented in 33 countries, has helped over 5.7 million people manage hypertension through primary care.

    However, the report urges countries to “go further” in three key areas and fully implement proven, cost-effective interventions:

    • Prevention: Addressing main risk factors like tobacco use, unhealthy diets and sedentary behavior can prevent many conditions. 
       
    • Early diagnosis and treatment: Health systems that detect risks early and act swiftly improve survival and economic participation. 
       
    • Financing solutions and global commitment: National health budgets must prioritize NCDs and mental health. Fiscal policies, such as excise taxes on tobacco, alcohol and sugar sweetened beverages, can fund reforms while improving population health.

    “Healthy diets and regular physical activity are medicine against NCDs,” said Dr. Barbosa. “We can prevent up to 40% of cancers by reducing tobacco use, improving diets, and promoting active lifestyles. And we can eliminate cervical cancer with vaccines, early screening, and treatment of precancerous lesions.”

    Building stronger health systems and seizing global momentum

    PAHO works to expand access to essential medicines and diagnostics, particularly through its pooled procurement mechanism, the PAHO Revolving Funds, and is also strengthening health systems to expand coverage and integrate NCD and mental health services. Currently, only 36% of people with hypertension have it under control and 58% of those with diabetes receive effective treatment.

    A pivotal opportunity to address this challenge will be the upcoming Fourth High-Level Meeting on NCDs and Mental Health in September during the United Nations General Assembly, where governments, civil society, academia and the private sector are expected to renew their commitments and adopt a new political declaration.

    PAHO urges all governments, partners, and communities to make health central to economic strategies, promote healthy lifestyles, strengthen fiscal and regulatory policies to address key risk factors, invest in primary care, and expand mental health services.

    “Health is the foundation of development, security, and prosperity,” Dr. Barbosa concluded. “Tackling NCDs and improving mental health gives us a clear path to a better future. But it requires bold, coordinated, data-driven policy. The time to act is now.”

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  • News: NATO Secretary General meets President Trump to bolster support for Ukraine, 14-Jul.-2025 – NATO

    1. News: NATO Secretary General meets President Trump to bolster support for Ukraine, 14-Jul.-2025  NATO
    2. Russia-Ukraine war updates: Kremlin needs time to ‘analyse’ Trump rhetoric  Al Jazeera
    3. Ukraine awaiting details on ‘billions of dollars’ worth of weapons promised by Trump  The Guardian
    4. Russian rouble, stock market gain after Trump’s statement on Russia  Reuters
    5. I’m ‘disappointed but not done’ with Putin, Trump tells BBC  BBC

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  • How to Recognize Burnout During Medical School, Residency

    How to Recognize Burnout During Medical School, Residency

    This transcript has been edited for clarity. 

    Let’s be real. Medical school and residency are demanding jobs, and we are going to be working way more hours than some of our peers. It is super important to take care of not only our physical health, but also our mental health during this time.

    Let’s talk about signs of burnout and some signs that you might need to take a mental reset. 

    Number one is chronic fatigue and poor sleep. If you’re noticing that you’re tossing and turning in your sleep or you are staying up with anxious thoughts and worries, this could be a sign that you are experiencing burnout.

    Also, if you suddenly find yourself getting sick more often than usual, it could be your body’s way of telling you that you are stressed, you are in a high cortisol state, and as a result, your immune system isn’t able to fight off illness as best as it can. Then, of course, there are emotional signs, too, like feeling sad, lonely, and isolated.These can all be signs of early-onset depression. 

    It is super important to recognize signs of burnout during residency and medical school because there is help if you need it.

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