Finerenone Outperforms Spironolactone for Heart Failure Exacerbation in HFpEF, With Nihar Desai, MD, MPH

Finerenone use was associated with lower risks of heart failure exacerbation and all-cause mortality compared to spironolactone in patients with 

heart failure with preserved ejection fraction (HFpEF)

, based on a recent retrospective cohort study.

Phase II studies have associated finerenone with reduced risks of hyperkalemia and deterioration in kidney function when compared with spironolactone and eplerenone in patients with 

. The recent FINEARTS-HF trial has also highlighted finerenone, investigating its efficacy in reducing heart failure hospitalization in patients with HFpEF. However, despite these trials, finerenone does not yet have an approved indication for HFpEF.

“Spironolactone is a very important and highly effective therapy. The evidence to support its use in patients with reduced ejection fraction heart failure are unequivocal,” Nihar Desai, MD, MPH, associate professor of medicine at Yale School of Medicine and a contributing author in this study, told 

 in an exclusive interview. “However, the question arises regarding mid-range and preserved ejection fraction patients; spironolactone actually doesn’t have that as part of its indications. In contrast, using finerenone in those patients with an EF of ≥40% saw substantial clinical benefits.”

Desai and colleagues performed a retrospective observational cohort study via the TriNetX database, identifying all patients with a diagnosis of HFpEF. The team notes the potential limitations of TriNetX’s lack of additional datapoints, such as echocardiographic parameters and NYHA functional class, and the possible misclassification of patients within the HFpEF category.

Patients were then further stratified based on finerenone or spironolactone use within 1 year of diagnosis. Concomitant spironolactone and/or finerenone use was excluded in both cohorts. The primary outcomes of the analysis were first or subsequent heart failure exacerbations, acute myocardial infarction, hypokalemia, ischemic stroke, all-cause mortality, sudden cardiac death, and hyperkalemia within a 1-year follow-up period. Acute myocardial infarction and ischemic stroke were included as secondary endpoints.

Ultimately, the study included 254,417 patients with HFpEF; after propensity score matching, 491 patients were enrolled in each cohort, yielding a total of 982 participants. During the follow-up, the finerenone arm saw substantially lower statistically significant risk of heart failure exacerbation (55.2% vs 72.9%; HR, 0.63; 95% CI, 0.54-0.74; 

 <.001). Additionally, finerenone was associated with lower risks of all-cause mortality compared to spironolactone (4.1% vs 11.8%; HR, 0.38; 95% CI, 0.23-0.64; 

Investigators also recorded a lower risk of hypokalemia in the finerenone cohort versus spironolactone (8.4% vs 15.1%; HR, 0.58; 95% CI, 0.4-0.85; 

 <.001). Despite not being statistically significant, similar trends were noted for hyperkalemia (13.8% vs 16.1%; HR, 0.96; 95% CI, 0.69-1.33). Sudden cardiac death was rare across both cohorts, affecting only 1 patient in the spironolactone arm and 10 in the finerenone arm.

Desai and colleagues also performed subgroup analyses for patients with CKD and 

. Those with CKD saw substantially lower risk of heart failure exacerbation with finerenone versus spironolactone (59.4% vs 74.1%; HR, 0.63; 95% CI, 0.53-0.74; 

 <.001). The diabetes mellitus subgroup also saw lower heart failure exacerbation risk with finerenone (56.6% vs 74%; HR, 0.59; 95% CI, 0.5-0.69; 

Despite the strength of these data, this study is solely hypothesis-generating. Desai and colleagues encourage further research, including head-to-head randomized controlled trials of finerenone versus spironolactone in HFpEF, to inform the debate over its safe and efficacious use in real-world settings.

“If we’re going to follow the evidence and what the literature would tell us, finerenone would be a primary strategy in those patients with an EF ≥40% if finerenone is not available, or if there are other barriers that might restrict the use of finerenone,” Desai said. “Spironolactone is maybe an option B for a patient on the edges, but for most of our patients, we believe the data – finerenone seems to be the most effective MRA for those patients.”

Editor’s Note: Desai reports disclosures with Amgen, AstraZeneca, Novartis, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, and others.

Almas T, Shelig M, Al-Hindawi A, et al. Steroidal versus non-steroidal mineralocorticoid receptor antagonists in heart failure with preserved ejection fraction: A propensity-matched multi-network nationwide cohort study. European Heart Journal - Quality of Care and Clinical Outcomes. Published online January 30, 2026. 

Pitt B, Kober L, Ponikowski P, et al. Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial. Eur Heart J. 2013;34(31):2453-2463. 

McCausland FR, Vaduganathan M, Claggett BL, et al. Finerenone and Kidney Outcomes in Patients With Heart Failure: The FINEARTS-HF Trial. J Am Coll Cardiol. 2025;85(2):159-168. 

Videos

Desai discusses his recent observational cohort study indicating finerenone’s substantial reduction of heart failure exacerbation risk in patients with HFpEF.

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Cardiology condition center page is a comprehensive resource for clinical news and insights on cardiovascular and cardiometabolic diseases. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for heart disease and cardiovascular events, as well as associated diabetes, renal failure, and more...

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The HCPLive heart failure page is a resource for medical news and expert insights on HF. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments for heart disease, reduced and preserved ejection fraction, and more.

Alex Hillenbrand is an assistant editor for 

. She earned her BA in English from Lafayette College in 2023 and went on to write for pop culture, entertainment, and sports media outlets before joining MJH Life Sciences in 2025. In her free time, Alex enjoys cooking, going on walks, and meeting new people. Contact her at mjhlifesciences.com.

are 8 clinical recommendations and 1 research-only recommendations to guide management of relapsed or refractory 

 in adolescents and young adults (AYAs), emphasizing immunotherapy approaches.

, the 2026 Guidelines for Management of Relapsed/efractory ALL in AYAs underscore a paradigm shift toward immunotherapies, including blinatumomab and inotuzumab, over chemotherapy while reinforcing the importance of patient-informed, individualized clinical decision-making.

AYAs sit in a unique pocket of clinical care management, especially in ALL, and are considered a high-risk population. This distinction stems from their distinct disease biology, including increased rates of T-ALL and Philadelphia-like (Ph-like) ALL compared with pediatric patients. Historically, AYAs have experienced inferior outcomes, driven in part by gaps between pediatric and adult treatment paradigms, challenges with treatment adherence, and higher rates of treatment-related toxicity.

Although adoption of pediatric-inspired regimens has been associated with improved survival among AYAs compared with traditional adult protocols, outcomes in the relapsed or refractory setting remain suboptimal, highlighting an ongoing treatment gap.

To address the gap in AYAs patients, a multidisciplinary panel of hematologists, AYA psychosocial care specialists, pharmacists, methodologists, and patient representatives created these guidelines. They used Grading of Recommendations Assessment, Development and Evaluation (GRADE), including GRADE Evidence-to-Decision frameworks, for evidence assessment and recommendation formation.

The panel focused on immunotherapy, targeted therapies, allogeneic hematopoietic stem cell transplantation (allo-HSCT), and central nervous system (CNS)-directed therapy.

In refractory or relapsed ALL, the panel recommends the use of targeted agents, such as blinatumomab and/or inotuzumab, to induce remission due to their efficacy and potentially favorable toxicity profiles. Although the evidence for survival benefits, remission rates, and reduced toxicity is of low certainty, panelists consider it relevant in guiding treatment.

Specifically, the guidelines recommend blinatumomab over chemotherapy for patients with first relapse or refractory B-cell ALL, based on low-certainty evidence demonstrating increased remission rates, improved survival, and reduced toxicity. Inotuzumab is similarly recommended over chemotherapy in this setting. These agents are increasingly incorporated into contemporary treatment strategies and may serve as bridges to subsequent therapies, including allo-HSCT, depending on patient- and disease-specific factors.

In contrast, while emerging therapies such as daratumumab and CD7-directed CAR T-cell approaches have demonstrated promising activity, particularly in T-ALL, the panel concluded the current evidence is insufficient to support routine use outside of clinical trials. This limitation is especially relevant for AYAs with relapsed or refractory T-ALL, including both nelarabine-naïve and nelarabine-exposed patients.

Overall, the panel acknowledged meaningful progress in immunotherapy for relapsed or refractory T-ALL but emphasized that available data do not yet justify widespread adoption beyond the clinical trial setting. Key evidence gaps include the lack of head-to-head comparisons between immunotherapies and chemotherapy, as well as a shortage of prospective trials designed to define optimal sequencing, combinations, and treatment duration tailored specifically to AYAs.

Accordingly, the guidelines issue a research-only recommendation that, when feasible, individuals with relapsed or refractory T-ALL be offered enrollment in clinical trials evaluating novel agents such as daratumumab, CAR T-cell therapies, BCL-2 inhibitors, tyrosine kinase inhibitors, and other emerging approaches. Further research is encouraged to assess both short- and long-term outcomes, including toxicity, fertility, and health-related quality of life.

DuVall AS, McNeer J, Cheung MC, et al. ASH 2026 Guidelines for Frontline Management of Acute Lymphoblastic Leukemia in Adolescents and Young Adults. 

. Published online February 11, 2026. doi:

https://doi.org/10.1182/bloodadvances.2021006469

Wang AY, Muffly LS, Stock W. Philadelphia Chromosome–Negative B-Cell Acute Lymphoblastic Leukemia in Adolescents and Young Adults. 

. Published online January 29, 2020:JOP.19.00197. doi:

Makhani S, Khalid N, Robinson K, Agarwal A, Hussain M, Goel R. Predictors of long-term survival in adolescents and young adults with acute lymphoblastic leukemia: 20 years of insight from a nationally representative database. 

Articles

ASH 2026 guidance for adolescents and young adults with relapsed/refractory ALL prioritizes immunotherapy-based salvage over conventional chemotherapy, reflecting distinct AYA biology and historically inferior outcomes. A multidisciplinary panel used GRADE methods to craft eight clinical recommendations plus one research-only recommendation, spanning targeted agents, transplant integration, and CNS-directed therapy. For first relapse or refractory B-ALL, blinatumomab and inotuzumab are favored despite low-certainty evidence, citing improved remission, survival, and toxicity profiles. For T-ALL, routine use of emerging agents remains trial-limited pending stronger comparative and sequencing data.

The American Society of Hematology released new 2026 Guidelines for Management of Relapsed/Refractory ALL in AYAs, discussing immunotherapy and personalized decision making. 


Hematology

ASH Releases 8 Recommendations for Relapsed, Refractory Acute Lymphoblastic Leukemia in Adolescents, Young Adults

Ashfaq Marghoob, MD, is a dermatologist specializing in the diagnosis and treatment of cancers of the skin and the director of the Memorial Sloan-Kettering regional skin cancer clinic.

Tips on Dermoscopy and Skin Cancer Detection, With Ashfaq Marghoob, MD

, highlighting dermoscopy of special sites and skin cancer detection, with its presenter emphasizing the unique microanatomy of palms, facial skin, soles, and nails.

This workshop was presented by Ashfaq Marghoob, MD, a dermatologist specializing in the diagnosis and treatment of skin cancer and the director of the Memorial Sloan-Kettering regional skin cancer clinic. Marghoob spoke with 

’s editorial team regarding the most important points highlighted in his dermoscopy workshop.

“The first and most important thing was to recognize that special sites in dermoscopy are defined by areas of the skin where the microanatomy differs from the rest of the non-glabrous skin on your body, except the face. So the non-glabrous skin, obviously, is everywhere other than palm soles, mucous membranes, and nails. But on the non-glabrous skin, the face is a special site, because the microanatomy on the face differs, and that is also true for the glabrous areas of the body.”

In his discussion of the dermoscopy workshop, Marghoob described the microanatomy of these areas as different than the rest of the body. The take-home point he highlighted for facial skin was the recognition of facial skin as having an attenuated and rich pattern.

“The next thing that we stressed was that melanoma on the face is derived from the stem cells that reside in the hair bulge, and therefore early melanoma is follicular centric,” Marghoob said. “So there are hyperpigmented follicular openings, irregularity around the follicle, and everything is around the follicle. The extension is from the follicle outward, as opposed to with benign lesions, which will be interfollicular and will be where the changes are, not in the follicle.”

Later in his discussion, Marghoob highlighted palms and soles exhibition of dermatoglyphics, with melanoma pigmentation on ridges and benign lesions in furrows. He further described nail unit dermoscopy highlights, noting clinical features such as nail dystrophy and triangular band shapes, which can overshadow dermoscopic findings.

For any additional information on the topics highlighted in Marghoob’s talk, view the full interview segment posted above.

The quotes used in this video summary were edited for clarity.

Marghoob reported no relevant financial disclosures of note.

Marghoob A. Dermoscopy Workshop: Special Site Dermoscopy. Presented at the 2026 Maui Derm Hawaii Conference, January 25-29.

Ring C, Cox N, Lee JB. Dermatoscopy. Clin Dermatol. 2021 Jul-Aug;39(4):635-642. doi: 10.1016/j.clindermatol.2021.03.009. Epub 2021 Mar 19. PMID: 34809768.


This interview with Marghoob was held on-site at Maui Derm, highlighting tips on dermoscopy and skin cancer detection from Marghoob’s workshop presentation.

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The HCPLive dermatology page is a resource for medical news and expert insights on skin disease. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments for dermatologic conditions, and more.

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 conference coverage page features articles, videos, and expert-led live coverage from major medical meetings throughout the year.

Jonggi Choi, MD, PhD, is an associate professor at Asan Medical Center, University of Ulsan College of Medicine, and visiting scholar at Mass General Hospital.

Shifting the Clinical Conversation Around Statins in PBC, With Jonggi Choi, MD, PhD

For many years, concerns about hepatotoxicity have contributed to hesitancy around prescribing statins in patients with chronic liver disease. While recent research has largely addressed and dispelled these concerns, a lack of studies specific to cholestatic conditions like 

A new study from Jonggi Choi, MD, PhD, and colleagues points to a reduced risk of hepatic decompensation and major liver events in patients with PBC taking statins, supporting a potential protective effect in this population.

, Choi addressed longstanding cautions around statins in liver disease head-on, explaining how his team’s findings may help shift the clinical conversation.

Check out part 1 of our discussion with Choi 

“Historically, there has been some concern and hesitancy among physicians prescribing statins in patients with chronic liver disease,” Choi acknowledged, noting that even though multiple studies have demonstrated the general safety of statins in chronic liver disease, apprehension still influences day-to-day prescribing decisions.

His study, which focused largely on stable patients with PBC, most of whom were already receiving ursodeoxycholic acid (UDCA) and had preserved liver function, found no evidence of harm associated with statin use. On the contrary, statins were linked to a significantly lower risk of future liver decompensation.

However, Choi emphasized that the findings should not be interpreted as definitive proof supporting the use of statins specifically for liver protection. Despite the use of a rigorous target trial emulation design to strengthen causal inference, he notes that the data remain observational. Still, he says the study should provide clinicians with reassurance that statins do not need to be withheld in patients with stable PBC or other chronic liver diseases when there is a clear cardiovascular indication.

Looking ahead, Choi outlined several critical next steps. Strengthening causal inference remains a priority, with confirmation ideally coming from randomized controlled trials.

He also highlighted the need for better phenotyping to determine whether statin benefits vary by fibrosis stage, biochemical response to UDCA, or coexisting metabolic risk factors. According to Choi, mechanistic studies are equally important, particularly to clarify how statins’ anti-inflammatory and antifibrotic effects interact with autoimmune cholestatic injury in PBC.

“I see this study as a strong signal-generating step that opens the door for both clinical trials and more refined observational narratives,” Choi said.

Editors’ Note: Choi reports relevant disclosures with Gilead.

Choi J, Xu J, Nguyen VH, et al. Association between statin use and hepatic decompensation in patients with primary biliary cholangitis: A target trial emulation study. 

Choi explains longstanding hesitancy around statin use in chronic liver disease, particularly cholestatic diseases like PBC, and how his research challenges these sentiments.

Hepatology

Cholangitis

cholangitis page, resources on the topics of medical news and expert insight into cholangitis can be found. Content includes articles, interviews, videos, podcasts, and breaking news on research, treatment, and drug development in PBC, PSC, and more!

Victoria Johnson joined the MJH Life Sciences in 2020 and has written for NeurologyLive, CGTLive, and now HCPLive. You can reach her at vjohnson@mjhlifesciences.com

The past several years have marked a pivotal shift in the treatment of chronic obstructive pulmonary disease, driven by breakthroughs that began reshaping clinical practice in 2024 and continued to evolve through 2025 and into 2026. Long managed primarily with bronchodilators and inhaled steroids, chronic obstructive pulmonary disease (COPD) has entered a new era with the approval of targeted biologic therapies such as dupilumab and mepolizumab.

 These agents, already well established in asthma, have expanded treatment possibilities for a subset of COPD patients defined not just by symptoms, but by underlying biology—particularly type 2 inflammation and eosinophilia.

Against this backdrop, a virtual clinical forum convened by 

and led by David G. Hill, MD, Director, Clinical Research, Waterbury Pulmonary Associates, brought together pulmonologists and advanced practice providers to share their experiences navigating the changing COPD and asthma landscape. The discussion centered on how frontline clinicians are identifying appropriate patients, integrating biomarkers like blood eosinophils into routine care, and balancing emerging evidence with the realities of payer access, patient adherence, and diagnostic uncertainty. 

As biologics move from theory into exam rooms, the forum highlighted both optimism and restraint. Panelists described meaningful improvements in select patients—particularly those with asthma–COPD overlap or steroid-responsive disease—while acknowledging that most COPD patients still lack disease-modifying options. The dialogue underscored a broader shift underway: from treating COPD as a single entity to approaching it as a collection of phenotypes requiring individualized, biologically informed care.

Throughout the forum, clinicians emphasized how recent biologic approvals have changed the way they think about asthma and COPD, particularly for patients who fall into gray areas such as asthma–COPD overlap. Blood eosinophils, bronchodilator responsiveness, and exacerbation patterns have become critical tools for identifying candidates for therapy escalation. Dupilumab emerged as a commonly favored option due to its mechanism, safety profile, and broader labeling, while mepolizumab was viewed as beneficial for select patients with higher eosinophil counts. Despite these advances, panelists repeatedly noted that access barriers, dosing logistics, and payer restrictions often shape real-world decision-making as much as clinical factors.

“I grew up in the era of mild persistent, moderate persistent, severe persistent type [asthma]. We didn't phenotype. We kind of just went with how severe they were and the more severe, the more steroids you gave. I think that has changed. We always knew we didn't want to use too much steroids, but we really didn't have the option. I think now with newer therapies, we have ways to minimize steroid usage, not in everybody, but… much more than we used to,” Paul Strachan, MD, Director of the Stony Brook Pulmonary Hypertension Center, said during the forum.

At the same time, the discussion made clear that biologics address only a fraction of the unmet need in COPD. Most patients continue to live with neutrophilic disease, progressive emphysema, and persistent symptoms that current therapies do not adequately control. Looking ahead, participants called for better biomarkers, earlier disease intervention, and a more personalized approach modeled after advances in oncology. From the frontline perspective, the future of asthma and COPD care lies not just in new drugs, but in redefining how these complex diseases are classified, studied, and treated.

Dupixent® (dupilumab) Approved in the U.S. as the First-ever Biologic Medicine for Patients with COPD. Regeneron Pharmaceuticals, Inc. September 27, 2024. https://www.globenewswire.com/news-release/2024/09/27/2954552/0/en/Dupixent-dupilumab-Approved-in-the-U-S-as-the-First-ever-Biologic-Medicine-for-Patients-with-COPD.html.

Johnson V. FDA Approves Mepolizumab for Eosinophilic COPD. News release. Article. HCPLive. https://www.hcplive.com/view/personalized-copd-treatment-lessons-biologic-trials-clinical-practice

Biologic therapies have begun reshaping COPD management by extending asthma-proven agents, including dupilumab and mepolizumab, to biologically defined COPD subsets characterized by type 2 inflammation and eosinophilia. Clinicians are increasingly using blood eosinophils, bronchodilator responsiveness, and exacerbation history to identify candidates, particularly in asthma–COPD overlap and steroid-responsive phenotypes. Real-world implementation remains constrained by payer policies, dosing logistics, and adherence challenges. Despite momentum, most COPD remains non–type 2, with persistent unmet need for disease-modifying strategies, better biomarkers, and earlier intervention.

Asthma

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Pulmonology

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From Inhalers to Immunology: Real-World Insights on Biologics in Asthma and COPD

Zhiyuan Wu, PhD, is a postdoctoral research fellow at the Harvard T.H. Chan School of Public Health.

Wu discusses his recent study spotlighting food source and quality as a more significant influence on CHD risk compared to simply cutting carbs or fat.

Structural Heart Disease

Food Quality More Important Than Carbs or Fat for Preventing Heart Disease, With Zhiyuan Wu, PhD

Upstream Bio announced positive topline results from the phase 2 VALIANT trial evaluating the efficacy and safety of verekitug in adults with severe asthma.


Allergy

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VALIANT: Verekitug Reduces Average Annual Asthma Flare-Ups in Phase 2 Trial

David Golden, MD, clinical associate professor of medicine at Johns Hopkins University School of Medicine.

Part 4 highlights how expanding epinephrine delivery options can reduce barriers, support earlier administration, and improve real-world anaphylaxis outcomes.

Special Reports

Anaphylaxis

The HCPLive anaphylaxis page is a comprehensive resource for clinical news and insights on acute allergic reactions. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for preventing anaphylaxis, and more.

Expanding Epinephrine Options to Reduce Barriers, Improve Early Use

In this segment, experts emphasize the importance of giving an infant experiencing anaphylaxis epinephrine at whatever dose may be available rather than delaying treatment.


Recognizing, Managing Anaphylaxis in Infants

In the second part of the special report, panelists delink epinephrine use from mandatory emergency department visits.

Delinking Epinephrine Use From Mandatory ED Visits

In the opening segment of this special report, panelists discuss updated anaphylaxis guidelines and early management priorities.

Updated Anaphylaxis Guidelines, Early Management Priorities 

Emily Aman, MPH, from the University of Rochester Medical Center

In an interview with HCPLive, Emily Aman, MPH, and Rachel White, share that most marginalized children with uncontrolled asthma miss specialist visits despite caregiver support due to existing barriers.

Caregiver Perceptions Highlight Gaps in Pediatric Asthma Specialist Access

Adam Bress, PharmD, MS, is a professor of the department of population health sciences at the University of Utah School of Medicine and director of the Integrating Medicine & Policy to Achieve Healthcare Transformation (IMPACT HSR) program.

Bress highlights the potential shortcomings of relying on the Apple Watch as a diagnostic tool for hypertension, discussing its potential for false negatives.

Hypertension

The HCPLive hypertension page is a resource for medical news and expert insights on high blood pressure. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments for hypertension, and more.

Apple Watch Hypertension Notifications May Give False Reassurance, With Adam Bress, PharmD, MS

Choi describes existing evidence on statin use in patients with liver disease and reviews his new research about their potential utility in PBC.

Statins and Improved Long-Term Liver Outcomes in PBC, With Jonggi Choi, MD, PhD

Tim Smith joined the MJH Life Sciences team in 2022 and is currently an associate editor for HCPLive. He is also the executive producer of two podcasts: Skin of Color Savvy and The Medical Sisterhood. Previously, he was the producer of the Lungcast podcast. He graduated from UC Berkeley and worked in multimedia journalism as a staff writer prior to joining MJH. You can contact him at tsmith@mjhlifesciences.com.

These data highlight the impact of rezpegaldesleukin therapy on adults with moderate-to-severe atopic dermatitis in the phase 2b REZOLVE-AD study.

Atopic Dermatitis

Atopic Dermatitis condition center page, audiences can find a variety of coverage mediums for medical news and updates, including articles, video interviews, podcasts, and breaking news on dermatitis research, treatment, and drug development.

Latest News

Finerenone Outperforms Spironolactone for Heart Failure Exacerbation in HFpEF, With Nihar Desai, MD, MPH

ASH Releases 8 Recommendations for Relapsed, Refractory Acute Lymphoblastic Leukemia in Adolescents, Young Adults

Tips on Dermoscopy and Skin Cancer Detection, With Ashfaq Marghoob, MD

Shifting the Clinical Conversation Around Statins in PBC, With Jonggi Choi, MD, PhD

From Inhalers to Immunology: Real-World Insights on Biologics in Asthma and COPD