Clinical considerations and recommended diagnostic algorithm for the differential diagnosis of conjunctivitis: a clinical practice review

Commentary

Over the last decade, there have been tremendous advances in genetic testing through the development of next-generation sequencing (NGS) technologies. This has led to plummeting costs of testing making it possible to test for multiple genes simultaneously at a cost comparable to testing for 1–2 genes through older Sanger sequencing technology. As a consequence, clinical practice has been greatly impacted resulting in the need to develop new models for genetic counseling and informed consent. This chapter will highlight clinical considerations when using NGS to evaluate for inherited cancer predisposition. Topics to be covered include factors to consider when conducting NGS tests, considerations of various multigene tests available, resulting paradigm shifts, and other clinical and laboratory considerations when testing is conducted. We will conclude with the evolving role of genetics health professionals given the emerging landscape and highlight the importance of education and outreach efforts.

BackgroundMedication-related osteonecrosis of the jaw (MRONJ), which was first reported as bisphosphonate-related osteonecrosis of the jaw (BRONJ) in bisphosphonate users, is a rare but severe soft and hard tissue disease induced by several types of medications. There has been a deluge of information about MRONJ, such as epidemiology, risk factors, clinical recommendations for dental treatment to prevent it, and treatment strategies in medication-prescribed users. The aim of this study was to comprehensively review recent articles and provide the current scientific information about MRONJ, especially clinical considerations or recommendations for dental treatment to prevent its occurrence.Materials and methodsThe current literature review was mainly based on 14 systematic reviews with or without meta-analysis, 4 position papers, 1 consensus statement, 1 clinical guideline, and 2 clinical reviews regarding MRONJ after a PubMed database and manual searches according to inclusion and exclusion criteria. Moreover, 53 articles were selected by manual search in regard to all references from selected articles and other articles identified on the PubMed search, irrespective of publication date, and inclusion and exclusion criteria.ResultsThe incidence and prevalence of MRONJ are relatively low, although they are clearly higher in cancer patients receiving high-dose antiresorptive agents or angiogenesis inhibitors rather than osteoporosis patients receiving oral bisphosphonates or denosumab. There are many types of local, systemic, and other risk factors for the development of MRONJ. Clinical recommendations are provided for each clinical situation of patients to prevent MRONJ. There are also treatment strategies for MRONJ in each stage.ConclusionsGeneral dentists should perform appropriate dental treatment to prevent MRONJ in the patients prior to or when receiving medications that could induce MRONJ. Moreover, there are treatment strategies for MRONJ in each stage that oral surgeons could follow. Adequate and updated clinical information regarding MRONJ based on scientific data is required whenever possible.

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The global rise in bariatric surgery among women of reproductive age has led to an increasing number of pregnancies occurring after significant metabolic and anatomical changes. While bariatric surgery improves fertility and metabolic health, its long-term impact on hepatobiliary physiology during pregnancy remains incompletely understood. This narrative review explores the hepatobiliary implications of pregnancy following bariatric surgery, summarizes maternal and fetal outcomes, and highlights clinical considerations for multidisciplinary management. A comprehensive search of PubMed, Scopus, and Web of Science databases was conducted for studies published between 2000 and 2025, using the terms “bariatric surgery,” “pregnancy,” “liver function,” “gallstones,” “cholestasis,” and “maternal outcomes.” Relevant clinical studies, reviews, and case reports were analyzed and synthesized narratively. Animal studies, non-English-language articles, and studies without pregnancy or hepatobiliary outcomes were excluded from analysis. Pregnancy after bariatric surgery is associated with improved metabolic and obstetric profiles compared with pregnancies in untreated obesity. However, rapid weight loss and altered bile acid metabolism predispose patients to hepatobiliary complications, including gallstone formation, biliary colic, and nutritional liver dysfunction. Liver function test abnormalities are frequent but often transient. Early conception (<12 months post-surgery) increases the risk of micronutrient deficiencies and hepatocellular stress. Close monitoring, nutritional optimization, and coordinated care among obstetricians, surgeons, and hepatologists are essential. Pregnancy following bariatric surgery presents unique hepatobiliary challenges requiring individualized, multidisciplinary management. Further research is needed to elucidate the pathophysiologic mechanisms linking altered bile acid metabolism and hepatic adaptation in this population.

Treatment of opioid use disorder (OUD) with buprenorphine has evolved considerably in the last decade as the scale of the OUD epidemic has increased along with the emergence of high-potency synthetic opioids (HPSOs) and stimulants in the drug supply. These changes have outpaced the development of prospective research, so a clinical consideration document based on expert consensus is needed to address pressing clinical questions. This clinical considerations document is based on a narrative literature review and expert consensus and will specifically address considerations for changes to the clinical practice of treatment of OUD with buprenorphine for individuals using HPSO. An expert panel developed 6 key questions addressing buprenorphine initiation, stabilization, and long-term treatment for individuals with OUD exposed to HPSO in various treatment settings. Broadly, the clinical considerations suggest that individualized strategies for buprenorphine initiation may be needed. The experience of opioid withdrawal negatively impacts the success of buprenorphine treatment, and attention to its management before and during buprenorphine initiation should be proactively addressed. Buprenorphine dose and dosing frequency should be individualized based on patients' treatment needs, the possibility of novel components in the drug supply should be considered during OUD treatment, and all forms of opioid agonist treatment should be offered and considered for patients. Together, these clinical considerations attempt to be responsive to the challenges and opportunities experienced by frontline clinicians using buprenorphine for the treatment of OUD in patients using HPSOs and highlight areas where prospective research is urgently needed.

Antibody-drug conjugates (ADCs) represent a promising class of anticancer therapies with rapidly expanding development. However, regulatory approval remains complex due to their unique pharmacological properties. We systematically analyzed U.S. Food and Drug Administration (FDA)’s clinical pharmacology considerations across all approved ADCs to identify consistent regulatory patterns and inform future development strategies. We comprehensively reviewed 13 FDA-approved ADCs as of March 2025, examining clinical pharmacology and/or multidisciplinary reviews from Drugs@FDA. Six key parameters from the FDA’s Clinical Pharmacology Considerations for Antibody-Drug Conjugates: Guidance for Industry (2024) were evaluated: bioanalytical methods, exposure–response relationships, intrinsic factors, extrinsic factors, QTc prolongation, and immunogenicity. For each parameter, we assessed: 1) submission completeness, 2) FDA’s assessment, and 3) whether they led to regulatory actions such as post-marketing requirements/commitments (PMRs/PMCs). All 6 clinical pharmacology considerations were consistently applied throughout ADC approval history, well before the issuance of formal guidance. The FDA maintained particularly rigorous standards across a few critical domains. Exposure—response interpretation considering critical safety issues, intrinsic factor analyses—particularly hepatic impairment and racial variations—and validated immunogenicity assays including the neutralizing antibody emerged as primary scrutiny points. These factors repeatedly triggered similar PMRs/PMCs across multiple ADCs, underscoring their regulatory significance. Core clinical pharmacology parameters consistently shape FDA assessments of ADCs. Proactive alignment with regulatory expectations can streamline development, mitigate potential delays, and reduce post-marketing obligations. Our historical analysis provides strategic insights that may support clinical investigators for optimizing future ADC development.

To provide an overview of clinical recommendations regarding genomic medicine relating to pain management and opioid use disorder. A literature review was conducted using the search terms pain management, pharmacogenomics, pharmacogenetics, pharmacokinetics, pharmacodynamics, and opioids on PubMed (inception to February 1, 2021), CINAHL (2016 through February 1, 2021), and EMBASE (inception through February 1, 2021). All relevant clinical trials, review articles, package inserts, and guidelines evaluating applicable pharmacogenotypes were considered for inclusion. More than 300 Food and Drug Administration-approved medications contain pharmacogenomic information in their labeling. Genetic variability may alter the therapeutic effects of commonly prescribed pain medications. Pharmacogenomic-guided therapy continues to gain traction in clinical practice, but a multitude of barriers to widespread pharmacogenomic implementation exist. Pain is notoriously difficult to treat given the need to balance safety and efficacy when selecting pharmacotherapy. Pharmacogenomic data can help optimize outcomes for patients with pain. With improved technological advances, more affordable testing, and a better understanding of genomic variants resulting in treatment disparities, pharmacogenomics continues to gain popularity. Unfortunately, despite these and other advancements, pharmacogenomic testing and implementation remain underutilized and misunderstood in clinical care, in part because of a lack of health care professionals trained in assessing and implementing test results. A one-size-fits-all approach to pain management is inadequate and outdated. With increasing genomic data and pharmacogenomic understanding, patient-specific genomic testing offers a comprehensive and personalized treatment alternative worthy of additional research and consideration.

Rapidly developing next-generation sequencing (NGS) technologies produce a large amount of data across the whole human genome and allow a large number of DNA samples to be analyzed simultaneously. Screening cell-free fetal DNA (cffDNA) obtained from maternal blood using NGS technologies has provided new opportunities for non-invasive prenatal diagnosis (NIPD) of fetal aneuploidies. One of the major challenges to the analysis of fetal abnormalities is the development of accurate and reliable algorithms capable of analyzing large numbers of short sequence reads. Several such algorithms have recently been developed. Here, we provide a review of recent NGS-based NIPD methods as well as the available algorithms for short-read sequence analysis. We furthermore introduce the practical application of these algorithms for the detection of different types of fetal aneuploidies, and compare the performance, cost and complexity of each approach for clinical deployment. Our review identifies several main technologies and trends in NGS-based NIPD. The main considerations for clinical development for NIPD and screening tests using DNA sequencing are: accuracy, intellectual property, cost and the ability to screen for a wide range of chromosomal abnormalities and genetic defects. The cost of the diagnostic test depends on the sequencing method, diagnostic algorithm and volume of the tests. If the cost of sequencing equipment and reagents remains at or around current levels, targeted approaches for sequencing-based aneuploidy testing and SNP-based methods are preferred.

AimTo review current classes of emollients in the market, their clinical efficacy in atopic dermatitis (AD) and considerations for choice of an emollient.MethodsPubMed Clinical Queries under Clinical Study Categories (with Category limited to Therapy and Scope limited to Narrow) and Systematic Reviews were used as the search engine. Keywords of ‘emollient or moisturizer’ and ‘atopic dermatitis’ were used.Overview of findingsUsing the keywords of ‘emollient’ and ‘atopic dermatitis’, there were 105 and 36 hits under Clinical Study Categories (with Category limited to Therapy and Scope limited to Narrow) and Systematic Reviews, respectively. Plant-derived products, animal products and special ingredients were discussed. Selected proprietary products were tabulated.ConclusionsA number of proprietary emollients have undergone trials with clinical data available on PubMed-indexed journals. Most moisturizers showed some beneficial effects, but there was generally no evidence that one moisturizer is superior to another. Choosing an appropriate emollient for AD patients would improve acceptability and adherence for emollient treatment. Physician’s recommendation is the primary consideration for patients when selecting a moisturizer/emollient; therefore, doctors should provide evidence-based information about these emollients.

In spite of the tremendous advances made in developing antidepressant treatments and exploring augmentation with second-generation antipsychotics (SGAs), significant obstacles remain for psychiatrists: How should clinicians make use of cutting-edge augmentation studies? How should they use the antipsychotics in their treatment algorithm? How should they think about dosing and side effects?The first major problem is there have been no great algorithmic studies on adjunctive strategies. In fact, the most useful algorithmic study was the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, from which SGAs were entirely absent. The second problem is that STAR*D showed a clear pattern in which the efficacy of an augmentation agent depended on its placement in the algorithm. Those agents occurring later in the algorithm, such as monoamine oxidase inhibitors (MAOIs), adjunctive triiodothyronine (T3), and adjunctive lithium, appeared to be less effective than adjunctive buspirone, which occurred earlier in the algorithm. This was not the result of a direct comparison. Because of these two problems, it is therefore difficult to determine how to rank the efficacy of SGAs among the agents investigated by the STAR*D study. Among clinical treatment strategies, SGAs might appear toward the end of first-line strategies, perhaps after combinations and stimulants but before buspirone.

Pediatric patients often have poor pregnancy outcomes. Systemic lupus erythematosus predominantly impacts women in their second to fourth decade of life, with childhood-onset disease being particularly aggressive. Reproductive issues are an important clinical consideration for pediatric patients with systemic lupus erythematosus (SLE), as maintaining good disease control and planning a pregnancy are important for maternal and fetal outcomes. In this clinical review, we will consider the safety of medications in managing childhood-onset SLE during conception, pregnancy, and breastfeeding. The developing fetus is at highest risk for teratogenicity from maternal medications during the period of critical organogenesis, which occurs between the first 3-8weeks following conception. Medications known to be teratogenic, leading to a specific pattern of malformations, include mycophenolic acid, methotrexate, and cyclophosphamide. These should be discontinued prior to a planned pregnancy or as soon as pregnancy is suspected. Hydroxychloroquine is safe and should be continued throughout pregnancy and breastfeeding in those without contraindications to it. Azathioprine and calcineurin inhibitors are felt to be compatible with pregnancy in usual doses and may be used prior to and throughout pregnancy and lactation. Non-fluorinated corticosteroids including methylprednisolone and prednisone are inactivated by the placenta and can be used if needed for maternal indication during gestation. Addition of aspirin may be considered around the 12th week of gestation for prevention of pre-eclampsia. Illustrative cases are presented that demonstrate management of adolescents with childhood-onset SLE through conception, pregnancy, and breastfeeding.

S.07.04 CYP2D6 genotype predicts antidepressant dose in the GENDEP project

Pharmacogenetic Decision Support Tools: A New Paradigm for Late-Life Depression?

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant hereditary disorder characterized by recurrent spontaneous epistaxis, mucocutaneous telangiectasias, and solid organ arteriovenous malformations (AVMs). Pulmonary hypertension (PH) is an increasingly recognized complication in patients with HHT, most often precipitated by high‐output heart failure in the presence of hepatic AVMs as well as pulmonary arterial hypertension in the form of a proliferative vasculopathy. The presence of PH in patients with HHT is associated with significant elevations in rates of morbidity and mortality. Additionally, there is growing recognition of a thromboembolic propensity in this population that increases the risk of chronic thromboembolic PH, posing unique clinical considerations regarding the use of anticoagulation. Patients with HHT are also at risk of PH due to disorders commonly seen in the general population, including left‐sided heart and lung disease. The etiology of PH in HHT is multifaceted and complex; the diagnostic approach and treatment strategies must consider the underlying pathophysiology of HHT. This comprehensive review summarizes current knowledge of PH in HHT, detailing the pathogenesis of known etiologies, diagnostic evaluation, and suggested treatment modalities as well as emerging therapies that may be of future interest.