Pharmacologic treatment of pediatric obesity

Question There is a large population of overweight and obese children in my clinic. What medications for treatment of obesity are effective and can be used in children?Answer Orlistat is the only medication indicated by the US Food and Drug Administration for the treatment of obesity in adolescents. It is approved by the Food and Drug Administration for use in adolescents aged 12 years and older. There is no single approach to successful treatment of obesity, and lifestyle modification should be maintained throughout the pharmacologic treatment.     

Psychotherapy and Medications for Eating Disorders: Better Together?

PurposeEating disorders are prevalent public health problems associated with broad psychosocial impairments and with elevated rates of psychiatric and medical comorbidities. Critical reviews of the treatment literature for eating disorders indicate that although certain specialized psychological treatments and specific medications show efficacy to varying degrees across the different eating disorders, many patients fail to derive sufficient benefit from existing treatments. This article addresses whether combining psychological and pharmacologic interventions confers any additional benefits for treating eating disorders.MethodsThis study was a critical review of randomized controlled trials (RCTs) testing combined psychological and pharmacologic treatment approaches for eating disorders with a focus on anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED).FindingsFor AN, 3 of the 4 RCTs reported no significant advantage for combining treatments; the fourth reported a statistically significant, albeit clinically modest, advantage. For BN, 10 of the 12 RCTs reported no significant advantage for combining treatments; 2 RCTs found that combining fluoxetine with specific psychological treatments enhanced outcomes relative to medication only but not relative to the psychological treatments only. For BED, of the 12 RCTs, only 2 (both with antiseizure medications) significantly enhanced both binge-eating and weight outcomes, and only 2 (with orlistat, a weight-loss medication) enhanced weight loss but not binge-eating outcomes.ImplicationsDespite the public health significance of eating disorders, the scope of research performed on the utility of combining treatments is limited. To date, the few RCTs testing combined pharmacologic plus psychological treatments for eating disorders have yielded mostly nonsignificant findings. Future RCTs should focus on testing additive benefits of medications with relevant mechanisms of action to available effective psychological interventions. In addition, future RCTs that test additive effects should use adaptive designs, which could inform treatment algorithms to enhance outcomes among both responders and nonresponders to initial interventions.     

Treatment of bulimia nervosa with ondansetron.

OBJECTIVE: To evaluate ondansetron as a treatment for bulimia nervosa. DATA SOURCE: Literature was accessed through MEDLINE (1966-November 2000). Key terms included ondansetron, bulimia nervosa, binge eating, and eating disorders. DATA SYNTHESIS: Treatment of bulimia nervosa includes cognitive behavioral therapy and antidepressants. Fluoxetine is approved by the Food and Drug Administration for binge eating and vomiting behaviors in moderate to severe bulimia nervosa. An evaluation of ondansetron for bulimia nervosa was conducted. CONCLUSIONS: Ondansetron for bulimia nervosa was reported to be effective in three small trials by one group of investigators, and may be an option after failure of traditional therapies. Further studies will define the role of serotonin (5-HT3) receptor antagonists in the management of bulimia nervosa.     

Topical Clascoterone: The First Novel Agent for Acne Vulgaris in 40 Years

PurposeAcne vulgaris is a ubiquitous condition in men and women starting in adolescence. It is often persistent and refractory to multiple treatment methods. Although multiple medications may be used on- or off-label for treatment, many adverse effects and risks exist with these treatments, and there has not been an agent with a novel mechanism of action introduced in 40 years. Clascoterone is a recently approved topical acne medication with the first novel mechanism of action since isotretinoin. The purpose of this article was to review the clinical data regarding the safety and efficacy of topical clascoterone for the treatment of acne vulgaris in male and female subjects aged >12 years.MethodsA literature search of PubMed, EMBASE, and MEDLINE was conducted for clinical trials published between January 2014 and March 2021 in the English language using the key words Winlevi, clascoterone, and acne vulgaris. Articles were selected if they were related to the approval by the US Food and Drug Administration of clascoterone or provided novel data regarding this drug entity.FindingsTwo Phase III randomized controlled trials (NCT02608450 and NCT02608476) were ultimately selected, as these trials provided pivotal information to the US Food and Drug Administration for the approval of topical clascoterone.ImplicationsThe findings of this review show that topical clascoterone is likely an effective and safe option for the treatment of acne vulgaris. It offers efficacy rates similar to those of current medications through a novel mechanism of action. Its place in therapy remains unclear, but it might be placed ahead of other androgen receptor antagonists such as spironolactone due to its avoidance of systemic side effects.     

Melatonin: Translation of Ongoing Studies Into Possible Therapeutic Applications Outside Sleep Disorders

PurposeMelatonin, a natural hormone mainly synthesized by the pineal gland, is regulated by circadian rhythm. Synthetic melatonin is not approved by the US Food and Drug Administration for any indication. However, melatonin receptor agonists such as ramelteon and tasimelteon are US Food and Drug Administration approved and are considered by the American Academy of Family Physicians for the treatment of insomnia. Due to the availability of over-the-counter products in some countries and the increasing use of melatonin, it is interesting to highlight knowledge regarding the potential benefits of melatonin outside sleep disorders.MethodsThis narrative review included published reports in EMBASE and MEDLINE databases between 1975 and 2021 relating to the therapeutic applications of melatonin.FindingsBased on the quality of the evidence published to date, the most promising non-insomnia indications are for treating ischemia/reperfusion injury, primary headache disorders, fibromyalgia, glucose control, and blood pressure control.ImplicationsMost of the studies were preclinical and in in vivo and in vitro phases. More clinical trials are needed before recommending melatonin as a treatment in clinical practice.     

New and Novel Therapies for Gynecologic Cancers

ObjectiveTo review recent therapies approved by the US Food and Drug Administration for the treatment of gynecologic malignancies.Data sourcesPubMed, FDA.gov, ASCO.org.ConclusionThe landscape for treating gynecologic malignancies is rapidly changing. Maintenance therapy now exists for women with advanced ovarian cancer after completing chemotherapy for both newly diagnosed and platinum-sensitive recurrent ovarian cancer. Anti-angiogenic therapy has many applications in gynecologic malignancies. Immunotherapy can be used in certain situations for women with gynecologic malignancies.Implications for Nursing PracticeBiologic agents and immunotherapy have distinct side-effect profiles that nurses need to be aware of to optimize patient care and outcomes.     

Laparoscopic adjustable gastric banding for morbid obesity

Morbid obesity, with its accompanying human and monetary costs, is a serious and growing health problem worldwide. Surgical treatments are recognized as being effective, but until recently, the available surgical options entailed invasive techniques that permanently altered the gastrointestinal tract. In June 2001, the US Food and Drug Administration approved an adjustable gastric banding system that can be implanted laparoscopically for the treatment of morbid obesity. This article discusses laparoscopic adjustable gastric banding, including patient selection and evaluation, perioperative care, and the importance of a team approach to patient management and follow-up care. AORN J 77 (May 2003) 924-940.     

Vortioxetine (Brintellix®) and Levomilnacipran (Fetzima®): The Two Newest Additions to the Antidepressant Formulary

In the final months of 2013, the US Food and Drug Administration approved two new antidepressant formulations. This column presents a review of the pertinent literature on both: vortioxetine (Brintellix®) and levomilnacipran (Fetzima®).     

Toripalimab for the treatment of melanoma

ABSTRACT

Introduction

Immune therapies have dramatically changed the treatment landscape for melanoma in the past decade. Ipilimumab, nivolumab, and pembrolizumab have been approved by U.S. Food and Drug Administration for the treatment of metastatic melanoma sequentially. Toripalimab, a humanized IgG4 monoclonal antibody against programmed cell death protein-1 (PD-1), was approved by National Medical Product Administration in China in 2018 as second-line therapy for metastatic melanoma.     

Voretigene neparvovec-rzyl for treatment of RPE65-mediated inherited retinal diseases: a model for ocular gene therapy development

ABSTRACT

Introduction: Over a decade of research and development culminated in the 2017 United States (US) Food and Drug Administration (FDA) approval of voretigene neparvovec-rzyl (VN) for RPE65 mutation-associated inherited retinal disease (IRD), the first approved gene therapy for a hereditary genetic disease in the US, and the first and only pharmacologic treatment for an IRD.

Areas covered: VN serves as a model for ocular gene therapy development, while RPE65 mutation-associated IRD serves as an example of a well-suited candidate disorder. This review also discusses development considerations for viral vector gene augmentation, and, studies that led to VN’s FDA approval. Subretinal injection of VN resulted in improved performance on the novel multi-luminance mobility test (MLMT), light sensitivity, and visual fields in patients with RPE65 mutation-associated IRD, which predominantly impairs rod function. Additionally, the dosage, administration technique, pharmacokinetics, and safety data of VN are reviewed.

Expert Opinion: As a model for development, special challenges associated with the introduction of this first ocular gene therapy include limited genetic testing in clinical practice, novel surgical complexity of ocular gene therapy administration, new functional vision endpoints, as well as unique development, launch, and reimbursement considerations associated with orphan therapies and one-time gene therapies.     

Lasmiditan Is a New Option for Acute Migraine Treatment

Lasmiditan is a new oral medication for treatment of acute migraine. It was approved by the U.S. Food and Drug Administration in October 2019 and is marketed under the brand name Reyvow (Eli Lilly and Company, Indianapolis, IN). It is the first of its kind in a new drug class called ditans. Lasmiditan has been studied as monotherapy for acute migraine treatment and as an abortive therapy for adults taking chronic migraine preventive medication. Lasmiditan may be an option for individuals who have had no relief with triptans or other acute migraine treatment agents or who are unable to use other migraine treatments because of contraindications.     

Comorbidities,Age, and Polypharmacy Limit the Use by US Older Adults with Nocturia of the Only FDA-approved Drugs for the Symptom

PurposeThe goal of this study was to determine if the US adult population with nocturia (waking from sleep at night to void) can easily take medications (desmopressin acetate) approved by the US Food and Drug Administration for nocturia. The study examined: (1) the prevalence of comorbid conditions, laboratory abnormalities, and concomitant medications that increase risk of desmopressin use; and (2) whether these factors are associated with age or nocturia frequency.MethodsUsing a cross-sectional analysis of four US National Health and Nutrition Examination Survey (NHANES) waves (2005–2012), a total of 4111 participants aged ≥50 years who reported ≥2 nightly episodes of nocturia were identified. The main outcome was frequency of contraindications and drug interactions as described in US Food and Drug Administration–approved prescribing information. These prescribing concerns were matched to examination findings, medical conditions, concomitant medications, and laboratory results of NHANES participants. The associations between prescribing concerns and nocturia severity and age groups were examined.FindingsThe mean participant age was 65.7 years (95% CI, 65.3–66.1), and 45.5% were male. Desmopressin prescribing concerns were present in 80.5% (95% CI, 78.0–82.9) of those ≥50 years of age with nocturia; 50.0% (95% CI, 47.0–53.0) had contraindications, and 41.6% (95% CI, 39.3–44.0) took a concomitant drug that could increase risk of low serum sodium. Desmopressin contraindications were higher with older age (P < 0.001) and present in 73.2% (95% CI, 69.3–77.1) of those ≥80 years of age.ImplicationsUsing NHANES data, this study showed that older US adults with nocturia have a high prevalence of medical conditions, concomitant medications, and baseline laboratory abnormalities that likely increase the risk of potentially severe adverse side effects from desmopressin use. A medication designed and approved for a clinical symptom that is most common in older adults could not be taken by most of the older adults with the symptom.     

Treatment options for menopausal hot flashes

Although alternatives exist, hormone therapy remains the most effective treatment for menopausal symptoms such as hot flashes, and it is the only treatment approved by the US Food and Drug Administration (FDA) for this indication. The FDA recommends using the lowest effective dose of hormones. New low-dose preparations and new dosage forms of hormone therapy are available.     

Approved monoclonal antibodies for cancer therapy

Background: Monoclonal antibodies are a rapidly expanding class of agents for the treatment of cancer. In 1997 rituximab became the first approved monoclonal antibody for the treatment of low grade B cell lymphoma. Since then several monoclonal antibodies have received approval from the United States Food and Drug Administration (US FDA) for the treatment of a variety of solid tumors and hematological malignancies. Objective/methods: To review the literature using Medline and summarize the mechanisms of action, indications and outcome of treatment of currently approved monoclonal antibodies used in clinical practice for patients with solid tumors and hematologic malignancies. Results/conclusions: An overview of the FDA approved monoclonal antibodies is provided. Monoclonal antibodies are currently used as the standard of care as first and second line therapy for a number of hematologic malignancies and solid tumors. Over the next 5 – 10 years additional monoclonal antibodies and monoclonal antibody conjugates will be approved by the US FDA and will dramatically affect the standard of care of many cancers.     

Lamivudine for chronic hepatitis B

Lamivudine (Epivir^®, GlaxoSmithKline) was approved by the US Food and Drug Administration for the treatment of adult patients with chronic hepatitis B in 1998, and has since been shown to be of benefit to selected patients with chronic hepatitis B. Drug resistance is the main issue encountered during therapy, with lamivudine resistant mutants emerging at a rate of approximately 15 to 30% per year of therapy. These mutants are associated with relapse of hepatitis, and occasionally hepatic decompensation. Despite this, therapeutic indications and guidelines for lamivudine therapy have now been drawn up, which indicate that lamivudine will be the first line therapy for hepatitis B e antigen-positive chronic hepatitis B patients, although its role in hepatitis B e antigen-negative patients remains controversial.     

Antidote review: fomepizole for methanol poisoning

Fomepizole (Antizol) was recently approved by the US Food and Drug Administration for treatment of methanol poisoning. By inhibiting the hepatic enzyme alcohol dehydrogenase, it presents formation of toxic metabolites with far fewer consequences than traditional ethanol therapy. It appears that fomepizole will become standard therapy for methanol intoxication as it is for ethylene glycol poisoning.     

Integrase strand transfer inhibitors in the management of HIV-positive individuals

Abstract

The use of highly active antiretroviral therapy against human immunodeficiency virus (HIV) can lead to rare instances of treatment failure and the emergence of drug resistance. HIV drug-resistant strains are archived in cellular reservoirs, and this can exclude the future efficacy of drugs or drug classes against which resistance has emerged. In addition, drug-resistant viruses can be transmitted between individuals. HIV drug resistance has been countered through the constant development of new antiretroviral drugs. Integrase strand transfer inhibitors, that actively block the integration of the HIV genome into the host DNA, represent the most recent antiretroviral drugs. Of these, raltegravir, elvitegravir, and dolutegravir are the only integrase strand transfer inhibitors that have been approved for human therapy by the US Food and Drug Administration. Dolutegravir is unique in its ability to seemingly evade HIV drug resistance in treatment-naïve individuals. Here, we review the use of integrase strand transfer inhibitors in the management of HIV, focusing on HIV resistance.     

Rates of Help-Seeking in US Adults With Lifetime DSM-5 Eating Disorders: Prevalence Across Diagnoses and Differences by Sex and Ethnicity/Race

ObjectiveTo investigate, in a nationally representative sample of US adults, the prevalence of help-seeking in individuals with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) eating disorders (EDs) and to examine sex and ethnic/racial differences.Patients and MethodsThe 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions-III (N=36,309) included respondents who met the criteria for specific lifetime DSM-5 EDs and answered questions regarding help-seeking for their ED symptoms (anorexia nervosa [AN]: n=275; bulimia nervosa [BN]: n=91; and binge-eating disorder [BED]: n=256).ResultsThe prevalence (standard error) estimates of ever seeking any help for AN, BN, and BED were 34.5% (2.80%), 62.6% (5.36%), and 49.0% (3.74%), respectively. Adjusting for sociodemographic characteristics, men and ethnic/racial minorities (non-Hispanic blacks and Hispanics) were statistically significantly less likely to ever seek help for BED than were women or non-Hispanic whites, respectively. Hispanics also were significantly less likely to seek help for AN relative to non-Hispanic whites.ConclusionThis was the first study in a nationally representative sample of US adults to examine rates of help-seeking, including by sex and ethnic/racial differences, across DSM-5–defined EDs. These findings emphasize the need to develop strategies to encourage help-seeking among individuals with EDs, particularly among men and ethnic/racial minorities.     

支气管热成形术治疗难治性支气管哮喘的研究进展

支气管热成形术(bronchial thermoplasty,BT)是一种新兴非药物治疗手段,通过可控的射频热量消融气管壁平滑肌(airway smooth muscle,ASM),可减轻气管收缩,具有较好的疗效且安全性高。目前已被美国食品药品监督管理局(FDA)和我国国家食品药品监督管理总局(CFDA)批准用于难治性支气管哮喘的临床治疗。本文就支气管热成形术的工作原理、操作方法和发展现状作一综述。