The Emerging Role of PD-1/PD-L1–Targeting Immunotherapy in the Treatment of Metastatic Urothelial Carcinoma

2017 ◽  
Vol 52 (1) ◽  
pp. 60-68 ◽  
Author(s):  
Morgan E. Gwynn ◽  
David L. DeRemer
Keyword(s):  
English Language ◽  
Data Extraction ◽  
Treatment Options ◽  
Single Agent ◽  
Objective Response ◽  
Study Selection ◽  
Programmed Death ◽  
Platinum Based Chemotherapy ◽  
Metastatic Urothelial Carcinoma ◽  
American Society

Objective: To summarize and evaluate immunotherapy agents targeting programmed cell death protein-1 (PD-1) and programmed death ligand-1 (PD-L1) recently approved for the treatment of metastatic urothelial carcinomas (UC). Data Sources: A literature review was performed using PubMed (2012 to June 2017), the American Society of Clinical Oncology abstract databases (2012 to June 2017 Annual Meetings/symposia), and the America Association for Cancer Research symposia (2012 to June 2017). A search using clinicaltrials.gov was conducted to identify studies for atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab. Study Selection and Data Extraction: English language phase I to III studies assessing PD-1 and PD-L1 in UC were incorporated. Data Synthesis: Atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab have demonstrated clinical efficacy with tolerable toxicities in patients with metastatic UC with disease progression following platinum-based chemotherapy. Anti–PD-1/PD-L1 therapies may provide overall survival advantage; these are currently being evaluated in ongoing phase 3 studies. Greater objective response rates seem to be observed in PD-L1–positive patients versus PD-L1–negative patients, but methodologies in this assessment differ among clinical trials. The identification of biomarkers that provide greater insight into patients who positively respond to PD-1/PD-L1 therapies are needed. Conclusions: Treatment options for metastatic UC have expanded to include PD-1/PD-L1 therapies. These agents should be strongly considered as second-line therapy over single-agent chemotherapy for patients who fail or progress after platinum-based treatment.

scholarly journals Challenges Experienced by Physiotherapists in Rehabilitation of Individuals With Poststroke Hemineglect: A Review Study

2020 ◽  
Vol 3 (1) ◽  
pp. 10-13
Author(s):  
Mridul Makkar ◽  
Narkeesh Arumugam ◽  
Divya Midha
Keyword(s):  
English Language ◽  
Data Extraction ◽  
Treatment Options ◽  
Low Frequency ◽  
Functional Independence ◽  
Mirror Therapy ◽  
Treatment Methods ◽  
Study Selection ◽  
Patients Experience ◽  
Theta Burst

Background: Hemineglect is the inability to sense stimuli given on the paretic side. It is most frequently seen in individuals with left hemiplegia resulting from temporoparietal lobe damage. On the basis of duration poststroke, hemineglect can be acute (<3 months) or chronic (>6 months). The patients experience many challenges in rehabilitation of motor function, cognitive function, and in gaining functional independence. Aim: To identify the challenges faced by physiotherapists in rehabilitation of individuals with poststroke hemineglect. Methodology: Data Identification: An English language literature search using Google Scholar, Scopus, PubMed, and Pedro was done. Study Selection: Articles were identified and those which fulfilled the specific requirements were selected. Data Extraction: In accordance with the inclusion criteria, 9 studies done between 1997 and 2017 were reviewed. Results: In this study, we reviewed a number of studies on the treatment of hemineglect which show a variety of treatment options. The various interventions include robotic mirror therapy, repeated parietal theta-burst stimulation, low-frequency transcranial magnetic stimulation, trunk rotation and scanning training, forced use therapy, prism glass adaptation, movement detection bracelets, each of which have different effects. Conclusion: There are a limited number of studies on the different treatment methods that are currently available. Further research is needed on these treatment methods to prove their efficacy and find a suitable method to overcome the challenges that the patients with hemineglect face at present.

Ozenoxacin: A Novel Topical Quinolone for Impetigo

2018 ◽  
Vol 52 (12) ◽  
pp. 1233-1237 ◽  
Author(s):  
Christopher Wren ◽  
Edward Bell ◽  
Lea S. Eiland
Keyword(s):  
Staphylococcus Aureus ◽  
English Language ◽  
Data Extraction ◽  
Phase 1 ◽  
Treatment Options ◽  
Current Treatment ◽  
Systemic Absorption ◽  
Clinical Role ◽  
Study Selection ◽  
Language Data

Objective: To review the data supporting Food and Drug Administration (FDA) labeling of ozenoxacin and evaluate its place in therapy for impetigo. Data Sources: A literature search was conducted using PubMed (1966 to May 2018) and Google Scholar (2000 to May 2018) with the search terms ozenoxacin, T-3912, and GF-001001-00. Other resources included clinicaltrials.gov , the manufacturing product label, and the FDA website. Study Selection and Data Extraction: All relevant English-language data from abstracts, phase 1 to 4 studies, and review articles were included. Data Synthesis: FDA labeling of ozenoxacin was based on 2 phase 3 studies conducted in patients 2 months of age and older. Ozenoxacin demonstrated efficacy and safety for use in bullous or nonbullous impetigo from Staphylococcus aureus or Streptococcus pyogenes as compared with placebo. The lack of systemic absorption results in minimal adverse drug reactions. Studies did not detect possible adverse events commonly associated with other quinolone antibiotics. Relevance to Patient Care and Clinical Practice: This topical quinolone has bactericidal activity against Gram-positive organisms, including methicillin-resistant Staphylococcus aureus. Ozenoxacin may have an expanded clinical role for the treatment of localized impetigo if resistance to current therapies increases significantly. However, ozenoxacin is unlikely to play a significant role in the treatment of impetigo in the foreseeable future, because of lack of direct comparative clinical efficacy data with currently recommended therapies and likely high cost. Conclusions: Ozenoxacin, the first nonfluorinated quinolone, is a safe, topical treatment for impetigo in patients 2 months of age and older. Although clinical trials demonstrate efficacy compared with placebo, comparative trials to current treatment options are needed to identify its therapeutic use.

Topical Aminophylline: Is it Safe and Effective in Causing Regional Fat Loss?

1997 ◽  
Vol 13 (2) ◽  
pp. 80-83
Author(s):  
Lisa M Tong ◽  
Kristin R Gericke
Keyword(s):  
Adverse Effects ◽  
English Language ◽  
Data Extraction ◽  
Treatment Options ◽  
Local Concentration ◽  
Drug Induced ◽  
Fat Loss ◽  
Study Selection ◽  
Data Source

Objective: To provide a better understanding of the efficacy and possible adverse effects of topical aminophylline in causing regional fat loss. Data Source: Pertinent English-language literature (1958–1995). Study Selection: Representative articles documenting mechanisms of action and types of drug-induced reactions, as well as treatment options. Data Extraction: Data were extracted only from articles that documented relevant and substantive information backed by clinical studies. Data Synthesis: Topical aminophylline 2% thigh cream has been introduced as a method of treating cellulite, or dimpled thighs and buttocks. The proposed method of action is by increasing local concentration, thereby stimulating lipolysis. Data from two small clinical trials showed that the cream reduced thigh girth and had no known adverse effects. However, adverse dermatologic effects caused by aminophylline have been reported in the past. Conclusions: Topical aminophylline cream appears to be a reasonable option for regional reduction of thigh girth for some people and has not shown any adverse effects. Nevertheless, larger, long-term studies need to be done.

Review of the Efficacy and Safety of Lemborexant, a Dual Receptor Orexin Antagonist (DORA), in the Treatment of Adults With Insomnia Disorder

2021 ◽  
pp. 106002802110084
Author(s):  
Kristin Waters
Keyword(s):  
Adverse Effects ◽  
Pharmacological Treatment ◽  
English Language ◽  
Data Extraction ◽  
Treatment Options ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Language Studies ◽  
Insomnia Disorder ◽  
Study Selection

Objective To provide an overview of the efficacy and safety of lemborexant in the treatment of insomnia disorder by assessing the currently available literature. Data Sources A literature search of PubMed was performed (2010 to March 2021) using the following search terms: lemborexant, sleep, orexin Study Selection and Data Extraction All relevant English-language studies were reviewed and considered, with a focus on phase 3 trials. Data Synthesis The efficacy and safety of lemborexant in the treatment of insomnia disorder in adults was demonstrated in 2 phase 3 trials. Lemborexant significantly reduced latency to persistent sleep compared with placebo. The first study also demonstrated a significant reduction compared with the active control zolpidem ER. Somnolence and headache were relatively common, but the marked adverse effects associated with other medications commonly used to treat insomnia, such as cognitive and psychomotor impairment and complex sleep-related behaviors, were not observed. Relevance to Patient Care and Clinical Practice Although nonpharmacological therapy is considered first-line treatment for insomnia disorder, pharmacological treatment is most commonly utilized. Lemborexant is a viable pharmacological treatment option for patients who are unable to tolerate the adverse effects associated with the most commonly prescribed medications for insomnia, such as benzodiazepines and sedative-hypnotics (Z drugs). This is especially true for geriatric patients, who may be more sensitive to these adverse effects. Conclusion Lemborexant can be recommended to treat insomnia disorder when pharmacological treatment is warranted. It has demonstrated efficacy in clinical trials and is likely better tolerated than most currently available treatment options.

scholarly journals EV-101: A Phase I Study of Single-Agent Enfortumab Vedotin in Patients With Nectin-4–Positive Solid Tumors, Including Metastatic Urothelial Carcinoma

2020 ◽  
Vol 38 (10) ◽  
pp. 1041-1049 ◽  
Author(s):  
Jonathan Rosenberg ◽  
Srikala S. Sridhar ◽  
Jingsong Zhang ◽  
David Smith ◽  
Dean Ruether ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Phase I ◽  
Urothelial Carcinoma ◽  
Solid Tumors ◽  
Phase Ii ◽  
Single Agent ◽  
Phase Iii ◽  
Programmed Death ◽  
Platinum Based Chemotherapy ◽  
Metastatic Urothelial Carcinoma

PURPOSE To assess the safety/tolerability and antitumor activity of enfortumab vedotin (EV), a novel investigational antibody-drug conjugate that delivers the microtubule-disrupting agent, monomethyl auristatin E, to cells that express Nectin-4. METHODS EV-101 is a phase I dose escalation/expansion study that enrolled patients with Nectin-4–expressing solid tumors (eg, metastatic urothelial carcinoma [mUC]) who progressed on ≥ 1 prior chemotherapy regimen and/or programmed death-1 receptor/programmed death ligand-1 [PD-(L)1] inhibitor, including a cohort of patients with mUC who received prior anti–PD-(L)1 therapy. Patients received escalating doses of EV up to 1.25 mg/kg on days 1, 8, and 15 of every 28-day cycle. Primary objectives were evaluation of safety/tolerability and pharmacokinetics; antitumor activity was a secondary objective. RESULTS Enrolled patients with mUC (n = 155) were heavily pretreated, with 96% having prior platinum-based chemotherapy and 29% receiving ≥ 3 lines of prior treatment. Maximum tolerated dose of EV was not established; however, the recommended phase II dose was identified as 1.25 mg/kg. Rash, peripheral neuropathy, fatigue, alopecia, and nausea were the most common treatment-related adverse events (TRAEs); the most common TRAEs were grade 1-2 in severity. Among the 112 patients with mUC treated with single-agent EV 1.25 mg/kg, the investigator-assessed confirmed objective response rate (ORR) was 43%, and duration of response was 7.4 months. Median overall survival (OS) was 12.3 months, and the OS rate at 1 year was 51.8%. Similar ORR and estimated median OS were observed in patients ≥ 75 years of age with and without prior anti–PD-(L)1 treatment, liver metastases, or upper-tract disease. CONCLUSION Single-agent EV was generally well tolerated and provided clinically meaningful and durable responses in patients with mUC; survival data are encouraging. A pivotal phase II and a confirmatory phase III study are ongoing.

Drug-Induced Photosensitivity: A Clinical Review

1996 ◽  
Vol 12 (2) ◽  
pp. 52-57
Author(s):  
Stacey Beasley ◽  
Oscar E Araujo ◽  
Franklin P Flowers
Keyword(s):  
English Language ◽  
Data Extraction ◽  
Treatment Options ◽  
Coal Tar ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Hypoglycemic Agents ◽  
Thiazide Diuretics ◽  
Antiinflammatory Drugs ◽  
Drug Induced ◽  
Study Selection

Objective: To provide an overview of drug-induced phototoxic and photoallergy reactions, the mechanism involved, and the most common classes of drugs causing these reactions. Data Source: Pertinent English-language literature (1987–1993). Study Selection: Representative articles documenting mechanisms and types of drug-induced photosensitivity reactions, as well as treatment options. Data Extraction: Data were extracted only from articles that documented relevant and substantive information backed by clinical studies. Data Synthesis: Drug-induced photosensitivity can be acute or chronic. The chromophore that absorbs the radiation and activates the process of photosensitivity results in color within the longer ultraviolet wavelength. The primary classes of drugs causing phototoxic reactions include nonsteroidal antiinflammatory drugs, thiazide diuretics, tetracycline, and quinolone antibiotics, tricyclic antidepressants, and amiodarone. Those causing photoallergic reactions include antihistamines, thiazide diuretics, sulfonamides, griseofulvin, sulfonylurea hypoglycemic agents, benzocaine, and coal tar preparations. Conclusions: The importance of understanding the mechanism of photosensitivity is stressed as well as the difficulty in determining whether a phototoxic or photoallergic reaction has occurred. Established classes of each type of photosensitivity are identified and the importance of recognizing treatment options is emphasized. Patients prone to photosensitizing reactions should be advised concerning how to manage these problems.

scholarly journals Vulvodynia: A Review of the Literature

2018 ◽  
Vol 35 (1) ◽  
pp. 11-24 ◽  
Author(s):  
Bobbi Jo Loflin ◽  
Kearsten Westmoreland ◽  
Nancy Toedter Williams
Keyword(s):  
English Language ◽  
Data Extraction ◽  
Treatment Options ◽  
Alternative Therapies ◽  
Ease Of Use ◽  
Unknown Etiology ◽  
Vulvar Vestibulitis ◽  
Vulvar Vestibulitis Syndrome ◽  
Medication Therapy ◽  
Study Selection

Objective: To evaluate the literature and educate the pharmacy community about the different treatment options for vulvodynia. Data Sources: Searches were performed through MEDLINE (1946-May 2018) using OVID and EBSCOhost, and Excerpta Medica (1974-May 2018) using EMBASE. Search terms included vulvar vestibulitis syndrome, vestibulodynia, vulvodynia, vulvar pain, provoked vulvar vestibulitis, and vulvodynia treatment. References of all relevant articles were then used to find additional applicable articles. Study Selection and Data Extraction: This review includes articles in the English language and human trial literature. Twenty-five trials explored the use of oral and topical medications in the treatment of vulvodynia. Data Synthesis: Vulvodynia is a poorly understood disease with an unknown etiology. Oral tricyclic antidepressants and gabapentin continue to be the most commonly used treatments for vulvodynia pain. This is due to their ease of use and patient preference. Topical treatments that have efficacy data are amitriptyline, gabapentin, lidocaine, baclofen, and hormones. This route of administration avoids systemic adverse effects and interpatient variability that accompanies oral administration. Alternative therapies more commonly used include physiotherapy, psychotherapy, and surgery. Treatment length may vary due to dose titrations and potential changes in medication therapy. Conclusions: Several medication and alternative therapies may be effective in treating vulvodynia. Current studies used wide dosing ranges, making it difficult to standardize therapy. No consistent method of assessing pain was used between studies, as well as a limited number being randomized and placebo controlled. Additional research is needed to increase knowledge and further develop vulvodynia treatments.

scholarly journals The Role of Pharmacists in Managing Adverse Events Related to Immune Checkpoint Inhibitor Therapy

2019 ◽  
Vol 33 (3) ◽  
pp. 338-349 ◽  
Author(s):  
Patrick Medina ◽  
Kate D. Jeffers ◽  
Van A. Trinh ◽  
R. Donald Harvey
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
English Language ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Data Extraction ◽  
Single Agent ◽  
Language Studies ◽  
Study Selection ◽  
Life Threatening

Objective: To provide an overview of immune checkpoint inhibitor (ICI) therapy-associated immune-related adverse events (irAEs) and their management, focusing on the key responsibilities for pharmacists in recognizing, distinguishing, and treating irAEs and in educating patients about irAEs and their management. Data Sources: Literature published from January 2000 to March 2018 available from online sources. Study Selection and Data Extraction: Relevant English-language studies, guidelines, and articles. Data Synthesis: ICI therapies have been approved for the treatment of several cancers as single-agent therapies, combined ICI therapies, or in combination with other agents. ICI therapies increase the activity of the immune system and consequently can have autoimmune-like adverse effects that are often termed irAEs. irAE management can be challenging as irAEs can vary in their frequency and severity among patients, according to the specific agent, and can occur at any time during treatment or after therapy discontinuation. Additionally, for patients treated with ICI therapies in combination with other therapies, ICI-associated irAEs must be distinguished from adverse events associated with chemotherapy or targeted therapies, which often require different management. Pharmacists can provide essential support to diagnose and manage irAEs. Relevance to Patient Care and Clinical Practice: Early and accurate diagnosis and prompt management of irAEs by pharmacists are critical to reduce the risk of severe or life-threatening complications and prevent premature ICI discontinuation. Conclusions: Pharmacists have a key role in the recognition, monitoring, and management of irAEs and in educating patients about irAEs associated with ICI therapies and the agents used to manage them.

Lead in Mineral or Multivitamin-Multimineral Products

2021 ◽  
pp. 106002802110233
Author(s):  
C. Michael White
Keyword(s):  
English Language ◽  
Data Extraction ◽  
The United States ◽  
Third Party ◽  
Reference Level ◽  
Study Selection ◽  
Pubmed Search ◽  
Zinc Supplements ◽  
Average Lead ◽  
Year 2000

Objective Assess the current daily interim reference level of lead and the amount contained in current mineral and multivitamin-multimineral (MVM) products. Data Sources PubMed search from 1980 to May 15, 2021, limited to the English language, via the search strategy ((mineral OR multivitamin OR calcium OR iron OR magnesium OR copper OR zinc OR chromium OR selenium) AND (heavy metals OR Pb OR lead)). Study Selection and Data Extraction Narrative review of studies assessing lead content in mineral or MVM products. Data Synthesis Products containing different calcium forms (dolomite, bone meal, natural carbonate) have historically had higher lead levels than others (refined carbonate, lactate, gluconate, acetate, sevelamer), but the gap has closed considerably since the year 2000. Although only limited assessments of magnesium and zinc supplements have been conducted, no alarming average lead amounts were found. MVM products assessed since 2007 had low median or mean lead concentrations. However, large interproduct differences exist, with many products having very little lead and some products having concerning amounts. Relevance to Patient Care and Clinical Practice It is difficult for pharmacists and consumers to know the amount of lead in an actual product unless it is tested in an independent third-party lab. The United States Pharmacopeia and NSF International will provide a seal on the products stating that the products have a low level of lead, but even so, children could receive more lead than the Food and Drug Administration’s Interim Reference Level. Conclusions The threat from lead exposure in mineral and MVM products have diminsihed considerably over time but some products can still have excessive amounts. Without third-party testing, it is difficult for clinicians and consumers to know which outlier products to avoid.

Recent Advances: Antiinfectives

1995 ◽  
Vol 29 (10) ◽  
pp. 1035-1040 ◽  
Author(s):  
Laurie L Briceland ◽  
John D Cleary ◽  
Courtney V Fletcher ◽  
Daniel P Healy ◽  
Charles A Peloquin
Keyword(s):  
Infectious Diseases ◽  
English Language ◽  
Data Extraction ◽  
Information Service ◽  
Ulcer Disease ◽  
Additional Information ◽  
Study Selection ◽  
Enterococcus Spp ◽  
Scientific Meetings ◽  
Clinically Significant

Objective: To update readers on the significant changes in infectious diseases pharmacotherapy. Data Sources: An Index Medians and Iowa Drug Information Service search (1993–1994) of English-language literature pertaining to the selected topic areas was performed. Additional information from abstracts presented at scientific meetings were identified by the authors. Study Selection and Data Extraction: All identified studies were screened and those judged relevant to the update were evaluated. Data Synthesis: New or clinically significant data since 1992 that related to peptic ulcer disease, microbial resistance (e.g., Enterococcus spp., Streptococcus pneumoniae, Mycobacterium tuberculosis, Candida albicans), immunomodulators, and AIDS were evaluated and compared with previous data. Conclusions: There have been several exciting and significant changes in infectious diseases pharmacotherapy evident from this review.

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