Real world use of oral treatments in interstitial cystitis/bladder pain syndrome in the UK: Outcome of a cross sectional study.

BACKGROUND: To describe the oral treatments people living with interstitial cystitis/bladder pain syndrome (IC/BPS) are using to treat their urologic condition in the UK. METHOD: A questionnaire hyperlink encompassing current and previous medications taken for IC/BPS with other sociodemographic and diagnostic indices was available to the Bladder Health UK website. Interested and fully consented individuals accessed and completed the survey. RESULTS: A total of 601 accessed the questionnaire of whom 173 participants responded (response rate: 28.7%) with a mean ± SD O'Leary/Sant scores of 20.12 ± 9.38. A sample size of 171 was estimated to be used in the survey. A fifth of the participants were not on any treatment at all. Amitriptyline was the most prevalent medication in use both alone and in combination. A shift in the use of unapproved (for IC/BPS) antidepressant, smooth muscle relaxant, opioids, gabapentenoids, and antibiotics was observed in the sample. There were no significant differences between the mean (SD) O'Leary/Sant scores of cohorts currently taking oral medications and those not taking it. More than two-thirds of the participants had been diagnosed with the disease more than 5 years. Just under a half (47.4%) of participants reported a history of allergy. CONCLUSION: Our study provides contemporary evidence that the treatments used for managing IC/BPS encompass a broad range of medications both recommended and not recommended by current guidelines. The latter suggests patients are willing to try novel treatments when more conventional ones are ineffective.

Cumulative Benefit Over 52 Weeks With Deucravacitinib Versus Apremilast in Moderate to Severe Plaque Psoriasis: POETYK PSO-1 Post Hoc Analysis.

INTRODUCTION: Deucravacitinib demonstrated superior efficacy to apremilast in patients with moderate to severe plaque psoriasis in the POETYK PSO-1 and PSO-2 clinical trials. In the study reported here, we aimed to determine the overall 52-week cumulative clinical benefit of treatment initiated with deucravacitinib versus apremilast and to compare the 52-week cumulative benefit of initiating and staying on deucravacitinib versus initiating apremilast and continuing or switching to deucravacitinib at week 24 of treatment. METHODS: This post hoc analysis of POETYK PSO-1 data (ClinicalTrials.gov identifier: NCT03624127) determined the cumulative clinical benefit of deucravacitinib 6 mg once daily and apremilast 30 mg twice daily in adults with moderate to severe plaque psoriasis. Patients treated with apremilast who did not achieve a 50% reduction in the Psoriasis Area and Severity Index (PASI 50) at week 24 were switched to deucravacitinib. The cumulative clinical benefit of deucravacitinib versus apremilast over 52 weeks was based on cumulative measures of ≥ 75% improvement from baseline in PASI score (PASI 75) and the proportion of patients with a static Physician Global Assessment score of 0 or 1 (sPGA 0/1). Ratios of area under the curve estimates between treatments were calculated and compared based on analysis of covariance regression models. RESULTS: Patients initiating deucravacitinib (N = 332) had a greater cumulative benefit as measured by the PASI 75 and sPGA 0/1 than those initiating apremilast (N = 168). Over 52 weeks, those initiating deucravacitinib experienced 50% more benefit as measured by PASI 75 and 58% more benefit as measured by sPGA 0/1 than those initiating apremilast. Results were consistent with the primary analysis when patients were classified by prior systemic and prior biologic therapy exposure. CONCLUSION: Results from this analysis corroborate the primary efficacy analysis supporting the use of deucravacitinib compared with apremilast for moderate to severe plaque psoriasis, regardless of prior systemic or biologic use.

Physiology of pregnancy and oral local anesthesia considerations.

Background: Safe and effective local anesthesia is a prerequisite for emergency oral surgeries and most dental treatments. Pregnancy is characterized by complex physiological changes, and increased sensitivity to pain. Pregnant women are particularly vulnerable to oral diseases, such as caries, gingivitis, pyogenic granuloma and third molar pericoronitis. Maternally administered drugs can affect the fetus through the placenta. Therefore, many physicians and patients are reluctant to provide or accept necessary local anesthesia, which leads to delays in the condition and adverse consequences. This review is intended to comprehensively discuss the instructions for local anesthesia in the oral treatment of pregnant patients. Methodology: An in-depth search on Medline, Embase, and the Cochrane Library was performed to review articles concerned with maternal and fetal physiology, local anesthetic pharmacology, and their applications for oral treatment. Results: Standard oral local anesthesia is safe throughout the pregnancy. At present, 2% lidocaine with 1:200,000 epinephrine is considered to be the anesthetic agent that best balances safety and efficacy for pregnant women. Maternal and fetal considerations must be taken into account to accommodate the physiological and pharmacological changes in the gestation period. Semi-supine position, blood pressure monitoring, and reassurance are suggested for high-risk mothers to reduce the risk of transient changes in blood pressure, hypoxemia, and hypoglycemia. For patients with underlying diseases, such as eclampsia, hypertension, hypotension, and gestational diabetes, the physicians should use epinephrine cautiously and control the dose of anesthetic. New local anesthesia formulations and equipment, which contribute to minimizing injection pain and relieving the anxiety, have and are being developed but remain understudied. Conclusions: Understanding the physiological and pharmacological changes during pregnancy is essential to ensure the safety and efficiency of local anesthesia. Optimal outcomes for the mother and fetus hinge on a robust understanding of the physiologic alterations and the appropriate selection of anesthetic drugs and approaches.

Comparative efficacy of oral drugs for chronic radiation proctitis - a systematic review.

BACKGROUND: Chronic radiation proctitis (CRP) is a long-term complication of pelvic radiotherapy that manifests as rectal bleeding, diarrhoea, fistula formation and obstruction. Treatments such as endoscopic argon plasma coagulation, hyperbaric oxygen therapy and rectal topical formalin have imposed a significant medical burden on CRP patients. In contrast, oral therapies offer a more accessible and acceptable option for managing CRP. Here, we conducted a systematic review of the efficacy of oral treatments for CRP to assess their potential as an effective and convenient treatment option for this condition. METHODS: We searched the Cochrane Central Register of Controlled Trials, PubMed, Web of Science, China National Knowledge Infrastructure and Chinese VIP in February 2021. We included post-radiotherapy participants with CRP that compared oral medicine alone or in combination with other treatments versus control treatments. The primary outcomes were bleeding, diarrhoea and symptom score. Heterogeneity between studies was checked using Cochrane Q test statistics and I2 test statistics. The Cochrane risk-of-bias tool was used to assess the quality of the included studies. RESULTS: We included 10 randomised controlled trials (RCTs) and 1 retrospective study with 898 participants. Three placebo-controlled trials evaluated the effects of oral sucralfate on CRP, with meta-analysis showing no significant different with placebo arm. Four trials on TCM demonstrated significant improvement of symptoms, especially for the 3 trials on oral TCM drinks. Retinyl palmitate and high-fibre diet were found to reduce rectal bleeding. The combination of oral pentoxifylline and tocopherol did not significantly change the process of CRP. CONCLUSIONS: Our study implies that oral TCM drinks, retinyl palmitate and a high-fiber diet showed significant improvement in CRP symptoms, but not with the combination of oral pentoxifylline and tocopherol. Further multicentre, larger-scale RCTs are needed to confirm the efficacy and safety of these treatments and optimize treatment strategies, ultimately improving the quality of life for patients with CRP.

Reduction of neuronal hyperexcitability with modulation of T-type calcium channel or SK channel in essential tremor.

Essential tremor is one of the most prevalent movement disorders. Propranolol and primidone are the first-line pharmacological therapies. They provide symptomatic control in less than 50% of patients. Topiramate, alprazolam, clonazepam, gabapentin, and botulinum toxin injections are the next line of treatments. These medications lead to modest improvements and are therefore commonly used as add-on agents. Surgical therapies, including deep brain stimulation (DBS) surgery and focused ultrasound beam targeted to the thalamus, are considered for treating tremor refractory to medications and lead to greater than 75% improvements in tremor symptoms. However, DBS is a costly and an invasive procedure; some patients report tolerance to benefits. Focused ultrasound therapy leading to brain lesions is associated with a possibility for permanent clinical deficits. Therefore, research efforts to develop the next generation of oral medications with greater benefits and lesser adverse effects are warranted. There is considerable evidence that the increased functions of calcium channels (P/Q-type and T-type channels) and reduced functions of calcium-activated potassium channels (SK channels) located in the neuronal membranes lead to tremor oscillations. Consequently, many new pharmacological studies have targeted these channels to leverage better clinical outcomes. The current review will discuss the pathophysiology, the specific importance of these channels, and the early clinical experience of using compounds targeting these channels to treat essential tremor.

New oral and topical approaches for the treatment of melasma.

Melasma is a common, therapeutically challenging, and universally relapsing disorder of hyperpigmentation that is most often observed in women and individuals with Fitzpatrick Skin Types III through VI. The pathogenesis of melasma is complex and protean. Contributing factors that are often implicated in the etiopathogenesis of this condition include a genetic predisposition, intense ultraviolet radiation exposure, and hormonal influences. Therapeutic interventions for melasma include a multimodality approach incorporating photoprotection agents, topical and oral skin lighteners, and resurfacing procedures. Given our expanding knowledge of the pathogenesis of melasma, new and effective treatments are expanding our therapeutic armamentarium. This article reviews new and emerging oral and topical treatments for melasma.

Novel oral-targeted therapies for mucosal healing in ulcerative colitis.

Ulcerative colitis (UC), a chronic, relapsing, remitting disease of the colon and rectum, is characterized by inflammatory ulceration of the mucosa. Current UC therapy relies on controlling acute episodes and preventing relapse. To predict modifications in the natural course of UC, mucosal healing (MH) has emerged as a major treatment goal. Endoscopic evaluation is considered the gold standard for assessing MH, which can be achieved by conventional drugs and biologics in many, but not all, patients. Consequently, interest is focusing on the development of new substances for UC therapy, and new oral agents are in the pipeline. This review will focus on the ability of newly developed oral drugs to induce and maintain MH in UC patients.

A Novel Approach to Better Characterize Medication Adherence in Oral Anticancer Treatments.

Purpose: This study aims to describe a 12-month medication adherence with oral anticancer medications (OAMs) in a routine care medication adherence program, and to better characterize non-persistence. Patients and methods:In this observational, one-centered, longitudinal study, medication adherence was monitored electronically while patients were taking part in a medication adherence program for 12 months or until treatment stop. Patients were >18 years and starting or taking one of the following OAMs: letrozole, exemestane, imatinib, sunitinib, capecitabine, or temozolomide. Non-persistence was defined as any premature treatment interruption due to patient's unilateral decision or to a medical decision because of adverse effects. The Kaplan Meier survival function estimate was used to characterize persistence, and Generalized Estimating Equations (GEE) were adopted to fit implementation. Statistical analyses were performed using the R software package. Results: Forty-three outpatients with various tumor entities were enrolled. Reasons for quitting the medication adherence program and/or OAM medication were characterized as OAM discontinuation due to adverse effects or toxicity (n = 5), planned OAM completion time (n = 10), OAM failure (cancer relapse) (n = 5) and non-compliance to the adherence program (n = 3). In persistent patients, the implementation rates were high (from 98% at baseline to 97% at 12 months). The probability of being persistent at 12 months was estimated at 85%. Conclusion: A better characterization of both persistence and implementation to OAMs in real life settings is crucial for understanding and optimizing medication adherence to OAMs. The complex identification of non-persistence underlines the need to carefully and prospectively assess OAM interruption or treatment switch reasons. The GEE analysis for describing implementation to OAMs will allow researchers and professionals to take advantage of the richness of longitudinal real-time data, to avoid reducing such data through thresholds and to put them into perspective with OAM blood levels.

[French national survey on incoming phone calls in oncology departments]. / Enquête nationale française sur les appels téléphoniques entrants en oncologie médicale.

INTRODUCTION: Oral therapies have shifted the follow-up of patients with cancer from hospital to home. As a consequence, the number of incoming calls has increased. To understand the source, reasons, management and burden of calls, we underwent a French national survey. The objective was to describe the way calls are managed in oncology departments. METHODS: The study was a prospective survey in a representative sample of French oncology specialists using oral therapies. RESULTS: Among 51 participating onco/radiotherapy departments, 86 % of specialists were oncologists or hematologists and 14 % radiation oncologists. Eighty percent were from public centers and 20 % from private ones. The median number of calls/week was 110. Sixty-six percent of calls were from patients and families and 23 % from general practitioners. Upon calls reception by the secretaries, half of them corresponded to a medical question. Sixty-five percent of centers did not have an established specific procedure and 70 % of responders did not specifically train their teams to address the management of calls. Sixty-five percent of the specialists spent more than 30min/day. Most of them considered it disturbing medical activities. Sixty-six percent of patients calls were related to adverse effects of treatments. Twenty-two percent of specialists declared at least one severe adverse effect linked to misinterpretation of a call. DISCUSSION: With the increase of oral therapies, incoming phone calls represent an important burden of work. To improve calls management, adaptations of organizations are needed.

BG-12 and its potential for the prevention of relapse in multiple sclerosis.

Multiple sclerosis (MS) arises from an immune attack on the central nervous system producing demyelination and axonal loss. Clinically the relapsing-remitting course is characterized by subacute onset of neurological symptoms usually with partial or complete recovery, while the progressive course, predominant in the later stages, is characterized by progressive disability in the absence of relapses. A number of disease-modifying treatments have been developed and are increasingly effective at targeting relapses. Early injectable therapies such as interferon and glatiramer acetate are only partially effective, but have a good safety record. Recently, natalizumab, an intravenous therapy, demonstrated increased effectiveness, but side effects complicate its use. The first oral therapy offering good efficacy and convenience, fingolimod, was approved in USA in 2010 and Europe in 2011. BG-12 is a potential novel oral therapy for MS, which has previously been used as a different formulation for psoriasis. It has anti-inflammatory and neuroprotective actions in vitro, which makes it a promising candidate for future therapies. Phase II studies showed that BG-12 reduced MRI inflammatory activity over placebo, which was confirmed in two Phase III studies indicating immune modulation may be its principal action rather than neuroprotection. In these studies, BG-12 reduced relapse rates consistently with variable effects on progression and few serious adverse events. With its favorable efficacy-tolerability profile, BG-12 could offer a substantial step forward for the care for subjects affected by relapsing MS.