How is safety of dermatology drugs assessed: trials,registries, and spontaneous reporting

ABSTRACT

Introduction: Skin conditions are common and highly varied in their etiology; therefore, a diverse array of therapeutics are utilized. Drug safety studies in dermatology can be challenging as there are over 3000 diagnoses to consider. As a result, dermatologists rely on data from multiple sources including clinical trials and real-world evidence.

Areas covered: In this review, we cover the main sources of safety data available, their strengths and weaknesses and how dermatologists should utilize such data. We use real-world examples of the different types of adverse events reported and how they are best captured by either randomized controlled trials or post-marketing pharmacovigilance methods. With multiple new therapies in dermatology, such as dupilumab for atopic dermatitis and janus-kinase inhibitors for alopecia areata the specialty is awash with evolving high-level evidence for their use. It is important to understand the optimal way to assess safety from trials but also appreciate the need for ongoing capture of safety data in clinical practice.

Expert opinion: In dermatology, there is a plethora of conditions to treat and clinical trials, post-marketing surveillance, such as drug registries and spontaneous reporting, all enable dermatologists to gain a more comprehensive understanding of the safety profiles of drugs being used.     

Comparison of DNA fragmentation levels in spermatozoa with different sex chromosome complements

Research question

Do spermatozoa with different sex chromosome complements (X and Y; aneuploidy and monosomy) exhibit different degrees of DNA damage?

Oral health behaviors of preschool children with cerebral palsy: a case‐control community‐based study

To describe and compare the oral health behaviors of preschool children with and without cerebral palsy (CP), and to assess the oral health knowledge and attitudes of their primary caregivers (PCGs). Seventy‐two preschool children with CP were recruited from 23 Special Child Care Centers in Hong Kong. An age‐ (±3 months) and gender‐matched sample of children from mainstream preschools was recruited as a “control group.” Assessment of children's oral health behaviors and the PCGs' oral health knowledge and attitudes was conducted using questionnaires. Preschool children with CP were less likely to have ever attended a dentist (p < 0.05). Tooth brushing frequency was similar between the two groups (p > 0.05), but PCGs of children with CP more frequently reported provision of tooth brushing assistance to their children (p < 0.001). PCGs in both groups had similar oral health knowledge and attitudes (p > 0.05). Difference in oral health behaviors existed between preschool children with and without CP. PCGs of children with and without CP had similar oral health knowledge and attitudes.     

Prostate cancer detection upon transrectal ultrasound-guided biopsy in relation to digital rectal examination and prostate-specific antigen level: what to expect in the Chinese population?

We investigated the prostate cancer detection rates upon transrectal ultrasound (TRUS)-guided biopsy in relation to digital rectal examination (DRE) and prostate-specific antigen (PSA), and risk factors of prostate cancer detection in the Chinese population. Data from all consecutive Chinese men who underwent first TRUS-guided prostate biopsy from year 2000 to 2013 was retrieved from our database. The prostate cancer detection rates with reference to DRE finding and PSA level of < 4, 4–10, 10.1–20, 20.1–50 and > 50 ng ml⁻¹ were investigated. Multivariate logistic regression analyses were performed to investigate for potential risk factors of prostate cancer detection. A total of 2606 Chinese men were included. In patients with normal DRE, the cancer detection rates were 8.6%, 13.4%, 21.8%, 41.7% and 85.2% in patients with PSA < 4, 4–10, 10.1–20, 20.1–50 and > 50 ng ml⁻¹ respectively. In patients with abnormal DRE, the cancer detection rates were 12.4%, 30.2%, 52.7%, 80.6% and 96.4% in patients with PSA < 4, 4–10, 10.1–20, 20.1–50 and > 50 ng ml⁻¹ respectively. Older age, smaller prostate volume, larger number of biopsy cores, presence of abnormal DRE finding and higher PSA level were associated with increased risk of prostate cancer detection upon multivariate logistic regression analyses (P < 0.001). Chinese men appeared to have lower prostate cancer detection rates when compared to the Western population. Taking the different risk factors into account, an individualized approach to the decision of TRUS-guided biopsy can be adopted.     

Implant treatment of macroglossia and edentulous mandible following radiotherapy for nasopharyngeal cancer: a case report.

Radiotherapy for the nasopharyngeal cancer patient with poor oral care may lead to severe deterioration of the dentition and may require multiple extractions. Although the use of an implant-retained overdenture can successfully restore the function and esthetics of edentulous patients, its use can be complicated by the tissue changes subsequent to head and neck irradiation. The difficulties in implant treatment planning for an edentulous patient with macroglossia and soft tissue changes following radiotherapy are discussed.     

Single-bottle adhesives behave as permeable membranes after polymerisation. II. Differential permeability reduction with an oxalate desensitiser

OBJECTIVES: This study examined the changes in hydraulic conductance and ultrastructure of dentine bonded with simplified etch-and-rinse adhesives to oxalate desensitiser pre-treated acid-etched dentine. METHODS: Human dentine disks were acid-etched, treated with an oxalate desensitiser (BisBlock, Bisco), and bonded with One-Step (OS), Single Bond (SB), OptiBond Solo Plus (OB) or Prime and Bond NT (PB). Similar disks from each group were acid-etched, and bonded without oxalate pre-treatment. Hydraulic conductance of the specimens was measured at 20 cm of water pressure and analysed with nonparametric statistical methods. Epoxy resin replicas of the smear layer-covered dentine and bonded dentine were examined with SEM for the extent of fluid transudation. Specimens bonded under perfusion were examined with TEM after tracer immersion. RESULTS: OB and PB exhibited a highly significant reversal of the reduced hydraulic conductance obtained with BisBlock on unbonded acid-etched dentine. Profuse water transudation across the bonded dentine was observed from the replicas. Adhesive interfaces were covered with spherical globules that interfered with dentine hybridization. Conversely, no significant difference in hydraulic conductance was observed in SB, between Bisblock pre-treated, unbonded and bonded acid-etched dentine. Significantly lower hydraulic conductance was shown on application of OS to Bisblock-treated acid-etched dentine. Water transudation was sparse, interfering surface globular structures were absent, and only angular subsurface crystals were seen in the dentinal tubules. CONCLUSIONS: Convective water fluxes through dentine may be reduced by applying Bisblock to acid-etched dentine before bonding with One-Step or Single Bond. However, reducing adhesive permeability with the use of oxalate desensitiser is not applicable to low acidity adhesives such as OptiBond Solo Plus and Prime and Bond NT.     

Hypohyperdontia: literature review and report of seven cases

Hypodontia in combination with hyperdontia (hypohyperdontia) is a condition of mixed numeric variation in the human dentition. A comprehensive review on the hypohyperdontia literatures reported prevalence ranges from 0.002% to 3.1%. Our seven cases of hypohyperdontia involved both the maxillary and the mandibular arches. A traditional narrative review is included to describe the prevalence, etiology, and previously reported cases on hypohyperdontia. Furthermore, we opine that comprehensive clinical and radiographic examinations are essential for recognizing such rare dental anomalies. Judicious use of radiographs not only enhances the detection of hypohyperdontia, but also leads to changes in the course of management.