Introduction: We aimed to investigate the pharmacokinetic properties and safety of melatonin administered by alternative routes of administration. Methods: This study employed a cross-over design in healthy female volunteers. Twenty-five milligrams of melatonin was administered intravenously, intravesically, rectally, transdermally, and vaginally. Blood samples were collected at specified time points up to 24 h following intravenous, intravesical, rectal, and vaginal administration, and up to 48 h following transdermal administration. Plasma melatonin concentrations were determined by radioimmunoassay. Sedation was evaluated by a simple reactiontime test, and sleepiness was assessed by the Karolinska Sleepiness Scale. Adverse events were registered for each route of administration. Results: Ten participants were included. We documented a mean (SD) time to maximal concentration of 51 (29) min for intravesical, 24 (20) min for rectal, 21 (8) h for transdermal, and 147 (56) min for vaginal administration. The mean (SD) elimination half-life was 47 (6) min for intravenous, 58 (7) min for intravesical, 60 (18) min for rectal, 14.6 (11.1) h for transdermal, and 129 (17) min for vaginal administration. The mean (SD) bioavailability was 3.6 (1.9)% for intravesical, 36.0 (28.6)% for rectal, 10.0 (5.7)% for transdermal, and 97.8 (31.7)% for vaginal administration. No significant changes in reaction times were observed following administration of melatonin by any of the administration routes. Increased tiredness was documented following transdermal administration only. No serious adverse effects were documented. Conclusion: Rectally and vaginally administered melatonin may serve as relevant alternatives to standard oral melatonin therapy. Transdermal delivery of melatonin displayed an extended absorption and can be applied if prolonged effects are intended. Intravesical administration displayed, as expected, a very limited bioavailability. Melatonin administered by these routes of administration was safe.

Purpose To systematically assess the validity of patient-reported outcome measures (PROMs) for patients undergoing inguinal hernia repair. Data sources A systematic review was performed according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guideline for systematic reviews of PROMs. PubMed, EMBASE and PsycINFO were consulted. Study selection Only studies explicitly aimed at validation of PROMs specific for patients with inguinal hernia were included. Data extraction Data regarding measurement properties of PROMs were extracted from the included studies. Each study was critically assessed for methodological quality and each PROM was evaluated for sufficient measurement properties. Results of data synthesis We included 15 studies, covering 11 different PROMs. The Carolinas Comfort Scale was the most frequently investigated PROM, being covered in five of the included publications. The included PROMs were evaluated according to nine different measurement properties, of which internal consistency and construct validity were the most frequently assessed. Evidence regarding content validity and structural validity was universally inadequate, according to the criteria for good measurement properties, as defined by the COSMIN. Conclusion Based on the current evidence, it is not possible to formulate recommendations for application of PROMs for patients undergoing inguinal hernia repair. Further validation of the included PROMs is necessary especially regarding content validity and structural validity.

There are many ways to determine the success of an inguinal hernia operation. Traditional measures are hernia recurrence, neuralgia, mesh infection, or rather the absence of these complications. While these traditional measures obviously have their merits, alternative outcomes are emerging, and researchers and clinicians are gaining an increasing interest in patient-reported outcomes and patient reported outcome measures (PROMs). PROMs are patient questionnaires concerning quality of life, chronic pain, disability, or other subjects that are best assessed by the patients. PROMs come in two different forms: generic and condition specific. The generic PROMs concern general symptoms and issues, while the condition-specific PROMs target patients with a certain condition. Inguinal hernia-specific PROMs typically address issues like mesh-related symptoms, groin pain, sexual dysfunction, etc. Clinical measurement instruments such as PROMs should be carefully validated according to standardized guidelines to ensure their psychometric measurement properties. Unfortunately, this type of evidence is often lacking when it comes to inguinal hernia-specific PROMs. In this review, we explain why PROMs are useful for patients with inguinal hernia and why one should use inguinal hernia-specific PROMs as opposed to the generic ones. We address the importance of population-specific validation and explain what type of evidence is lacking. Last, we discuss the future prospects of using PROMs for patients with inguinal hernia.