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Study protocols for the GEPard project: systematic analysis of sex- and gender-specific differences in the efficacy of perioperative pain management - a two-pronged approach

Por: Floren · S. · Segelcke · D. · Machacek · P. A. · Vollert · J. · Norda · H. · Rohde · I. · Gilron · I. · Pogatzki-Zahn · E. M.
Introduction

Postoperative pain is common, with approximately one-third of surgical patients experiencing severe acute pain and 10–20% developing chronic post-surgical pain (CPSP). Evidence shows that female patients are at higher risk of pain after sex non-specific surgery, thus sex- or gender-specific differences in pain treatment efficacy with potential consequences for perioperative pain management are to be expected. Considering the clinical and societal burden of poorly managed postoperative pain, the GEPard project comprises two systematic reviews, GEPard 1: sex- and/or gender-specific differences in efficacy of perioperative pain management for certain (major) surgical procedures in adult patients; and GEPard 2: sex- and/or gender-specific differences in the dosing, efficacy and adverse effects of the most common systemic perioperative non-opioid- and co-analgesics across all sex non-specific surgical procedures in adult patients.

Methods and analysis

The reviews will be conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Cochrane Handbook. MEDLINE, Embase, Cochrane Library, Web of Science, Scopus, ClinicalTrials.gov and PsycINFO will be searched. We will include randomised controlled trials (RCTs) and systematic reviews/meta-analyses reporting outcomes disaggregated by sex and/or gender in adult surgical patients. For GEPard 1, this applies to selected major surgical procedures; for GEPard 2, to all non-sex-specific surgical procedures. Interventions include regional anaesthesia, systemic analgesics and psychological strategies for GEPard 1 and non-opioid- as well as co-analgesics for GEPard 2. Two reviewers will independently screen and extract the data. Cochrane Risk of Bias Tool 2.0 (RoB 2) and AMSTAR 2 tools will assess study quality. Random-effects or Bayesian meta-analyses will be performed where possible; otherwise, narrative synthesis will be applied. GRADE methodology will assess evidence certainty.

Ethics and dissemination

No ethical approval is required for these reviews. Findings will be disseminated via peer-reviewed publications, patient organisations and professional societies. Data will be shared via Zenodo or Open Science Framework (OSF), following FAIR principles.

PROSPERO registration number

The systematic review protocols for both reviews have been registered in PROSPERO on 29 August 2025 (Registration-ID: CRD420251121393 (GEPard1), CRD420251121536 (GEPard2).

Lets trace: Leishmaniasis in Tuscany (Italy), tracking, research, analysis and continuous evaluation - a retrospective study protocol on underreporting of human cases, geolocation and public health implications

Por: Cosma · C. · Maia · C. · Bonaccorsi · G. · Bonanni · P. · Bianchi · L. · Brunelli · T. · Infantino · M. · Manfredi · M. · Veneziani · F. · Spinicci · M. · Zammarchi · L. · Bartoloni · A. · Malentacchi · F. · Venturini · E. · Galli · L. · Ricci · S. · Profili · F. · Voller · F. · Del Riccio
Introduction

Leishmaniases are a group of vector-borne diseases caused by parasites of the genus Leishmania, which are renowned for increasing global spread due to factors like climate change, globalisation, urbanisation and migration. Leishmaniasis is classified as a neglected tropical disease but is endemic in several areas of the Mediterranean Basin, including Italy, where Leishmania infantum is most involved as the parasite, phlebotomine sand fly as the vector and dog as the principal reservoir. Effective surveillance of communicable infectious diseases is a goal worldwide for organisations such as the WHO and for local and national governments but is an unfulfilled objective. Even in Italy and particularly in the region of Tuscany, despite mandatory reporting, significant gaps each year are identified between reported cases and hospital admissions. By estimating the underreporting of confirmed human leishmaniasis cases, this protocol aims to suggest actions to strengthen the current epidemiological surveillance system to enable timely and effective public health intervention in human and veterinary populations.

Methods and analysis

This retrospective multicentre study, conducted in the Central Tuscany Health District, the most populous area of the Tuscany region with approximately 1.6 million inhabitants, is based on the analysis of data collected from 2014 to 2024 using diagnostic laboratory, hospital and regional information system sources. The primary objective is to estimate the degree of underreporting of leishmaniasis in this area through the application of capture-recapture models. The secondary objective is to analyse the clinical and demographic characteristics of individuals diagnosed as confirmed leishmaniasis cases between January 2014 and December 2024, as well as to perform a geolocation analysis of the cases. The study includes the entire population, both adult and paediatric, of the Central Tuscany Health District who underwent laboratory testing for leishmaniasis (serological tests identifying the presence of antibodies; parasitological examination with evidence of amastigotes in aspirates, smears or biopsy sections; culture examination of aspirates, biopsies and/or peripheral blood positive for the presence of promastigotes; identification of Leishmania nucleic acid in aspirates, biopsies and/or peripheral blood samples via molecular diagnosis).

Ethics and dissemination

The study is being conducted in accordance with the protocol approved by the Ethics Committee of the Tuscany Region – Pediatrics Section, in November 2024. Ethics Committee opinion register number: 219/2024. Because the study uses only pseudonymised, routinely collected administrative and laboratory data with no direct patient contact or intervention, individual informed consent was not required, as confirmed by the Ethics Committee. Findings will be submitted to a peer-reviewed journal, presented at international conferences and presented at stakeholder workshops.

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