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  • Palviainen, Mari J.; Junnikkala, Sami; Raekallio, Marja; Meri, Seppo; Vainio, Outi (2015)
  • Chabok, A; Thorisson, A; Nikberg, M; Schultz, JK; Sallinen, V (2021)
    Left-sided colonic diverticulitis is a common condition with significant morbidity and health care costs in Western countries. Acute uncomplicated diverticulitis which is characterized by the absence of organ dysfunction, abscesses, fistula, or perforations accounts for around 80% of the cases. In the last decades, several traditional paradigms in the management of acute uncomplicated diverticulitis have been replaced by evidence-based routines. This review provides a comprehensive evidence-based and clinical-oriented overview of up-to-date diagnostics with computer tomography, non-antibiotic treatment, outpatient treatment, and surgical strategies as well as follow-up of patients with acute uncomplicated diverticulitis.
  • Paavola, Anne; Bernards, Christopher M.; Rosenberg, Per H. (2016)
    In order to avoid the risks of sideeffects of epidural local anesthetics and opioids, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) epidurally would be an interesting option of analgesic therapy. The fairly short duration of action of spinally administered NSAIDs, e.g., ibuprofen, may be prolonged by using controlled release poloxamer gel formulation. Using a microdialysis technique we studied the epidural and intrathecal pharmacokinetics of ibuprofen after its epidural administration as a poloxamer 407 formulation or a solution formulation. In addition, plasma ibuprofen concentrations were analyzed from central venous blood samples. Ibuprofen concentrations in the epidural space were significantly higher and longer lasting after the epidural gel injection compared with the epidural solution injection. The epidural AUC of ibuprofen was over threefold greater after epidural ibuprofen gel injection compared with the ibuprofen solution injection (p <0.001). The systemic absorption of ibuprofen from 25% poloxamer 407 gel was very low. The in situ forming poloxamer gel acted as a reservoir allowing targeted ibuprofen release at the epidural injection site and restricted ibuprofen molecules to a smaller spinal area. Ibuprofen diffusion from the epidural space to the intrathecal space was steady and prolonged. These results demonstrate that the use of epidurally injectable poloxamer gel can increase and prolong ibuprofen delivery from epidural space to the CSF enhancing thus ibuprofen entry into the central neuroaxis for spinal analgesia. Further toxicological and dose-finding studies are justified. (C) 2016 Elsevier B.V. All rights reserved.
  • Koskensalo, Vilja; Tenca, Andrea; Udd, Marianne; Lindström, Outi; Rainio, Mia; Jokelainen, Kalle; Kylänpää, Leena; Färkkilä, Martti (2020)
    Background The European Society of Gastrointestinal Endoscopy recommends rectal indomethacin or diclofenac before endoscopic retrograde cholangiopancreatography (ERCP) to prevent post-ERCP pancreatitis. However, data on the prophylactic effect in patients with primary sclerosing cholangitis (PSC) are lacking. Methods This was a retrospective case-control study. In 2009-2018, a total of 2000 ERCPs were performed in 931 patients with PSC. Case procedures (N = 1000 after November 2013) were performed after administration of rectal diclofenac. Control procedures (N = 1000 before November 2013) were performed with the same indication but without diclofenac. Acute post-ERCP pancreatitis and other ERCP-related adverse events (AEs) were evaluated. Results Post-ERCP pancreatitis developed in 49 (4.9%) procedures in the diclofenac group and 62 (6.2%) procedures in the control group (p = 0.241). No difference existed between the groups in terms of the severity of pancreatitis or any other acute AEs. The risk of pancreatitis was elevated in patients with native papilla: 11.4% in the diclofenac group and 8.7% in the control group (p = 0.294). In adjusted logistic regression, diclofenac did not reduce the risk of pancreatitis (odds ratio (OR) = 1.074, 95% confidence interval 0.708-1.629, p = 0.737). However, in generalised estimation equations with the advanced model, diclofenac seemed to diminish the risk of pancreatitis (OR = 0.503) but not significantly (p = 0.110). Conclusion In this large patient cohort in a low-risk unit, diclofenac does not seem to reduce the risk of post-ERCP pancreatitis in patients with PSC. The trend in the pancreatitis rate after ERCP is decreasing. The evaluation of the benefits of diclofenac among PSC patients warrants a randomised controlled study targeted to high-risk patients and procedures.
  • Rainio, Mia; Lindström, Outi; Udd, Marianne; Louhimo, Johanna; Kylänpää, Leena (2017)
    Background Nonsteroidal anti-inflammatory drugs have an inhibitory role in pathogenesis of pancreatitis. Guidelines from the European Society of Gastrointestinal Endoscopy recommend routine rectal administration of 100 mg of diclofenac or indomethacin immediately before or after ERCP for all patients without contraindications. Aims Our aim was to evaluate the effect of diclofenac in preventing post-ERCP pancreatitis (PEP) in a high-volume, low-PEP-risk ERCP unit. Methods The rate and severity of PEP were compared in groups of 1000 historical controls prior to the routine use of diclofenac and in 1000 patients receiving 100 mg diclofenac before ERCP. Results PEP occurred in 56 (2.8%) of the 2000 patients, and the rate of the pancreatitis was 2.8% in control group and 2.8% in diclofenac group (p = 1.000). The PEP rate among the native papilla patients was 3.9% in control group and 3.6% in diclofenac group (p = 0.803). In subgroup analysis of patients with a high risk of PEP, diclofenac neither prevented PEP nor made its course milder. Conclusions In an unselected patient population in a center with a low incidence of PEP, diclofenac seems to have no beneficial effect.
  • Wilkosz, Natalia; Rissanen, Sami; Cyza, Malgorzata; Szybka, Renata; Nowakowska, Maria; Bunker, Alex; Rog, Tomasz; Kepczynski, Mariusz (2017)
    Uptake of piroxicam, a non-steroidal anti-inflammatory drug, from the intestines after oral intake is limited due to its low solubility and its wide use is associated with several side effects related to the gastrointestinal tract. In this study, all-atom molecular dynamics (MD) simulations and fluorescent spectroscopy were employed to investigate the interaction of piroxicam in neutral, zwitterionic, and cationic forms with lipid bilayers composed of phosphatidylcholine, cholesterol, and PEGylated lipids. Our study was aimed to assess the potential for encapsulation of piroxicam in liposomal carriers and to shed more light on the process of gastrointestinal tract injury by the drug. Through both the MD simulations and laser scanning confocal microscopy, we have demonstrated that all forms of piroxicam can associate with the lipid bilayers and locate close to the water-membrane interface. Conventional liposomes used in drug delivery are usually stabilized by the addition of cholesterol and have their bloodstream lifetime extended through the inclusion of PEGylated lipids in the formulation to create a protective polymer corona. For this reason, we tested the effect of these two modifications on the behavior of piroxicam in the membrane. When the bilayer was PEGylated, piroxicam localize to the PEG layer and within the lipid headgroup region. This suggests that PEGylated liposomes are capable of carrying a larger quantity of piroxicam than the conventional ones. (C) 2017 Elsevier B.V. All rights reserved.
  • Kress, Hans-Georg; Ahlbeck, Karsten; Aldington, Dominic; Alon, Eli; Coaccioli, Stefano; Coluzzi, Flaminia; Huygen, Frank; Jaksch, Wolfgang; Kalso, Eija; Kocot-Kepska, Magdalena; Mangas, Ana Cristina; Margarit Ferri, Cesar; Morlion, Bart; Mueller-Schwefe, Gerhard; Nicolaou, Andrew; Perez Hernandez, Concepcion; Pergolizzi, Joseph; Schaefer, Michael; Sichere, Patrick (2014)
  • Saavalainen, L.; But, A.; Tiitinen, A.; Härkki, P.; Gissler, M.; Haukka, J.; Heikinheimo, O. (2019)
    STUDY QUESTION Is all-cause and cause-specific mortality increased among women with surgically verified endometriosis? SUMMARY ANSWER The all-cause and cause-specific mortality in midlife was lower throughout the follow-up among women with surgically verified endometriosis compared to the reference cohort. WHAT IS KNOWN ALREADY Endometriosis has been associated with an increased risk of comorbidities such as certain cancers and cardiovascular diseases. These diseases are also common causes of death; however, little is known about the mortality of women with endometriosis. STUDY DESIGN, SIZE, DURATION A nationwide retrospective cohort study of women with surgically verified diagnosis of endometriosis was compared to the reference cohort in Finland (1987-2012). Follow-up ended at death or 31 December 2014. During the median follow-up of 17years, 2.5 million person-years accumulated. PARTICIPANTS/MATERIALS, SETTING, METHODS Forty-nine thousand nine hundred and fifty-six women with at least one record of surgically verified diagnosis of endometriosis in the Finnish Hospital Discharge Register between 1987 and 2012 were compared to a reference cohort of 98824 age- and municipality-matched women. The age (meanstandard deviation) of the endometriosis cohort was 36.49.0 and 53.612.1years at the beginning and at the end of the follow-up, respectively. By using the Poisson regression models the crude and adjusted all-cause and cause-specific mortality rate ratios (MRR) and 95% confidence intervals (CI) were assessed. Calendar time, age, time since the start of follow-up, educational level, and parity adjusted were considered in the multivariate analyses. MAIN RESULTS AND THE ROLE OF CHANCE A total of 1656 and 4291 deaths occurred in the endometriosis and reference cohorts, respectively. A lower all-cause mortality was observed for the endometriosis cohort (adjusted MRR, 0.73 [95% CI 0.69 to 0.77])-there were four deaths less per 1000 women over 10years. A lower cause-specific mortality contributed to this: the adjusted MRR was 0.88 (95% CI 0.81 to 0.96) for any cancer and 0.55 (95% CI 0.47 to 0.65) for cardiovascular diseases, including 0.52 (95% CI 0.42 to 0.64) for ischemic heart disease and 0.60 (95% CI 0.47 to 0.76) for cerebrovascular disease. Mortality due to alcohol, accidents and violence, respiratory, and digestive disease-related causes was also decreased. LIMITATIONS, REASONS FOR CAUSATION These results are limited to women with endometriosis diagnosed by surgery. In addition, the study does not extend into the oldest age groups. The results might be explained by the characteristics and factors related to women's lifestyle, and/or increased medical attention and care received, rather than the disease itself. WIDER IMPLICATIONS OF THE FINDINGS These reassuring data are valuable to women with endometriosis and to their health care providers. Nonetheless, more studies are needed to address the causality. STUDY FUNDING/COMPETING INTEREST This research was funded by the Hospital District of Helsinki and Uusimaa and The Finnish Medical Foundation. None of the authors report any competing interest in relation to the present work; all the authors have completed the disclosure form.
  • Ortúzar, Maite; Esterhuizen, Maranda; Olicón-Hernández, Darío Rafael; González-López, Jesús; Aranda, Elisabet (2022)
    The presence of emerging contaminants in the environment, such as pharmaceuticals, is a growing global concern. The excessive use of medication globally, together with the recalcitrance of pharmaceuticals in traditional wastewater treatment systems, has caused these compounds to present a severe environmental problem. In recent years, the increase in their availability, access and use of drugs has caused concentrations in water bodies to rise substantially. Considered as emerging contaminants, pharmaceuticals represent a challenge in the field of environmental remediation; therefore, alternative add-on systems for traditional wastewater treatment plants are continuously being developed to mitigate their impact and reduce their effects on the environment and human health. In this review, we describe the current status and impact of pharmaceutical compounds as emerging contaminants, focusing on their presence in water bodies, and analyzing the development of bioremediation systems, especially mycoremediation, for the removal of these pharmaceutical compounds with a special focus on fungal technologies.
  • Coccolini, Federico; Corradi, Francesco; Sartelli, Massimo; Coimbra, Raul; Kryvoruchko, Igor A.; Leppaniemi, Ari; Doklestic, Krstina; Bignami, Elena; Biancofiore, Giandomenico; Bala, Miklosh; Marco, Ceresoli; Damaskos, Dimitris; Biffl, Walt L.; Fugazzola, Paola; Santonastaso, Domenico; Agnoletti, Vanni; Sbarbaro, Catia; Nacoti, Mirco; Hardcastle, Timothy C.; Mariani, Diego; De Simone, Belinda; Tolonen, Matti; Ball, Chad; Podda, Mauro; Di Carlo, Isidoro; Di Saverio, Salomone; Navsaria, Pradeep; Bonavina, Luigi; Abu-Zidan, Fikri; Soreide, Kjetil; Fraga, Gustavo P.; Carvalho, Vanessa Henriques; Batista, Sergio Faria; Hecker, Andreas; Cucchetti, Alessandro; Ercolani, Giorgio; Tartaglia, Dario; Galante, Joseph M.; Wani, Imtiaz; Kurihara, Hayato; Tan, Edward; Litvin, Andrey; Melotti, Rita Maria; Sganga, Gabriele; Zoro, Tamara; Isirdi, Alessandro; De'Angelis, Nicola; Weber, Dieter G.; Hodonou, Adrien M.; TenBroek, Richard; Parini, Dario; Khan, Jim; Sbrana, Giovanni; Coniglio, Carlo; Giarratano, Antonino; Gratarola, Angelo; Zaghi, Claudia; Romeo, Oreste; Kelly, Michael; Forfori, Francesco; Chiarugi, Massimo; Moore, Ernest E.; Catena, Fausto; Malbrain, Manu L. N. G. (2022)
    Background Non-traumatic emergency general surgery involves a heterogeneous population that may present with several underlying diseases. Timeous emergency surgical treatment should be supplemented with high-quality perioperative care, ideally performed by multidisciplinary teams trained to identify and handle complex postoperative courses. Uncontrolled or poorly controlled acute postoperative pain may result in significant complications. While pain management after elective surgery has been standardized in perioperative pathways, the traditional perioperative treatment of patients undergoing emergency surgery is often a haphazard practice. The present recommended pain management guidelines are for pain management after non-traumatic emergency surgical intervention. It is meant to provide clinicians a list of indications to prescribe the optimal analgesics even in the absence of a multidisciplinary pain team. Material and methods An international expert panel discussed the different issues in subsequent rounds. Four international recognized scientific societies: World Society of Emergency Surgery (WSES), Global Alliance for Infection in Surgery (GAIS), Italian Society of Anesthesia, Analgesia Intensive Care (SIAARTI), and American Association for the Surgery of Trauma (AAST), endorsed the project and approved the final manuscript. Conclusion Dealing with acute postoperative pain in the emergency abdominal surgery setting is complex, requires special attention, and should be multidisciplinary. Several tools are available, and their combination is mandatory whenever is possible. Analgesic approach to the various situations and conditions should be patient based and tailored according to procedure, pathology, age, response, and available expertise. A better understanding of the patho-mechanisms of postoperative pain for short- and long-term outcomes is necessary to improve prophylactic and treatment strategies.
  • Kuusniemi, Kristiina; Pöyhiä, Reino (2016)
    This paper is a summary of presentations on postoperative pain control by the authors at the 2014 PainForum meeting in People's Republic of China. Postoperative pain is often untreated or undertreated and may lead to subsequent chronic pain syndromes. As more procedures migrate to the outpatient setting, postoperative pain control will become increasingly more challenging. Evidence-based guidelines for postoperative pain control recommend pain assessment using validated tools on a consistent basis. In this regard, consistency may be more important than the specific tool selected. Many hospitals have introduced a multidisciplinary acute pain service (APS), which has been associated with improved patient satisfaction and fewer adverse events. Patient education is an important component of postoperative pain control, which may be most effective when clinicians chose a multimodal approach, such as paracetamol (acetaminophen) and opioids. Opioids are a mainstay of postoperative pain control but require careful monitoring and management of side effects, such as nausea, vomiting, dizziness, and somnolence. Opioids may be administered using patient-controlled analgesia systems. Protocols for postoperative pain control can be very helpful to establish benchmarks for pain management and assure that clinicians adhere to evidence-based standards. The future of postoperative pain control around the world will likely involve more and better established APSs and greater communication between patients and clinicians about postoperative pain. The changes necessary to implement and move forward with APSs is not a single step but rather one of continuous improvement and ongoing change.
  • Bally, Michele; Dendukuri, Nandini; Rich, Benjamin; Nadeau, Lyne; Helin-Salmivaara, Arja; Garbe, Edeltraut; Brophy, James M. (2017)
    OBJECTIVE To characterise the determinants, time course, and risks of acute myocardial infarction associated with use of oral non-steroidal anti-inflammatory drugs (NSAIDs). DESIGN Systematic review followed by a one stage bayesian individual patient data meta-analysis. DATA SOURCES Studies from Canadian and European healthcare databases. REVIEW METHODS Eligible studies were sourced from computerised drug prescription or medical databases, conducted in the general or an elderly population, documented acute myocardial infarction as specific outcome, studied selective cyclo-oxygenase-2 inhibitors (including rofecoxib) and traditional NSAIDs, compared risk of acute myocardial infarction in NSAID users with non-users, allowed for time dependent analyses, and minimised effects of confounding and misclassification bias. EXPOSURE AND OUTCOMES Drug exposure was modelled as an indicator variable incorporating the specific NSAID, its recency, duration of use, and dose. The outcome measures were the summary adjusted odds ratios of first acute myocardial infarction after study entry for each category of NSAID use at index date (date of acute myocardial infarction for cases, matched date for controls) versus non-use in the preceding year and the posterior probability of acute myocardial infarction. RESULTS A cohort of 446 763 individuals including 61 460 with acute myocardial infarction was acquired. Taking any dose of NSAIDs for one week, one month, or more than a month was associated with an increased risk of myocardial infarction. With use for one to seven days the probability of increased myocardial infarction risk (posterior probability of odds ratio >1.0) was 92% for celecoxib, 97% for ibuprofen, and 99% for diclofenac, naproxen, and rofecoxib. The corresponding odds ratios (95% credible intervals) were 1.24 (0.91 to 1.82) for celecoxib, 1.48 (1.00 to 2.26) for ibuprofen, 1.50 (1.06 to 2.04) for diclofenac, 1.53 (1.07 to 2.33) for naproxen, and 1.58 (1.07 to 2.17) for rofecoxib. Greater risk of myocardial infarction was documented for higher dose of NSAIDs. With use for longer than one month, risks did not appear to exceed those associated with shorter durations. CONCLUSIONS All NSAIDs, including naproxen, were found to be associated with an increased risk of acute myocardial infarction. Risk of myocardial infarction with celecoxib was comparable to that of traditional NSAIDS and was lower than for rofecoxib. Risk was greatest during the first month of NSAID use and with higher doses.
  • Tolska, H. K.; Hamunen, K.; Takala, A.; Kontinen, V. K. (2019)
    Background: Intense pain can last several days after tonsillectomy. It is often undertreated and improved analgesic strategies that can be safely used at home are needed. Methods: We conducted a systematic review and meta-analysis on the effectiveness of systemic medications used for post-tonsillectomy pain in adult and adolescent (13 yr old) patients. Studies were identified from PubMed, the Cochrane Library, and by hand searching reference lists from studies and review articles. Randomised, double-blind, placebo-controlled studies reporting on pain intensity or use of rescue analgesia were included. Results: Twenty-nine randomised controlled trials representing 1816 subjects met the inclusion criteria. Follow-up time was Conclusions: Single analgesics and dexamethasone provide only a weak to moderate effect for post-tonsillectomy pain on the day of operation and thus a multimodal analgesic strategy is recommended. Short follow-up times and clinical heterogeneity of studies limit the usefulness of results.
  • Järvinen, Erkka; Deng, Feng; Kiander, Wilma; Sinokki, Alli; Kidron, Heidi; Sjöstedt, Noora (2022)
    Glucuronidation and sulfation are the most typical phase II metabolic reactions of drugs. The resulting glucuronide and sulfate conjugates are generally considered inactive and safe. They may, however, be the most prominent drug-related material in the circulation and excreta of humans. The glucuronide and sulfate metabolites of drugs typically have limited cell membrane permeability and subsequently, their distribution and excretion from the human body requires transport proteins. Uptake transporters, such as organic anion transporters (OATs and OATPs), mediate the uptake of conjugates into the liver and kidney, while efflux transporters, such as multidrug resistance proteins (MRPs) and breast cancer resistance protein (BCRP), mediate expulsion of conjugates into bile, urine and the intestinal lumen. Understanding the active transport of conjugated drug metabolites is important for predicting the fate of a drug in the body and its safety and efficacy. The aim of this review is to compile the understanding of transporter-mediated disposition of phase II conjugates. We review the literature on hepatic, intestinal and renal uptake transporters participating in the transport of glucuronide and sulfate metabolites of drugs, other xenobiotics and endobiotics. In addition, we provide an update on the involvement of efflux transporters in the disposition of glucuronide and sulfate metabolites. Finally, we discuss the interplay between uptake and efflux transport in the intestine, liver and kidneys as well as the role of transporters in glucuronide and sulfate conjugate toxicity, drug interactions, pharmacogenetics and species differences.