| 1. |
- Affas, Fatin, et al.
(författare)
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Pain control after total knee arthroplasty : a randomized trial comparing local infiltration anesthesia and continuous femoral block
- 2011
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Ingår i: Acta Orthopaedica. - New York : Taylor & Francis. - 1745-3674 .- 1745-3682. ; 82:4, s. 441-447
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Pain after total knee arthroplasty (TKA) is usually severe, and epidural analgesia or femoral nerve block has been considered to be an effective pain treatment. Recently, local infiltration analgesia (LIA) has become increasingly popular but the outcome of this method regarding the analgesic effect has not been fully evaluated. We compared local infiltration analgesia and femoral block with regard to analgesia and morphine demand during the first 24 h after TKA.METHODS: 40 patients undergoing TKA under spinal anesthesia were randomized to receive femoral nerve block (group F) or peri- and intraarticular infiltration analgesia (group LIA) with a mixture containing ropivacaine, ketorolac, and epinephrine. All patients had access to intravenous patient-controlled analgesia (PCA) with morphine postoperatively. Pain intensity at rest and upon movement was assessed on a numeric rating scale (0-10) on an hourly basis over 24 h if the patients were awake.RESULTS: The average pain at rest was marginally lower with LIA (1.6) than with femoral block (2.2). Total morphine consumption per kg was similar between the 2 groups. Ancillary analysis revealed that 1 of 20 patients in the LIA group reported a pain intensity of > 7 upon movement, as compared to 7 out of 19 in the femoral block group (p = 0.04).INTERPRETATION: Both LIA and femoral block provide good analgesia after TKA. LIA may be considered to be superior to femoral block since it is cheaper and easier to perform.
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| 2. |
- Al Dabbagh, Zewar, et al.
(författare)
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No signs of dose escalations of potent opioids prescribed after tibial shaft fractures : a study of Swedish National Registries
- 2014
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Ingår i: BMC Anesthesiology. - London : BioMed Central. - 1471-2253 .- 1471-2253. ; 14, s. 4-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The pattern of opioid use after skeletal trauma is a neglected topic in pain medicine. The purpose of this study was to analyse the long-term prescriptions of potent opioids among patients with tibial shaft fractures.Methods: Data were extracted from the Swedish National Hospital Discharge Register, the National Pharmacy Register, and the Total Population Register, and analysed accordingly. The study period was 2005-2008.Results: We identified 2,571 patients with isolated tibial shaft fractures. Of these, 639 (25%) collected a prescription for opioids after the fracture. The median follow-up time was 17 (interquartile range [IQR] 7-27) months. Most patients with opioid prescriptions after fracture were male (61%) and the median age was 45 (16-97) years. The leading mechanism of injury was fall on the same level (41%). At 6 and 12 months after fracture, 21% (95% CI 17-24) and 14% (11-17) were still being treated with opioids. Multiple Cox regression-analysis (adjusted for age, sex, type of treatment, and mechanism of injury) revealed that older patients (age >50 years) were more likely to end opioid prescriptions (Hazard ratio 1.5 [95% CI 1.3-1.9]). During follow-up, the frequency of patients on moderate and high doses declined. Comparison of the daily morphine equivalent dose among individuals who both had prescriptions during the first 3 months and the 6th month indicated that the majority of these patients (11/14) did not have dose escalations.Conclusions: We did not see any signs in registry-data of major dose escalations over time in patients on potent opioids after tibial shaft fractures.
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| 3. |
- Gustafsson, Lars L., et al.
(författare)
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The 'wise list'- a comprehensive concept to select, communicate and achieve adherence to recommendations of essential drugs in ambulatory care in Stockholm
- 2011
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - Copenhagen : Blackwell Publishing. - 1742-7835 .- 1742-7843. ; 108:4, s. 224-233
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to present and evaluate the impact of a comprehensive strategy over 10 years to select, communicate and achieve adherence to essential drug recommendations (EDR) in ambulatory care in a metropolitan healthcare region. EDRs were issued and launched as a 'Wise List' by the regional Drug and Therapeutics Committee in Stockholm. This study presents the concept by: (i) documenting the process for selecting, communicating and monitoring the impact of the 'Wise List'; (ii) analysing the variation in the number of drug substances recommended between 2000 and 2010; (iii) assessing the attitudes to the 'Wise List' among prescribers and the public; (iv) evaluating the adherence to recommendations between 2003 and 2009. The 'Wise List' consistently contained 200 drug substances for treating common diseases. The drugs were selected based on their efficacy, safety, suitability and cost-effectiveness. The 'Wise List' was known among one-third of a surveyed sample of the public in 2002 after initial marketing campaigns. All surveyed prescribers knew about the concept and 81% found the recommendations trustworthy in 2005. Adherence to recommendations increased from 69% in 1999 to 77% in 2009. In primary care, adherence increased from 83% to 87% from 2003 to 2009. The coefficient of variation (CV%) decreased from 6.1% to 3.8% for 156 healthcare centres between these years. The acceptance of the 'Wise List' in terms of trust among physicians and among the public and increased adherence may be explained by clear criteria for drug recommendations, a comprehensive communication strategy, electronic access to recommendations, continuous medical education and involvement of professional networks and patients.
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| 4. |
- Kling, Anders, 1965-
(författare)
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5-HT2A : a serotonin receptor with a possible role in joint diseases
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundSerotonin (5-HT), an amino acid derivative and neurotransmitter, has for long been studied in relation to inflammation. It is an endogenous ligand for several different types of serotonin receptors. The serotonin receptor 5-HT2A has been reported to have a role in the pathophysiology of arthritis in animal experiment models. However, no studies into this subject have been reported in man.ObjectiveThe objectives of this project were firstly, to examine possible associations for the 5-HT2A receptor and also for the gene (HTR2A) encoding for the receptor with arthritis in man and secondly, to explore possible mechanisms underlying such associations.MethodsThe density and affinity of platelet 5-HT2A receptors were determined in 43 patients with a common inflammatory joint disease, i. e., rheumatoid arthritis (RA), in comparison with matched controls using a radio-ligand assay. The effects of treatment with prednisolone on 5-HT2A density and affinity were also examined in 27 individuals diagnosed with polymyalgia rheumatica before and after start of treatment. In addition, possible candidate HTR2A genes were studied in relation to RA in two Swedish cohorts incorporating a total of 2450 RA patients. Furthermore, a register study using reports of joint symptoms as adverse drug reactions (ADRs) in the Swedish and the WHO ADR databases was undertaken. The proportion of reports concerning joint symptoms in relation to all ADR reports and to sales figures was analysed for 5-HT2A blocking atypical antidepressant substances compared with another group of antidepressants, i. e., selective serotonin re-uptake inhibitors (SSRIs), used for similar clinical indications.ResultsThe mean density of 5-HT2A receptors in RA patients was significantly lower than in controls, 45.3 versus 57.4 fmol/mg protein (p = 0.004). There was no significant difference in affinity. Variation of four single nucleotide polymorphisms (SNPs) (rs6314, rs1328674, rs6313 and rs6311) in the HTR2A gene was associated with RA, although not significantly so for all SNPs after testing for multiple comparisons. The proportion of joint symptoms reported as ADRs, relative to all ADRs was significantly higher for the 5-HT2A blocking antidepressants compared with the SSRIs in both databases (p< 0.001). In the Swedish material the comparison of ADRs was also related to sales figures, showing a considerable higher frequency of joint symptoms for the 5-HT2A antagonists (p< 0.001). The density of 5-HT2A receptors increased after treatment with prednisolone in 23 out of 27 individuals. The mean density at baseline was 45.2 versus 64.9 fmol/mg protein at the end of the study (p=0.001). There were no significant differences in affinity during the treatment period, although a low affinity at baseline was a predictor for higher density following treatment with prednisolone.ConclusionsThe density of 5-HT2A receptors, reflecting the number of receptors, was markedly reduced in a cohort of patients with RA from Northern Sweden. This may depend, at least in part, on an association between RA and certain HTR2A SNPs. Genetically determined or acquired low levels of accessible 5-HT2A receptors may contribute to susceptibility for development of joint symptoms, not only in RA but more generally, e. g., joint ADRs caused by 5-HT2A blocking atypical antidepressants. The benefits of treatment with glucocorticoids may, at least partially, be mediated by an effect on 5-HT2A receptors.
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| 5. |
- Stiller, Carl-Olav
(författare)
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Neurotransmission in CNS regions involved in pain modulation : neurochemical effects of analgesic drugs and spinal cord stimulation in the spinal cord and midbrain periaqueductal grey of the rat
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The dorsal hom of the spinal cord and the midbrain penaqueductal grey matter (PAG) are important regions for pain modulation. In this thesis the effects of opioids and spinal cord stimulation (SCS) on the release of gamma-amino butyric acid (GABA), substance P (SP) and neurotensin (NT) were investigated in these regions of the rat by in vivo microdialysis. In addition, the effect of the adenosine A1 analogue R-phenyl-isopropyl-adenosine (R-PIA), on the binding of SP to its receptor was studied in vitro in the dorsal horn by autoradiography. R-PIA has previously been shown to inhibit the pain like behaviour induced by spinal administration of SP in rodents, and may also alleviate pain in man R-PIA (0.1 myM) was found to increase the affinity of the SP-receptor in the rat dorsal hom via a GTP dependent mechanism, while the number of available binding sites remained unchanged in the presence of R-PIA. These results suggest that effects of R-PIA and other adenosine analogues on SP-binding may be of importance for the previously reported effects of these substances on pain related behaviour. Significantly decreased extracellular levels of the inhibitory neurotransmitter GABA were detected in the dorsal hom of rats that had lesions of the sciatic nerve and showed signs of allodynia (i.e. hypersensitivity to light touch). SCS, a method used for alleviation of neuropathic pain in man, induced a significant increase of the extracellular GABA level in the dorsal horn of neuropathic rats that responded to SCS with a reversal of allodynia. In contrast, no change in GABA release was detected in other nerve lesioned rats, that did not respond behaviourally to SCS. In the PAG, where GABA is regarded to mediate a tonic suppression of descending pain inhibitory pathways, a decreased extracellular GABA level was observed following repeated SCS. This finding may indicate a supraspinal mechanism contributing to the analgesic effect of SCS. The effect of morphine on the release of GABA in the PAG was monitored by microdialysis combined with capillary electrophoresis with laser induced fluorescence detection (CE-LIF). In a separate experiment CE-LIF was found to have a higher sensitivity for GABA than HPLC with electrochernical detection. Local administration of an analgesic dose of morphine (100 myM) in the PAG, via the dialysis probe, decreased the extracellular GABA level in the PAG by almost 50 percent in a naloxone reversible manner. These results support the hypothesis that opioids induce activation of descending pain inhibitory pathways by an inhibition of tonically active GABA neurons in the PAG. In other experiments, morphine (10 myM) and the my-opioid selective agonist DAGO (1myM) administered via a microdialysis probe in the ventromedial PAG, were found to induce a significant, naloxone-reversible and calcium dependent increase of the extracellular level of neurotensin-like immunoreactivity in microdialysates obtained at the same site. Since NT induces a potent antinociception upon microinjection in the PAG, these findings may suggest that an increased release of NT in the PAG contributes to opioid analgesia. In conclusion, several neurochemical effects at spinal and supraspinal level were demonstrated in response to treatment with opioids and SCS. These effects may indicate that opiates and SCS act via previously unknown mechanisms to alleviate pain.
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| 6. |
- Weiss, Rüdiger J., et al.
(författare)
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Long-term follow-up of opioid use in patients with acetabular fractures
- 2012
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Ingår i: Injury Extra. - London, United Kingdom : Elsevier. - 1572-3461. ; 43:7, s. 49-53
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Chronic pain and the pattern of opioid use after skeletal fractures has been a neglected topic in pain medicine. Pelvic and in particular acetabular fractures represent some of the most troublesome injuries for patients with a high incidence of chronic pain after fracture. We examined the long-term opioid analgesic use among patients with acetabular fractures and analysed if potential risk factors would predict a prolonged opioid therapy.Patients and methods: Data were extracted from medical databases such as the Swedish National Hospital Discharge Register and the National Pharmacy Register. The study period was 2005–2008. Kaplan–Meier analysis constructed the cumulative opioid consumption with 95% confidence intervals (CI). Cox multiple-regression model was used to study risk factors for a prolonged opioid prescription after admission for fracture. An age- and sex-matched control group was included for comparisons.Results: We identified 1017 patients with isolated acetabular fractures. The proportion of dispensing opioids for these patients was 39%, which was 7 times higher than in the age- and sex-matched non-fracture controls (n = 5077). The median follow-up time was 14 (interquartile range [IQR] 5–24) months. Most patients with opioid use after fracture were male (60%) and the median age was 76 (IQR 61–85) years. The leading mechanism of injury was fall on the same level (52%). At 6 and 12 months after fracture, 41% (95% CI 36–47) and 33% (28–39) were still treated with opioids. The multiple Cox regression-analysis (adjusted for age, sex, type of treatment, and mechanism of injury) revealed that younger patients (age <70 compared with ≥70 years) were more likely to end using opioids (Hazard ratio 2.0 [95% CI 1.5–2.7]). The median daily morphine equivalent dose was 22 (IQR 14–42) mg within the first month after fracture.Discussion: During follow-up, the frequency of patients on moderate and high doses was falling off. There was no evidence of analgesic tolerance in the majority of the patients who were treated for at least 6 months. To set our findings into perspective, studies of patterns of chronic opioid use among patients with other types of fractures would be valuable.
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| 7. |
- Wikner, Birgitta Norstedt, et al.
(författare)
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Maternal use of thyroid hormones in pregnancy and neonatal outcome
- 2008
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 87:6, s. 617-627
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To describe neonatal outcome including the presence of congenital malformations in infants born to women substituted with thyroid hormones, and the maternal characteristics of these women. Design. Register study based on prospectively collected data in relation to delivery. Setting. Swedish Health Registers. Population. All pregnant women (n = 848,468) and all infants born (n = 861,989) in Sweden from 1 July 1995 to 31 December 2004. Methods. Women who reported the use of thyroid hormones in early pregnancy or obtained a prescription for thyroid hormones later in pregnancy (n = 9,866), as well as their infants (n = 10,055) were identified from the Swedish Medical Birth Register. The reference population consisted of all women giving birth and their offspring during the same time interval. Main outcome measures. Neonatal outcome, malformations and maternal characteristics. Data were analyzed with adjustments for identified confounders. Results. Women using thyroxine had an increased rate of pre-eclampsia, diabetes (pre-existing or gestational), cesarean sections and inductions of labour compared to women in the reference population. The risk for preterm birth was marginally increased (OR 1.13, 95% CI 1.03-1.25). Neonatal thyroid disease was found in eight infants (seven with thyreotoxicosis and one unspecified), the expected number was 0.2. No further anomalies in neonatal diagnoses were found. A small but statistically significant risk for congenital malformations (OR = 1.14, 95% CI 1.05-1.26) was found. Conclusion. Women on thyroid substitution during pregnancy had an increased risk for some pregnancy complications, but their infants were only slightly affected.
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| 8. |
- Wikner, Birgitta Norstedt, et al.
(författare)
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Use of benzodiazepines and benzodiazepine receptor agonists during pregnancy: maternal characteristics
- 2007
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Ingår i: Pharmacoepidemiology and Drug Safety. - : Wiley. - 1053-8569 .- 1099-1557. ; 16:9, s. 988-994
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Tidskriftsartikel (refereegranskat)abstract
- Background Use of benzodiazepine (BZD) drugs or hypnotic benzodiazepine receptor agonists (HBRAs) during pregnancy may represent a hazard for the foetus. In order to analyse this in an adequate way, knowledge of maternal characteristics as putative confounders is needed. Methods In the Swedish Medical Birth Register, 2149 pregnant women using BZDs or HBRAs were identified, 1944 of them in early pregnancy. These women were compared with other women (n = 859 455) giving births during the same period (1 July 1995-31 December 2004). The following maternal characteristics were studied: age, parity, smoking habits, education, previous miscarriages, years of involuntary childlessness as an estimate of subfertility, concomitant drug use and some pregnancy complications. Results Use and/or reporting of BZDs or HBRAs increased with maternal age. It was higher at first and 4+ parity and increased markedly with maternal smoking. Women with low education reported a higher use than women with high education. Previous miscarriage or subfertility had little impact on the use of these drugs. Preterm birth and caesarean section (also at term birth) were more common than expected. In women using BZDs or HBRAs, other types of psychoactive drugs were used in excess. Conclusions Women using BZDs or HBRAs differ in many aspects from women not using those drugs. These differences may act as confounders in the analysis of pregnancy outcome.
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| 9. |
- Wikner, Birgitta Norstedt, et al.
(författare)
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Use of benzodiazepines and benzodiazepine receptor agonists during pregnancy: neonatal outcome and congenital malformations
- 2007
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Ingår i: Pharmacoepidemiology and Drug Safety. - : Wiley. - 1053-8569 .- 1099-1557. ; 16:11, s. 1203-1210
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Tidskriftsartikel (refereegranskat)abstract
- Background Exposure to Benzodiazepines (BZD) during foetal life has been suggested to contribute to neonatal morbidity and some congenital malformations, for example, orofacial clefts. Here we aimed to study the neonatal outcome and congenital malformations in neonates whose mothers reported use of BZD and/or hypnotic benzodiazepine receptor agonists (HBRA) during pregnancy. Methods In the Swedish Medical Birth Register we identified 1979 infants whose mothers (n = 1944) reported use of BZD and/or HBRA in early pregnancy. An additional 401 infants were studied, born to 390 mothers who were prescribed such drugs during late pregnancy. Neonatal outcome including congenital malformations after exposure was compared with that of all births (n = 873 879). Results An increased risk for preterm birth and low birth weight was detected in the exposed population. The rate of relatively major congenital malformations was moderately increased among infants exposed in early pregnancy (adjusted OR = 1.24, 95%CI 1.00-1.55), not explained by known teratogenic maternal co-medication. A higher than expected number of infants with pylorostenosis or alimentary tract atresia (especially small gut) was found. This was, however, based on only seven infants for each group of malformation without association to any specific BZD or HBRA. The earlier proposed increased risk for orofacial clefts was not confirmed in our study. Conclusions Maternal use of BZD and/or HBRA may increase the risk for preterm birth and low birth weight and cause neonatal symptoms, but does not appear to have a strong teratogenic potential. The tentative association with pylorostenosis and alimentary tract atresia needs confirmation. Copyright (C) 2007 John Wiley & Sons, Ltd.
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