Paracervical block as pain treatment during second-trimester medical termination of pregnancy: an RCT with bupivacaine versus sodium chloride.

STUDY QUESTION: Can paracervical block (PCB) administered before the onset of pain decrease women's pain experience during second-trimester medical termination of pregnancy (MToP)? SUMMARY ANSWER: There were no clinically significant differences between groups receiving PCB with bupivacaine or saline with regard to the highest and lowest pain intensity, morphine consumption or induction-to abortion interval. WHAT IS KNOWN ALREADY: The most common side effect of misoprostol is pain; nevertheless, there are sparse studies in pain and pain treatment during MToP, especially in second-trimester abortion. Pain reported in second-trimester medical abortion is often intense, and peaks when the fetal expulsion occurs. STUDY DESIGN, SIZE, DURATION: A double-blinded RCT was carried out from May 2012 until April 2015. A power calculation was based on a previous pilot study showing that the proportion of women with severe pain [visual analogue scale (VAS) ≥7] was 63%. A clinically significant reduction was considered to yield 35% with severe pain, and with a power of 80% and significance level of 5% (two-sided) 112 women were needed. Accounting for a 20% drop-out rate, a total of 140 women were needed. The primary outcome, pain intensity measured as any VAS ≥7, was analysed using a generalized estimating equations model. The level of significance was set to P < 0.05 two-sided. A computer generated randomization list with block size of 10 was used. The treatment allocation was placed in a sealed, opaque, envelope and picked consecutively. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 589 women attending a gynaecological clinic had a second-trimester abortion during the study period and 276 were invited to participate. A total of 113 women undergoing abortion from 13 weeks of gestation and above were recruited, of which 55 were randomly allocated to receive a PCB with bupivacaine and 58 a PCB with sodium chloride 1 h after the first dose of misoprostol. The full analysis set (FAS) population was defined as all randomized women that had at least one value for any of the outcomes (n = 102). The per-protocol (PP) population was defined as a subset of the FAS excluding patients with major protocol deviations or without a value for the primary outcome (n = 99). Pain was measured by VAS at misoprostol initiation (baseline) and repeated every 30 min until fetal expulsion. The primary outcome was the highest VAS pain intensity at any time point. MAIN RESULTS AND THE ROLE OF CHANCE: The highest pain intensity, did not show any differences at a cut-off of VAS ≥7 [risk ratio (RR): 1.1; 95% confidence interval (CI): 0.9-1.5; P = 0.0.292]. In the PP analyses, there were 75% women in the bupivacaine group and 64% in the sodium chloride group with VAS ≥7 (RR: 1.2; 95% CI: 0.9-1.5; P = 0.235). Most women did not experience pain at the misoprostol start, 19 women scored a VAS of >0, ranging from 1 to 4 with a mean of 1.8 and median of 2 (P = 1.000). Immediately prior to PCB, 61 women scored a VAS of >0, from 1 to 10 with a mean of 2.0 and median of 1 (P = 0.771). There was a 48% loss of VAS scores at the time of expulsion and the remaining scores did not differ between groups (RR: 1.5; 95% CI: 0.9-2.5). A subgroup analysis of primipara did not show any difference in highest pain intensity VAS ≥7 (RR: 1.2; 95% CI: 0.9-1.6; P = 0.283). No statistically significant differences were observed between groups with regard to the highest and lowest (P = 553 and 0.182) pain intensity and morphine consumption (P = 0.772). Side effects were reported by 28 women (14 women in each group), with no differences between groups. Most common was nausea and vomiting in connection to morphine injection. LIMITATIONS, REASONS FOR CAUTION: Nearly 60% of the invited women did not want to participate in the study (fear of needles and fear of receiving the placebo) therefore women who tolerate pain may have been overrepresented in the study population. Data collection was stopped, in error, when 113 participants had been recruited. The loss to follow-up was, however, only 11 women (10%), which was lower than expected but intrinsically the study did not fully reach the intended number of women, which may have influenced the results. In addition, the obstetrical and gynaecological background of participating women differs. The participants were informed that they had a 50% chance of receiving a PCB with active substance, which could theoretically have affected their expectations and pain experience (placebo effect). The frequent attention at VAS scoring and the overall care provided may also have affected the participants in a positive way, and helped women to feel supported and more relaxed during the abortion. WIDER IMPLICATIONS OF THE FINDINGS: The highest pain intensity was severe (VAS: 7-10) among 65-75% of the participants, as reported for first-trimester medical abortion; however, the maximal pain scores remain high despite the PCB. There is, therefore, a clear need for more optimal pain treatment but only limited data exist on pain treatment during MToP over all gestational lengths. As PCB was well tolerated, did not cause any serious side effects and had no negative impact on the abortion process and efficacy, another approach may be worth exploring, namely PCB given on demand at the onset of painful contractions. STUDY FUNDING/COMPETING INTERESTS: The study was supported by grants from the Swedish Research Council (grant no: 2012-2844), ALF (Karolinska Institutet - Stockholm County Council, Agreement on Medical Research and Training) funding, the Karolinska Institutet, Stockholm South General Hospital, and Swedish Nurses in the Area of Pain - SSOS together with GlaxoSmithKline. None of the authors have any conflicts of interest. TRIAL REGISTRATION NUMBER: The trial was registered with ClinicalTrials.gov (identifier: NCT01617564) and The EudraCT (number: 2010-020780-21) and was approved by The Regional Ethical Review Board at Karolinska Institutet (dnr: 2007/1277-31/2 and 2010/410-31/1). TRIAL REGISTRATION DATE: Clinical trial registration was done in May 2012 before initiation of patient recruitment. DATE OF FIRST PATIENT'S ENROLMENT: 29 May 2012.

A review of video exposure monitoring as an occupational hygiene tool.

This study reviews use of video exposure monitoring (VEM, also known as PIMEX) as an occupational hygiene tool since its inception in the mid-1980s. VEM involves the combination of real-time monitoring instruments, usually for gases/vapours and dust, with video of the worker's activities. VEM is an established method used by practitioners in different countries. The technical aspects of these VEM systems are described, then applications of VEM are discussed, focussing on task analysis, training (risk communication), encouraging worker participation in and motivation for improvements in the workplace environment and occupational hygiene research. The experiences from these applications are used to illustrate how exposure visualization with video can act as a catalyst, initiating a change process in the workplace. Finally, the role of VEM as a workplace improvement tool, now and in the future, is discussed.

Analysis of adrenocortical secretory responses during acute an prolonged immune stimulation in inflammation-susceptible and -resistant rat strains.

Endogenous corticosterone secreted during immune challenge restricts the inflammatory process and genetic variations in this neuroendocrine-immune dialogue have been suggested to influence an individuals sensitivity to develop chronic inflammatory disorders. We have tested inflammation-susceptible Dark Agouti (DA) rats and resistant, MHC-identical, PVG.1AV1 rats for their abilities to secrete corticosterone in response to acute challenge with bacterial lipopolysaccharide (LPS) or a prolonged activation of the nonspecific immune system with arthritogenic yeast beta-glucan. Intravenous injection of LPS triggered equipotent secretion of corticosterone in both rat strains. Interestingly, peak concentrations of corticosterone did not differ significantly between the strains. Intradermal injection of beta-glucan caused severe, monophasic, polyarthritis in DA rats while PVG.1AV1 responded with significantly milder joint inflammation. Importantly, serial sampling of plasma from glucan-injected DA and PVG.1AV1 rats did not reveal elevated concentrations of plasma corticosterone at any time from days 1-30 postinjection compared to preinjection values, in spite of the ongoing inflammatory process. Interestingly, adrenalectomized, beta-glucan-challenged DA rats responded with an aggravated arthritic process, indicating an anti-inflammatory role for the basal levels of corticosterone that were detected in intact DA rats challenged with beta-glucan. Moreover, substitution with subcutaneous corticosterone-secreting pellets, yielding moderate stress-levels, significantly attenuated the arthritic response. In contrast, adrenalectomized and glucan-challenged PVG.1AV1 rats did not respond with an elevated arthritic response, suggesting that these rats contain the arthritic process via corticosterone-independent mechanisms. In conclusion, the hypothalamic-pituitary-adrenal axis in both rat strains exhibited strong activation after challenge with LPS. This contrasted to the basal corticosterone levels observed strains during a prolonged arthritic process. No correlation between ability to secrete corticosterone and susceptibility to inflammation could be demonstrated. Basal levels of endogenous corticosterone appeared to restrain inflammation in beta-glucan-challenged DA rats whereas resistance to inflammation in PVG.1AV1 rats may be mediated via corticosterone-independent mechanisms.

Contaminant dispersion in the vicinity of a worker in a uniform velocity field.

The transportation of gaseous contaminant from a low and moderate low impulse (momentum<1 m s(-1)) source to the breathing zone was studied in a uniform air stream flow. Results of the effects of the direction and the velocity of principal air flow, convection due to a human body, arm movement of a human being and the type of source on the concentration profiles are presented. Three important results were obtained. Firstly, for a given low and moderate impulse low impulse contaminant source in the near field of a worker, his/her orientation relative to the principal air flow direction is the most important factor in reducing occupational exposure, with an air velocity of about 0.3 m s(-1). Secondly, the effect of convection resulting from body heat on air flow was lower than expected. Thirdly, arm movements influence contaminant dispersion, and should be included when models assessing exposure are developed. The present data can also be used to validate existing computational fluid dynamic (CFD) models.

Reduction of exposure to solvents and formaldehyde in surface-coating operations in the woodworking industry.

A 1-year study has been performed at a company which manufacturers office furniture, and can be subdivided into three phases: measurement of exposure prior to remedial measures; remedial measures whose purpose was to reduce exposure; and new measurements after remedial measures. Remedial measures concentrated on changes which would reduce exposure to solvents. These measures fall into two categories: (i) the training of employees about the way airborne pollutants spread and ways of avoiding exposure; and (ii) locating and eliminating important sources of emission. Employees were trained mainly by the PIMEX (PIcture Mix EXposure) method for showing them how exposure depended on methods of work and conditions at the workplace. The most important sources of solvent emissions were pin-pointed by the GridMap method. The results show that exposure can be greatly reduced through training, adjustment of existing equipment and minor technical measures. This is the case even when exposure is initially at a concentration which is clearly below hygienic limit values. This approach should also reduce exposure to formaldehyde, though this could not be evaluated because the raw materials used changed during the study.

Video filming and pollution measurement as a teaching aid in reducing exposure to airborne pollutants.

A method called PIMEX has been developed for investigation of the causes of exposure to airborne pollutants at workplaces. The method involves measurement of the subject's exposure with a personal, direct-reading instrument. The sampling signal is transmitted by telemetry to a special video mixer. A video camera is also connected to the video mixer. The camera is used for filming the subject. The video mixer's output signal is fed to a monitor which continuously shows how the subject works and how exposure varies. The method has been used for producing two films on the causes of exposure to solvent and effective measures for reducing exposure: one deals with screen printing and the other with surface treatment at wood-processing plants. The films have been shown at a large number of workplaces at discussions about workplace conditions, proving useful tools in efforts to reduce workplace risks and giving rise to concrete measures and increased interest in the workplace environment.