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Postpartum pain during intercourse is a prevalent and distressing problem that has substantial consequences for affected couples. Partner perceptions-such as how partners perceive women's pain self-efficacy-contribute to an individual's pain experience. This study examined whether partners under- or over-estimate women's intercourse pain self-efficacy at three months postpartum and the implications of this bias for women's pain and couples' sexual functioning at three and six months postpartum. Women who reported pain during intercourse and their partners (N = 89 couples) completed online measures assessing pain self-efficacy (own or partner perceptions), pain intensity, and sexual functioning at three and six months postpartum. Analyses were based on the Truth and Bias Model of Judgement and Response Surface Analysis. Partners were accurate in their estimates of women's pain self-efficacy (i.e., their estimates were positively correlated with women's), but they also underestimated it by perceiving women to be less efficacious than women themselves reported. When couples showed greater agreement for lower levels of pain self-efficacy at three months, women reported greater pain intensity and both partners reported poorer sexual functioning at three and six months postpartum. Findings may inform interventions that promote pain self-efficacy to improve partner support and couples' sexual functioning. Perspective When women report-and their partners perceive-low levels of women's self-efficacy for managing painful intercourse, women report greater postpartum pain during intercourse and couples indicate poorer sexual functioning. These findings suggest that interventions aimed at promoting couples' agreement at high pain self-efficacy may improve their adjustment to postpartum pain. Contributors to the ongoing epidemic of prescription opioid abuse, addiction, and death include opioid tolerance, withdrawal symptoms, and possibly opioid-induced hyperalgesia (OIH). Thirty stable chronic non-malignant pain patients entered a six-month long, randomized, double-blind, dose-response, two-center trial of the potent opioid levorphanol, conducted over a decade ago during an era of permissive opioid prescribing. Eleven were taking no opioids at study entry and eleven were taking between 35-122 morphine equivalents (MEQ). Five weeks titration preceded twenty weeks stable dosing. Tolerance and OIH were inferred individually based on chronic pain ratings, Brief Pain Inventory scores, and results of the Brief Thermal Sensitization (BTS) model at five opioid dosing sessions. Seventeen patients completed. The average final daily opioid dose was 132; range 14-300; average addition 105 MEQ. After observed dosing, the BTS area of hyperalgesia changed minimally but the painfulness of skin heating was reduced. Weekly 0-100 VAS pain ratings (average 64 at study entry, 48 at end titration, 45 at end stable dosing) decreased a median 19%, but eight completed with higher VAS ratings. Three completers had evidence of both tolerance and hyperalgesia. A fully-powered trial similar to this feasibility study is ethically questionable. A large-scale pragmatic trial is more realistic. Trial Registration NCT00275249 Evolution of Analgesic Tolerance With Opioids Perspective A double-blind, six-month, high-dose opioid feasibility trial, completed years ago, provides critically important data for clinically defining analgesic tolerance and opioid-induced hyperalgesia (OIH). Overall benefit was small, and 18% of patients had evidence of both tolerance and OIH. Future work requires a different approach than a classic RCT design. Complex regional pain syndrome (CRPS) results in chronic and excruciating pain in patients. Conventional therapies lack effectiveness, rendering it one of the most difficult to treat neurological conditions.. Electroacupuncture (EA) is an effective alternative therapy for pain relief. Here, we investigated whether EA exerts analgesic effect on a rat model of CRPS type-I (CRPS-I) and related mechanisms. The rat chronic post-ischemic pain (CPIP) model was established to mimic CRPS-I. 100Hz EA exerted robust and persistent anti-allodynic effect on CPIP model compared with 2Hz EA or sham EA. EA markedly suppressed the overexpression of CXCL12/CXCR4 in spinal cord dorsal horn (SCDH) of CPIP model, leading to substantial decrease in neuronal and glial cell activities in SCDH. Pharmacological blocking CXCR4 mimicked EA-induced anti-allodynic effect and related cellular events in SCDH, whereas exogenous CXCL12 abolished EA's effect. CXCR4 signaling resulted in ERK activation in SCDH, contributing to mechanical allodynia of CPIP model rats, whereas EA markedly reduced ERK activation. Therefore, we demonstrated that EA interferes with CXCL12/CXCR4 signaling in SCDH and downstream ERK pathway to exert robust anti-allodynic effect on an animal model of CRPS-I. Our work suggests that EA may be a potential therapeutic option for CRPS-I in clinic. PERSPECTIVE Our work identified that EA exerts robust anti-allodynic effect on an animal model of CRPS-I, via mechanisms involving inhibition of CXCL12/CXCR4 signaling. EA further attenuates downstream neuronal and glial cell activation and ERK pathway in SCDH. This work suggests that EA may be a potential therapeutic option for CRPS-I management in clinic. OBJECTIVES We examined factors associated with follow-up blood cultures (FUBCs) in patients with monomicrobial Gram-negative (GN) bloodstream infection (BSI) and investigated the impact of FUBCs on therapeutic management and patient outcome. METHODS A retrospective cohort analysis was conducted of adult patients diagnosed with GN-BSI at a tertiary-care university hospital during 2013-2016. FUBCs performed between 24 hours and 7 days after index BCs was the exposure variable. Risk factors for 30-day mortality were analysed by multivariate Cox analysis on the overall cohort, including FUBCs as a time-varying covariate and on 11 matched patients according to Sequential Organ Failure Assessment (SOFA) score and time to FUBC. RESULTS In 278 (17.6%) of 1576 patients, FUBCs were performed within a median of 3 and 2 days after index BCs and active antibiotic therapy initiation. Persistent BSI was found in 107 (38.5%) of 278 patients. FUBCs were performed in more severely ill patients, with nonurinary sources, difficult-to-treat pathogens and receipt of initial inappropriate therapy. Source control and infectious disease consultation rates were higher among patients with preceding FUBCs and was associated with longer treatment duration. Thirty-day mortality was 10.4%. Independent risk factors for mortality were Charlson comorbidity index (hazard ratio (HR) 1.12) SOFA (HR 1.11), septic shock (HR 2.64), urinary source (HR 0.60), central venous catheter source (HR 2.30), complicated BSI (HR 2.10), carbapenem resistance (HR 2.34), active empiric therapy (HR 0.68), source control (HR 0.34) and FUBCs (HR 0.48). Association between FUBCs and lower mortality was confirmed in the 274 matched pairs. CONCLUSIONS FUBCs were performed in more severe GN-BSIs, yielding a high rate of persistent BSI. In this context, FUBCs were associated with lower mortality. OBJECTIVES Mueller-Hinton (MH) agar is recommended by EUCAST and CLSI for disc diffusion antimicrobial susceptibility testing. Using EUCAST methodology, we evaluated the performance of 21 internationally available brands of dehydrated MH agar from 17 manufacturers. METHODS MH plates were prepared in-house and evaluated against four quality control (QC) strains tested in triplicate, using EUCAST disc diffusion methodology. This resulted in 30 disc-QC strain combinations and 90 readings per MH brand. All brands were tested blindly and in parallel. Results were evaluated against targets and ranges in the EUCAST QC tables. The agar depth, pH and concentration of five cations were measured for all brands. RESULTS Six brands of MH agar (Bio-Rad, Biolife, Oxoid, Sigma MH 2, BD BBL MH II and CRITERION) demonstrated excellent performance, with ≥99% of zone diameter readings within QC ranges and ≥70% on target ±1 mm. The poorest performance was seen for Biolab and Merck MH, with 10% (9/90) and 23% (21/90) of readings outside the QC ranges, respectively. Of all readings, 4.9% (93/1890) were out of range, mainly related to trimethoprim sulfamethoxazole (n = 25), aminoglycosides (n = 25) and fluoroquinolones (n = 15). The cation content differed considerably between the agars, and for four brands pH values were outside the acceptable range 7.2-7.4. DISCUSSIONS This study evaluated the performance and content of 21 brands of MH dehydrated media. Six brands showed excellent performance with all investigated antimicrobial classes. Others exhibited problems with one or more classes of agents. This could partly be explained by differences in concentration of specific chemical components and pH. OBJECTIVES To evaluate the performance of an isothermal microcalorimetry (IMC) method for determining the MICs among extensively drug-resistant Gram-negative bacilli. METHODS A collection of 320 clinical isolates (n = 80 of each) of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii from Sweden, Spain, Italy and the Netherlands were tested. The MICs were determined using the IMC device calScreener (Symcel, Stockholm, Sweden) and ISO-broth microdilution as the reference method. Essential agreement, categorical agreement, very major errors (VME), major errors (ME) and minor (mE) errors for each antibiotic were determined. RESULTS Data from 316 isolates were evaluated. Four errors (two ME, one VME, one mE) among 80 K. pneumoniae, six errors (four ME, one VME, one mE) among 79 E. coli, 15 errors (seven VME, three ME, five mE) among 77 P. aeruginosa and 18 errors (12 VME, two ME, four mE) among 80 A. baumannii were observed. Average essential agreement and categorical agreement of the IMC method were 96.6% (95% confidence interval, 94.2-99) and 97.1% (95% confidence interval, 95.4-98.5) respectively when the MICs were determined at the end of 18 hours. Categorical agreement of the IMC method for prediction of MIC by the end of 8 hours for colistin, meropenem, amikacin, ciprofloxacin and piperacillin/tazobactam were 95%, 91.4%, 94%, 95.2% and 93.7% respectively. MSC-4381 research buy CONCLUSIONS The IMC method could accurately determine the MICs among extensively drug-resistant clinical isolates of E. coli, K. pneumoniae, P. aeruginosa and A. baumannii isolates. OBJECTIVES To expand on previous reports of synergy between polymyxin B (PMB) and minocycline (MIN) against Acinetobacter baumannii; and to gain insight into the qualitative and quantitative determinants of their synergy. METHODS A semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model was developed on the basis of data from in vitro time-kill experiments with determination of resistant bacterial count to describe the effects of PMB and MIN alone and in combination. The model was enriched by complementary experiments providing information on the characteristics of the resistant subpopulation. RESULTS The model successfully described the data and made possible quantification of the strength of interaction between the two drugs and formulation of hypotheses about the mechanisms of the observed interaction. The effect of the combination was driven by MIN, with PMB acting as an helper drug; simulations at clinically achievable concentrations showed that 1.5 mg/L MIN +0.2 mg/L PMB is expected to produce sustained killing over 30 hours, while 0.

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