Effects of reduced uterine perfusion pressure on blood pressure and metabolic factors in pregnant rats

BACKGROUND: Elements of metabolic syndrome (eg, dyslipidemia and impaired glucose metabolism) are often present in preeclamptic pregnancies. Currently it is unclear whether these metabolic aberrations presage preeclampsia, or if these manifestations result from placental ischemia and the ensuing proinflammatory state usually present in preeclampsia. METHODS: The present study employed chronic reductions in uterine perfusion pressure (RUPP) to generate a rat model of pregnancy-induced hypertension (PIH) for the evaluation of fasting plasma concentrations of triglycerides (TGs), glucose, resistin, insulin, and glucose tolerance in late-gestation rats. RESULTS: Mean arterial pressure was increased (130 +/- 2.1 mm Hg v 100 +/- 4.3 mm Hg; all values, mean +/- SEM), and fetal weight decreased (1.93 +/- 0.08 g v 2.19 +/- 0.06 g), in RUPP dams compared with normal pregnant (NP) control dams. Maternal fasting glucose (4.2 +/- 0.3 mmol L(-1) v 3.1 +/- 0.4 mmol L(-1); P < .05) was increased in RUPP compared with NP dams. Serum TGs (2.62 +/- 0.29 mmol L(-1) v 2.45 +/- 0.51 mmol L(-1)), insulin (9.9 +/- 0.7 microU mL(-1) v 8.5 +/- 0.7 microU mL(-1)), resistin (46.25 +/- 4.19 pg mL(-1) v 49.71 +/- 4.01 pg mL(-1)), and glucose area under the curve (650 +/- 35 mmol min L(-1) v 570 +/- 34 mmol min L(-1)) were not different between the RUPP and NP dams. CONCLUSIONS: Although these findings do not rule out the hypothesis that preexisting symptoms of metabolic syndrome may contribute to the onset of preeclampsia, these data clearly show that pregnancy-induced hypertension resulting from RUPP does not elicit manifestations of metabolic syndrome in late-gestation rat dams.     

Evaluating the impact of individual alcohol licensing decisions on local health and crime: a natural experiment with synthetic controls

BackgroundLocal authorities in England can influence the local alcohol environment by contributing to the licensing process and controlling the enforcement of existing licenses. However, a gap remains in the availability of quantitative evidence of effectiveness and impact of these local interventions, including a shortage of public health evidence around individual premises. Natural experiments offer the opportunity to evaluate these interventions where formal randomisation is not possible. We aimed to assess whether it is possible to quantitatively evaluate three natural experiments of alcohol licensing decisions at small spatial scale.MethodsThree situations presenting a natural experiment were identified in different English Local Authority areas by public health or licensing practitioners: (i) the closure of a nightclub in 2013, (ii) the closure of a restaurant-nightclub following reviews in 2016, and (iii) the implementation of new local licensing guidance (LLG) in 2013/14. We obtained monthly numbers of reported incidents of emergency department admissions for alcohol-related reasons, ambulance call-outs, and various crimes at lower/middle-super-output-area level (from 2010–14 for case i, 2015–17 for case ii, and 2008–14 for case iii). Bayesian structural timeseries were used to compare trends to their counterfactuals, approximated by synthetic controls based on time series of the same outcomes in other, comparable, areas.FindingsClosure of the nightclub was associated with temporary reductions in antisocial behaviour (–18%; 95% Bayesian Credible Interval [BCI] –37 to –4); equivalent to 60 averted incidents in 4 months. Closure of the restaurant-nightclub was not associated with measurable changes in outcomes. There was some evidence that the LLG introduction was associated with a reduction in drunk and disorderly behaviour (–42%, 95% BCI –109 to 23), but this reduction equated to less than one incident per month. The unplanned end of the LLG might have contributed to an increase in domestic violence (11%, 95% BCI –10 to 35), corresponding to two additional incidents per month.InterpretationIt is possible to evaluate the impact of local alcohol policies, even at the level of individual premises, using this methodology. We provide quantitative evidence that local government actions to influence the local alcohol environment can have a positive impact on health and crime in the area but could also have unintended consequences.FundingThis work was funded by the National Institute for Health Research School for Public Health Research (NIHR SPHR), a partnership between the Universities of Sheffield, Bristol, Cambridge, Exeter, and University College London); the London School for Hygiene and Tropical Medicine; the LiLaC collaboration between the Universities of Liverpool and Lancaster and Fuse; and the Centre for Translational Research in Public Health, a collaboration between Newcastle, Durham, Northumbria, Sunderland and Teesside Universities. The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR, or the UK Department of Health.     

Validation of a modified version of the brief pain inventory for painful diabetic peripheral neuropathy

Neuropathic pain is the focus of current clinical research, clinical identification, and treatment. It is unique from nociceptive pain and requires evaluation of the relevance and utility of common pain measures created for other painful conditions. This study evaluated the psychometric properties of a modified Brief Pain Inventory (BPI) for patients with painful diabetic peripheral neuropathy (BPI-DPN). Participants were patients with painful DPN (n=255) enrolled in a DPN Burden of Illness survey referred through 17 outpatient settings (primary care physicians, endocrinologists, neurologists, and anesthesiologists). Patients completed the BPI-DPN, and self-report measures of health-related quality of life, mood sleep, and healthcare utilization. Construct, criterion and discriminant validity, and internal consistency reliability were evaluated. Principal axis factoring with oblimin rotation revealed two interpretable factors (eigenvalues>1.0), consistent with most published BPI validation studies; a severity scale comprising the four BPI Severity items and an interference scale comprising the seven Interference items, which satisfied criteria for interpretability and model fit. Cronbach's alpha was high (0.94) for both scales. Mean pain Severity was highly correlated with Bodily Pain from the Medical Outcomes Study Short Form-12, version 2 (rs=0.63, P < 0.001), the Pain/Discomfort item in the Euro-QoL (rs=0.58, P < 0.001), and a verbal rating scale measure of pain severity (rs=0.74, P < 0.001). Individual BPI-DPN Interference domains were moderately correlated (rs's >0.5, P < 0.001) with analogous measures, and the Sleep Interference item had a high, significant association with the three primary Medical Outcome Study-Sleep scale subscales (rs's=0.66-71, P < 0.001). Worst Pain and Interference ratings were significantly associated with hospital utilization and outpatient visits due to DPN. These results replicate, in a pure peripheral neuropathic pain condition, the BPI psychometric characteristics documented in populations with nociceptive or mixed pain conditions. The BPI-DPN is a promising instrument in the evaluation of painful DPN.     

Alcohol Abuse and Cardiac Disease

Background

Understanding the relationship between alcohol abuse, a common and theoretically modifiable condition, and the most common cause of death in the world, cardiovascular disease, may inform potential prevention strategies.

Clinical characteristics and pain management among patients with painful peripheral neuropathic disorders in general practice settings.

Alleviating chronic pain is a global healthcare priority. Understanding the medical profile and current treatment patterns in patients with painful neuropathic disorders (PNDs) is crucial to the development of effective pain management strategies. Thus, our objective was to describe the demographic and clinical characteristics of persons with PNDs and their use of pain medications. Using the general practice research database, we categorized PNDs in two ways: Pure PNDs (which include diabetic neuropathy, postherpetic neuralgia, etc.; N=16,690) and Mixed PNDs (which include back/neck pain with neuropathic involvement; N=14,309). On average, PND patients were 55 years old (Pure, 55.4 [SD=16.9] years; Mixed, 54.3 [SD=16.4] years). Over a third had other chronic pain-related (Pure, 37.5%; Mixed, 37.1%) and nearly a quarter had non-pain related (Pure, 28.1%; Mixed, 24.1%) comorbidities. Use of medications with clinically demonstrated efficacy in PNDs was higher among patients with Pure PNDs (tricyclic antidepressants [Pure, 16.6%; Mixed, 10.1%]; 2nd generation antidepressants [Pure, 11.0%; Mixed, 9.7%]; and antiepileptics [Pure, 12.2%; Mixed, 2.6%]), whereas use of NSAIDs (Pure, 43.1%; Mixed, 65.2%) and opioids (Pure, 8.5%; Mixed, 14.3%) was higher among patients with Mixed PNDs. Average daily doses of select neuropathic pain-related medications among PND patients (Pure and Mixed) were lower than those recommended for neuropathic pain. Among both Pure and Mixed PND patients, use and doses of evidenced-based neuropathic pain-related medications was low, and lower than the use of NSAIDs (a medication class with no proven efficacy for PNDs) in each group, suggesting possible sub-optimal neuropathic pain management among these patients.     

Pharmacokinetics of cefepime in patients undergoing continuous ambulatory peritoneal dialysis.

The pharmacokinetics of cefepime were studied in 10 male patients receiving continuous ambulatory peritoneal dialysis therapy. Five patients received a single 1,000-mg dose and the other five received a single 2,000-mg dose; all doses were given as 30-min intravenous infusions. Serial plasma, urine, and peritoneal dialysate samples were collected; and the concentrations of cefepime in these fluids were measured over 72 h by using a high-performance liquid chromatographic assay with UV detection. Pharmacokinetic parameters were calculated by noncompartmental methods. The peak concentrations in plasma and the areas under the plasma concentration-versus-time curve for the 2,000-mg dose group were twice as high as those observed for the 1,000-mg dose group. The elimination half-life of cefepime was about 18 h and was independent of the dose. The steady-state volume of distribution was about 22 liters, and values for the 1,000- and 2,000-mg doses were not significantly different. The values for total body clearance and peritoneal dialysis clearance were about 15 and 4 ml/min, respectively. No dose dependency was observed for the clearance estimates. Over the 72-h sampling period, about 26% of the dose was excreted intact into the peritoneal dialysis fluid. For 48 h postdose, mean concentrations of cefepime in dialysate at the end of each dialysis interval exceeded the reported MICs for 90% of the isolates (MIC90s) for bacteria which commonly cause peritonitis resulting from continuous peritoneal dialysis. A parenteral dose of 1,000 or 2,000 mg of cefepime every 48 h would maintain the antibiotic levels in plasma and peritoneal fluid above the MIC90s for the most susceptible bacteria for the treatment of systemic and intraperitoneal infections [corrected].     

Current issues in global tuberculosis control.

Despite attempts to standardize tuberculosis (TB) control strategies, there remains wide variation in the selection and implementation of control strategies within and among nations. Some of this variation is appropriate; based on wide variations in the available resources, the prevalence of TB infection, the incidence of TB disease, the relative contribution of reactivation versus recent transmission to incident cases, and the rate of HIV co-infection. This review will discuss three controversial questions relevant to global TB control: (1) What is the role of the treatment of latent TB infection in global TB control? (2) What are successful strategies to control immigrant TB in low incidence countries? (3) What are successful strategies to control TB in persons with HIV infection?     

Inhibitory effects of interferon on mouse megakaryocytic progenitor cells in culture

Mouse bone marrow cells were grown in plasma clots, megakaryocyte formation was stimulated with human urinary erythropoietin (Ep). The expression of megakaryocyte colony forming units (CFUM) and of single megakaryocyte forming units (M) was evaluated after seven days in culture. Usually ten times more M than CFUM were found. Megakaryocytic colony formation showed a linear dependence on cell dose from 0.5 to 2 X 10(5) cells/clot. The colony size frequency distribution exhibited a single peak in the two-cell size class, followed by a continuous decrease, suggesting that cell division may occur asynchronously in cells making up a colony. Mouse L cell interferon (IF) in doses from 10 to 1000 U/ml was included in clots together with Ep. This resulted in a biphasic, dose dependent reduction of colony formation and of single megakaryocyte formation. At all doses tested CFUM were more sensitive to IF than M. These observations are best explained by a differential inhibitory effect of IF on replication of two or more classes of megakaryocytic progenitor cells.