Caesarean Delivery Rate Review: An Evidence-Based Analysis.

BACKGROUND: In 2007, caesarean deliveries comprised 28% of all hospital deliveries in Ontario. Provincial caesarean delivery rates increased with maternal age and varied by Local Health Integration Network. However, the accepted rate of caesarean delivery in a low-risk maternal population remains unclear. OBJECTIVES: To review the literature to assess factors that affect the likelihood of experiencing a caesarean delivery, and to examine Ontario caesarean delivery rates to determine whether there is rate variation across the province. DATA SOURCES: Data sources included publications from OVID MEDLINE, OVID MEDLINE In-Process and Other Non-Indexed Citations, OVID Embase, EBSCO Cumulative Index to Nursing & Allied Health Literature (CINAHL), and EBM Reviews, as well as data from the Canadian Institute for Health Information Discharge Abstracts Database and the Better Outcomes and Registry Network. REVIEW METHODS: A mixed-methods approach was used, which included a systematic review of the literature to delineate factors associated with the likelihood of caesarean delivery and an analysis of administrative and clinical data on hospital deliveries in Ontario to determine provincial caesarean delivery rates, variation in rates, and reasons for variation. RESULTS: Fourteen systematic reviews assessed 14 factors affecting the likelihood of caesarean delivery; 7 factors were associated with an increased likelihood of caesarean delivery, and 2 factors were associated with a decreased likelihood. Five factors had no influence. One factor provided moderate-quality evidence supporting elective induction policies in low-risk women. The overall Ontario caesarean delivery rate in a very-low-risk population was 17%, but varied significantly across Ontario hospitals. LIMITATIONS: The literature review included a 5-year period and used only systematic reviews. The determination of Robson class for women is based on care received in hospital only, and the low-risk population may have included data from women with obstetrical conditions that warranted a caesarean delivery. CONCLUSIONS: There is moderate-quality evidence that-compared with expectant management-an induction policy is associated with a decrease in caesarean delivery rates in low-risk women. There is significant caesarean delivery rate variation among Ontario hospitals.

DAPK2 is a novel regulator of mTORC1 activity and autophagy.

Autophagy is a tightly regulated catabolic process, which is upregulated in cells in response to many different stress signals. Inhibition of mammalian target of rapmaycin complex 1 (mTORC1) is a crucial step in induction of autophagy, yet the mechanisms regulating the fine tuning of its activity are not fully understood. Here we show that death-associated protein kinase 2 (DAPK2), a Ca(2+)-regulated serine/threonine kinase, directly interacts with and phosphorylates mTORC1, and has a part in suppressing mTOR activity to promote autophagy induction. DAPK2 knockdown reduced autophagy triggered either by amino acid deprivation or by increases in intracellular Ca(2+) levels. At the molecular level, DAPK2 depletion interfered with mTORC1 inhibition caused by these two stresses, as reflected by the phosphorylation status of mTORC1 substrates, ULK1 (unc-51-like kinase 1), p70 ribosomal S6 kinase and eukaryotic initiation factor 4E-binding protein 1. An increase in mTORC1 kinase activity was also apparent in unstressed cells that were depleted of DAPK2. Immunoprecipitated mTORC1 from DAPK2-depleted cells showed increased kinase activity in vitro, an indication that DAPK2 regulation of mTORC1 is inherent to the complex itself. Indeed, we found that DAPK2 associates with components of mTORC1, as demonstrated by co-immunoprecipitation with mTOR and its complex partners, raptor (regulatory-associated protein of mTOR) and ULK1. DAPK2 was also able to interact directly with raptor, as shown by recombinant protein-binding assay. Finally, DAPK2 was shown to phosphorylate raptor in vitro. This phosphorylation was mapped to Ser721, a site located within a highly phosphorylated region of raptor that has previously been shown to regulate mTORC1 activity. Thus, DAPK2 is a novel kinase of mTORC1 and is a potential new member of this multiprotein complex, modulating mTORC1 activity and autophagy levels under stress and steady-state conditions.

Impact of advanced (open) access scheduling on patients with chronic diseases: an evidence-based analysis.

BACKGROUND: The goal of advanced access scheduling is to eliminate wait times for physician visits by ensuring access to same-day appointments, regardless of urgency or health care need. The intent is to reduce delays in access, leading to improvements in clinical care and patient satisfaction, and reductions in the use of urgent care. OBJECTIVE: To evaluate whether implementation of an advanced access scheduling system reduced other types of health service utilization and/or improved clinical measures and patient satisfaction among adults with chronic diseases. DATA SOURCES AND REVIEW METHODS: A literature search was performed on January 29, 2012, for studies published from 1946 (OVID) or 1980 (EMBASE) to January 29, 2012. Systematic reviews, randomized controlled trials, and observational studies were eligible if they evaluated advanced access implementation in adults with chronic diseases and reported health resource utilization, patient outcomes, or patient satisfaction. Results were summarized descriptively. RESULTS: One systematic review in a primary care population and 4 observational studies (5 papers) in chronic disease and/or geriatric populations were identified. The systematic review concluded that advanced access did not improve clinical outcomes, but there was no evidence of harm. Findings from the observational studies in chronic disease populations were consistent with those of the systematic review. Advanced access implementation was not consistently associated with changes in clinical outcomes, patient satisfaction, or health service utilization. LIMITATIONS: All studies were retrospective: 3 studies (4 papers) included historical controls only, and 1 included contemporaneous controls. Findings were inconsistent across studies for a number of outcomes. CONCLUSIONS: Based on low to very low quality evidence, advanced access did not have a statistically (or clinically) significant impact on health service utilization among patients with diabetes and/or coronary artery disease (CAD). Very low quality evidence showed a significant reduction in the proportion of patients with diabetes and CAD admitted to hospital whose length of stay was greater than 3 days. Evidence was inconsistent for changes in clinical outcomes for patients with diabetes or CAD. Very low quality evidence showed no increase in patient satisfaction with an advanced access scheduling system.

Guidelines for managing domestic abuse when male and female partners are patients of the same physician. The Delphi Panel and the Consulting Group.

OBJECTIVE: To provide clinical guidelines for primary care physicians who are dealing with domestic abuse and who have both the abused woman and her partner as patients. PARTICIPANTS: A 15-member expert panel with members having experience in family practice, gynecology, emergency medicine, medical ethics, nursing, psychology, law, and social work; an 11-member consulting group with members representing medicine, consumers, police, psychology, social work, and nursing; and participants from focus groups including 48 previously abused women and 10 previously abusive men. Members of the expert panel and the consulting group were recruited by the research team. Focus group members were recruited through the agencies from which they were receiving services. EVIDENCE: Available research information, and opinions of the expert panel, the consulting group, and the focus group participants. CONSENSUS PROCESS: Scoring of 144 clinical scenarios was performed by the expert panel using a modified Delphi technique involving 4 iterations. Scenarios were rated in terms of best practice for primary care physicians dealing with suspected and confirmed cases of physical abuse. Consulting group members and focus group participants then commented on the panel's results. Final guidelines were approved by the panel and the consulting group, with comments reserved in the guidelines for information from focus group participants. CONCLUSIONS: It is not a conflict of interest for the physician to deal with abuse of the female partner when both partners are patients. Both patients have a right to autonomy, confidentiality, honesty, and quality care. Patients should be dealt with independently, thereby facilitating assessment of the magnitude and severity of the victim's injuries. Physicians should not discuss the possibility of domestic abuse with the male partner without the prior consent of the abused female partner. Joint counseling is generally inadvisable and should be attempted only when the violence has ended, provided both partners give independent consent and the physician has adequate training and skills to deal with the situation without escalating the violence. If the physician feels unable to deal effectively with either patient because of the dual relationship, referral to another qualified physician is preferred.

Pharmacokinetic interaction of propoxyphene with ethanol.

In order to study the effects of ethanol on the pharmacokinetics of propoxyphene, six healthy male volunteers were each given (1) propoxyphene 65 mg p.o. preceded by 1 h by ethanol 0.9 g/kg lean body weight and followed for 7.5 h by ethanol dosed to maintain breath ethanol at 800-1000 mg/l; and (2) propoxyphene 65 mg p.o. with orange juice in the same volume and frequency as ethanol. Ethanol did not induce any significant changes in apparent t 1/2 or Cmax of propoxyphene or norpropoxyphene. The average norpropoxyphene/propoxyphene ratio decreased by a mean 36%.

Ethanol-induced spontaneous norepinephrine release from the rat vas deferens.

Acute ethanol exposure increases norepinephrine (NE) turnover both centrally and peripherally. One of the mechanisms by which ethanol could increase NE turnover is by increasing spontaneous NE release. The effect of ethanol on spontaneous NE release was investigated using tritium release from l-[3H]NE-labeled vasa deferentia as an index of NE release. Ethanol, 65 mM, increased spontaneous tritium release by 8% and pargyline, 100 mg/kg b.wt., pretreatment increased the ethanol effect by 63%. Ethanol alone (22 mM) had no effect on tritium release; however, with pargyline pretreatment tritium release increased by 13%. Combined reserpine, 5 mg/kg, and pargyline, 100 mg/kg, abolished these ethanol effects. Preincubation with tyramine, 1.8 microM, and omitting calcium from Krebs-bicarbonate buffer also abolished the ethanol effect. Butanol and propanol were more potent and methanol less potent than ethanol in increasing spontaneous tritium release. The mechanism consistent with all the above observations is that ethanol increases spontaneous exocytosis due to a nonspecific effect on presynaptic and vesicular membranes.

Comparative efficacy of propranolol and chlordiazepoxide in alcohol withdrawal.

Propranolol alone was more effective than either chlordiazepoxide or a combination of chlordiazepoxide and propranolol in alleviating the symptoms of the alcohol withdrawal syndrome.