Assessment of Problem-Solving: A Key to Successful Diabetes Self-Management

Problem-solving skill is important for chronic illness self-management. This project prospectively evaluated a measure of diabetes problem-solving skill for its reliability, convergent validity, sensitivity to intervention, and relationship to change in behavior. Postmenopausal women with type 2 diabetes (N = 279) participated in a RCT to evaluate a lifestyle modification program. The 9-item Diabetes Problem-Solving Inventory (DPSI) was used to assess how patients cope with challenges to diabetes self-care. The DPSI was found to have good inter-rater reliability and internal consistency for a brief scale, be moderately stable over time, and relate significantly to hypothesized variables. DPSI scores improved significantly more in the lifestyle change condition than in controls and were related to improved outcomes. Mediation analyses indicated that the increase in problem-solving was a partial mediator of outcomes. Results support the reliability, predictive ability, and sensitivity to change of the DPSI. Directions for future research on problem-solving and chronic illness are discussed.     

Dominant paternal transmission of Cornelia de Lange syndrome: a new case and review of 25 previously reported familial recurrences.

The Cornelia de Lange syndrome (CdLS) is an autosomal dominant multisystem disorder characterized by somatic and cognitive retardation, characteristic facial features, limb abnormalities, hearing loss, and other organ system involvement. The vast majority of cases (99%) are sporadic, with rare familial occurrences having been reported. Most individuals with CdLS do not reproduce as a result of the severity of the disorder. Maternal transmission has been well documented, as have several cases of multiple-affected children being born to apparently unaffected parents. Paternal transmission has rarely been reported. A case is reported here of a father with classic features of CdLS with a similarly affected daughter. A review of the reported familial cases of CdLS is summarized.     

Modulation of cerebellar activities by acupuncture stimulation: evidence from fMRI study

Recent neuroimaging studies have revealed that acupuncture stimulation modulates human central nervous system including cerebral limbic/paralimbic and subcortical structures. Due to the wide and intricate connections with cerebrum, we hypothesized that anatomically specific areas in human cerebellum are also modulated by acupuncture stimulation beyond classical involvement of cerebellum in motor coordination. Functional MRI (fMRI) was used to investigate neural substrates responding to the acupuncture stimulation of Pericardium 6 (PC6, Neiguan), an acupoint relevant for the management of nausea including vestibular-related motion sickness. Sham stimulation near the acupoint and tactile stimulation on the skin of the acupoint were given as separate conditions. Psychophysical scores as well as the heart and respiratory rates were measured during each condition. Acupuncture manipulation on PC6, in comparison to the sham acupuncture and tactile stimulation conditions, selectively activated left superior frontal gyrus, anterior cingulate gyrus, and dorsomedial nucleus of thalamus. Acupuncture-specific neural substrates in cerebellum were also evident in declive, nodulus, and uvula of vermis, quadrangular lobule, cerebellar tonsil, and superior semilunar lobule. Negative MR signal changes, often seen during the acupuncture of analgesic points, were not observed in the present study. Our data suggest that cerebellum serves as important activation loci during the acupuncture stimulation of PC6, and clinical efficacy of PC6 may be mediated by the cerebellar vestibular neuromatrix.     

A new method for introducing screws into locking plates

A secure and reliable method is described to ensure that a screw arrives at, and is screwed into, a locking plate without mishap under theatre conditions.     

Tolerability and Pharmacokinetics of Delayed-Release Dimethyl Fumarate Administered With and Without Aspirin in Healthy Volunteers

Background

Delayed-release dimethyl fumarate (DR-DMF) has cytoprotective and antiinflammatory properties and has recently been approved in the United States as an oral treatment for relapsing forms of multiple sclerosis. The most common adverse events associated with DR-DMF are flushing and gastrointestinal (GI) events, the incidences of which diminish over time.

Objective

The purpose of this study was to evaluate the tolerability and pharmacokinetic (PK) profile of DR-DMF with or without concomitant acetylsalicylic acid (aspirin), a cyclooxygenase inhibitor.

Methods

Healthy volunteers (N = 56) were randomized to receive different dosing regimens of DR-DMF or matching placebo with or without pretreatment with 325 mg aspirin for 4 days. Plasma levels of the active metabolite monomethyl fumarate were assessed on days 1 and 4. Flushing and GI events were assessed using patient-reported scales. Potential flushing mediators were explored.

Results

DR-DMF showed a safety, tolerability, and PK profile consistent with previous clinical experience, with no evidence of accumulation. Pretreatment with aspirin had no effect on the primary PK parameters, AUC_0–10h, or C_max. Flushing severity, assessed by 2 subject-reported rating scales, was generally mild and was rated highest at the start of treatment. Pretreatment with aspirin reduced flushing incidence and intensity without affecting GI events or the PK profile of DR-DMF. In some DR-DMF–treated individuals, plasma concentrations of a prostaglandin D₂ (PGD₂) metabolite were increased.

Conclusions

In healthy volunteers, DR-DMF was well tolerated over 4 days of dosing, with a PK profile consistent with that previously reported and no evidence of accumulation. Aspirin pretreatment reduced the incidence and intensity of flushing without affecting GI events or the DR-DMF PK profile. Elevated levels of PGD₂ in some DR-DMF–treated individuals suggest that flushing may be, at least in part, prostaglandin mediated. ClinicalTrials.gov identifier: ID: NCT01281111.     

Transdermal flux predictions for selected selective oestrogen receptor modulators (SERMs): Comparison with experimental results

The aim of this work was to evaluate the feasibility of delivering transdermally a series of highly lipophilic compounds (log P ~ 4–7), comprising several selective oestrogen receptor modulators and a modified testosterone (danazol). The maximum fluxes of the drugs were predicted theoretically using the modified Potts & Guy algorithm (to determine the permeability coefficient (k_p) from water) and the calculated aqueous solubilities. The correction provided by Cleek & Bunge took into account the contribution of the viable epidermal barrier to the skin permeation of highly lipophilic compounds. Experimental measurements of drug fluxes from saturated hydroalcoholic solutions were determined in vitro through excised pig skin. Overall, the predicted fluxes were in good general agreement (within a factor of 10) with the experimental results. Most of the experimental fluxes were greater than those predicted theoretically suggesting that the 70:30 v/v ethanol–water vehicle employed may have had a modest skin penetration enhancement effect. This investigation shows that the transdermal fluxes of highly lipophilic compounds can be reasonably predicted from first principles provided that the viable epidermis, underlying the stratum corneum, is included as a potentially important contributor to the skin's overall barrier function. Furthermore, the absolute values of the measured fluxes, when considered in parallel with previous clinical studies, indicate that it might be feasible to topically deliver a therapeutically useful amount of some of the compounds considered to treat cancerous breast tissue.     

Implementing national standards for cancer pain management: Program model and evaluation

The purpose of this quasi-experimental (pre- and posttest) study was to test a model pain management program (PMP) to implement the American Pain Society (APS) quality assurance standards for the management of acute and chronic cancer pain using a continuous quality improvement (CQJ) approach to improve professionals' knowledge and skills, patient satisfaction, and to identify areas needing improvement. The sample consisted of 1210 nurse responses and 698 interviews of patients with pain during hospitalization at a major urban cancer center. The PMP provided a structure (standards), educational opportunities, and training in CQI methods. Outcome measures included a patient evaluation questionnaire and concerns checklist: nurse knowledge, attitude and barriers questionnaire; and focus groups to identify areas needing improvement. Significant improvements were found in patients' satisfaction, nurses' knowledge and attitude scores, and reductions in nurses' perceptions of barriers. Focus groups revealed the need for improved communication among disciplines about pain and better assessment of patients unable to self-report. The program met its goal of implementing the APS standards, educating nurses, and identifying “system” problems, and improving overall patient satisfaction.     

Endoscopy of the small bowel in inflammatory bowel disease

With the heterogeneous clinical presentation of IBD, endoscopy plays an integral role in the initial diagnosis of Crohn's disease. Although radiographic tests are often supplemental in the evaluation of Crohn's disease, they previously had been the only modality available allowing for visualization of much of the small bowel. The advent of small bowel endoscopy allows for direct visualization, and often biopsy, of the small bowel, allowing for confirmation of diagnosing and extent of involvement. Currently, the only mode for obtaining biopsies from beyond the ligament of Treitz is via push enteroscopy or intraoperative enteroscopy. Knowing the extent of disease can also help explain recalcitrant symptoms or lack of response to certain therapies. With the advent of capsule endoscopy, endoscopic visualization of the entire small intestine is now possible with a relatively noninvasive test. Further advancements in capsule endoscopy may relegate push enteroscopy and intraoperative enteroscopy to those cases in which biopsies or therapy are required. In the future, total enteroscopy with new enteroscopes may become more widely available, allowing biopsies and therapy in all segments of the small intestine, without the need for operative intervention.