Evidence-based clinical guidelines: a new system to better determine true strength of recommendation

RATIONALE, AIMS AND OBJECTIVES: Clinical practice guidelines often grade the 'strength' of their recommendations according to the robustness of the supporting research evidence. The existing methodology does not allow the strength of recommendation (SOR) to be upgraded for recommendations for which randomized controlled trials are impractical or unethical. The purpose of this study was to develop a new method of determining SOR, incorporating both research evidence and expert opinion. METHODS: A Delphi technique was employed to produce 10 recommendations for the role of exercise therapy in the management of osteoarthritis of the hip or knee. The SOR for each recommendation was determined by the traditional method, closely linked to the category of research evidence found on a systematic literature search, and on a visual analogue scale (VAS). Recommendations were grouped A-D according to the traditional SOR allocated and the mean VAS calculated. Difference across the groups was assessed by one-way ANOVA variance analysis. RESULTS: Mean VAS scores for the traditional SOR groups A-D and one proposition which was 'not recommended' showed significant linearity on one-way ANOVA. However, certain recommendations which, for practical reasons, could not assessed in randomized controlled trials and therefore could not be recommended strongly by the traditional methodology, were allocated a strong recommendation by VAS. CONCLUSIONS: This new system of grading strength of SOR is less constrained than the traditional methodology and offers the advantage of allowing SOR for procedures which cannot be assessed in RCTs for practical or ethical reasons to be upgraded according to expert opinion.     

Perceived Spouse Responses to Pain: The Level of Agreement in Couple Dyads and the Role of Catastrophizing, Marital Satisfaction, and Depression

The primary objective of this study was to examine whether individuals with chronic pain (“participants”) and their spouses agree on perceptions of solicitous, distracting, and punishing spouse responses to pain. The second aim was to examine the role of participant catastrophizing (a negative mental set about pain), participant and spouse marital satisfaction, and participant and spouse depression in participant perceptions of spouse responses, spouse perceptions of their responses, and agreement between participants and spouses. Individuals with chronic musculoskeletal pain and their spouses (N=108 couples) completed questionnaire packets. Examination of overall group averages (participants vs. spouses) indicated little or no differences between participant and spouse ratings. Examination of individual agreement in participant and spouse ratings indicated substantial disagreement. The proposed moderators predicted both participant and spouse perceptions and jointly made minor contributions to dyad agreement. Although neither participant nor spouse perceptions of spouse responses are necessarily a reflection of actual behavior, the lack of agreement in this study suggests it may not be valid to use only patient perceptions in research related to spouse responses.     

Apoptosis is not altered by clomiphene citrate in pseudopregnant rat uteri

Clomiphene citrate (CC) remains one of the most often prescribed synthetic oestrogens used in the treatment of infertility even though the ensuing pregnancy rates are low. CC alters the uterine environment on most levels. Ovariectomised rats were treated with 5 mg progesterone (P) for 3 days and a 0.5 microg injection of oestrogen (E) on the third day (PP(PE)) thus inducing pseudopregnancy and rendering the uterus receptive to implantation 24 h later. Using this model, we investigated apoptosis in the rat uterus treated with 0.25 mg CC given prior to the PP(PE) treatment. Apoptotic cells in the uterus were localised using TUNEL and visualised with a FITC marker. There was a similar increase in apoptosis in the uterine luminal epithelium in the PP(PE) and CCPP(PE) treated animals; no changes were observed in apoptosis in the other uterine compartments when compared to the control. The CCPP(PE)-treated tissue showed tall epithelial cells with long microvilli while the PP(PE) tissue had short microvilli and low cuboidal epithelium. These results suggest that CC does not disrupt the normal apoptotic activity seen at implantation, but does change the morphology of the luminal epithelium, suggesting that these cellular changes could influence successful implantation.     

A new conceptualization of alexithymia in the general adult population: implications for research involving older adults

OBJECTIVE: The purpose of this study is to test the validity of existing conceptualizations of the alexithymia concept, with particular reference to aging. METHODS: Two hundred and forty-eight healthy adults completed measures of alexithymia and psychosocial functioning; younger and older adults (n=121) also completed a measure of emotional responsiveness. RESULTS: Older adults engaged in less introspective thought traditionally thought to denote increased alexithymia. However, reduced introspection was associated with improved mental wellbeing, and, thus, could not be construed as a deficit. Difficulty identifying and describing emotions did not differentiate older and younger adults, but were both associated with heightened depression, anxiety, and poor perceived quality of life. CONCLUSIONS: In clinical practice and research, the Toronto Alexithymia Scale (TAS) is almost exclusively used, with "total" score typically used to index alexithymia. As one of the subscales of the TAS measures reduced introspection, calculating total scores may not be appropriate and may particularly overestimate levels of alexithymia in older adulthood.     

Fluid Dynamics in Man of an Intraperitoneal Drug Delivery Solution: 4% Icodextrin

Interest in targeting drugs into the peritoneal cavity for intra-abdominal cancers or infections is undergoing a revival as recent clinical trials have demonstrated, not only a regional advantage in concentration of the active agent, but also improved long-term outcomes. Solutions currently used for intraperitoneal (IP) drug delivery have short residence times, however, which can limit the exposure of all areas of the peritoneum to the active agent. Icodextrin 4% solution was compared with saline and a glucose-based peritoneal dialysis solution in a clinical study of IP residence time. The study was carried out during the fortnightly rest phase in 9 patients undergoing 5-fluorouracil (5-Fu) IP treatment for colorectal cancer. The volume remaining in the peritoneal cavity was measured at 0, 12, 24, 48, 72, and 96 hr after an instillation of 2 liters of each fluid. Saline (n = 3 dwells) and glucose (n = 3 dwells) peritoneal dialysis solutions were almost fully absorbed by 24 hr, and the patients experienced discomfort when using these solutions. In contrast, icodextrin 4% solution (n = 188 dwells) maintained its instilled volume for up to 48 hr, and half the instilled volume remained after 72 and 96 hr. This result would allow extensive and prolonged coverage of the peritoneal surface. Icodextrin 4% solution may be an effective vehicle to deliver therapeutic agents into the peritoneal cavity.