Consistent Evidence Of Benefit Research Articles

Donor-recipient human leukocyte antigen A mismatching is associated with hepatic artery thrombosis, sepsis, graft loss, and reduced survival after liver transplant.

Human leukocyte antigen (HLA) matching is not routinely performed for liver transplantation as there is no consistent evidence of benefit; however, the impact of HLA mismatching remains uncertain. We explored the effect of class I and II HLA mismatching on graft failure and mortality. A total of 1042 liver transplants performed at a single center between 1999 and 2016 with available HLA typing data were included. The median follow‐up period was 9.38 years (interquartile range 4.9–14) and 350/1042 (33.6%) transplants resulted in graft loss and 280/1042 (26.9%) in death. Graft loss and mortality were not associated with the overall number of mismatches at HLA‐A, HLA‐B, HLA‐C, HLA‐DR, and HLA‐DQ loci. However, graft failure and mortality were both increased in HLA mismatching on graft failure and mortality the presence of one (p = 0.004 and p = 0.01, respectively) and two (p = 0.01 and p = 0.04, respectively) HLA‐A mismatches. Elevated hazard ratios for graft failure and death were observed with HLA‐A mismatches in univariate and multivariate Cox proportional hazard models. Excess graft loss with HLA‐A mismatch (138/940 [14.7%] mismatched compared with 6/102 [5.9%] matched transplants) occurred within the first year following transplantation (odds ratio 2.75; p = 0.02). Strikingly, transplants performed at a single all grafts lost due to hepatic artery thrombosis were in HLA‐A–mismatched transplants (31/940 vs. 0/102), as were those lost due to sepsis (35/940 vs. 0/102). In conclusion, HLA‐A mismatching was associated with increased graft loss and mortality. The poorer outcome for the HLA‐mismatched group was due to hepatic artery thrombosis and sepsis, and these complications occurred exclusively with HLA‐A–mismatched transplants. These data suggest that HLA‐A mismatching is important for outcomes following liver transplant. Therefore, knowledge of HLA‐A matching status may potentially allow for enhanced surveillance, clinical interventions in high‐risk transplants or stratified HLA‐A matching in high‐risk recipients.

Going digital: a narrative overview of the effects, quality and utility of mobile apps in chronic disease self-management.

Objective Smartphone health applications (apps) are being increasingly used to assist patients in chronic disease self-management. The effects of such apps on patient outcomes are uncertain, as are design features that maximise usability and efficacy, and the best methods for evaluating app quality and utility. Methods In assessing efficacy, PubMed, Cochrane Library and EMBASE were searched for systematic reviews (and single studies if no systematic review was available) published between January 2007 and January 2018 using search terms (and synonyms) of 'smartphone' and 'mobile applications', and terms for each of 11 chronic diseases: asthma, chronic obstructive lung disease (COPD), diabetes, chronic pain, serious mental health disorders, alcohol and substance addiction, heart failure, ischaemic heart disease, cancer, cognitive impairment, chronic kidney disease (CKD). With regard to design features and evaluation methods, additional reviews were sought using search terms 'design', 'quality,' 'usability', 'functionality,' 'adherence', 'evaluation' and related synonyms. Results Of 13 reviews and six single studies assessing efficacy, consistent evidence of benefit was seen only with apps for diabetes, as measured by decreased glycosylated haemoglobin levels (HbA1c). Some, but not all, studies showed benefit in asthma, low back pain, alcohol addiction, heart failure, ischaemic heart disease and cancer. There was no evidence of benefit in COPD, cognitive impairment or CKD. In all studies, benefits were clinically marginal and none related to morbid events or hospitalisation. Twelve design features were identified as enhancing usability. An evaluation framework comprising 32 items was formulated. Conclusion Evidence of clinical benefit of most available apps is very limited. Design features that enhance usability and maximise efficacy were identified. A provisional 'first-pass' evaluation framework is proposed that can help decide which apps should be endorsed by government agencies following more detailed technical assessments and which could then be recommended with confidence by clinicians to their patients. What is known about the topic? Smartphone health apps have attracted considerable interest from patients and health managers as a means of promoting more effective self-management of chronic diseases, which leads to better health outcomes. However, most commercially available apps have never been evaluated for benefits or harms in clinical trials, and there are currently no agreed quality criteria, standards or regulations to ensure health apps are user-friendly, accurate in content, evidence based or efficacious. What does this paper add? This paper presents a comprehensive review of evidence relating to the efficacy, usability and evaluation of apps for 11 common diseases aimed at assisting patients in self-management. Consistent evidence of benefit was only seen for diabetes apps; there was absent or conflicting evidence of benefit for apps for the remaining 10 diseases. Benefits that were detected were of marginal clinical importance, with no reporting of hard clinical end-points, such as mortality or hospitalisations. Only a minority of studies explicitly reported using behaviour change theories to underpin the app intervention. Many apps lacked design features that the literature identified as enhancing usability and potential to confer benefit. Despite a plethora of published evaluation tools, there is no universal framework that covers all relevant clinical and technical attributes. An inclusive list of evaluation criteria is proposed that may overcome this shortcoming. What are the implications for practitioners? The number of smartphone apps will continue to grow, as will the appetite for patients and clinicians to use them in chronic disease self-management. However, the evidence to date of clinical benefit of most apps already available is very limited. Design features that enhance usability and clinical efficacy need to be considered. In making decisions about which apps should be endorsed by government agencies and recommended with confidence by clinicians to their patients, a comprehensive but workable evaluation framework needs to be used by bodies assuming the roles of setting and applying standards.

Newborn Screening: Are We Ready for It?

The newborn screening (NBS) programme is a complex and organised system consisting of family and personal education, biochemical tests, confi rmatory biochemical and genetic tests, diagnosis, therapy, and patient follow-up. The programme identifi es treatable metabolic disorders, possibly when still asymptomatic, by using dried blood spot (DBS). Over the last 20 years, tandem mass spectrometry (TMS) has become the leading technology in NBS programmes and has been shown to be versatile, sensitive and specifi c. There is consistent evidence of benefi ts from NBS for many disorders detected by TMS as well as for congenital hypothyroidism, cystic fi brosis and congenital adrenal hyperplasia by immune-enzymatic methods. Some methods were developed for the detection of lysosomal storage disorders (LSDs), and even if for some of them there is a reliable and relatively simple test, a reasonable associated therapy may still not be available. Therefore the inclusion of LSDs in NBS is still under debate.

Impact of cotrimoxazole prophylaxis on the health of breast-fed, HIV-exposed, HIV-negative infants in a resource-limited setting

WHO guidelines recommend cotrimoxazole prophylaxis (CTXP) in all HIV-exposed negative infants who are still breastfeeding. This is based on the evidence of efficacy in HIV-infected infants, but there is no evidence of benefit in HIV-negative, breast-fed infants. We assessed the impact of CTXP on diarrhoeal and respiratory morbidity in breast-fed, HIV-exposed negative infants in a community programme. CTXP for more than 60 days showed no consistent evidence of benefit for incidence of lower respiratory tract infection [incidence rate ratio (IRR) 0.71, 95% confidence interval (CI) 0.39-1.26; P = 0.241] but an increased incidence of diarrhoea (IRR = 1.38, 95% CI 0.98-1.94; P = 0.065). The guidelines should be reconsidered by conducting a randomized control trial.

Integrating Tools for Breast Cancer Risk Assessment, Risk Reduction, and Early Detection

Commentary on Graubard et al., [p. 2430][1] In 2010, it is projected that there will be 207,090 diagnoses and 39,840 deaths from breast cancer among women in the United States. Approximately 10,300 will be diagnosed before the age of 40 ([1][2]), the age when the American Cancer Society ([2][3])

Suggested Improvements to the Overt Aggression Scale-Modified

Back to table of contents Previous article Next article LETTERFull AccessSuggested Improvements to the Overt Aggression Scale-ModifiedJeffrey A. Mattes M.D.,Jeffrey A. Mattes M.D.Search for more papers by this author,Published Online:1 Jan 2010https://doi.org/10.1176/jnp.2010.22.1.123.e1AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: The lack of a standard efficacy measure for outpatient studies of impulsive aggression led Coccaro et al. 1 to modify the Overt Aggression Scale (OAS) 2 to create the OAS-Modified (OAS-M). The one large (N=246) study to date which used the OAS-M 3 found that the total aggression score had a large variance and was highly skewed, which prevented the use of parametric statistics including covariance analyses. The large variance and skewness seemed due to the scoring system—to calculate the aggression scores, frequencies are multiplied by severity ratings, but there is no upper limit on frequencies. Therefore a patient who has many episodes of relatively mild irritability can have a very high total aggression score, much higher than a patient who, less frequently, has much more serious aggression (this also impairs face validity). Also, the calculated aggression scores have not yielded better drug-placebo discrimination than the much simpler global ratings. 4 Given the above, and my prior experience with the OAS-M, I modified the OAS-M as follows: 1.To improve face validity, reduce skewness, and limit the effect of high frequency of mild aggression, the scoring system was modified so that frequencies were categorized into one of five ratings (e.g., a score of 3 equals 4–10 times/week).2.Some of the descriptive anchor points seemed to require modification. For example, “engaged in a verbal argument with someone” was rated worse than “cursed or personally insulted someone.” The anchors were therefore changed to “mild,” “moderate,” and “severe,” with descriptions to illustrate each severity level.3. Because of the unclear relationships between aggression and suicidal behavior, 1 ratings of “assault against self” were eliminated. 4.A “moderately severe” option was added to the Global Overt Irritability rating to create more of an interval scale, and slight changes in wording were made.5. The global ratings of overt aggression and subjective irritability were not combined (the two do not consistently correlate highly 1 ). This revised OAS-M was then used in two fairly small placebo-controlled studies in outpatients with impulsive aggression, one with oxcarbazepine (N=48) 4 and one with levetiracetam (N=40). 5 Using the revised OAS-M resulted in clear and consistent evidence of benefit in the oxcarbazepine study (reliability can be inferred if a rating significantly discriminates an active medication from placebo). In the levetiracetam study, there was not a significant drug-placebo difference, but interrater reliability of the revised OAS-M was evaluated with 20 patients evaluated by two raters: Intraclass correlation coefficients were high (e.g., 0.918 for total aggression and 0.878 for global overt aggression, both significant at p<0.001). Supporting validity, correlations among the OAS-M measures and other aggression ratings were high in the levetiracetam study, and patient-rated global improvement and the hostility rating of the Brief Psychiatric Rating Scale also showed significant drug-placebo differences in the oxcarbazepine study. Thus, the revised OAS-M seems more likely to discriminate between effective medication and placebo. Details about the rationale for the revised OAS-M (and a copy) can be obtained from the author ([email protected]).Psychopharmacology Research Association of Princeton, Princeton, NJ

Suggested Improvements to the Overt Aggression Scale-Modified

Back to table of contents Previous article Next article LETTERFull AccessSuggested Improvements to the Overt Aggression Scale-ModifiedJeffrey A. Mattes M.D.,Jeffrey A. Mattes M.D.Search for more papers by this author,Published Online:1 Jan 2010https://doi.org/10.1176/jnp.2010.22.1.123.e1AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: The lack of a standard efficacy measure for outpatient studies of impulsive aggression led Coccaro et al. 1 to modify the Overt Aggression Scale (OAS) 2 to create the OAS-Modified (OAS-M). The one large (N=246) study to date which used the OAS-M 3 found that the total aggression score had a large variance and was highly skewed, which prevented the use of parametric statistics including covariance analyses. The large variance and skewness seemed due to the scoring system—to calculate the aggression scores, frequencies are multiplied by severity ratings, but there is no upper limit on frequencies. Therefore a patient who has many episodes of relatively mild irritability can have a very high total aggression score, much higher than a patient who, less frequently, has much more serious aggression (this also impairs face validity). Also, the calculated aggression scores have not yielded better drug-placebo discrimination than the much simpler global ratings. 4 Given the above, and my prior experience with the OAS-M, I modified the OAS-M as follows: 1.To improve face validity, reduce skewness, and limit the effect of high frequency of mild aggression, the scoring system was modified so that frequencies were categorized into one of five ratings (e.g., a score of 3 equals 4–10 times/week).2.Some of the descriptive anchor points seemed to require modification. For example, “engaged in a verbal argument with someone” was rated worse than “cursed or personally insulted someone.” The anchors were therefore changed to “mild,” “moderate,” and “severe,” with descriptions to illustrate each severity level.3. Because of the unclear relationships between aggression and suicidal behavior, 1 ratings of “assault against self” were eliminated. 4.A “moderately severe” option was added to the Global Overt Irritability rating to create more of an interval scale, and slight changes in wording were made.5. The global ratings of overt aggression and subjective irritability were not combined (the two do not consistently correlate highly 1 ). This revised OAS-M was then used in two fairly small placebo-controlled studies in outpatients with impulsive aggression, one with oxcarbazepine (N=48) 4 and one with levetiracetam (N=40). 5 Using the revised OAS-M resulted in clear and consistent evidence of benefit in the oxcarbazepine study (reliability can be inferred if a rating significantly discriminates an active medication from placebo). In the levetiracetam study, there was not a significant drug-placebo difference, but interrater reliability of the revised OAS-M was evaluated with 20 patients evaluated by two raters: Intraclass correlation coefficients were high (e.g., 0.918 for total aggression and 0.878 for global overt aggression, both significant at p<0.001). Supporting validity, correlations among the OAS-M measures and other aggression ratings were high in the levetiracetam study, and patient-rated global improvement and the hostility rating of the Brief Psychiatric Rating Scale also showed significant drug-placebo differences in the oxcarbazepine study. Thus, the revised OAS-M seems more likely to discriminate between effective medication and placebo. Details about the rationale for the revised OAS-M (and a copy) can be obtained from the author ([email protected]).Psychopharmacology Research Association of Princeton, Princeton, NJ

Best practices for elderly hip fracture patients

To determine evidence-based best practices for elderly hip fracture patients from the time of hospital admission to 6 months postfracture. MEDLINE, Cochrane Library, CINAHL, Embase, PEDro, Ageline, NARIC, and CIRRIE databases were searched for potentially eligible articles published between 1985 and 2004. Two independent reviewers determined studies appropriate for inclusion using standardized selection criteria, extracted data, evaluated internal validity, and then rated studies according to levels of evidence. Only Level 1 or 2 evidence was included in our summary of clinical recommendations. Spinal anesthesia, pressure-relieving mattresses, perioperative antibiotics, and deep vein thromboses prophylaxes had consistent evidence of benefit. Routine preoperative traction was not associated with any benefits and should be abandoned. Types of surgical management, postoperative wound drainage, and even "multidisciplinary" care, lacked sufficient evidence to determine either benefit or harm. There was little evidence to either determine best subacute rehabilitation practices or to direct ongoing medical issues (e.g., nutrition). Studies conducted during the subacute recovery period were heterogeneous in terms of treatment settings, interventions, and outcomes studied and had no clear evidence for best treatment practices. The evidence for perioperative practices is relatively robust and evidence-based perioperative treatment guidelines can be easily established. Conversely, more evidence is required to better guide the care of elderly patients with hip fracture during the subacute recovery period and convalescence.