Appropriateness Of Clinical Use Research Articles

Establishing the TSH reference intervals for healthy adults aged over 70 years: the Australian ASPREE cohort study.

As thyroid disorders are common amongst the elderly, this study aims to evaluate the reference interval (RI) for thyroid stimulating hormone (TSH) in healthy adults aged 70 years and over. A proposed RI was determined from the Australian participants of the ASPirin in Reducing Events in the Elderly (ASPREE) randomised trial. Participants had nohistory of cardiovascular disease, thyroid cancer, dementia, or life-threatening illnesses. Participants prescribed with any thyroid-related medication at baseline were excluded. TSH levels were measured using a commercial chemiluminescence microparticle immunoassay. The RI was determined using the middle 95th percentile of the logarithmic transformed data of baseline TSH. Cox proportional hazard regression models were used to validate the RI by assessing disease incidence over time. A total of 10,995 participants had baseline TSH measures. Median (IQR) age was 73.9 (71.8-77.3) years. We propose a RI of 0.34-3.75 mU/L. TSH levels did not differ by age or sex. At baseline, there was no association between symptoms associated with thyroid disease and levels of TSH. Over the follow-up period of up to 11 years, no association was seen between baseline TSH levels and relevant disease outcomes for participants within the RI. From a group of initially healthy, community-dwelling adults aged >=70 years, we propose a RI of TSH to best represent euthyroidism. This concentration was not associated with an increased risk of thyroid related symptoms or outcomes, confirming its appropriateness for clinical use.

Dry eye symptom questionnaires show adequate measurement precision and psychometric validity for clinical assessment of vision-related quality of life in glaucoma patients.

To ascertain the presence of Dry Eye Syndrome (DES) in patients being treated for glaucoma, using subjective and objective methods and to examine DES impact on their quality of life (QOL). A cross-sectional study was conducted by employing 156 glaucoma patients recruited from treatment centers in the Cape Coast Metropolis in Ghana. All the participants underwent dry eye examination and completed the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ), the Dry Eye-related Quality of Life Score (DEQS) and the Ocular Surface Disease Index (OSDI). Comparisons of the clinical tests, NEI VFQ-25 subscale item and composite scores and scores of DEQS and OSDI were made among subgroups divided according to the presence of dry eye symptoms or signs. Multivariate logistic regression analysis was performed to investigate the factors that influence DES related-QOL among the patients. The study involved 156 subjects with a mean age of 47.88 ± 16.0 years and made up of 81 (51.9%) females and 75 (48.1%) males. A One-Way ANOVA was conducted, and the F-statistic (F) indicated that there was a significant difference in the mean scores of the groups. There were significantly lower Tear break-up time (TBUT) values found in the group with definite dry compared with the group without DES and the group that was symptomatic with no signs DES in both eyes, [(F(3,151) = 13.703, p<0.001 (RE): (F(3,152) = 18.992, p<0.001 (LE)]. Similar results were found for Schirmer test (ST) [(F (3,151) = 28.895, p<0.001 (RE): (F (3,152) = 17.410, p<0.001 (LE)]. There was statistically significant difference in the mean composite score (64.93 ± 20.27) for the NEI VFQ-25 and sub-scale score of ocular pain, which was significantly lower in the group with definite dry as compared to other sub-groups (F(3,152) = 4.559, p = 0.004). OSDI scores of the group with definite dry eye (47.69-19.17) and the group that was symptomatic but with no signs (38.90-22.44) were significantly higher than those without dry eye and those that were asymptomatic but had a sign (F(3,152) = 17.896, p<0.001), with a similar trend occurring in the groups with relation to DEQS scores (F(3,152) = 8.775, p<0.001). There was a strong correlation between the DEQS and the OSDI questionnaires, and a weak correlation between the DEQS and the NEI VFQ-25 questionnaire after adjusting for all other factors (all p < 0.01). The study established a high presence of DES and consequently low DES related-QOL in glaucoma patients. Dry eye questionnaires are able to discriminate those who have definite dry eye from the other groups, showing its appropriateness for clinical use in glaucoma patients. Ocular surface evaluation should be conducted among glaucoma patients on topical anti-glaucoma therapy to ensure the timely detection and treatment of signs and symptoms of DES and improvement of dry-eye related QOL.

Effect of pharmacy management on turnaround time of 4-factor prothrombin complex concentrate.

The change in turnaround time of 4-factor prothrombin complex concentrate (PCC) when managed by the pharmacy department compared to blood bank management was evaluated. A retrospective analysis evaluated blood bank versus pharmacy management of PCC. Blood bank management was evaluated from November 2014 to November 2015, and pharmacy management was evaluated from December 2015 to July 2016. Chart review was performed on all patients who received PCC during these study periods. The primary outcome was the difference in median time from order entry to administration between management groups. Comparisons were made for the appropriateness of clinical use, length of stay, and discharge status. The primary outcome was analyzed using a Mann-Whitney U test. Secondary outcomes were analyzed using the chi-square test or Fisher's exact test. Descriptive statistics were utilized to analyze secondary outcomes. Forty-three patients received PCC in the blood bank group, and 22 patients received PCC in the pharmacy group. Median turnaround time of PCC was lower in the pharmacy group (43 minutes; interquartile range [IQR], 32-65 minutes) compared to the blood bank group (62 minutes; IQR; 39-110 minutes; p = 0.032). PCC use was clinically appropriate for 55% of patients (n = 12) in the pharmacy group compared with 37% of patients (n = 16) in the blood bank group (p = 0.182). There were no significant differences between the blood bank and pharmacy groups with regard to hospital length of stay or in-hospital mortality. Conversion of PCC management from the blood bank to the pharmacy was associated with a significant decrease in time to PCC administration.

External Validity of a Risk Stratification Score Predicting Early Distant Brain Failure and Salvage Whole Brain Radiation Therapy After Stereotactic Radiosurgery for Brain Metastases

A scoring system using pretreatment factors was recently published forpredicting the risk of early (≤6months) distant brain failure (DBF) and salvage whole brain radiation therapy (WBRT) after stereotactic radiosurgery (SRS) alone. Four risk factors were identified: (1) lack of prior WBRT; (2) melanoma or breast histologic features; (3) multiple brain metastases; and (4) total volume of brain metastases <1.3cm3, with each factor assigned 1 point. The purpose of this study was to assess the validity of this scoring system and its appropriateness for clinical use in an independent external patient population. We reviewed the records of 247 patients with 388 brain metastases treated with SRS between 2010 at 2013 at Levine Cancer Institute. The Press (Emory) risk score was calculated and applied to the validation cohort population, and subsequent risk groups were analyzed using cumulative incidence. The low-risk (LR) group had a significantly lower risk of early DBF than did the high-risk (HR) group (22.6% vs 44%, P=.004), but there was no difference between the HR and intermediate-risk (IR) groups (41.2% vs 44%, P=.79). Total lesion volume <1.3cm3(P=.004), malignant melanoma (P=.007), and multiple metastases (P<.001) were validated as predictors for early DBF. Prior WBRT and breast cancer histologic features did not retain prognostic significance. Risk stratification for risk of early salvage WBRT were similar, with a trend toward an increased risk for HR compared with LR (P=.09) but no difference between IR and HR (P=.53). The 3-level Emory risk score was shown to not be externally valid, but the model was able to stratify between 2 levels (LR and not-LR [combined IR and HR]) for early (≤6months) DBF. These results reinforce the importance of validating predictive models in independent cohorts. Further refinement of this scoring system with molecular information and in additional contemporary patient populations is warranted.

Commentary on "Development and Initial Validation of the Pediatric Neuromuscular Recovery Scale".

“How should I apply this information?” The Pediatric Neuromuscular Recovery Scale (NRS) is an objective tool designed to measure restored movement patterns following spinal cord injury. Unlike traditional measures, it aims to measure a patient's movement capacity compared with their pre-injury status and examine restoration of function versus compensation. Developed by a team of experts, this 13-item tool fills a current void in the ability to objectively measure recovery. Other outcome measures tend to emphasize function without assessing quality of movement. The Pediatric NRS is designed for children aged 1 to 12 years. It is appropriate for clinical use in any setting, although specialized equipment is needed for the treadmill-based testing. It can also be used as an evaluation tool to assist in developing a plan of care and to demonstrate recovery as a result of intervention. “What should I be mindful about when applying this information?” This article documents the involved process of developing this objective tool. Because the scale is complex, it requires specific instruction to the child and clinician training. While the Pediatric NRS includes age-appropriate tasks, it does not include developmental positioning; therefore, it is not designed to track gross motor development. Rather, it assesses a child's neuromuscular capacity and requires supplemental outcome measures for the child's functional and developmental status. As such, comparing a child's function with preinjury movement patterns, as the adult NRS does, presents a challenge for the young, developing child. Behavioral and psychosocial factors, often seen with pediatric populations, may also impact the scoring of this measure. The Pediatric NRS offers an opportunity to monitor recovery of movement patterns; however, more information is needed to determine its reliability, validity, and appropriateness for clinical use. Lauren White, PT, DPT, PCS Sarah Greenemeier, PT, DPT Kennedy Krieger Institute International Center for Spinal Cord Injury Baltimore, Maryland

Neurobehavioural assessment and diagnosis in disorders of consciousness: a preliminary study of the Sensory Tool to Assess Responsiveness (STAR)

ABSTRACTThe Sensory Tool to Assess Responsiveness (STAR) is an interdisciplinary neurobehavioural diagnostic tool for individuals with prolonged disorders of consciousness. It utilises current diagnostic criteria and is intended to improve upon the high misdiagnosis rate in this population. This study assesses the inter-rater reliability of the STAR and its diagnostic validity in comparison with the Coma Recovery Scale–Revised (CRS-R) and the Wessex Head Injury Matrix (WHIM). Participants were patients with severe acquired brain injury resulting in a disorder of consciousness, who were admitted to the Royal Leamington Spa Rehabilitation Hospital between 1999 and 2009. Patients underwent sensory stimulation sessions during their period of admission, which were recorded on video. Using this footage, patients were re-assessed for this study using the STAR, WHIM and CRS-R criteria. The STAR demonstrated “moderate” inter-rater reliability, “substantial” diagnostic agreement with the CRS-R, and “moderate” agreement with the WHIM. There were no significant differences between diagnoses assigned by the different assessments. The STAR demonstrated a good degree of inter-rater reliability in identification of diagnoses for patients with disorders of consciousness. The diagnostic outcomes of the STAR agreed at a good level with the CRS-R, moderately with the WHIM, and did not significantly differ from either. This demonstrates the reliability and validity of the STAR, showing its appropriateness for clinical use. Future longitudinal studies and research into the STAR's applicability in long-stay rehabilitation are indicated.

Oral nutritional supplements: Training and controls can improve appropriateness of clinical use in an acute care hospital

Total prescriptions 613 309 49,60% Adherence to protocol: yes 271 (56%) 204 (66%) +10% Adherence to protocol: no 342 (44%) 105 (34%) 10% Adherence to guide-line (sample check only on prescription adherent to protocol) Sample size 30 32 Adherence to guide-line: yes 22 (73,33%) 27 (84,38%) +11,05% Adherence to guide-line: no 8 (26,67%) 5 (15,62%) 11,05% 22. ORAL NUTRITIONAL SUPPLEMENTS: TRAINING AND CONTROLS CAN IMPROVE APPROPRIATENESS OF CLINICAL USE IN AN ACUTE CARE HOSPITAL

Comprehensive Mutation Analysis for Congenital Muscular Dystrophy: A Clinical PCR-Based Enrichment and Next-Generation Sequencing Panel

The congenital muscular dystrophies (CMDs) comprise a heterogeneous group of heritable muscle disorders with often difficult to interpret muscle pathology, making them challenging to diagnose. Serial Sanger sequencing of suspected CMD genes, while the current molecular diagnostic method of choice, can be slow and expensive. A comprehensive panel test for simultaneous screening of mutations in all known CMD-associated genes would be a more effective diagnostic strategy. Thus, the CMDs are a model disorder group for development and validation of next-generation sequencing (NGS) strategies for diagnostic and clinical care applications. Using a highly multiplexed PCR-based target enrichment method (RainDance) in conjunction with NGS, we performed mutation detection in all CMD genes of 26 samples and compared the results with Sanger sequencing. The RainDance NGS panel showed great consistency in coverage depth, on-target efficiency, versatility of mutation detection, and genotype concordance with Sanger sequencing, demonstrating the test's appropriateness for clinical use. Compared to single tests, a higher diagnostic yield was observed by panel implementation. The panel's limitation is the amplification failure of select gene-specific exons which require Sanger sequencing for test completion. Successful validation and application of the CMD NGS panel to improve the diagnostic yield in a clinical laboratory was shown.

S33 Validation of the GLI-2012 Multi-Ethnic Spirometry Reference Equations in London School Children

The Global Lung Function Initiative (GLI) recently published the first global all-age (3–95 years) multi-ethnic reference equations for spirometry (Quanjer 2012 ERJ). <h3>Aim</h3> To assess the agreement of the GLI reference range to contemporary lung function data from children living in Britain to verify its appropriateness for clinical use in this population. <h3>Methods</h3> Anthropometry and spirometry were undertaken within a mobile laboratory in primary school children recruited to the Size and Lung function In Children study during one school year (2011–2012). Spirometry Z-scores were calculated using the GLI-2012 reference range, using the ‘Black equation’ for South Asian children, for whom a specific equation has yet to be developed. <h3>Results</h3> Spirometry data from 728 (47% boys; 35% White; 28% Black; 26% South Asian; 11% other/mixed race) healthy children aged 5–11 years from eight London schools were eligible for inclusion. Mean (SD) age of 8 (1.6) years was similar across the 4 ethnic groups. After adjustment for age and sex, Black children were significantly heavier and taller compared to other groups, while South Asians were significantly lighter. When compared with White children, after adjusting for age, sex and standing height, FEV1 was significantly lower by a mean(95%CI) of 14% (11%; 16%) in Black; 11% (9%; 14%) in South Asian and 4% (1%; 8%) in the “other”/mixed race children. Similar patterns were seen for FVC but FEV1/FVC was similar across all groups. When expressed according to ethnic-specific reference equations the mean (SD) for FVC, FEV1 and FEV1/FVC for the White, Black and other groups approximated 0(1) suggesting that the GLI equations are appropriate for use in this population (Figure). Mean (95%CI) FVC and FEV1 were however 3% (–0.1%; 6.1%, p=0.07) higher in South Asian than Black children. <h3>Conclusions</h3> This study shows that the GLI-2012 equations are appropriate for use in children across a wide range of ethnicities. Of the currently available equations, the ‘Black equation’ provides the best fit for South Asian children, although it results in slight over-estimation of lung function, emphasising the need to develop specific coefficients for this group.

Clinical appropriateness of blood component transfusion: regulatory requirements and standards set by the Scientific Society in Italy.

Decision-making in health care is strongly conditioned by values of patients and providers, available resources, and information showing effectiveness/efficacy of a particular health care intervention. Clinical decisions concerning treating patients should, as far as possible, be evidence-based1; this is, to a great extent, current clinical dogma, and many medical practitioners in all disciplines are now, to some extent, utilising it2. Evidence-based medicine (EBM) can be defined as conscientious, explicit and judicious use of current best evidence in making decisions about care of individual patients3. It combines clinical judgment and experience with best available scientific evidence to improve medical decision-making and should provide clinicians, health care systems and policy-makers with instruments to appropriately evaluate scientific evidence supporting various diagnostic and therapeutic activities. This represents a radical departure from usual and customary methods for making treatment decisions concerning patients and has led to EBM being a discipline taught in medical schools and teaching hospitals4. Transfusion medicine (TM) is currently adopting principles and research methodologies that support EBM5, and high-level research has actually been undertaken at same rate as in all medical specialties combined in terms of numbers of randomised controlled trials and meta-analyses1. EBM in TM not only refers to best research evidence, but is often based on a broader range of inputs, including public expectations about transfusion safety and issues concerning precautionary principle; this implies that criteria for evaluating efficacy and cost-effectiveness of interventions in TM may differ substantially from those used in other areas6. The increasing need to deliver sufficient and safe blood components of high quality may be cause of an excessive focus on supply side of blood transfusion chain rather than clinical problem facing patients and clinicians7. An overwhelming concentration on blood supply can lead to appropriate clinical utilisation of blood components being ignored as a potentially useful instrument to maintain blood supply itself, although physicians should always consider clinical appropriateness as a must, under professional, scientific and ethical points of view. Hence, the appropriateness of transfusion practices will only improve, not by expecting clinicians to be gatekeepers of blood supply, but with better patient blood management based on a sound understanding of pathophysiology and better evidence for transfusion efficacy7. Based on above considerations, appropriateness of transfusion practices should systematically mean that blood components are transfused only when there is evidence for potential benefit, there are no valid alternatives, safe and quality products are available, and risks and benefits are carefully assessed before decision to transfuse is made. Recent European regulatory acts in field of blood transfusion (Directive of Council 2002/98/EC8 and Directives of Commission 2005/61/EC9 and 2005/62/EC10), while focusing on fundamental issues concerning quality, safety, traceability, haemovigilance, etc., do not actually take into consideration promotion and assessment of appropriateness of clinical use of blood components11. Indeed, Community's legislative framework excludes actual therapeutic use of blood components. Moreover, its provisions are no longer applicable when components are sent for further processing into medicinal products, when pharmaceutical legislation comes into force12. The appropriateness of clinical use of blood components is addressed by Recommendation Rec(2002)1113, which is indeed an excellent guideline to member states on how and what to do to implement optimal use of blood and blood products in clinical setting, but no mandatory act at European level establishes that appropriateness of transfusion practices must be promoted, monitored, assessed and, when necessary, improved. This review is aimed at providing an overview of Italian regulatory framework and of requirements of Italian standards of TM on assessment of appropriateness of blood transfusion.

Comparative study of two Japanese rhinoconjunctivitis quality-of-life questionnaires

Conclusion. Two questionnaires were used to assess quality of life (QOL) in allergic rhinitis: the Japanese translation of the Rhino-conjunctivitis Quality of Life Questionnaire (RQLQJ) and an original Japanese QOL questionnaire (JRQLQ). Either questionnaire may be used to assess QOL depending on differences in target domains. Objectives. Although pollinosis is a common disease which has a major impact on patient QOL, no internationally standardized questionnaire has been available in Japan until now. The aim of this study was to compare two currently available QOL questionnaires for allergic rhinitis in Japan—the RQLQJ and JRQLQ—in terms of their appropriateness for clinical use and their psychometric properties. Material and methods. A multicenter, inter-group, cross-sectional study was conducted in 187 adult symptomatic patients with Japanese cedar pollinosis in 2003. Patient scores on the two questionnaires were compared in terms of both overall and comparable domains. We also examined the acceptability, construct and reliability of both questionnaires. Results. The questionnaires were highly correlated in terms of both overall and comparable domain scores. In addition, both questionnaires had equal and satisfactory psychometric validity, demonstrating that they are both useful tools for assessing QOL in rhinitis. However, when compared with each other, the JRQLQ focuses mainly on activities of daily life and is simpler, while the RQLQJ focuses mainly on rhinitis-related health and is more responsive.