A healthy dietary pattern is associated with microbiota diversity in recently diagnosed bipolar patients: The Bipolar Netherlands Cohort (BINCO) study.

BACKGROUND: Diet largely impacts the gut microbiota, and may affect mental and somatic health via the gut-brain axis. As such, the relationship between diet and the microbiota in Bipolar Disorder (BD) could be of importance, but has not been studied before. The aim was therefore to assess whether dietary quality is associated with the gut microbiota diversity in patients with recently diagnosed BD, and whether changes occur in dietary quality and microbiota diversity during their first year of treatment. METHODS: Seventy recently (<1 year) diagnosed patients with BD were included in the "Bipolar Netherlands Cohort" (BINCO), and a total of 45 participants were assessed after one year. A 203-item Food Frequency Questionnaire (FFQ) data yielded the Dutch Healthy index (DHD-15), and the microbiota composition and diversity of fecal samples were characterized by 16S rRNA gene amplicon sequencing at baseline and 1-year follow-up. Associations and changes over time were analyzed using multivariate regression analyses and t-tests for paired samples. RESULTS: Included patients had a mean age of 34.9 years (SD ± 11.2), and 58.6 % was female. Alpha diversity (Shannon diversity index), richness (Chao1 index) and evenness (Pielou's Evenness Index) were positively associated with the DHD-15 total score, after adjustment for sex, age and educational level (beta = 0.55; P < 0.001, beta = 0.39; P = 0.024, beta = 0.54; P = 0.001 respectively). The positive correlations were largely driven by the combined positive effect of fish, beans, fruits and nuts, and inverse correlations with alcohol and processed meats. No significant changes were found in DHD-15 total score, nor in microbiota diversity, richness and evenness indexes during one year follow-up and regular treatment. CONCLUSION: A healthy and varied diet is associated with the diversity of the microbiota in BD patients. Its potential consequences for maintaining mood stability and overall health should be studied further.

Evidence for Underregistration of Suicide.

In this case report, we will present two cases in which the Dutch municipal coroner registered a natural death, but treating psychiatrists doubted the validity of this decision on the grounds of clinical data and investigation. For both cases, we present evidence that deaths likely resulted from suicide, raising serious doubts about the accuracy of the registered cause of death. According to the WHO bulletin on suicide prevention, the national registration of suicide is unsatisfactory in many countries. The Netherlands is listed by the WHO as having one of the most accurate registration procedures. Nevertheless, there are indications that national registration, even in the Dutch system, is not infallible. In this case report, we present several ways in which the registration process is liable to error and evidence for underregistration of suicide rates.

Overexpression of alpha4 chain-containing laminins in human glial tumors identified by gene microarray analysis.

Differential gene expression in tumors often involves growth factors and extracellular matrix/basement membrane components. Here, 11,000- gene microarray was used to identify gene expression profiles in brain tumors including high-grade gliomas [glioblastoma multiforme (GBM) and anaplastic astrocytoma], low-grade astrocytomas, or benign extra-axial brain tumors (meningioma) in comparison with normal brain tissue. Histologically normal tissues adjacent to GBMs were also studied. All GBMs studied overexpressed 14 known genes compared with normal human brain tissue. Overexpressed genes belonged to two broad groups: (a) growth factor-related genes; and (b) structural/extracellular matrix-related genes. For most of these 14 genes, expression levels were lower in low-grade astrocytoma than in GBM and were barely detectable in normal brain. Despite normal-appearing histology, gene expression patterns of tissues immediately adjacent to GBM were similar to those of their respective primary GBMs. Two genes were consistently up-regulated in both high-grade and low-grade gliomas, as well as in histologically normal tissues adjacent to GBMs. These genes coded for the epidermal growth factor receptor (previously reported to be overexpressed in gliomas) and for the alpha4 chain of laminin, a major blood vessel basement membrane component. Changes in expression of this laminin chain have not been previously associated with malignant tumors. Overexpression of laminin alpha4 chain in GBM and astrocytoma grade II by gene microarray analysis was confirmed by semiquantitive reverse transcription-PCR and immunohistochemistry. Importantly, an alpha4 chain-containing laminin isoform, laminin-8 (alpha4beta1gamma1), was expressed mainly in blood vessel walls of GBMs and histologically normal tissues adjacent to GBMs, whereas another alpha4 chain-containing laminin isoform, laminin-9 (alpha4beta2gamma1), was expressed mainly in blood vessel walls of low-grade tumors and normal brain. GBMs that overexpressed laminin-8 had a shorter mean time to tumor recurrence (4.3 months) than GBMs with overexpression of laminin-9 (9.7 months, P = 0.0007). Up-regulation of alpha4 chain-containing laminins could be important for the development of glioma-induced neovascularization and glial tumor progression. Overexpression of laminin-8 may be predictive of glioma recurrence.

Quality of life in patients with heart failure: do gender differences exist?

OBJECTIVE: The purpose of this study was to evaluate gender differences in quality of life (QOL) in a large sample of age-matched and ejection fraction (EF)-matched patients with heart failure. DESIGN: Matched comparisons of secondary data were used. SETTING: The setting consisted of multicenter Studies of Left Ventricular Dysfunction trials. SAMPLE: The sample included 1382 patients (691 men and 691 women) who were age-matched and EF-matched. OUTCOME MEASURES: Global QOL and the QOL dimensions of physical function, emotional distress, social health, and general health were measured using the Ladder of Life, items from the Profile of Mood States Inventory, the Functional Status Questionnaire, the beta-Blocker Heart Attack Trial instrument, and an item from the RAND Medical Outcomes Study instrument. RESULTS: Women had significantly worse general life satisfaction, physical function, and social and general health scores than men. There were no significant differences found between gender groups for current life situation or emotional distress. After controlling for New York Heart Association classification, women still had significantly worse ratings for intermediate activities of daily living (a sub-dimension of physical functioning) and social activity. CONCLUSIONS: Despite controlling for age, EF, and New York Heart Association classification, women had worse QOL ratings than did men for intermediate activities of daily living and social activity. Research should focus on identifying why differences exist and developing measures to improve QOL, particularly physical functioning, in women with heart failure.

Vaccination of malignant glioma patients with peptide-pulsed dendritic cells elicits systemic cytotoxicity and intracranial T-cell infiltration.

In this Phase I trial, patients' peripheral blood dendritic cells were pulsed with peptides eluted from the surface of autologous glioma cells. Three biweekly intradermal vaccinations of peptide-pulsed dendritic cells were administered to seven patients with glioblastoma multiforme and two patients with anaplastic astrocytoma. Dendritic cell vaccination elicited systemic cytotoxicity in four of seven tested patients. Robust intratumoral cytotoxic and memory T-cell infiltration was detected in two of four patients who underwent reoperation after vaccination. This Phase I study demonstrated the feasibility, safety, and bioactivity of an autologous peptide-pulsed dendritic cell vaccine for patients with malignant glioma.

Gene expression abnormalities in human glial tumors identified by gene array.

Novel genes specific for human oligodendroglioma and glioblastoma multiforme (GBM) were detected using the gene array analysis [18,376 genes Gene Discovery Array (GDA) from Incyte Genomics, Inc.]. Eleven genes were chosen based on the highest ratios of differential expression identified by GDA between histologically normal adjacent tissue and brain tumor tissue. The differential expression of those 11 genes was verified by semiquantitative RT-PCR and Northern analysis on 22 samples of glial and other tumors of the brain, as well as of normal embryonic and adult brain tissue. Gene no. 5 (an EST) was more expressed by GDA analysis in histologically normal adjacent brain tissue than in the corresponding oligodendroglioma. By RT-PCR, this gene was expressed in a number of brain tumors but not in normal adult and embryonic brain. By GDA analysis, gene no. 7 (oligophrenin-1) gave the highest ratio compared to other genes in brain tissue adjacent to the GBM vs. GBM. By RT-PCR, oligophrenin-1 was expressed in tumors and tumor-adjacent tissue, whereas meningioma and corpus callosum were negative. Gene no. 11 (an EST) was expressed only in brain tumors but not in normal brain by Northern analysis (message size 1.5 kb) and RT-PCR. GDA analysis successfully identified genes preferentially expressed in brain tumors, which was confirmed by Northern analysis and semiquantitative RT-PCR. The validity of gene arrays for tumor-specific gene discovery is discussed. Study of differential gene expression in glial tumors should help identify the mechanism/s of transformation of normal glial cells to malignant.

Can practice guidelines be transported effectively to different settings? Results from a multicenter interventional study.

RATIONALE: Although clinical guidelines have become increasingly popular as a means to reduce variation in care, increase efficiency, and improve patient outcomes, little is known about their effectiveness when they are transported outside their original setting, or about the factors that influence their successful translation into clinical practice. This study assessed whether a clinical guideline for low-risk chest pain patients, implemented with a standardized protocol, could be effectively transported to five hospital settings. METHODS: In a prospective, interventional trial, a standardized protocol for low-risk chest pain was implemented at each site. A total of 553 consecutively hospitalized low-risk patients with chest pain were enrolled during a 3-month baseline period followed by a standardized 6-month intervention period. During the intervention period, each patient's physician was contacted about eligibility for discharge within the specified 2-day guideline period. Guideline adherence (discharged within 48 hours) and postdischarge patient outcomes were measured. Local guideline champions were interviewed about their implementation experience. RESULTS: Guideline adherence during the intervention period ranged from 61% to 100%, with only two sites achieving significant increases of > or = 10% from the baseline values. Guideline implementation did not affect clinical outcomes or patient satisfaction. Implementation factors such as preexisting hospital environment, implementation team staffing, and the rapid identification and resolution of barriers may influence the successful translation of guidelines into practice. CONCLUSIONS: Even with a standardized implementation protocol, consistent results across institutions were not obtained when a clinical guideline for chest pain was implemented beyond its original setting. These findings demonstrate the importance of understanding the local factors that influence guideline implementation.

Predictors of quality of life in women with heart failure. SOLVD Investigators. Studies of Left Ventricular Dysfunction.

BACKGROUND: Two and one half million women have heart failure (HF). Yet little is known about quality of life (QOL) in this population and the factors influencing it. Given the importance of QOL as an outcome of care, we conducted a study to evaluate predictors of QOL in women with HF. METHODS: Using baseline QOL data collected in the Studies of Left Ventricular Dysfunction (SOLVD) trials, we studied predictors of QOL in 691 women with HF. Univariate, bivariate, and multiple regression analyses were used. Potential predictors included age, education, tobacco use, social isolation, life stresses, comorbidity index, New York Heart Association (NYHA) class, HF symptoms, etiology, and medications. We measured global QOL and QOL dimensions of physical function, emotional distress, and social and general health. RESULTS: Women were older (61+/-10.5 years), predominantly Caucasian (75%), and their mean ejection fraction was 0.27 (+/-6.51). Variables with the strongest relationship to QOL included dyspnea, NYHA class, and life stresses. As dyspnea, life stresses, and NYHA class increased, QOL decreased. Additionally, smoking behavior and vasodilator use was associated with decreased QOL. Heart failure etiology of ischemic origin was associated with decreased social life satisfaction, and use of digitalis was predictive of increased social life satisfaction. Finally, increasing age was related to an increase in general life satisfaction. CONCLUSION: Symptom amelioration, which may improve functional ability, has the greatest potential for increasing QOL in women with HF. Programs to increase physical activity in women with HF should be developed and tested. Finally, clinicians may need to optimize HF medications in women.

CD4 T cell traffic control: in vivo evidence that ligation of OX40 on CD4 T cells by OX40-ligand expressed on dendritic cells leads to the accumulation of CD4 T cells in B follicles.

We report here that CD40- but not lipopolysaccharide (LPS)-activated murine dendritic cells (DC) express OX40-ligand (OX40L) as has been reported in humans. To understand how OX40 ligation affects differentiation of CD4 T cells at the time of priming, we constitutively expressed OX40L on DC using the DC-specific promoter of CD11c. Transgenic mice showed greatly increased numbers of CD4 but not CD8 T cells in their B cell areas. This effect was to a great extent immunization dependent, as spleen and lymphoid tissue with no germinal center reactions from mice which had not been deliberately immunized did not show marked CD4 T cell accumulation. The increased numbers of CD4+ CD62low cells in transgenic mice suggest that it is activated CD4 T cells that accumulate within B cell follicles. These data are consistent with the notion that physiological engagement of OX40 (CD134) on activated CD4 T cells either initiates their migration into or causes them to be retained in B follicles. In contrast, LPS-treated CD did not up-regulate OX40L expression. This dichotomy provides a molecular explanation of how DC might integrate environmental and accessory signals to control cytokine differentiation and migration in CD4 effector cells.

Can practice guidelines safely reduce hospital length of stay? Results from a multicenter interventional study.

BACKGROUND: Although practice guidelines about appropriate lengths of stay have been widely promulgated, their effects on patient outcomes are not clear. Our objective was to study the effects of length of stay practice guidelines on patient outcomes. PATIENTS AND METHODS: We performed a prospective, nonrandomized, interventional trial in six geographically distributed hospitals, among consecutively hospitalized "low-risk" patients with total hip replacement, hip fracture, or knee replacement. Case managers provided physicians with patient risk information based on guideline recommendations. We measured length of stay, compliance with recommended guideline length of stay, health status, hospital readmission rates, return to emergency department, return to work and recreation, and patient satisfaction. RESULTS: A total of 560 patients were included in the study. For patients with knee replacement, there was a statistically significant increase in practice guideline compliance (27% baseline versus 53% intervention, P <0.0001) and reduction in length of stay (5.2 days versus 4.6 days, P <0.001) when compared with the baseline period. For hip replacement patients, there similarly was an increase in practice guideline compliance (66% baseline versus 82% intervention, P = 0.01) and reduction in length of stay (5.1 days versus 4.8 days, P = 0.03). Significant reductions in length of stay were not observed for patients recovering after hip fracture despite a significant increase in guideline compliance. There were few statistically significant changes in patient outcomes related to reductions in lengths of stay, including health status, hospital readmission rates, return to emergency department, return to work and recreation, and patient satisfaction. For patients undergoing hip replacement, very short lengths of stay (shorter than the guideline recommendation) were associated with an increased rate of discharging patients to nursing homes and rehabilitation facilities (21% versus 7%, P = 0.01), and hip fracture patients with very short lengths of stay required more visits to the doctor after discharge (56% versus 25%, P = 0.04). CONCLUSION: Reductions in lengths of stay were most often associated with no significant change in patient outcomes. However, very short lengths of stay were associated with increased intensity of care following discharge for patients undergoing hip surgery, indicating possible cost shifting (the cost incurred by transferring patients to rehabilitation facilities may have been greater than had the patients remained in the acute care hospital for an additional 1 or 2 days and been sent directly home). These results emphasize the importance of monitoring the effects of cost containment and other systematic efforts to change patient care at the local level.

A prospective, multicenter study of a pneumonia practice guideline.

OBJECTIVE: To study the effect of a length of stay practice guideline on patient outcomes. DESIGN: A prospective, nonrandomized, interventional trial. SETTING: Six geographically distributed hospitals. PATIENTS: Two hundred forty-two consecutively hospitalized "low-risk" patients with pneumonia. MEASUREMENTS AND RESULTS: One hundred fifty-two patients (63%) completed the mailed postdischarge survey and were included in the analysis. Data were prospectively collected for 85 patients from the baseline observation period (B) and 67 patients from the intervention period (I). During the I, case managers provided physicians with patient risk information based on guideline recommendations. There was no significant change in guideline compliance (B vs I: 76.5% vs 83.6%; p=0.32) or length of stay (B vs I: 3.5 days [95% confidence interval, 3.2 to 3.8] vs 3.6 days [95% confidence interval, 3.3 to 4.0]). Also, there were no statistically significant effects of the intervention on patient outcomes, care following hospital discharge, and patient satisfaction scores. CONCLUSION: Patients in this study often had shorter lengths of stay than recommended by the practice guideline. This suggests that the external environment may have had a greater effect on physician behavior and length of stay than the practice guideline itself. Moreover, it demonstrates the importance of continuous assessment of physician practices immediately prior to, during, and after application of the clinical practice guideline.

Targeted expression of major histocompatibility complex (MHC) class II molecules demonstrates that dendritic cells can induce negative but not positive selection of thymocytes in vivo.

It is well established that lymphoid dendritic cells (DC) play an important role in the immune system. Beside their role as potent inducers of primary T cell responses, DC seem to play a crucial part as major histocompatibility complex (MHC) class II+ "interdigitating cells" in the thymus during thymocyte development. Thymic DC have been implicated in tolerance induction and also by some authors in inducing major histocompatibility complex restriction of thymocytes. Most of our knowledge about thymic DC was obtained using highly invasive and manipulatory experimental protocols such as thymus reaggregation cultures, suspension cultures, thymus grafting, and bone marrow reconstitution experiments. The DC used in those studies had to go through extensive isolation procedures or were cultured with recombinant growth factors. Since the functions of DC after these in vitro manipulations have been reported to be not identical to those of DC in vivo, we intended to establish a system that would allow us to investigate DC function avoiding artificial interferences due to handling. Here we present a transgenic mouse model in which we targeted gene expression specifically to DC. Using the CD 11c promoter we expressed MHC class II I-E molecules specifically on DC of all tissues, but not on other cell types. We report that I-E expression on thymic DC is sufficient to negatively select I-E reactive CD4+ T cells, and to a less complete extent, CD8+ T cells. In contrast, it only DC expressed I-E in a class II-deficient background, positive selection of CD4+ T cells could not be observed. Thus negative, but not positive, selection events can be induced by DC in vivo.

Redirecting the complete T cell receptor/CD3 signaling machinery towards native antigen via modified T cell receptor.

We show that a chimeric T cell receptor (TCR) beta chain consisting of a single-chain Fv portion derived from a monoclonal antibody and the full TCR beta chain is able to assemble functionally with endogenous TCR/CD3 components and transfer the antibody specificity as well as the TCR specificity into TCR beta- as well as into TCR beta+ T cells. This allows the incorporation new non-major histocompatibility complex-restricted ligand specificities into the intact TCR/CD3 complex which can exploit the full range of biological activities of the endogenous TCR signaling machinery. This approach can provide wider opportunities to redirect T cells to virus or tumor antigen-bearing cells.

Evaluation of a pneumonia practice guideline in an interventional trial.

There are few available data to define the medically necessary duration of stay for patients hospitalized with pneumonia. Therefore, we investigated the safety and effectiveness of a practice guideline that provided information about switching patients from parenteral to oral antimicrobials and early hospital discharge. The study was a prospective controlled study with an alternate month design. The practice guideline was studied in 146 "low-risk" pneumonia patients hospitalized during a 22-month period. Medical care consistent with the practice guideline occurred in 64% and 76% of patients during control and intervention periods, respectively (p=0.15). There were no differences in patient outcomes in the control and intervention groups when measured 1 mo after hospital discharge, including hospital readmission rates, health-related quality of life, and patient satisfaction. Explicit and implicit review revealed that 98.6% (95% confidence interval [CI]: 95.1%, 99.8%) of low-risk patients would not have benefited from continued hospitalization after the fourth hospital day. The 30-d survival rate of the low-risk pneumonia patients was 99.3% (95% CI: 96.2%, 100%) and patient outcomes appeared to be favorable compared with previously published values. We conclude that duration of hospital stay was frequently consistent with the practice guideline in both study groups, and patient outcomes remained unchanged. The guideline will require additional testing before it can be recommended for use.

Total knee replacement. A guideline to reduce postoperative length of stay.

In a retrospective study in an academic, acute-care community hospital, we studied the possible safety and effectiveness of a practice guideline recommending early discharge from the hospital for patients having uncomplicated total knee replacement. Of 206 patients receiving knee replacements, 162 (79%) were classified by the guideline as being at low risk for complications between the 4th and 7th postoperative days. Use of the guideline could have reduced the postoperative length of stay from 7.3 +/- 2.6 days to 4 days for the 112 patients (54%) who became low risk on the 4th postoperative day. Explicit and implicit review of the quality of care determined that 157 patients (96.9%; 95% confidence interval, (92.9%, 99.0%) could have been safely transferred from the acute-care hospital to an appropriate setting when they became classified at low risk between the 4th and 7th postoperative days. Clinical practice guidelines can possibly be used to reduce the postoperative length of acute-care hospital stay for patients having knee replacements. This guideline requires further study in a controlled clinical trial before it can be recommended for use.

Measuring and improving physician compliance with clinical practice guidelines. A controlled interventional trial.

OBJECTIVE: To determine factors that may lead physicians not to comply with clinical practice guidelines. DESIGN: Retrospective analysis of patients whose physicians were not compliant with discharge recommendations from a prospective, controlled interventional trial of a guideline to reduce hospital length of stay for patients admitted for chest pain. SETTING: A large community teaching hospital. PARTICIPANTS: Patients admitted with chest pain who were not discharged according to a practice guideline. RESULTS: 79 (34%) of 230 patients with chest pain classified as being at low risk by concurrent or retrospective review were not discharged by day 3 (the guideline recommendation). Of these 79 patients, 33 (42%) were misclassified at concurrent review (10 were falsely classified as being at high risk and 23 were falsely classified as being at low risk). Of 46 correctly classified patients, 11 (14%) were classified as having noncompliant physicians because of health care system inefficiencies. The status of 7 (9%) patients was changed to high risk between initial classification and potential discharge. For 15 patients (19%), no obvious reason for delayed discharge was found, but they had a higher severity of illness than did low-risk patients discharged according to the guideline as measured by mean time-insensitive predictive instrument scores (41.3% +/- [SD] 14.1% compared with 31.5% +/- 14.3%; P = 0.017). In 13 patients (16%), physicians refused to follow the guideline recommendations. CONCLUSIONS: In measuring and attempting to improve physician compliance with a length-of-stay guideline, physician refusal accounts for a small percentage (16%) of noncompliance. Implementation issues, health care system inefficiency, and severity of illness were the predominant reasons why physicians did not comply with guidelines. Our study further supports the principle that clinical practice guidelines should complement rather than be a substitute for physician judgment.

Reducing lengths of stay in the coronary care unit with a practice guideline for patients with congestive heart failure. Insights from a controlled clinical trial.

Although more than 1,000 medical practice guidelines have been developed, there have been few evaluations of their use in clinical practice or information to judge whether practice guidelines can be used to reduce health care costs. For this reason, the authors conducted a prospective controlled clinical trial with an alternating-month design at a large teaching community hospital to study the use of a practice guideline to promote early transfer of patients admitted to a hospital with congestive heart failure (CHF) from the coronary care unit (CCU) and intermediate care unit to unmonitored beds. The practice guideline was supported by locally derived risk information and recommended consideration of early "step-down" transfer of low-risk patients with CHF 24 hours after hospital admission. Physicians caring for patients identified as "low risk" received concurrent personalized written and verbal reminders concerning the guideline recommendation. Study subjects were patients admitted to a hospital CCU and intermediate care unit between November 1, 1991 and April 30, 1993 with a diagnosis of CHF or pulmonary edema. Ninety patients with CHF were identified as low risk according to the guideline during the study period. Feedback of the practice guideline recommendation was not associated with a significant increase in physician adoption of the guideline or shorter lengths of stay in the CCU or intermediate care unit. Physicians may have compensated for statistically insignificant reductions in monitored lengths of stay by increasing the length of stay in unmonitored beds (1.80 +/- 2.32 to 4.02 +/- 4.09 days, P = .002) and the total length of stay (4.73 +/- 2.43 to 6.71 +/- 5.44 days, P = .03). Quality of patient care, patient outcomes, and patient satisfaction were not affected by the guideline. Our study results suggest that implementation of a locally derived practice guideline for patients with CHF did not result in adoption of the guideline by physicians. The complexity of implementing the guideline, changes in physician practice before the study, and the failure of the guideline to address the continuum of patient care across monitored and unmonitored beds may have accounted for rejection of the guideline. Our experience demonstrates that practice guidelines, whenever possible, should be evaluated in prospective trials before they should be disseminated for widespread use.

Hip replacement and hip hemiarthroplasty surgery: potential opportunities to shorten lengths of hospital stay.

The potential safety and effectiveness of a practice guideline recommending a 5-day postoperative stay in the acute care hospital for hip surgery patients without clinical findings predictive of a complicated hospital course was studied retrospectively in 230 patients hospitalized for total hip replacement, total hip replacement with osteotomy, or hip hemiarthroplasty. Seventy percent of total hip replacement and hip hemiarthroplasty patients were classified as being at "low risk" for complications by the guideline (161 patients, or 73% of patients who remained hospitalized). Use of the guideline could have reduced the hospital length of stay from 8.4 days (standard deviation 3.3) to 5.9 days for these selected low-risk patients. Moreover, physicians' implicit review determined that 0% of patients (95% confidence interval, 0% to 2.3%) had a complication that would have benefited from continued stay in an acute care hospital after the fifth postoperative day. Our practice guideline may have the potential to safely reduce acute care hospital length of stay for patients recovering after total hip replacement and hip hemiarthroplasty. The guideline will require further study in a prospective clinical trial before it can be recommended for widespread use.