Meta‐analysis: A Brief Introduction

Meta‐analysis is the process of combining data from multiple sources and analyzing it together to increase power and provide a clearer picture of the effect of intervention or exposure on an outcome. The process is not complicated, but requires a great deal of attention to detail. A specific set of inclusion criteria for studies must be defined. Published or available study results may be affected by publication bias of several different types, so the researcher should be sure to conduct a thorough search of available databases in order to include unpublished findings. Following selection, the group of studies should be examined using funnel plots or statistical tests. Meta‐analysis models themselves must be selected to properly reflect the combined studies. Both fixed‐ and random‐effects modeling are discussed. Two case studies are presented, illustrating a well‐conducted meta‐analysis and a meta‐analysis that was more controversial.     

A memory‐shape temperature‐dependent nickel‐titanium device for colonic anastomosis in laparoscopic surgery

Minimally invasive surgery is a growing issue in medicine and is also increasingly being used for colonic surgery. With this procedure, the involved colon is dissected laparoscopically, exteriorized through a small incision and the segment containing the tumor is resected. The anastomosis is done extraperitoneally either by hand suture or with a stapler. Our study was designed to evaluate the feasibility of using a memory‐shape compression anastomosis clip (CAC) to perform colonic anastomosis in laparoscopy. Ten patients who were scheduled for laparoscopic colonic surgery entered the study. In five patients, the anastomosis was performed with the CAC and in five patients, with a stapler. To perform anastomosis with CAC, the two edges of the resected colon are placed parallel. Two 5‐mm incisions are made close to the edges, where the CAC is introduced in an open position after being cooled in ice water at 0°C, using a special applier. The applier introduces the clip which clamps the two bowel loops together, creating a small incision through the clamped walls, and then releasing the clip inside the intestine. The two 5‐mm incisions are then sutured. The clip is expelled with the stool within five to seven days after the operation, creating a perfect uniform anastomosis. Neither group had complications related to the anastomosis. Our study shows that the use of the CAC for colonic laparoscopic surgery is simple, very efficient and shortens operation time. It creates a uniform anastomosis, coming close to the no‐touch concept in surgery, may prevent infection, and is low in cost compared to the stapler.     

COMPREHENSIVE POST‐ARTHROSCOPIC MANAGEMENT OF A MIDDLE‐AGED ADULT WITH GLENOHUMERAL OSTEOARTHRITIS: A CASE REPORT

Comprehensive Arthroscopic Management (CAM) is a new glenohumeral debridement procedure developed as a joint preserving alternative to total shoulder arthroplasty (TSA). The procedure consists of several arthroscopic components including: A. scar tissue and chondral debridement, B. synovectomy, C. inferior humeral osteoplasty, D. capsular release, E. axillary nerve decompression, and F. tenodesis of the long head of the biceps. In this case, an active, middle age patient who failed physical therapy treatment and corticosteroid injections was evaluated and diagnosed with glenohumeral osteoarthritis. Anterior‐ posterior (AP) and axillary radiographs showed grade IV changes of the articular cartilage, confirming the diagnosis. The patient was not an ideal candidate for TSA because of her age, activity level, and concern for implant survival; therefore surgical intervention was performed using the CAM procedure. After the surgery, the patient demonstrated increased joint space as shown using radiographic imaging. The patient underwent intensive postoperative rehabilitation with a heavy emphasis on joint range of motion (ROM) and capsular mobility. By eight weeks she achieved 85% active ROM compared to her uninvolved shoulder, and a 55% improvement on the Pennsylvania Shoulder Score. Radiographic imaging provided an understanding of the severity of the arthritic changes present in this patient, identified the limited potential of continued conservative management, and showed structural changes that may be correlated with improved function following the surgical intervention. For patients less than 55 years of age diagnosed with severe glenohumeral osteoarthritis, the CAM procedure and intensive, motion focused therapy presents a promising treatment combination.

Level of Evidence:

IIIb     

Pregnancy‐associated plasma protein A: A biomarker in acute ST‐elevation myocardial infarction (STEMI)

Background. Elevated circulating levels of pregnancy‐associated plasma protein A (PAPP‐A), a novel marker of atherosclerotic plaque instability, are associated with increased risk of future cardiac events in patients with acute coronary syndromes (ACS). However, little is known of the kinetics or clinical significance of circulating PAPP‐A after plaque rupture in acute ST‐elevation myocardial infarction (STEMI).

Aim. To evaluate the 48‐hour release of pregnancy‐associated plasma protein A (PAPP‐A) and its association with 12‐month outcome in patients with acute ST‐elevation myocardial infarction (STEMI).

Methods. Sixty‐two consecutive STEMI patients were included (40 men and 22 women, median age 67.5 years (range 34–84)), of whom 54 (87.1%) received reperfusion therapy. PAPP‐A was measured at admission and 6–12, 24 and 48 hours thereafter. In 14 patients, samples were obtained also at 1, 2 and 4 hours.

Results. There was an early peak of circulating PAPP‐A during the first 12 hours from symptom onset, followed by rapid normalization. A second, late PAPP‐A elevation was noticed in 20/62 patients (32.3%). Admission PAPP‐A >10.0?mIU/L (highest tertile) was associated (P = 0.049) with increased 12‐month risk of cardiovascular death or non‐fatal myocardial infarction. Moreover, the combination of failed early reperfusion together with late PAPP‐A elevation was strongly (7/13 versus 10/49 patients, P = 0.016) associated with adverse outcome. Admission PAPP‐A did not correlate with admission C‐reactive protein or cardiac troponin I.

Conclusions. PAPP‐A is elevated early in STEMI and then declines rapidly, a pattern consistent with release from the ruptured plaque. The variability of PAPP‐A kinetics at 48 hours reflects the success of reperfusion. This study also shows that PAPP‐A may have prognostic value in STEMI.     

A non‐invasive tissue‐specific molecular delivery method of cancer gene therapy

A Japanese word, monozukuri (literally translated “making things”) is the philosophy of first having the idea and then the faith in the technical expertise and experience to accomplish the result. We believe that the concept of engineering is monozukuri. Through the process of monozukuri, engineered natural science based on mathematics and physics has been developed. Medicine is the field of study which has been developed for maintaining daily healthy life with diagnosis, treatment, examination, and protection. Biomedical engineering is the interdisciplinary study of engineering and medicine, and should be developed based on monozukuri. In this particular research, we have developed a physical molecular delivery method for cancer gene therapy using nano/microbubbles and ultrasound. First, the behavior of cavitation bubbles and subsequent shock wave phenomena involved in the mechanism of molecular delivery were analyzed, combining theory and computer simulation. In a second step, the methodology was optimized in vitro and in vivo. Finally, the therapeutic potential of the method in pre‐clinical models was evaluated using transgenes relevant to cancer gene therapy instead of reporter genes, and whole body, non‐invasive imaging using single photon emission computed tomography (SPECT/CT) was used to evaluate the selectivity of gene delivery in vivo.     

IMMEDIATE EFFECTS OF A DYNAMIC ROTATION‐SPECIFIC WARM‐UP ON X‐FACTOR AND X‐FACTOR STRETCH IN THE AMATEUR GOLFER

Background

Recent evidence suggests performing a warm‐up prior to golf can improve performance and reduce injuries. While some characteristics of effective golf warm‐ups have been determined, no studies have explored the immediate effects of a rotational‐specific warm‐up with elements of motor control on the biomechanical aspects of the full X‐Factor and X‐Factor Stretch during the golf swing.

Methods

Thirty‐six amateur golfers (mean ± SD age: 64 ± 8 years old; 75% male) were randomized into a Dynamic Rotation‐Specific Warm‐up group (n=20), or a Sham Warm‐up group (n=16). X‐Factor and X‐Factor Stretch were measured at baseline and immediately following the warm‐up. Mixed model ANCOVAs were used to determine if a Group*Time interaction existed for each variable with group as the between‐subjects variable and time as the within‐subjects variable.

Results

The mixed model ANCOVAs did not reveal a statistically significant group*time interaction for X‐Factor or X‐Factor Stretch. There was not a significant main effect for time for X‐Factor but there was for X‐Factor Stretch. These results indicate that neither group had a significant effect on improving X‐Factor, however performing either warm‐up increased X‐Factor Stretch without significant difference between the two.

Conclusions

The results of this study suggest that performing the Dynamic Rotation‐Specific Warm‐up did not increase X‐Factor or X‐Factor Stretch when controlled for age compared to the Sham Warm‐up. Further study is needed to determine the long‐term effects of the Dynamic Rotation‐Specific Warm‐up on performance factors of the golf swing while examining across all ages.

Level of Evidence

2b     

Self‐Directed learning: A matched control trial

There is a conflict between the limited period of schooling for medical students and the unlimited expansion of knowledge in medicine. In response, the trend in medical education has been to move away from the conventional goal of information transfer and toward a goal of cultivation of medical students’ abilities and intelligence, including self‐directed learning. In 1983, students admitted to Sun Yatsen University of Medical Sciences were randomly divided into a pilot group that experienced self‐directed learning (SDL) and a conventional learning group. The SDL group (n = 102) received self‐learning guidelines and a 30% to 57% reduction in the number of lecture hours. The SDL students organized their own group discussions. They then took the same examinations as the control group. For all examinations that met reliability criteria, the total scores for the SDL group were higher than or equal to the total scores for the control group, indicating successful cultivation of the students’ self‐learning abilities. The readjustments that have subsequently been made in the school's curricula are also described.     

A case of gynaecomastia with poly‐substance abuse

Hypnotherapy continues to be a misunderstood and maligned subject Its effectiveness, nevertheless, is perhaps becoming more clearly demonstrated and appreciated. Contemporary views emphasize indirect as well as direct hypnotic suggestion, the use of hypnosis as a context for amplifying other forms of psychotherapy, and the desirability of an individualized approach to cater for clients' unique needs and goals. In the field of addictive behaviours, it is argued with reference to clinical data and empirical research, that hypnotherapy is a valuable tool in assisting individuals to achieve greater control. As applicable to all forms of psychotheapy, however, commitment to desired changes, active participation in the therapeutic process and a good working alliance are prerequisite.     

SYSTEMATIC REVIEW AND META‐ANALYSIS: A PRIMER

The use of an evidence‐based approach to practice requires “the integration of best research evidence with clinical expertise and patient values”, where the best evidence can be gathered from randomized controlled trials (RCTs), systematic reviews and meta‐analyses. Furthermore, informed decisions in healthcare and the prompt incorporation of new research findings in routine practice necessitate regular reading, evaluation, and integration of the current knowledge from the primary literature on a given topic. However, given the dramatic increase in published studies, such an approach may become too time consuming and therefore impractical, if not impossible. Therefore, systematic reviews and meta‐analyses can provide the “best evidence” and an unbiased overview of the body of knowledge on a specific topic. In the present article the authors aim to provide a gentle introduction to readers not familiar with systematic reviews and meta‐analyses in order to understand the basic principles and methods behind this type of literature. This article will help practitioners to critically read and interpret systematic reviews and meta‐analyses to appropriately apply the available evidence to their clinical practice.     

A multi‐centre survey on the team concept of instrument design in gyn‐endoscopy

The objective of this study is to evaluate the current role of gynaecologists in the design of gynaecological endoscopic instruments. The study is a cross –sectional observational study conducted in the UK, the USA, Canada & Germany. Each leader of the Department of Obstetrics & Gynaecology in 1014 hospitals in the above countries participated in the study. The current role in conceptual design and the expression of design concepts were measured. One hundred and eighty‐four centres were analysed due to a Pareto effect. 91% admit that a better conceptual design can improve the overall safety of gynaecological endoscopy. 98% believe the design team should include engineers, gynaecologists and gynaecological ancillary staff. Only 18% of the centres have been involved in the design of gynaecological endoscopic instruments. A brilliant response came from the University of Michigan where collaboration already exists between the gynaecological minimally invasive surgeons and the school of engineering. The current role of gynaecologists in the design of gynaecological endoscopic instruments is passive because of the difficulty with design expression rather than conceptual design. The respondents therefore expressed the need for a design team to improve the ergonomics of endoscopic instruments and thereby improve the overall safety of gynaecological endoscopic surgery. The team concept of instrument design, taken to its logical conclusion, leads to the proposition of a global design team by 2005 so as to involve all the stakeholders of gyn‐endoscopic instruments.     

Nt‐proBNP in haemodialysis patients: A preliminary study

Objective. N‐terminal pro‐brain natriuretic peptide (Nt‐proBNP) is a marker of left ventricular function. Although many factors can increase left ventricular dysfunction in haemodialysis patients, the role of Nt‐proBNP is uncertain. Material and methods. Serum concentrations of Nt‐proBNP and troponin T were measured by electrochemiluminescence and C‐reactive protein by immunoturbidimetry in 52 dialysis patients followed‐up for 36 months. Results. Nt‐proBNP correlated (p<0.05) with time on haemodialysis (rho = 0.345), left ventricular mass index (r = 0.596), troponin T level (r = 0.605) and age (r = 0.296). Patients with a history of heart disease showed higher levels of Nt‐proBNP (median; minimum‐maximum ngl/L) (15,571; 1,553–209,451) than those without (4,535; 751–115,078) (p<0.01). Sensitivity and specificity of Nt‐proBNP in the detection of left ventricular dysfunction (ventricular ejection fraction <45?%) were 1.0 and 0.782, respectively. In the univariate analysis, patients with Nt‐proBNP levels ?33,314?ng/L, CRP ?5?mg/L or troponin T ?0.1?µg/L had poorer probabilities of 1‐year, 2‐year and 3‐year survival than patients with lower levels. Unfavourable prognostic factors in the multivariate analysis were CRP >5?mg/L and Tn T >0.1?µg/L. Conclusions. Nt‐proBNP showed good diagnostic performance for detecting left ventricular dysfunction and was an important predictor of mortality in haemodialysis patients in the univariate analysis. In the multivariate analysis, Nt‐proBNP lost its prognostic value, whereas for CRP and Tn T it was maintained.     

Patient‐treatment matching with anti‐craving medications in alcohol‐dependent patients: A review on phenotypic,endophenotypic and genetic indicators

Objectives: Craving plays an important role in the development and maintenance of alcohol dependence and in relapse after periods of abstinence. Anti‐craving compounds, such as acamprosate, naltrexone or serotonergic compounds, are found to be only moderately effective. These moderate effects might be due to inadequate matching of specific patients to specific treatments. In 1999, Verheul et al. proposed a three‐pathway model of craving in alcoholics, which hypothesised that reward drinkers would better respond to naltrexone, relief drinkers to acamprosate and obsessive drinkers to serotonergic compounds. However, these matching hypotheses are not yet validated. This article reviews the literature on predictors and matching variables of the effectiveness of pharmacological interventions in alcohol dependent patients directed at the reduction of craving and the prevention of relapse.

Methods: Studies were selected through a literature search in September 2004, focusing on matching or predicting variables for anti‐craving compounds in the treatment of alcoholics. Matching or predicting variables were categorised as either phenotypic (e.g., level of baseline anxiety), endophenotypic (e.g., physiological cue reactivity) or genetic (e.g., µ opioid receptor polymorphisms).

Results: Studies using clinical or phenotypic effect modifiers have produced inconsistent and rather disappointing results. In contrast, the predictive value of genetic effect modifiers are quite promising (e.g., µ opioid receptor polymorphisms). No studies that looked at endophenotypic predicting or matching variables were identified.

Conclusion: It is concluded that phenotypic matching variables might be too distal, i.e., far removed from the pathogenic process, and that matching research should shift its attention toward more proximal variables (e.g., genetic and endophenotypic variables).     

A SURVEY OF EXERCISE‐RELATED LEG PAIN IN COMMUNITY RUNNERS

Purpose/Background:

Exercise‐related leg pain (ERLP) is a common problem in runners. The purposes of this study were to 1) report ERLP occurrence among adult community runners; 2) determine ERLP impact on daily activities; and 3) determine if there is a relationship between ERLP occurrence and selected potential risk factors including sex, age, years of running, ERLP history, body mass index (BMI), orthotic use, menstrual function, and training variables.

Methods:

Community runners registered for a local race were invited to complete a questionnaire including demographics and potential risk factors. Analyses of differences (t‐test) and relationships (Chi‐square) were conducted and relative risk (RR) values were calculated.

Results:

225 registered runners (105 male, 120 female) participated; 63.6% reported ERLP history, and 35.1% reported ERLP in the 3 months preceding the race with bilateral medial ERLP as the most common presentation. Of the 79 runners who experienced ERLP during the 3 months preceding the race, ERLP caused 41.8% to reduce their running and interfered with walking or stair climbing in < 10%. Chi square analyses showed no significant association of sex, menstrual function, orthotic use, or BMI with ERLP occurrence. Significant associations were observed between ERLP history and ERLP occurrence in the previous year (RR=3.39; 2.54‐4.52 95% CI), and between ERLP in the 3 months preceding the race and both years running and training mileage. Greater ERLP occurrence was observed in runners with less than 3 years experience (RR = 1.53; 1.08‐2.17 95% CI) and runners who ran fewer than 15 miles/week (RR = 1.47; 1.04‐2.08 95% CI). Those runners with < 3 years running experience and a race pace of 9 min/mile or > were at greater risk for ERLP when compared to other participants (RR=1.53; 1.07‐2.18 95% CI).

Conclusion:

Interfering ERLP was common among this group of community runners. Risk factors included ERLP history, training mileage < 15 miles/week, and < 3 years running experience. Further investigation is warranted to identify factors which may increase a community runner''s risk of developing ERLP.

Level of Evidence:

2b.     

A Data‐Rich Recruitment Core to Support Translational Clinical Research

Background

Underenrollment of clinical studies wastes resources and delays assessment of research discoveries. We describe the organization and impact of a centralized recruitment core delivering comprehensive recruitment support to investigators.

Methods

The Rockefeller University Center for Clinical and Translational Science supports a centralized recruitment core, call center, Research Volunteer Repository, data infrastructure, and staff who provide expert recruitment services to investigators. During protocol development, consultations aim to optimize enrollment feasibility, develop recruitment strategy, budget, and advertising. Services during study conduct include advertising placement, repository queries, call management, prescreening, referral, and visit scheduling. Utilization and recruitment outcomes are tracked using dedicated software.

Results

For protocols receiving recruitment services during 2009–2013: median time from initiation of recruitment to the first enrolled participant was 10 days; of 4,047 first‐time callers to the call center, 92% (n = 3,722) enrolled in the Research Volunteer Repository, with 99% retention; 23% of Repository enrollees subsequently enrolled in ≥1 research studies, with 89% retention. Of volunteers referred by repository queries, 49% (280/537) enrolled into the study, with 92% retained.

Conclusions

Provision of robust recruitment infrastructure including expertise, a volunteer repository, data capture and real‐time analysis accelerates protocol accrual. Application of recruitment science improves the quality of clinical investigation.     

EFFECTS OF A DRY‐LAND STRENGTHENING PROGRAM IN COMPETITIVE ADOLESCENT SWIMMERS

Background

Shoulder pain is common in competitive young swimmers. A relationship between shoulder strength and shoulder soreness in competitive young swimmers may indicate need for strengthening.

Purpose

To determine if a shoulder exercise program will improve shoulder strength and decrease pain in competitive young swimmers.

Study Design

Randomized control

Methods

Participants (10 control, 11 experimental), randomly assigned to a control or experiment group, completed the 12 week program. Strength was measured prior to the study for shoulder flexion, abduction, external rotation, internal rotation, and extension on the dominant arm using handheld dynamometry. The experimental group was then assigned exercises to be performed three times per week. The control group was instructed not to perform the exercises. All participants were re‐tested at six and twelve weeks following initiation of the study.

Results

The changes in strength for each muscle group and pain were compared between groups using a mixed design two‐way ANOVA. The experimental group significantly increased external rotation strength compared to the control group. Shoulder soreness was not significantly different between groups.

Conclusion

Adolescents who perform shoulder strengthening significantly increased their external rotation strength compared to adolescents who only participated in a regular swimming regimen.     

VALIDATION OF A NEW METHOD FOR ASSESSING SCAPULAR ANTERIOR‐POSTERIOR TILT

Background:

Electromagnetic tracking systems have enabled some investigators and clinicians to measure tri‐planar scapular motion; yet, they are not practical and affordable options for all clinicians. Currently, the ability to affordably quantify scapular motion is limited to monitoring only the motion of scapular upward rotation, with use of a digital inclinometer.

Hypothesis/Purpose:

The objective of this study was to determine the criterion‐related validity of a modified digital inclinometer when used to measure the motion of scapular anterior‐posterior (AP) tilt.

Materials & Methods:

Thirteen volunteers, free from any history of shoulder injury, reported for a single testing session. Each subject underwent a brief shoulder and posture examination in order to confirm the absence of pathology. Subjects actively performed clinically relevant amounts of humeral elevation in the scapular plane while in a seated position. An electromagnetic tracking system (Ascension Technology, Burlington, VT) and a modified inclinometer (Pro 360, Baseline®, Fabrication Enterprises, White Plains, NY) were used to acquire scapular AP tilt over the same shoulder motions. Criterion‐related validity was determined using Pearson Product Moment correlations.

Results:

Correlation analyses revealed significant moderate to good associations (r = 0.63 to 0.86, p < 0.01) between scapular AP tilt measures obtained with a digital inclinometer and an electromagnetic tracking system.

Conclusions

A modified digital inclinometer is a moderately valid device to use for the quantification of scapular AP tilt. Further study is warranted to establish reliability and to validate use of the device in patients with shoulder injury or pathology. The modified inclinometer expands the clinician''s ability to quantify scapular kinematic motion during the clinical evaluation and rehabilitation process.

Level of Evidence:

Level 3