Adaptation of the 2015 American College of Rheumatology treatment guideline for rheumatoid arthritis for the Eastern Mediterranean Region: an exemplar of the GRADE Adolopment

BACKGROUND: It has been hypothesized that adaptation of health practice guidelines to the local setting is expected to improve their uptake and implementation while cutting on required resources. We recently adapted the published American College of Rheumatology (ACR) Rheumatoid Arthritis (RA) treatment guideline to the Eastern Mediterranean Region (EMR). The objective of this paper is to describe the process used for the adaptation of the 2015 ACR guideline on the treatment of RA for the EMR. METHODS: We used the GRADE-Adolopment methodology for the guideline adaptation process. We describe in detail how adolopment enhanced the efficiency of the following steps of the guideline adaptation process: (1) groups and roles, (2) selecting guideline topics, (3) identifying and training guideline panelists, (4) prioritizing questions and outcomes, (5) identifying, updating or conducting systematic reviews, (6) preparing GRADE evidence tables and EtD frameworks, (7) formulating and grading strength of recommendations, (8) using the GRADEpro-GDT software. RESULTS: The adolopment process took 6 months from January to June 2016 with a project coordinator dedicating 40% of her time, and the two co-chairs dedicating 5% and 10% of their times respectively. In addition, a research assistant worked 60% of her time over the last 3 months of the project. We held our face-to-face panel meeting in Qatar. Our literature update included five newly published trials. The certainty of the evidence of three of the eight recommendations changed: one from moderate to very low and two from low to very low. The factors that justified a very low certainty of the evidence in the three recommendations were: serious risk of bias and very serious imprecision. The strength of five of the recommendations changed from strong to conditional. The factors that justified the conditional strength of these 5 recommendations were: cost (n = 5 [100%]), impact on health equities (n = 4 [80%]), the balance of benefits and harms (n = 1 [20%]) and acceptability (n = 1 [20%]). CONCLUSION: This project confirmed the feasibility of GRADE-Adolopment. It also highlighted the value of collaboration with the organization that had originally developed the treatment guideline. We discuss the implications for both guideline adaptation and future research to advance the field.(AU)

The relationship between HbA1c and fasting plasma glucose in patients with increased plasma liver enzyme measurements.

BACKGROUND: HbA(1c) is currently being introduced for diagnostic purpose in diabetes. Previous studies have, however, indicated that patients with liver disease have false low HbA(1c) levels. We therefore investigated the correlation between HbA(1c) and plasma glucose in patients with different levels of increased liver enzyme concentrations. METHODS: Data from 10,065 patients with simultaneous measurement of HbA(1c), venous fasting plasma glucose, alanine aminotransferase and γ-glutamyl transferase were extracted from our laboratory database. Correlations were investigated in four patient groups divided according to their liver enzyme concentrations. RESULTS: The correlation between HbA(1c) and plasma glucose was high in all groups, with r = 0.77 for men and r = 0.78 for women (P < 0.001), a correlation confirmed with multiple regression analysis (P < 0.001). However, interaction analysis revealed that linear regression lines were significantly different for men and women, with increase of both liver enzyme measurements and also, for women, with increased alanine aminotransferase. When compared with biological variation for HbA(1c), only men with increased measurements of both liver enzymes had a clinically important decrease in HbA(1c). CONCLUSIONS: Increased liver enzyme concentrations do not bias the correlation between HbA(1c) and fasting plasma glucose. However, men with low plasma glucose and increased concentrations of both liver enzymes do have a slightly decreased HbA(1c) and, if the clinical suspicion is strong enough, one should consider supplement testing.

Periapical radiography and cone beam computed tomography for assessment of the periapical bone defect 1 week and 12 months after root-end resection.

OBJECTIVES: Our aim was to compare periapical radiography and cone beam CT (CBCT) for assessment of the periapical bone defect 1 week and 12 months after root-end resection. METHODS: 50 patients (58 teeth) with a persisting apical periodontitis in a root-filled tooth (incisor, canine or premolar) were treated with root-end resection. 1 week and 12 months post-operatively, a CBCT scan (NewTom 3G) and a periapical radiograph (Digora) were obtained. Three observers detected and measured the periapical bone defects on periapical radiographs and CBCT images (coronal and sagittal sections). RESULTS: 1 week post-operatively, a periapical bone defect area was measured in all teeth by all observers. The defect was 10% smaller on periapical radiographs (mean = 12.4 mm2, SD = 8.2) than on the CBCT images measured in the coronal plane (mean = 13.0 mm2, SD = 7.8), a difference which was not statistically significant (P = 0.58). 12 months post-operatively (n = 52), there was considerable variation between the observers' detection of a remaining defect on the periapical radiographs and the CBCT images. The average agreement between the periapical radiograph and the CBCT images in the coronal sections was 67%, and more defects were detected on CBCT than on periapical radiographs. CONCLUSIONS: On average, the periapical bone defect measured on periapical radiographs was approximately 10% smaller than on coronally sectioned CBCT images 1 week post-operatively. More remaining defects were detected 1 year after periapical surgery on CBCT images than on periapical radiographs, but it is uncertain how this information is related to success or failure after root-end resection.

Randomized clinical trial of root-end resection followed by root-end filling with mineral trioxide aggregate or smoothing of the orthograde gutta-percha root filling--1-year follow-up.

AIM: To compare healing after root-end resection with a root-end filling of mineral trioxide aggregate (MTA) or smoothing of the orthograde gutta-percha (GP) root filling. METHODOLOGY: Forty-four patients (consisting of 52 teeth with periapical infection), average age of 54.6 years (range 30-77) participated in a randomized clinical trial (RCT) comparing the MTA and GP treatment methods. Radiographs produced 1-week and 12 months post-operatively were compared after blinding for treatment method, and healing was assessed as complete, incomplete, uncertain, or unsatisfactory. RESULTS: Six teeth were not available for the 12-month follow-up: three teeth (GP) had been re-operated because of pain and two teeth (one GP, one MTA) had been extracted because of root fracture (these five teeth were classified as failures). One patient (GP) was not available for recall. In the GP group, seven teeth (28%) showed complete healing, six teeth (24%) incomplete healing, six teeth (24%) uncertain healing and two teeth (8%) unsatisfactory healing after 1 year. In the MTA group, 22 teeth (85%) showed complete healing, three teeth (12%) incomplete healing, and none were scored as uncertain or unsatisfactory healing after 1 year. The difference in healing between the GP and the MTA groups was significant (P < 0.001). CONCLUSIONS: The results from this RCT emphasize the importance of placing a root-end filling after root-end resection. Teeth treated with MTA had significantly better healing (96%) than teeth treated by smoothing of the orthograde GP root filling only (52%).

Renal hemodynamics in young and old spontaneously hypertensive rats during intrarenal infusion of arginine vasopressin.

BACKGROUND/AIMS: To gain insight into the effect of arginine vasopressin (AVP) on renal hemodynamics in hypertensive rats, we investigated the vasoconstrictive response to AVP on total renal blood flow (RBF) and total and zonal glomerular filtration rate (GFR) in young and old spontaneously hypertensive rats (SHR). A hypothesis of increased AVP sensitivity in the juxtamedullary cortex of SHR was tested. METHODS: Total RBF and total and zonal GFR were studied in 10- and 40-week-old SHR and normotensive Wistar-Kyoto rats (WKY). RBF was recorded by a flowmeter before infusion of AVP and immediately after injection of a bolus dose of 10 ng AVP. Whole kidney GFR and its intracortical distribution was measured by the tubular uptake of 125I- and 131I-labelled aprotinin before and during a continuous infusion of AVP 5 ng/min. Ligand binding measurements of preglomerular V1a receptors were performed in young and old rats. RESULTS: RBF decreased by 43 +/- 3% in 10-week SHR (9.2 +/- 0.5 vs. 5.2 +/- 0.3 ml x min(-1) x g(-1)), significantly more than 10-week WKY where RBF decreased by 35 +/- 3% (9.6 +/- 0.7 vs. 6.5 +/- 0.5 ml x min(-1) x g(-1)) (p < 0.05). The effect of AVP on RBF was attenuated in 40-week-old rats where the decline in RBF was 29 +/- 5% in SHR and 23 +/- 4% in WKY (p > 0.05). GFR decreased by 6 +/- 3% (1.03 +/- 0.04 vs. 0.96 +/- 0.04 ml x min(-1) x g(-1), p < 0.05) in 10-week SHR and was unchanged in 10-week WKY (1.10 +/- 0.07 vs. 1.08 +/- 0.04 ml x min(-1) x g(-1), p > 0.10). GFR decreased by 11 +/- 10% in 40-week SHR and by 4 +/- 4% in 40-week WKY (p > 0.05). AVP infusion significantly increased filtration fraction in all groups except 40-week SHR, indicating that AVP has the strongest vasoconstrictive effect on postglomerular vessels. The intrarenal distribution of GFR was unchanged in the normotensive and hypertensive groups. V1a receptor density was upregulated in young SHR compared to young WKY (p < 0.05), but downregulated in old compared to young SHR (p = 0.05). CONCLUSION: The results indicate that AVP sensitivity is not increased in the juxtamedullary cortex in SHR and the reduced vasoconstrictive effect in old SHR is due to a reduced density of V1a receptors.

Crepitation and clicking as signs of TMD in preschool children.

Children [N = 540, age 5.1 +/- 0.72 (SD)], were tested for association between temporomandibular (TM) joint sounds and symptoms of TM disorder (TMD). The prevalence of TMJ sounds as found by auscultation and confirmed by self-report was 16.7%. There was significant association after Bonferroni correction between the presence of TM joint sounds, as reported by the children, and all but one of the eleven pain/dysfunction variables. There was significant association also between crepitation as heard at auscultation and palpation tenderness in the TMJ and masseter areas (p < 0.001), but not between clicking and any of the TMD variables. Agreement between subjects and examiners regarding the presence of TMJ sounds was poor (kappa = 0.097). The results indicate that joint sounds and TMD symptoms are common already in small children and thus demonstrate a possible early onset of TMD. Patients' own reports of TMJ sounds may have more clinical relevance than auscultation findings.

Effects of a myofunctional appliance on orofacial muscle activity and structures.

The aim of the study was to examine the effect of an oral shield treatment on orofacial muscle activity and facial morphology in children with lip and/or tongue dysfunction. The sample consisted of 7 girls and 2 boys, 7 to 12 years old. EMG recordings with and without the shield in situ were obtained when the shield was placed, and 3, 6, and 12 months later. Lateral cephalograms were obtained at the initial and 1-year stages. The lip muscles showed dominant activity when the subjects were sucking on an empty straw and during swallowing; this was strongest during the first 3 months. The mentalis, buccinator, and digastric muscles generally showed weaker activity. The anterior temporal muscle showed dominant activity during maximal clench, but after the 3-month stage a significant decrease was noted. After 1 year of treatment, no significant changes in overjet or overbite were observed. Most of the craniofacial growth changes were normal for the age group. The results indicate that treatment with an oral shield caused a decrease in orofacial muscle activity during oral functions. Although there was a slight average retraction of the maxillary incisors, the change in position was not statistically significant.

Stress-related molar responses to the transpalatal arch: a finite element analysis.

The finite element method of analysis (FEM) was used to analyze theoretically the effects of a transpalatal arch (TPA) on periodontal stresses of molars that were subjected to typical retraction forces. The purposes of this investigation were (1) to construct an appropriate finite element model, (2) to subject the model to orthodontic forces and determine resultant stress patterns and displacements with and without the presence of a TPA, and (3) to note any differences in stress patterns and displacements between models with and without a TPA. Because anchorage is stress-dependent, a TPA must be able to modify periodontal stresses as a prerequisite for increasing orthodontic anchorage. A finite element model, consisting of two maxillary first molars, their associated periodontal ligaments and alveolar bone segments, and a TPA, was constructed. The model was subjected to simulated orthodontic forces (2 N per molar) with and without the presence of the TPA. Resultant stress patterns at the root surface, periodontal ligament, and alveolar bone, as well as displacements with and without a TPA, were calculated. Analysis of the results revealed minute differences of less than 1% of the stress range in stress values with respect to the presence of a TPA. Modification of bone properties to allow for increased displacement levels confirmed the ability of the TPA to control molar rotations; however, no effect on tipping was noted. Results suggested that the presence of a TPA has no effect on molar tipping, decreases molar rotations, and affects periodontal stress magnitudes by less than 1%. The final results suggest an inability of the TPA to modify orthodontic anchorage through modification of periodontal stresses.

Assessing apical deformation and transportation following the use of LightSpeed root-canal instruments.

The LightSpeed root canal instrument is similar in design to the Canal Master instrument with the exception of being engine driven and fabricated from nickel-titanium alloy. The purpose of the design of these instruments is to reduce apical transportation of the canal during cleansing and shaping procedures. Twenty extracted human molar teeth with roots of varying degrees of curvature were used in this study. A double exposure radiographic technique was used to assess the presence or absence of apical transportation resulting between the initial instrument and the final instrument, a size 50 LightSpeed. Only one of the 20 teeth examined exhibited apical transportation. Results of this study suggest that little or no apical canal transportation could be expected when curved canals are instrumented using the LightSpeed root canal instruments.

Successful treatment of phenol poisoning with charcoal hemoperfusion.

A 50-y-old Caucasian female inadvertantly received 30 ml of 89% phenol (26.9 g, 0.44 g/kg bw) [corrected]. At 23 min post-injection the patient was unresponsive and in shock. By 4 h post-injection she required large doses of vasopressors. At 4.5 h, charcoal hemoperfusion (CHP) was begun and she received that for 6 h and 20 min. Her clinical status improved during the CHP and she made a complete recovery. Phenol levels drawn prior to and after the procedure correlated her recovery with the improving phenol levels. CHP appears to have efficacy in severe acute phenol intoxication.

Classification of temporomandibular joint sounds based upon their reduced interference distribution.

Temporomandibular joint (TMJ) sounds were recorded in 98 orthodontic retention patients, mean age 19 +/- 8.6 (s.d.) years, by interview, auscultation and electronic recording. Sounds were found by auscultation in 41% and by interview in 32% of the subjects, more often in females than in males (P < 0.05). A new method for time-frequency analysis, the reduced interference distribution (RID), was used to classify the electronic sound recordings into five subclasses, RID types 1-5, based upon location and number of their energy peaks. RID types 1-3 had a few energy peaks close in time. RID types 4-5, typical of subjects with crepitation, had multiple energy peaks occurring close in time for a period of 20-300 ms. RID type 1, found in 45% of the subjects, typical of patients with clicking, had its dominant energy peak located in a frequency range < 600 Hz and was significantly more common in the female than in the male subjects (P < 0.01). RID type 2, found in 68% of the subjects, with the dominant peak in the range 600-1200 Hz, and RID type 3, found in 38% of the subjects, with the peak in the frequency range > 1200 Hz, were found to have a similar gender distribution. RID type 4, found in 49% of the subjects, had the energy peaks distributed in the frequency range < 600 Hz. RID type 5, found in 43% of the subjects, more often in females than in males (P < 0.05), had the peaks distributed over the whole frequency range from about 30 Hz up to about 3000 Hz. In conclusion, a more detailed classification could be made of the TMJ sounds by displaying the RIDs than by auscultation. This suggests that RID classification methods may provide a means for differentiating sounds indicating different types of pathology.

Oral parafunctions as temporomandibular disorder risk factors in children.

Oral parafunctions are generally considered to be important factors in the etiology of temporomandibular disorders (TMDs) and many reports have been published about their prevalence in adults and schoolchildren. However, few have included significant numbers of children below the age of 7. The aim of this study was to examine the association between parafunctions and oral/facial TMD-related pain in preschool children. Bruxism, nail biting, and thumb sucking were found to be significantly associated with important oral/facial pain symptoms of clinical interest in the diagnoses of TMD indicating that those parafunctions are risk factors. The study included 525 4- to 6-year-old African-American and Caucasian children, mean age 5.1 +/- 0.65 (SD). An alpha level of 5% was chosen for comparison with a Pearson Chi-Square test. Bonferroni correction was made and a p-value of < 0.005 was accepted as significance level. Only 28% of the children had no history of any parafunction. More girls (82%) than boys (63%) in the Caucasian subgroup had at least one parafunction (p approximately 0.00017). No such difference was found in the African-American subgroup where the corresponding figures were 71% for girls and 73% for boys. Thumb sucking was reported by 57% of the children, more often by Caucasian girls (69%) than by Caucasian boys (43%) (p < 0.00001). Thirty percent still had the habit. Forty-one percent had a history of nail biting. Bruxism was noted in 20% of the children, but occurred mostly in combination with other parafunctions and was seldom (in 3.4%) the only parafunction. Of the 10 pain variables, bruxism was significantly associated with eight, thumb sucking with three, and nail biting with two. Analysis with logistic regression confirmed the results. Association does not, however, tell if a parafunction is the cause or the consequence of pain, or if a third factor is causing both pain and increased prevalence of oral parafunctions. Further prospective longitudinal studies including higher age groups are needed to clarify those relations and to determine if there are long-term effects of childhood parafunctions.

Race and gender as TMD risk factors in children.

The aim of this study was to record the prevalence in preschool children of oral/facial pain symptoms of clinical interest in the diagnoses of temporomandibular disorders (TMD) and to analyze the association with the race and gender factors. Children, 525 4-6 year olds, mean age 5.1 +/- 0.65 (SD), 326 Caucasian and 199 African American, from a preschool and kindergarten program in a low income industrial area, who participated in a voluntary oral health examination, were examined. Comparisons were made using Chi-Square test. An alpha-level of 5% was chosen, and the effect of making multiple comparisons was compensated for by Bonferroni correction. No gender differences were found, but racial differences were observed regarding six of the 10 variables. Twenty-five percent of the children had recurrent (at least one to two times per week) headache. Thirteen percent had recurrent earache, African-American children more often than Caucasian children (p approximately 0.0038). Thirteen percent had recurrent temporomandibular joint (TMJ) pain, and 11% had recurrent neck pain. Pain or tiredness in the jaws during chewing was reported by 29% of the children, more often by African-American than by Caucasian (p < 0.00001). Pain at jaw opening occurred in 13% of the children, more often in the African-American than in the Caucasian children (p approximately 0.00004). Palpation pain was found in the posterior TMJ area in 28%, in the lateral TMJ area in 22%, in the masseter area in 19%, in the anterior temporalis area in 15% and was found more often in all of those regions in the African-American than in the Caucasian children (p approximately 0.00001), except for the temporalis area. In conclusion, this study showed that mild, but distinct, TMD-related oral/facial pain symptoms occur already by ages 4-6 with significant differences in distribution observed between the African-American and the Caucasian races. While gender seems to play a negligible role in this age group, this does not necessarily mean that race is a causative factor. The pain symptoms may be caused by other factors with different distribution in the two racial subgroups.

Prevalence of signs and symptoms of craniomandibular disorders and orofacial parafunction in 4-6-year-old African-American and Caucasian children.

Children, 4-6 years old, 153 Caucasian and 50 African-American, from a pre-school and kindergarten programme in a low income industrial area, who participated in a voluntary oral health examination, were questioned and examined for signs and symptoms of craniomandibular disorders (CMD) and of oral parafunctions. Most of the CMD signs and symptoms were mild. Eight per cent had recurrent (at least 1-2 times per week) TMJ pain, and 5% had recurrent neck pain, African-American children more often than Caucasian children (P < 0.05). Seventeen per cent had recurrent headache. Three per cent had recurrent earache. Pain or tiredness in the jaws during chewing was reported by 25% of the children, more often by African-American than by Caucasian children (P < 0.001) and more often by girls than by boys (P < 0.05). Pain at jaw opening occurred in 10% of the children, more often in the African-American than in the Caucasian group (P < 0.001). Thirteen per cent of the children had problems in opening the mouth. Deviation during opening was observed in 17% and reduced opening in 2%. Reduced lateral movements, locking or luxation were not observed in any child. Palpation pain was found in the lateral TMJ area in 16%, in the posterior TMJ area in 25%, in the temporalis and masseter areas in 10%, and pain for all regions was found more often in the African-American than in the Caucasian children (P < 0.01). Thirty-four per cent of the African-American, and 15% of the Caucasian children admitted to having ear noises (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Association between CMD signs and symptoms, oral parafunctions, race and sex, in 4-6-year-old African-American and Caucasian children.

The associations between oral parafunctions, signs and symptoms of craniomandibular disorders (CMD), race, and sex were analysed in recordings from 203 4-6-year-old African-American and Caucasian children. Significant correlations were found between bruxism, nail biting, thumb sucking and most of the CMD signs and symptoms. There were also significant associations between most of the signs and symptoms and race, while significant association with sex was found only regarding headache, TMJ sounds and chewing pain. Significant associations were found between most CMD signs and TMJ sounds supporting the view that joint sound recordings have diagnostic value. There were also significant associations between the pain variables recorded by questionnaire and those recorded by palpation, which indicates that reliable data can be obtained by interviewing children as young as five. The results of this study support the concept that oral parafunctions have a significant role in the aetiology of CMD. The results also show that race and sex need to be considered when analysing the possible aetiological role of oral parafunctions in CMD. Longitudinal studies, beginning with low age groups are needed to better determine the role of childhood oral parafunctions in CMD aetiology.

The TMJ-ear connection.

This article documents the existence of three structures that traverse through the petrotympanic fissure. These structures are the mandibular malleolar ligament, the chorda tympani nerve and the anterior tympanic artery. The mandibular malleolar ligament or the disk-malleolar ligament originates on the anterior process of the mallous. It traverses through the petro-tympanic fissure and attaches to the posterior portion of the capsule and disk of the temporomandibular joint. The chorda tympani nerve supplies sensory feeling to the posterior two thirds of the tongue. The anterior tympanic artery supplies blood to the area of the tympanic membrane. Clinical experience with implants that impinge or cover ear problems and other symptoms. Removal of these implants and placements with devices that do not cover these structures often relieve these symptoms.

Androgen receptor affinity of 5'-acyl furanosteroids.

Syntheses of 5'-acyl furanosteroids are described from the corresponding unsubstituted [3,2-b]furanosteroids using acid anhydrides and acid chlorides in the presence or absence of Lewis acids. New methods have been developed to prepare 5'-acetyl derivatives: reduction of a 5'-trichloroacetyl intermediate either by sodium formaldehyde sulfoxylate or with 10% Pd/C. Most of these 5'-acyl derivatives bind to the rat ventral prostate androgen receptor. However the antiandrogenic activity was diminished when compared with 4,5'-methylsulfonyl furanosteroid. Biological studies revealed that 5'-acyl furanosteroids were either androgens or modest antiandrogens. The electrostatic potential maps of the substructures of 3, 4, and 5'-acetyl syn- and anti-furanosteroids showed striking differences which may explain, to some extent, the lack of significant antiandrogenic activity of 5'-acyl furanosteroids.