The scope of computerized simulation in competency-based maxillofacial training: a systematic review.

Oral and maxillofacial surgery (OMS) teaching is set to undergo a paradigm shift towards competency-based training. With increasing focus on resident skill development and patient safety, computerized simulators are likely to play a more mainstream role in OMS training. A systematic review of the available literature was conducted, in accordance with the PRISMA guidelines, to highlight the scope of computerized simulation in OMS teaching. A PubMed search was performed by two independent reviewers, and 35 articles published in English between 2010 and 2021 that reported the use of computerized simulation for teaching maxillofacial procedures were included in the analysis. Eight articles on minor oral surgery, seven on orthognathic surgery, five on maxillofacial trauma, five on cleft lip and palate surgery, three articles each on nerve block techniques, endoscopic procedures, and reconstructive surgery, and one article on fibre-optic intubation reported the use of computerized simulation that can be applied to OMS training. Ten randomized controlled trials were identified in the search. However there was marked heterogeneity among the studies. Simulator training for skill acquisition mentored by an expert OMS educator could offer holistic resident training; however more studies that test common themes of resident training such as knowledge acquisition and skill development are necessary.

Results of mapping patients expectation using SERVQUAL.

BACKGROUND: Understanding expectations of the patients towards the quality of services that hospitals providing is very important in quality in healthcare. With every health care organization claiming its services to be the best, benchmarking and comparing them to ascertain the real best is very difficult but much required in this competitive world. Patients have a varied need depending upon the resources and criticality of disease. The aim of the study was to identify the factors linked with patient's expectations contributing to the quality of the service delivered by the hospital. MATERIALS AND METHODS: Multi-speciality hospitals were visited to survey indoor and outdoor patients of different age groups. Omega coefficient and Cronbach α test were used to test the questionnaire's validity and reliability. The factor analysis technique was used to identify factors determining patient expectations. The SERVQUAL framework was used to categorize evaluation criteria. RESULTS: The resultant factors show variations in prioritizing service demands by the patients. Such a system would enable the patients to select a hospital capable of delivering best quality services. CONCLUSION: This study identifies the factors that contribute in delivering high quality service by the hospital. It gives a futuristic view to design a framework for evaluating the quality of the service delivered by a hospital.

Finite element analysis of patient-specific TMJ implants to replace bilateral joints with simultaneous correction of facial deformity.

INTRODUCTION: Finite element analysis (FEA) is a method to mimic the biomechanical behaviour of an object under various loading scenarios, and may be used during virtual planning of the TMJ prosthesis. Here we present an interesting case report where FEA was done to biomechanically evaluate patient specific total joint replacement prosthesis for bilateral TMJ replacement. CASE REPORT: A 22 year old young girl visited our outpatient clinic with a chief complaint of retruded chin and limited mouth opening for the last 15 years. After clinical and radiographic examination, her corrective surgery was virtually planned on Mimics software. The Implants were studied under simulated loading scenarios in ANSYS to understand the structural integrity of the implant for different loading conditions. RESULTS: Maximum Von-Mises Stress on Condylar component is 151.9 MPa and Maximum Von-Mises Stress on Fossa component is 0.377 MPa. The minimum safety factor of the fossa component was about 15, which is safe enough to complete 100 million cycles. The maximum von-mises stress were detected at the screw holes in the condylar components of the implant. The screw holes were therefore the areas prone to highest chance of failure in the design. CONCLUSION: We conclude that FEA based biomechanical analysis is important prerequisite during customized reconstruction of TMJ. In today's scenario of patient specific TMJ reconstruction, FEA based designing and planning of stress distribution along the bone and calculation of maximum strain in the prosthesis, further aids in the proper designing of this implant and enhances the post-operative clinical results.

Prospective evaluation of psychological burden in patients with oral cancer.

The high morbidity and mortality that is associated with oral cancer places a huge psychological burden on patients. The purpose of this prospective study was to evaluate levels of depression, anxiety, and stress, at three time points using DASS-21 (Depression, Anxiety and Stress Scale-21). We also compared DASS-21 with HADS (Hospital Anxiety and Depression Scale). A total of 111 patients were enrolled and 75 of them completed the questionnaires at diagnosis, one month after treatment, and three months after discharge. Scores were high for stress at diagnosis, and for depression at the other time points, but were low for anxiety at all three. The results of Friedman's ANOVA showed that mean ranks for depression and stress were significant (p<0.05). Scores for depression and stress rose significantly between diagnosis and three months after operation, but those for anxiety (which had increased between diagnosis and operation p>0.05), were stable three months postoperatively. The DASS-21 was a useful method of evaluating stress. Correlation of the results from the two questionnaires showed a strongly positive association. We therefore recommend psychological intervention to improve overall outcome.

Current Practices in Choosing Estimands and Sensitivity Analyses in Clinical Trials: Results of the ICH E9 Survey.

BACKGROUND: An addendum to the International Conference on Harmonisation E9 (ICH E9) guidance document (Statistical Principles for Clinical Trials) is currently under development. The aim of the addendum is to promote harmonized standards on the choice of estimand (a well-defined measure of the treatment effect that is being estimated) in clinical trials and to describe a consensual framework for planning, conducting, and interpreting sensitivity analyses of clinical trial data. METHODS: In order to help understand current practices relating to the choice of estimands and sensitivity analyses for clinical trials, the ICH E9 working group developing the addendum conducted a survey with a primary focus on clinical trials involving drugs, vaccines, and biologics. The survey was distributed electronically between May 19, 2015, and June 11, 2015, to various stakeholder groups within ICH, including industry, regulatory, and academic communities. A total of 1305 respondents participated. RESULTS: Of the 1305 respondents 547 (42%), 344 (26%) and 283 (22%) were from Europe, USA and Japan respectively. Over half of the respondents work in pharmaceutical companies, and approximately a quarter of respondents noted oncology as the primary therapeutic area they work in. Over half of the respondents (595, 55%) noted the treatment effect being estimated was 'in the entire target population of patients regardless of whether they will take treatment as instructed'. The most common methods for handling missing data in primary analyses were mixed-models repeated measures (555, 56% respondents) and last observation carried forward (549, 55% respondents). The majority of respondents (816, 83%) noted they conducted sensitivity analyses to estimate treatment effects in different ways compared to the primary analysis by using alternative assumptions (627, 78%) and/or using alternative statistical methods (616, 76%). CONCLUSIONS: The survey results have provided useful information to the ICH E9 working group on current practices on the choice of primary estimands for measuring treatment effects in confirmatory clinical trials, and approaches used to select sensitivity analyses.

Pre-arthroplasty simultaneous maxillomandibular distraction osteogenesis for the correction of post-ankylotic dentofacial deformities.

The aim of this study was to evaluate the hard and soft tissue changes after pre-arthroplasty simultaneous maxillomandibular distraction osteogenesis for the correction of post-ankylotic dentofacial deformities. This prospective study included 10 patients with unilateral temporomandibular joint (TMJ) ankylosis who presented with a facial deformity and a maxillary cant. Informed patient consent was obtained for participation. Simultaneous maxillomandibular distraction was planned based on clinical and radiographic examinations. A horizontal mandibular osteotomy was performed in the ramus and the distractor device was fixed. A bilateral Le Fort I osteotomy was then performed and a four-hole straight plate was fixed on the contralateral zygomatic buttress to act as a fulcrum. After a latency period of 5 days, the distractor was activated twice daily by 0.5mm until the required vertical lengthening was achieved. Intermaxillary fixation was maintained during the entire distraction period. After a consolidation period of 8-12 weeks, the distractor was removed. The TMJ ankylosis was released and a temporal fascia interpositional arthroplasty was performed as second surgery, along with a genioplasty if needed. All patients were followed up for a period of 12-24 months. A marked improvement in the facial asymmetry was noted in all cases. The occlusal cant and mandibular retrusion improved satisfactorily, and the average postoperative inter-incisal opening was 35.6mm. Pre-arthroplasty simultaneous maxillomandibular distraction offers a good treatment outcome, as it allows improvements in facial aesthetics as well as function.

Pre-arthroplastic and simultaneous mandibular distraction for correction of facial deformity in temporomandibular joint ankylosis.

INTRODUCTION: In cases of temporomandibular joint (TMJ) ankylosis, interposition arthroplasty allows return of functional jaw movements. In order to improve the facial appearance, distraction osteogenesis is the treatment of choice, and may be timed either as a pre-arthroplastic, simultaneous or post-arthroplastic procedure. This study was planned to compare the treatment outcomes of pre-arthroplastic distraction (PAD) and simultaneous arthroplastic distraction (SAD) to establish the better treatment modality in terms of improvement in function and aesthetics. MATERIALS AND METHODS: This prospective randomized experimental study included 20 children and adolescents suffering from facial deformity due to long standing unilateral TMJ ankylosis. They were randomly allocated to the two surgical groups with ten in each group. RESULT: Both groups resulted in good facial symmetry and aesthetics. Initially, during the distraction period, mouth opening of SAD group scored less than that of PAD group but became comparable in 30 days. More pain at the distraction site and over the normal TMJ was observed in PAD group. The excursive movements were almost comparable in both the groups. CONCLUSION: We conclude that both procedures are effective in correcting the post-ankylotic deformity and improving function. Although PAD has better control over movement of the distracting segment, the contralateral TMJ may experience pain. SAD requires a shorter management period but is associated with a temporary decrease in function. Also, control of distraction may be difficult and chances of reankylosis are always there.

Genomic expression in non syndromic cleft lip and palate patients: A review.

Cleft lip and palate are common congenital anomalies with significant medical, psychological, social, and economic ramifications, affecting one in seven hundred live births. Genetic causes of non syndromic cleft lip and/or palate (NSCLP) include chromosomal rearrangements, genetic susceptibility to teratogenic exposures, and complex genetic contributions of multiple genes. Development of the orofacial clefts in an individual will depend on the interaction of several moderately effecting genes with environmental factors. Several candidate genes have been genotyped in different population types, using case parent trio or case control design; also genes have been sequenced and SNPs have been reported. Quantitative and molecular analysis have shown linkage and association studies to be more relevant. Recent literature search shows genome wide association studies using microarray. The aim of this paper was to review the approaches to identify genes associated with NSCLP and to analyze their differential expressions. Although no major gene has been confirmed, a lot of research is ongoing to provide an understanding of the pathophysiology of the orofacial clefts.

Rank-based principal stratum sensitivity analyses.

We describe rank-based approaches to assess principal stratification treatment effects in studies where the outcome of interest is only well-defined in a subgroup selected after randomization. Our methods are sensitivity analyses, in that estimands are identified by fixing a parameter and then we investigate the sensitivity of results by varying this parameter over a range of plausible values. We present three rank-based test statistics and compare their performance through simulations, and provide recommendations. We also study three different bootstrap approaches for determining levels of significance. Finally, we apply our methods to two studies: an HIV vaccine trial and a prostate cancer prevention trial.

Odds ratio of risk factors for oral submucous fibrosis in a case control model.

Our aim was to calculate the odds ratio (OR) of various epidemiological, social, behavioural, and dietary risk factors for oral submucous fibrosis in a population-based case control study. We did this in rural and urban Lucknow by organising oral health camps in the community, where a total of 3136 subjects were enrolled. Panmasala, a dry commercial preparation containing areca nut, slaked lime, catechu, and condiments, with or without tobacco, was the most important aetiological factor for the disease. The 95% confidence interval (CI) of the OR for tobaccoless panmasala ranged from 4.77 to 6.88 and for tobacco panmasala from 4.55 to 9.71. OR using multivariate analysis was 14.09 for tobaccoless panmasala and 5.39 for tobacco panmasala. Patients who use panmasala are at high risk of developing oral submucous fibrosis.

Hydroxyapatite/collagen block with platelet rich plasma in temporomandibular joint ankylosis: a pilot study in children and adolescents.

The aim of this study was to evaluate the feasibility of using preshaped hydroxyapatite/collagen condyles as carriers for platelet-rich plasma after gap arthroplasty in patients with temporomandibular ankylosis, to assess the aesthetic and functional outcomes, and to find out if neocondylar regeneration was possible. We studied 19 patients with temporomandibular joint ankylosis (25 joints), in whom preshaped hydroxyapatite/collagen condyles with platelet-rich plasma were fixed to the ramus with a titanium miniplate, and temporal fascia was placed in between. We evaluated the type of ankylosis, mouth opening before and after operation, deviation on mouth opening, lateral excursion, protrusion, postoperative anterior open bite, radiographic assessment, and complications. All patients showed appreciable improvements in mouth opening and excursion of the jaw. There were a few complications such as mild fever, and temporary involvement of the facial nerve, which improved with time. No open bite or recurrence was reported during the 18 months' follow up. Radiographic evaluation at 3 months showed a less opaque condyle, but the opacity at 18 months was more defined, suggesting a newly formed condyle. A preshaped hydroxyapatite/collagen condyle with platelet-rich plasma improves both aesthetics and function. However, a long term study is required to follow the growth patterns to see if the patients develop any facial deformity as they grow.

Oral verrucous lesions: Controversies in diagnosis and management.

AIMS: Oral verrucous lesions, typically presenting as slowly enlarging, grey or white, warty, exophytic overgrowths on the buccal mucosa or gingiva may be verrucous carcinoma (VC), verrucous hyperplasia (VH), proliferative verrucous leukoplakia (PVL), or may show the conventional invasive pattern of squamous cell carcinoma (SCC). This study was undertaken with the aim to report the demography of different types of oral verrucous lesions and evaluate their long-term outcome. MATERIAL & METHODS: This clinical study comprised 15 patients with verrucous lesions of the oral cavity who underwent biopsy for confirmation of diagnosis. RESULTS: Among these, 12 (80%) were male and only three (20%) were female. The age distribution ranged from 32 to 74 years with a median age of 45 years at the time of diagnosis. The most common site of VC within the oral cavity was the buccal mucosa (46.7%). 5 were proven cases of VC, 3 PVL and 7 VH. All cases of VH, PVL were managed by surgical excision, while VC was managed by surgical excision with superficial ostectomy followed by two cycles of chemotherapy additionally, if micro-invasion was observed on histopathological examination. The 2-year overall survival and tumour control rate was 93.4%. Recurrence was not seen in any patient till the time of analysis at a follow up of 3-5 years. CONCLUSION: Accurate diagnosis of the verrucous lesions is important and should be differentiated from grade I squamous cell carcinoma. Management should be based upon the nature, behaviour and malignant potential of the lesion.

An Ad5-vectored HIV-1 vaccine elicits cell-mediated immunity but does not affect disease progression in HIV-1-infected male subjects: results from a randomized placebo-controlled trial (the Step study).

BACKGROUND: The Step study was a randomized trial to determine whether an adenovirus type 5 (Ad5) vector vaccine, which elicits T cell immunity, can lead to control of human immunodeficiency virus (HIV) replication in participants who became HIV-infected after vaccination. METHODS: We evaluated the effect of the vaccine on trends in HIV viral load, CD4+ T cell counts, time to initiation of antiretroviral therapy (ART), and AIDS-free survival in 87 male participants who became infected with HIV during the Step study and who had a median of 24 months of post-infection follow-up. RESULTS: There was no overall effect of vaccine on mean log(10) viral load (estimated difference between groups, -0.11; P = .47). In a subset of subjects with protective HLA types (B27, B57, B58), mean HIV-1 RNA level over time was lower among vaccine recipients. There was no significant difference in CD4+ T cell counts, time to ART initiation, or in AIDS-free survival between HIV-1-infected subjects who received vaccine versus those who received placebo. CONCLUSIONS: HIV RNA levels, CD4+ T cell counts, time to initiation of ART, and AIDS-free survival were similar in vaccine and placebo recipients. There may have been a favorable effect of vaccine on HIV-1 RNA levels in participants with HLA types associated with better control of HIV-1.

Random control trial of dermis-fat graft and interposition of temporalis fascia in the management of temporomandibular ankylosis in children.

Temporomandibular ankylosis is a disabling condition that affects hygiene and cosmetic appearance. Several interpositional grafts such as meniscus, muscle, fascia, skin, cartilage, fat, dura, alloplastic materials and xenografts have been used to prevent recurrence of ankylosis. We studied the advantages and disadvantages of dermis fat graft as an interposition material after arthroplasty and compared it with temporalis fascia interposition. Seventeen patients with temporomandibular ankylosis involving 20 joints were randomly divided into two groups; the first group had operations for interposition of dermis-fat graft that was taken from the groin. Patients in control group had operations to interpose temporalis fascia and muscle from the same surgical site. All were assessed by age, sex, etiology, clinical features and post surgical complications. The groups were matched in age and the male: female ratio was 0.89:1.The median duration of ankylosis was 7.3 (range 2-11) years. Postoperative and follow up interincisal mouth opening was satisfactory with good healing of the dermis-fat graft donor site. We conclude that the use of dermis fat grafts has minimal donor site morbidity, and is a safe and effective interposition material to prevent the recurrence of temporomandibular ankylosis.

Vaccine clinical trials--a statistical primer.

We discuss some of the key statistical issues that arise in all stages of vaccine development and, where necessary, contrast drug and vaccine clinical trials.

Statistical considerations for noninferiority/equivalence trials in vaccine development.

Noninferioritylequivalence designs are often used in vaccine clinical trials. The goal of these designs is to demonstrate that a new vaccine, or new formulation or regimen of an existing vaccine, is similar in terms of effectiveness to the existing vaccine, while offering such advantages as easier manufacturing, easier administration, lower cost, or improved safety profile. These noninferioritylequivalence designs are particularly useful in four common types of immunogenicity trials: vaccine bridging trials, combination vaccine trials, vaccine concomitant use trials, and vaccine consistency lot trials. In this paper, we give an overview of the key statistical issues and recent developments for noninferioritylequivalence vaccine trials. Specifically, we cover the following topics: (i) selection of study endpoints; (ii) formulation of the null and alternative hypotheses; (iii) determination of the noninferioritylequivalence margin; (iv) selection of efficient statistical methods for the statistical analysis of noninferioritylequivalence vaccine trials, with particular emphasis on adjustment for stratification factors and missing pre-or post-vaccination data; and (v) the calculation of sample size and power.

Relative risk estimation and inference using a generalized logrank statistic.

When comparing two survival distributions with proportional hazard functions, the logrank test is optimal for testing the null hypothesis that the constant hazard ratio (relative risk) is one. In this paper, we focus on (i) testing for departures from a relative risk other than one, and (ii) estimation of the relative risk. The standard tool to address both (i) and (ii) is the Cox proportional hazards model. However, the performance of the Cox model can be less than optimal with small samples. We show why this is the case, and propose a simple alternative method of estimation and inference based on a generalized logrank (GLR) statistic. While the GLR and Cox model approaches are asymptotically similar, empirical results reveal that the GLR approach is notably more efficient than the Cox model when the number of subjects is small (< 100 subjects per treatment group). An example based on survival times of cervical cancer patients is used to illustrate the proposed methodology.

Comparative studies of two-times-daily versus three-times-daily indinavir in combination with zidovudine and lamivudine.

OBJECTIVES: To compare the efficacy and safety of two-times-daily versus three-times-daily indinavir in combination with zidovudine and lamivudine. DESIGN: Two multicenter, open-label, randomized 24-week studies. METHODS: Adults HIV-1 infection, HIV-1 RNA greater than 10000 copies/ml, and no prior lamivudine or protease inhibitor therapy were eligible. In a pilot study (Study A), patients received indinavir at 800 mg every 8 h, 1000 mg every 12 h, or 1200 mg every 12 h. In a subsequent study (Study B), patients received indinavir at 800 mg every 8 h or 1200 mg every 12 h. All subjects received zidovudine (300 mg) and lamivudine (150 mg) every 12 h. An intent-to-treat analysis was used. RESULTS: In Study A, which enrolled 88 patients, neither HIV-1 RNA nor CD4 cell responses differed significantly between treatment groups at 24 weeks when corrected for multiple comparisons. Study B enrolled 433 patients, but was prematurely discontinued when interim analysis suggested greater efficacy of three-times-daily indinavir. Of the first 87 patients reaching week 24, HIV-1 RNA was less than 400 copies/ml in 91% receiving three-times-daily versus 64% receiving two-times-daily indinavir (P < 0.01). CONCLUSION: Three-times-daily indinavir appears more efficacious than two-times-daily dosing when administered with zidovudine and lamivudine. Two-times-daily indinavir dosing should only be considered in situations characterized by favorable pharmacokinetic drug-drug interactions.

Simultaneous testing strategy for comparing two treatments in a stratified binomial trial.

The Mantel-Haenszel (M-H) procedure is commonly used to compare two treatments in a stratified binomial trial. However, this procedure is asymptotically optimal only if the odds ratio is constant across strata. We propose an alternative analytic strategy based on the simultaneous use of two statistics, ZS and ZI, each involving a weighted averaging of within-stratum differences between proportions. The two treatments are declared significantly different at overall level alpha if either min(ZS, ZI) > Zalpha/2 or max(ZS, ZI) > Zalpha*/2, where alpha* is data dependent. Our strategy is shown to be more powerful than the M-H and other related procedures. Numerical examples are provided for illustration.

Virological and immunological effects of combination antiretroviral therapy with zidovudine, lamivudine, and indinavir during primary human immunodeficiency virus type 1 infection.

Forty-seven patients presenting with primary human immunodeficiency virus (HIV) infection were treated with zidovudine 200 mg 3 times a day, lamivudine 150 mg 2 times a day, and indinavir 800 mg 3 times a day for 1 year. From a mean pretreatment viral RNA level of 4.93 log(10) copies/mL, the proportions of patients having <500 copies/mL at 24 and 52 weeks were 92.0% and 89.2%, respectively. For the 35 patients with data available at 24 and 52 weeks, the corresponding proportions for the <50 copies/mL analysis were 86.6% and 79.3%, respectively. The change in virus load was -2.19 and -2.41 log(10) copies/mL at weeks 8 and 52, respectively. CD4 cell counts increased, from a mean of 546 cells/mm(3), by 142 cells/mm(3) at week 24 and by 210 cells/mm(3) at week 52. Three patients discontinued the study because of drug-related toxicity. Six (12.8%) patients had adverse experiences associated with nephrolithiasis. Combination therapy with zidovudine, lamivudine, and indinavir during primary HIV infection results in a profound and sustained reduction in virus load with concurrent recovery of the CD4 cell population.