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1.
Cochrane Database Syst Rev ; 1: CD013855, 2021 01 27.
Article in English | MEDLINE | ID: mdl-33502759

ABSTRACT

BACKGROUND: Caries is one of the most prevalent and preventable conditions worldwide. If identified early enough then non-invasive techniques can be applied, and therefore this review focusses on early caries involving the enamel surface of the tooth. The cornerstone of caries detection and diagnosis is a visual and tactile dental examination, although alternative approaches are available. These include illumination-based devices that could potentially support the dental examination. There are three categories of illumination devices that exploit various methods of application and interpretation, each primarily defined by different wavelengths, optical coherence tomography (OCT), near-infrared (NIR), and fibre-optic technology, which incorporates more recently developed digital fibre optics (FOTI/DIFOTI). OBJECTIVES: To estimate the diagnostic test accuracy of different illumination tests for the detection and diagnosis of enamel caries in children or adults. We also planned to explore the following potential sources of heterogeneity: in vitro or in vivo studies with different reference standards; tooth surface (occlusal, proximal, smooth surface, or adjacent to a restoration); single or multiple sites of assessment on a tooth surface; and the prevalence of caries into dentine. SEARCH METHODS: Cochrane Oral Health's Information Specialist undertook a search of the following databases: MEDLINE Ovid (1946 to 15 February 2019); Embase Ovid (1980 to 15 February 2019); US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov, to 15 February 2019); and the World Health Organization International Clinical Trials Registry Platform (to 15 February 2019). We studied reference lists as well as published systematic review articles. SELECTION CRITERIA: We included diagnostic accuracy study designs that compared the use of illumination-based devices with a reference standard (histology, enhanced visual examination with or without radiographs, or operative excavation). These included prospective studies that evaluated the diagnostic accuracy of a single index test and studies that directly compared two or more index tests. Both in vitro and in vivo studies of primary and permanent teeth were eligible for inclusion. We excluded studies that explicitly recruited participants with caries into dentine or frank cavitation. We also excluded studies that artificially created carious lesions and those that used an index test during the excavation of dental caries to ascertain the optimum depth of excavation. DATA COLLECTION AND ANALYSIS: Two review authors extracted data independently and in duplicate using a standardised data extraction form and quality assessment based on QUADAS-2 specific to the clinical context. Estimates of diagnostic accuracy were determined using the bivariate hierarchical method to produce summary points of sensitivity and specificity with 95% confidence regions. The comparative accuracy of different illumination devices was conducted based on indirect and direct comparisons between methods. Potential sources of heterogeneity were pre-specified and explored visually and more formally through meta-regression. MAIN RESULTS: We included 24 datasets from 23 studies that evaluated 16,702 tooth surfaces. NIR was evaluated in 6 datasets (673 tooth surfaces), OCT in 10 datasets (1171 tooth surfaces), and FOTI/DIFOTI in 8 datasets (14,858 tooth surfaces). The participant selection domain had the largest number of studies judged at high risk of bias (16 studies). Conversely, for the index test, reference standard, and flow and timing domains the majority of studies were judged to be at low risk of bias (16, 12, and 16 studies respectively). Concerns regarding the applicability of the evidence were judged as high or unclear for all domains. Notably, 14 studies were judged to be of high concern for participant selection, due to selective participant recruitment, a lack of independent examiners, and the use of an in vitro study design. The summary estimate across all the included illumination devices was sensitivity 0.75 (95% confidence interval (CI) 0.62 to 0.85) and specificity 0.87 (95% CI 0.82 to 0.92), with a diagnostic odds ratio of 21.52 (95% CI 10.89 to 42.48). In a cohort of 1000 tooth surfaces with a prevalence of enamel caries of 57%, this would result in 142 tooth surfaces being classified as disease free when enamel caries was truly present (false negatives), and 56 tooth surfaces being classified as diseased in the absence of enamel caries (false positives). A formal comparison of the accuracy according to device type indicated a difference in sensitivity and/or specificity (Chi2(4) = 34.17, P < 0.01). Further analysis indicated a difference in the sensitivity of the different devices (Chi2(2) = 31.24, P < 0.01) with a higher sensitivity of 0.94 (95% CI 0.88 to 0.97) for OCT compared to NIR 0.58 (95% CI 0.46 to 0.68) and FOTI/DIFOTI 0.47 (95% CI 0.35 to 0.59), but no meaningful difference in specificity (Chi2(2) = 3.47, P = 0.18). In light of these results, we planned to formally assess potential sources of heterogeneity according to device type, but due to the limited number of studies for each device type we were unable to do so. For interpretation, we presented the coupled forest plots for each device type according to the potential source of heterogeneity. We rated the certainty of the evidence as low and downgraded two levels in total due to avoidable and unavoidable study limitations in the design and conduct of studies, indirectness arising from the in vitro studies, and imprecision of the estimates. AUTHORS' CONCLUSIONS: Of the devices evaluated, OCT appears to show the most potential, with superior sensitivity to NIR and fibre-optic devices. Its benefit lies as an add-on tool to support the conventional oral examination to confirm borderline cases in cases of clinical uncertainty. OCT is not currently available to the general dental practitioner, and so further research and development are necessary. FOTI and NIR are more readily available and easy to use; however, they show limitations in their ability to detect enamel caries but may be considered successful in the identification of sound teeth. Future studies should strive to avoid research waste by ensuring that recruitment is conducted in such a way as to minimise selection bias and that studies are clearly and comprehensively reported. In terms of applicability, any future studies should be undertaken in a clinical setting that is reflective of the complexities encountered in caries assessment within the oral cavity.


Subject(s)
Dental Caries/diagnosis , Fiber Optic Technology , Spectroscopy, Near-Infrared , Tomography, Optical Coherence , Transillumination/methods , Datasets as Topic , Dental Enamel , False Negative Reactions , False Positive Reactions , Humans , Reference Standards , Selection Bias , Sensitivity and Specificity
2.
Knee Surg Sports Traumatol Arthrosc ; 29(7): 2364-2369, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33386425

ABSTRACT

PURPOSE: The purpose of this study was to evaluate the rate of return to play (RTP) in patients who underwent Type V superior labrum anterior-posterior (SLAP) repair compared to patients who underwent isolated Bankart repair in the setting of traumatic anterior shoulder instability. METHODS: A retrospective review of patients who underwent arthroscopic Bankart repair and SLAP repair by a single surgeon between 2012 and 2017 was performed. Additionally, these were pair-matched in a 1:2 ratio for age, sex, sport and level of pre-operative play, with those undergoing isolated arthroscopic Bankart repair alone as a control group. RTP, level of RTP and the timing of RTP were assessed. RESULTS: The study included a total of 96 patients, with 32 in the study group and 64 in the control group, and a mean follow-up of 59 months. Overall, there was no significant difference in the overall rate of return to play (26/32 (81.3%) vs 56/64 (87.5%), n.s), but there was a significantly higher rate of RTP at the same/higher level in the control group (14/32 (43.6%) vs 43/64 (67.2%), p = 0.0463). There was no significant difference in timing of RTP between the groups (n.s). There was no significant difference in recurrent instability (6/32 (18.8%) vs 5/64 (7.8%), n.s) but there was a significant difference in revision rates (5/32 (15.6%) vs. 2/64 (3.1%), p = 0.0392) between the Type V SLAP repair group and the control group. CONCLUSION: Following arthroscopic repair, patients with Type V SLAP tears had a similar overall rate of RTP when compared directly to a control group of patients who underwent arthroscopic Bankart repair alone. However, those who underwent Type V SLAP repair reported significantly lower rates of RTP at the same or higher level compared to the control group. LEVEL OF EVIDENCE: III.


Subject(s)
Arthroscopy/methods , Athletic Injuries/surgery , Joint Instability/surgery , Return to Sport , Shoulder Joint/surgery , Adolescent , Adult , Female , Humans , Male , Recurrence , Retrospective Studies , Rotator Cuff Injuries/surgery , Rupture/surgery , Shoulder Injuries , Young Adult
3.
J Shoulder Elbow Surg ; 29(7): 1332-1336, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32088079

ABSTRACT

PURPOSE: The purpose of this study is to evaluate clinical outcomes and recurrence among women who have undergone an arthroscopic Bankart repair for recurrent anterior shoulder instability. METHODS: A retrospective review of patients with anterior shoulder instability that have undergone an arthroscopic Bankart repair between 2012-2017 was performed. Patients were followed up to assess their visual analog scale (VAS) score, Rowe score, Shoulder Instability-Return to Sport after Injury (SIRSI), and the Subjective Shoulder Value (SSV) and their satisfaction level. Whether they were able to return to sport, the timing of return, and the level to which they returned were reported. RESULTS: Our study included 31 female patients (34 shoulders), with a mean follow-up of 51.9 months. Overall, 82.4% (28/34 shoulders) were satisfied/very satisfied with their surgery. The mean scores were as follows: Rowe, 79.2; SIRSI, 53.9; SSV, 81.9; and VAS, 1.9. Of the 29 patients (32 shoulders) who played sport prior to surgery, 24 returned to play and 17 returned to the same or higher level. One patient suffered a recurrent dislocation and 2 patients suffered recurrent subluxation. No patients underwent a revision procedure. CONCLUSION: Female patients with anterior shoulder instability treated with arthroscopic Bankart repair have low recurrence rates, with good patient-reported outcomes and high satisfaction rates. Of those participating in sport prior to surgery, there was a high rate of return to play. The overall rate of complications was low, with a low rate of revision surgery.


Subject(s)
Arthroplasty , Arthroscopy , Joint Dislocations/surgery , Joint Instability/surgery , Shoulder Dislocation/surgery , Adolescent , Adult , Female , Humans , Male , Middle Aged , Patient Reported Outcome Measures , Recurrence , Reoperation , Retrospective Studies , Return to Sport , Sex Factors , Shoulder Joint/surgery , Young Adult
4.
Ir J Med Sci ; 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39134837

ABSTRACT

BACKGROUND: Approximately 1 in 5 patients with autosomal dominant polycystic kidney disease (ADPKD) will undergo a native nephrectomy in their lifetime. These can be emergent or planned and the indications can range from space for kidney transplant, pain, hematuria and frequent urinary tract infections (UTIs). Due to the diverse nature of presentations, there is a lack of certainty about outcomes and optimal management. AIMS: This study aimed to evaluate preoperative indications and perioperative/postoperative complications in this patient cohort. METHODS: This retrospective review included 41 patients with ADPKD who underwent unilateral or bilateral nephrectomy in a single hospital between 2010 and 2020. We collected data on patient demographics, surgical indications, histological results and postoperative complications. We sourced this information using the hospital's patient medical records. RESULTS: The main indications for nephrectomy were pain (39.5%) and bleeding (41.8%). Further indications included recurrent UTIs (16.3%), space for transplantation (27.9%), query malignancy (4.7%) and compressive gastropathy (2.3%). With regard to side, 55.8% were right-sided, 23.3% were left-sided, and 20.9% were bilateral. Seven percent of nephrectomy specimens demonstrated malignancy. Postoperative morbidity included requiring blood transfusion and long hospital stay. Thirty-seven percent of patients received a postoperative blood transfusion. There was no immediate or postoperative mortality associated with any of the cases reviewed. CONCLUSIONS: In conclusion, this study demonstrates that native nephrectomy remains a safe operation for patients with ADPKD. Although further research is needed into, transfusion protocols, adjunctive therapies, such as TAE and research into timing of nephrectomy are still needed.

5.
medRxiv ; 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-39006416

ABSTRACT

Background: MUC1 and UMOD pathogenic variants cause autosomal dominant tubulointerstitial kidney disease (ADTKD). MUC1 is expressed in kidney, nasal mucosa and respiratory tract, while UMOD is expressed only in kidney. Due to haplo-insufficiency ADTKD- MUC1 patients produce approximately 50% of normal mucin-1. Methods: To determine whether decreased mucin-1 production was associated with an increased COVID-19 risk, we sent a survey to members of an ADTKD registry in September 2021, after the initial, severe wave of COVID-19. We linked results to previously obtained ADTKD genotype and plasma CA15-3 (mucin-1) levels and created a longitudinal registry of COVID-19 related deaths. Results: Surveys were emailed to 637 individuals, with responses from 89 ADTKD- MUC1 and 132 ADTKD- UMOD individuals. 19/83 (23%) ADTKD- MUC1 survey respondents reported a prior COVID-19 infection vs. 14/125 (11%) ADTKD- UMOD respondents (odds ratio (OR) 2.35 (95%CI 1.60-3.11, P = 0.0260). Including additional familial cases reported from survey respondents, 10/41 (24%) ADTKD- MUC1 individuals died of COVID-19 vs. 1/30 (3%) with ADTKD- UMOD , with OR 9.21 (95%CI 1.22-69.32), P = 0.03. The mean plasma mucin-1 level prior to infection in 14 infected and 27 uninfected ADTKD- MUC1 individuals was 7.06±4.12 vs. 10.21±4.02 U/mL ( P = 0.035). Over three years duration, our longitudinal registry identified 19 COVID-19 deaths in 360 ADTKD- MUC1 individuals (5%) vs. 3 deaths in 478 ADTKD- UMOD individuals (0.6%) ( P = 0.0007). Multivariate logistic regression revealed the following odds ratios (95% confidence interval) for COVID-19 deaths: ADTKD- MUC1 8.4 (2.9-29.5), kidney transplant 5.5 (1.6-9.1), body mass index (kg/m 2 ) 1.1 (1.0-1.2), age (y) 1.04 (1.0-1.1). Conclusions: Individuals with ADTKD- MUC1 are at an eight-fold increased risk of COVID-19 mortality vs. ADTKD- UMOD individuals. Haplo-insufficient production of mucin-1 may be responsible.

6.
BDJ Open ; 9(1): 40, 2023 Aug 26.
Article in English | MEDLINE | ID: mdl-37633985

ABSTRACT

OBJECTIVE/AIM: Optimal oral health behaviours are crucial to avoid preventable dental diseases and maintain good oral health. This research aimed to evaluate the impact of a digital oral health intervention (Know Your OQ™) in changing knowledge, attitudes and practices related to oral health. MATERIALS & METHODS: Two studies were conducted with a total of 296 healthy adults. Demographic data as well as knowledge, attitudes, and practices (KAPs) related to oral health were collected before and after completion of the Know Your OQ™ intervention. The KAPs questionnaire included 19 multiple choice questions. Comprehension and feedback were also collected. RESULTS: In total, 134 (45%) male and 162 (55%) female participants completed the two studies. Across both studies, 5 out of 7 knowledge questions and 2 out of 5 attitude questions showed significant changes pre/post-intervention with participants increasing their knowledge and improving their attitudes towards oral health. Only 1 practice changed in the first study, however, in the second study, 4 out of 7 practice questions showed significant changes pre/post-intervention. Comprehensibility was high across both studies with overall, positive feedback on the intervention. CONCLUSION: A digital oral health intervention was successful in increasing knowledge, changing attitudes and self-reported practices with regards to oral health in a diverse sample of the US population.

7.
Knee ; 37: 87-94, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35728392

ABSTRACT

BACKGROUND: There is an increased risk of anterior cruciate ligament (ACL) rupture and subsequent ACL reconstruction in patients <18 years old due to their high levels of sporting participation. PURPOSE: The purpose of this study was to assess the rate and timing of return to play (RTP) in paediatric and adolescent patients following ACL reconstruction, and to compare the outcomes between those undergoing ACL reconstruction with bone patella tendon bone autograft (BTB) and hamstring tendon (HT) autograft. STUDY DESIGN: Level of Evidence: Level III; Retrospective Comparative Cohort Study. METHODS: The institutional ACL registry was screened for patients <18 that had undergone a primary ACL reconstruction. Outcomes were analysed for patients undergoing either a BTB or HT autograft for rate and timing of return to play, functional outcomes and subsequent knee injuries. Statistical analysis was performed using SPSS. RESULTS: 358 (BTB; 253, HT; 105) patients were followed up for 24-months (95% follow up). 86 athletes (27 BTB; 59 HT) were aged 13-15 years old with no significant difference in RTP rate or timing between graft types, however, there was a difference in ipsilateral re-ruptures (10.2% HT vs 0% BTB p = 0.03). 272 athletes (226 BTB; 46 HT) were aged 16-18 years old with no significant difference in RTP rate or timing between graft types, or ipsilateral re-ruptures (8.7% HT vs 2.7% BTB p = 0.07). Concurrent ligament, meniscal or chondral injuries found at the time was treated as necessary. CONCLUSION: Paediatric and adolescent patients undergoing ACL reconstruction with either BTB or HT had high rates of return to play. This was seen in both subgroups with 13-15-year-olds mostly receiving a HT graft repair and 16-18-year-olds mainly receiving a BTB repair. A moderate re-rupture rate was seen at 24-months. However longer follow up is needed to truly see the long-term impact of such an injury at such a young age.


Subject(s)
Anterior Cruciate Ligament Injuries , Anterior Cruciate Ligament Reconstruction , Hamstring Tendons , Adolescent , Anterior Cruciate Ligament Injuries/etiology , Anterior Cruciate Ligament Injuries/surgery , Anterior Cruciate Ligament Reconstruction/adverse effects , Bone-Patellar Tendon-Bone Grafting , Child , Cohort Studies , Hamstring Tendons/transplantation , Humans , Retrospective Studies , Return to Sport
8.
Article in English | MEDLINE | ID: mdl-31662412

ABSTRACT

OBJECTIVE: To examine the association between peripheral blood lymphocyte pharmacodynamics and autoimmune adverse events (AEs) or return of disease activity in alemtuzumab-treated patients with relapsing-remitting MS. METHODS: Patients received 2 alemtuzumab courses (12 mg/d IV; 5 days at baseline, 3 days 12 months later) in the 2-year Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis studies (NCT00530348 and NCT00548405) and could then receive as-needed alemtuzumab or other disease-modifying therapy in a 4-year extension (NCT00930553). Lymphocytes were phenotyped quarterly over 2 years using fluorescence-activated cell sorting. Pharmacodynamic assessments included counts of total lymphocytes, CD3+ T cells, CD4+/CD8+ T cells (total/naive/memory/regulatory [Treg]), and CD19+ B cells (total/immature/mature/memory) and ratios of CD19+ (total/immature/mature/memory) to Treg (CD4+/CD8+) counts. Assessed autoimmune AEs included immune thrombocytopenia, nephropathies, and thyroid events. Efficacy assessments included relapses, 6-month confirmed disability worsening (CDW), and MRI disease activity. RESULTS: Lymphocyte repopulation patterns, including ratios between distinct lymphocyte subsets (e.g., CD19+ to Treg cell count ratios), showed no significant differences over 2 years in patients developing/not developing autoimmune AEs, relapses, CDW, or MRI activity through 6 years following alemtuzumab. Lymphocyte kinetics were also unrelated to multiple autoimmune AEs or extreme clinical phenotypes. CONCLUSIONS: Repopulation kinetics of the evaluated peripheral lymphocyte subsets did not predict autoimmune AE occurrence or disease activity, including return of disease activity after 2 alemtuzumab courses. Further study is needed to investigate potential antigen-level markers of treatment response.


Subject(s)
Alemtuzumab/pharmacology , Autoimmune Diseases/chemically induced , Immunologic Factors/pharmacology , Kidney Diseases/chemically induced , Lymphocytes/drug effects , Multiple Sclerosis, Relapsing-Remitting , Thrombocytopenia/chemically induced , Thyroid Diseases/chemically induced , Adolescent , Adult , Alemtuzumab/administration & dosage , Alemtuzumab/adverse effects , Female , Humans , Immunologic Factors/administration & dosage , Immunologic Factors/adverse effects , Lymphocyte Count , Male , Middle Aged , Multiple Sclerosis, Relapsing-Remitting/blood , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Multiple Sclerosis, Relapsing-Remitting/physiopathology , Recurrence , Young Adult
9.
J Comput Assist Tomogr ; 33(6): 967-72, 2009.
Article in English | MEDLINE | ID: mdl-19940669

ABSTRACT

With continuing developments in computed tomography (CT) technology and its increasing use of CT imaging, the ionizing radiation dose from CT is becoming a major public concern particularly for high-dose applications such as cardiac imaging. We recently proposed a novel interior tomography approach for x-ray dose reduction that is very different from all the previously proposed methods. Our method only uses the projection data for the rays passing through the desired region of interest. This method not only reduces x-ray dose but scatter as well. In this paper, we quantify the reduction in the amount of x-ray dose and scattered radiation that could be achieved using this method. Results indicate that interior tomography may reduce the x-ray dose by 18% to 58% and scatter to the detectors by 19% to 59% as the FOV is reduced from 50 to 8.6 cm.


Subject(s)
Radiation Dosage , Radiation Protection/methods , Tomography, X-Ray Computed/methods , Calibration , Humans , Phantoms, Imaging , Scattering, Radiation
10.
J Dent ; 74 Suppl 1: S2-S9, 2018 07.
Article in English | MEDLINE | ID: mdl-29929584

ABSTRACT

Dental epidemiological research permits accurate tracking of the prevalence and distribution of oral disease across population groups, enabling planning and evaluation of public health interventions and healthcare service provision. This first section of this paper aimed to review traditional assessment methods in dental epidemiology and to consider the methodological and logistical benefits provided by digital imaging, both generally and specifically in relation to an established dual-camera system. The remainder of this paper describes the results of a semi-structured examination of an image archive from previous research utilising a dual-camera system, exploring whether the diagnostic yield of the images might be increased. Common oral conditions are presented alongside suggestions of the diagnostically useful data displayed in example images. Possible scoring mechanisms are discussed with consideration of the limitations that might be encountered for each condition. The retrospective examination suggests further data is obtainable from images acquired using the dual-camera system, however, consideration should be given to how best to validate this clinically. Additionally, other imaging modalities are discussed whilst taking into account the potential limitations of the dual-camera system.


Subject(s)
Dental Equipment , Diagnostic Equipment , Epidemiologic Methods , Image Processing, Computer-Assisted/methods , Dental Caries/diagnostic imaging , Dental Enamel Hypoplasia , Dental Plaque/diagnostic imaging , Dental Plaque/microbiology , Epidemiology/instrumentation , Fluorosis, Dental/diagnostic imaging , Gingivitis/diagnostic imaging , Humans , Image Processing, Computer-Assisted/instrumentation , Malocclusion/diagnostic imaging , Photography, Dental/instrumentation , Photography, Dental/methods , Tooth/diagnostic imaging
11.
Neurology ; 89(11): 1107-1116, 2017 Sep 12.
Article in English | MEDLINE | ID: mdl-28835401

ABSTRACT

OBJECTIVE: To evaluate 5-year efficacy and safety of alemtuzumab in treatment-naive patients with active relapsing-remitting MS (RRMS) (CARE-MS I; NCT00530348). METHODS: Alemtuzumab-treated patients received treatment courses at baseline and 12 months later; after the core study, they could enter an extension (NCT00930553) with as-needed alemtuzumab retreatment for relapse or MRI activity. Assessments included annualized relapse rate (ARR), 6-month confirmed disability worsening (CDW; ≥1-point Expanded Disability Status Scale [EDSS] score increase [≥1.5 if baseline EDSS = 0]), 6-month confirmed disability improvement (CDI; ≥1-point EDSS decrease [baseline score ≥2.0]), no evidence of disease activity (NEDA), brain volume loss (BVL), and adverse events (AEs). RESULTS: Most alemtuzumab-treated patients (95.1%) completing CARE-MS I enrolled in the extension; 68.5% received no additional alemtuzumab treatment. ARR remained low in years 3, 4, and 5 (0.19, 0.14, and 0.15). Over years 0-5, 79.7% were free of 6-month CDW; 33.4% achieved 6-month CDI. Most patients (61.7%, 60.2%, and 62.4%) had NEDA in years 3, 4, and 5. Median yearly BVL improved over years 2-4, remaining low in year 5 (years 1-5: -0.59%, -0.25%, -0.19%, -0.15%, and -0.20%). Exposure-adjusted incidence rates of most AEs declined in the extension relative to the core study. Thyroid disorder incidences peaked at year 3 and subsequently declined. CONCLUSIONS: Based on these data, alemtuzumab provides durable efficacy through 5 years in the absence of continuous treatment, with most patients not receiving additional courses. CLINICALTRIALSGOV IDENTIFIER: NCT00530348; NCT00930553. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that alemtuzumab durably improves efficacy outcomes and slows BVL in patients with RRMS.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Immunologic Factors/therapeutic use , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Alemtuzumab , Antibodies, Monoclonal, Humanized/adverse effects , Brain/diagnostic imaging , Brain/drug effects , Disability Evaluation , Follow-Up Studies , Humans , Immunologic Factors/adverse effects , Multiple Sclerosis, Relapsing-Remitting/diagnostic imaging , Organ Size , Time Factors , Treatment Outcome
12.
Neurology ; 89(11): 1117-1126, 2017 Sep 12.
Article in English | MEDLINE | ID: mdl-28835403

ABSTRACT

OBJECTIVE: To evaluate 5-year efficacy and safety of alemtuzumab in patients with active relapsing-remitting multiple sclerosis and inadequate response to prior therapy. METHODS: In the 2-year Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) II study (NCT00548405), alemtuzumab-treated patients received 2 courses (baseline and 12 months later). Patients could enter an extension (NCT00930553), with as-needed alemtuzumab retreatment for relapse or MRI activity. Annualized relapse rate (ARR), 6-month confirmed disability worsening (CDW; ≥1-point Expanded Disability Status Scale [EDSS] score increase [≥1.5 if baseline EDSS = 0]), 6-month confirmed disability improvement (CDI; ≥1-point EDSS decrease [baseline score ≥2.0]), no evidence of disease activity (NEDA), brain volume loss (BVL), and adverse events (AEs) were assessed. RESULTS: Most alemtuzumab-treated patients (92.9%) who completed CARE-MS II entered the extension; 59.8% received no alemtuzumab retreatment. ARR was low in each extension year (years 3-5: 0.22, 0.23, 0.18). Through 5 years, 75.1% of patients were free of 6-month CDW; 42.9% achieved 6-month CDI. In years 3, 4, and 5, proportions with NEDA were 52.9%, 54.2%, and 58.2%, respectively. Median yearly BVL remained low in the extension (years 1-5: -0.48%, -0.22%, -0.10%, -0.19%, -0.07%). AE exposure-adjusted incidence rates in the extension were lower than in the core study. Thyroid disorders peaked at year 3, declining thereafter. CONCLUSIONS: Alemtuzumab provides durable efficacy through 5 years in patients with an inadequate response to prior therapy in the absence of continuous treatment. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that alemtuzumab provides efficacy and slowing of brain atrophy through 5 years.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Immunologic Factors/therapeutic use , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Alemtuzumab , Antibodies, Monoclonal, Humanized/adverse effects , Atrophy/diagnostic imaging , Atrophy/prevention & control , Brain/diagnostic imaging , Brain/drug effects , Disability Evaluation , Follow-Up Studies , Humans , Immunologic Factors/adverse effects , Kaplan-Meier Estimate , Multiple Sclerosis, Relapsing-Remitting/diagnostic imaging , Organ Size , Time Factors , Treatment Outcome
13.
Microbes Infect ; 8(1): 61-72, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16269262

ABSTRACT

Characteristic features of the persistent chlamydial developmental cycle, associated with chronic infections in both humans and animals, include the generation of non-replicative, morphologically aberrant bodies which are distinct from normal propagating reticulate bodies. Previous studies have correlated these morphological and metabolic changes with differential expression of diverse functional subsets of chlamydial genes. To further investigate these correlations, we compared mRNA expression of predicted chlamydial signal transduction genes between normal Chlamydophila pneumoniae A-03 infections in HEp-2 cells and those treated with gamma interferon (IFN-gamma) by using real-time RT-PCR. Inspection of the Cp. pneumoniae genome revealed at least 39 candidate signal transduction genes, of which 30 were differentially expressed in Cp. pneumoniae mediated persistence. Functional sub-groups of differentially expressed signal transduction genes include chlamydial GTPases (hflX, ychF, yhbZ and yphC), linked to bacterial cellular processes such as cell cycle control and ribosome assembly and stability. Other up-regulated signal transduction genes sharing similarity to bacterial stress response genes (htrA, surE, lytB and hrcA) were also detected. The transcriptional changes observed for the majority of signal transduction genes appear to be unique for Cp. pneumoniae, as similar changes were not observed in recent whole genomic analysis of C. trachomatis IFN-gamma mediated persistence. These results suggest that chlamydial signal transduction genes play potentially important roles in the establishment and maintenance of Cp. pneumoniae persistence, likely as part of the IFN-gamma response stimulon as described for C. trachomatis, but with considerable differences in the transcriptional profile.


Subject(s)
Chlamydophila Infections/immunology , Chlamydophila Infections/microbiology , Chlamydophila pneumoniae/genetics , Gene Expression Regulation, Bacterial , Interferon-gamma/immunology , Signal Transduction/genetics , Cell Line , Chlamydophila Infections/chemically induced , Chlamydophila pneumoniae/drug effects , Chlamydophila pneumoniae/ultrastructure , Gene Expression Profiling , Humans , Interferon-gamma/pharmacology , RNA, Messenger/genetics , RNA, Messenger/metabolism
14.
J Spec Oper Med ; 15(2): 123-131, 2015.
Article in English | MEDLINE | ID: mdl-26125176

ABSTRACT

The 2010 Department of Defense (DoD) Instruction 6000.16, Military Health Support for Stability Operations, established medical stability operations as a core military mission. National military leaders appreciated that to better manage risks for US military personnel operating in far forward locations, reduce cost and footprint requirements for operations, and aid partner nations with providing service to relevant populations in underserviced/undergoverned the US military would need to be employed strategically in efforts to build partner nation medical capacity. Medical Stability Operations has evolved into Global Health Engagement in the lexicon of planners but the goal is still the same. This article used a technical report authored by the RAND Corporation as the basis of a case study of a Special Operations Command Africa (SOCAF) Mission to the country of Niger to build a casualty evacuation capability. The case study evaluates the utility of a hypothetical framework developed by the RAND researchers relative to the actual events and outcomes of an actual mission. The principal finding is that the RAND technical report is of value to planners, Operators, and trainers as a systematic approach to successful building partner capacity in health (BPC-H) missions. The article also offers several examples of metrics that aid leadership in making better decisions as to when corrective actions might be required.


Subject(s)
Capacity Building , Global Health , Military Medicine , Humans , Niger , United States , United States Department of Defense
15.
Expert Opin Pharmacother ; 12(1): 99-117, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21108580

ABSTRACT

IMPORTANCE OF THE FIELD: Statins are widely accepted as the drugs of choice for achieving increasingly stringent low-density lipoprotein cholesterol (LDL-C) goals for dyslipidemic patients. However, when making treatment decisions, outcomes data from clinical trials are of greater importance than LDL-C-lowering ability. AREAS COVERED IN THIS REVIEW: This review will provide an update on current lipid treatment guidelines in the context of statin trial evidence, with particular focus on the incremental benefit of more potent statin therapy compared with lower doses. The discussion will also address combination therapy, statin safety, goal attainment and treatment adherence. MEDLINE searches (1966 to July 2010) were performed. WHAT THE READER WILL GAIN: The reader will gain a comprehensive review of the evidence base for statin therapy and an appreciation of other issues that affect treatment choice. TAKE HOME MESSAGE: It is important to remember why we need to partner with our patients: to ensure that they are established on, and continue to adhere to, their appropriate evidence-based statin dose with a goal of achieving lipid targets, but more importantly to prevent cardiovascular disease-related morbidity and mortality. We treat patients to reduce clinical cardiovascular events, not just to control lipids and other important risk factors.


Subject(s)
Coronary Disease/prevention & control , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Primary Prevention/methods , Cholesterol, LDL/blood , Clinical Trials as Topic , Coronary Disease/blood , Coronary Disease/complications , Drug Therapy, Combination , Dyslipidemias/blood , Dyslipidemias/complications , Dyslipidemias/drug therapy , Female , Humans , Male
16.
JAMA ; 291(14): 1696-7; author reply 1698, 2004 Apr 14.
Article in English | MEDLINE | ID: mdl-15082689
17.
Microb Pathog ; 34(1): 11-6, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12620380

ABSTRACT

Chlamydia pneumoniae is associated with several chronic human diseases, including chronic obstructive pulmonary disease and atherosclerotic cardiovascular disease. During chronic disease, organisms are believed to exist in a persistent phase that is not well understood at the genetic level. Long-term in vitro continuous infections are spontaneously persistent and are less susceptible than in vitro acute infections to treatment with antibiotics, and are therefore particularly relevant as an in vitro model of in vivo chronic disease. Real-time reverse transcriptase-PCR (r-t RT-PCR) was used to quantitate transcript copy numbers of 13 genes in continuous and acute infections with C. pneumoniae. The set of genes studied encodes proteins with known or predicted functions in the cell membrane, the inclusion membrane, cell division, metabolism, and immunopathology. Significant upregulation was seen for five genes (CPn0483, nlpD, ompA, pmp1 and porB) in continuous cultures. The genes omcB, pmp1, and porB, all of which encode membrane proteins, shared similar patterns of expression over both acute and continuous profiles. These results show that Chlamydia in the long-term continuous model of persistence have a unique transcription profile, adding to our knowledge of regulation of this important stage of chlamydial growth.


Subject(s)
Bacterial Proteins/biosynthesis , Chlamydophila Infections/metabolism , Chlamydophila pneumoniae/genetics , Gene Expression Regulation, Bacterial , Membrane Proteins/biosynthesis , Acute Disease , Bacterial Outer Membrane Proteins/biosynthesis , Bacterial Outer Membrane Proteins/genetics , Bacterial Proteins/genetics , Cell Cycle Proteins/biosynthesis , Cell Cycle Proteins/genetics , Chaperonins/biosynthesis , Chaperonins/genetics , Chlamydophila Infections/microbiology , Chlamydophila pneumoniae/growth & development , Chlamydophila pneumoniae/metabolism , Chronic Disease , Computer Systems , Humans , Membrane Proteins/genetics , Porins/biosynthesis , Porins/genetics , RNA, Bacterial/biosynthesis , RNA, Bacterial/genetics , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , RNA, Ribosomal, 16S/biosynthesis , RNA, Ribosomal, 16S/genetics , Reverse Transcriptase Polymerase Chain Reaction
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