Appendix 1 Guidelines Protocol Worksheets

Transcription

1 Appendix 1 Guidelines Protocol Worksheets Guidelines Protocol Worksheet Fluoride Title of the Guideline The Use of Fluoride for Caries Prevention in Sjögren s Patients Steering Committee Domenick Zero, Chair; Ava Wu; Mabi Singh Clinical (PICO) Questions 1. In primary Sjögren s disease patients, does the use of a topical fluoride compared to no topical fluoride reduce the incidence, arrest or reverse coronal or root caries? 2. In primary Sjögren s disease patients, is one topical fluoride agent more effective than another in reducing the incidence, or to arrest or reverse coronal or root caries? Systematic Review Parameters Sample characteristics 18 and older Any sex, race, ethnicity, menopausal status Disease characteristics Primary Sjögren s; However, if insufficient evidence exists in primary Sjögren s, studies on secondary Sjögren s and other causes of xerostomia will be considered Any published criteria for Sjögren s Patients with flow rates consistent with Xerostomia from any cause Intervention/exposure Fluoride Comparisons RCTs are ideal, but other studies will be included in the literature search for consideration and review (study selection criteria to be refined further - after abstract review) Primary and secondary endpoints Primary: Reduction in the incidence, arrest or reversal of coronal or root caries Secondary: Decreased s. mutans, lactobacillus, and plaque; remineralization; increased Unstimulated Whole Salivary Flow (UWSF) rate Publication type: Published journal articles searched via PubMed and Cochrane Study design/methods Specify study design(s): Meta-analyses, systematic reviews, RCTs Cohort studies 1

2 Case control studies Quality criteria other than design (e.g., sample size, follow-up period, validated and reliable measures, analyses): Minimum length of study of 12 months Other parameters Language: English only Year of publication: 1960 until <end date to be determined> Definitions for Quality Criteria (for Study Quality Assessment Tables) Provide definitions for quality criteria that pertain to particular topics and/or clinical questions (Categories and definitions below are adapted from AHRQ and Cochrane approaches.) The goal is to keep these as consistent as possible across groups. Make revisions, if necessary, below for your particular topic/clinical question(s). 1) Reproducible methodology: (e.g., study design and inclusion and exclusion criteria were clearly defined) 2) Adequate randomization: (e.g., methods used to randomize subjects to treatment were adequate) 3) Concealed allocation: (e.g., adequate method was used to conceal allocation to treatment arms) 4) Sufficient sample size: (e.g., sample size was sufficient to address relevant clinical question(s), power calculations provided) Minimum sample size of 50 5) Comparable groups: (e.g., groups' baseline characteristics and prognostic factors were similar) 6) Validated and reliable measures: (e.g., interventions and outcomes specified and clearly defined, outcomes assessed with standardized, valid, and reliable measures, reasonable uniformity in administration) Primary Outcome: Incidence, arrest or reversal of coronal or root caries Secondary Outcomes: Decreased s. mutans, lactobacillus, and plaque; remineralization; increased salivary flow 7) Adequate follow-up: (e.g., overall loss-to-follow-up and differential loss-to-follow-up assessed adequately and below defined threshold) Less than 20% loss to follow-up; Sufficient length of study - 12 months 8) Appropriate analyses: (e.g., analyses appropriate and relevant to the nature of outcomes data, controlled for confounding, number of explanatory variables used in the analyses appropriate for the sample size, all subjects analyzed in originally allocated groups (i.e., ITT analysis), incomplete outcome data adequately addressed) 9) Accurate results: (e.g., results reported were thorough, clear, and with no discrepancies, conclusions were supported by results, with possible biases and limitations considered) Calibration of examiners; Adequate statistical power analysis/power calculation done a priori 10) Insignificant conflicts of interest: (e.g., conflicts of interest were reported and insignificant) Funding sources cited Limitations of the Literature Based on your preliminary assessment of the literature, do you feel there is enough evidence in the literature to make evidence-based recommendations? YES, an evidence-based recommendation will be feasible. 2

3 We will assess the literature for studies in caries prevention in Sjögren s and other xerostomia patients, but we understand that the literature is limited, especially in Sjögren s, and that all recommendations largely will be expert consensus-based for caries prevention in Sjögren s. NO (OR) We should move directly to an expert consensus-based recommendation. Explain why a consensus-based recommendation is warranted: Study design criteria not met: (specify threshold for overall evidence) Overall study quality criteria: (specify threshold for overall evidence quality) Others (old data, out-of-date criteria for Sjögren s, too much heterogeneity) We should refer to another body of literature* to extrapolate to the Sjögren s population (e.g., lupus). Specify the non-sjögren s literature/population: any xerostomia population, including radiation for head and neck cancer; medication-induced; elderly Specify the justification for any extrapolations: While we d prefer to have studies solely in Sjögren s, similarities are comparable with caries prevention strategies for all xerostomia patients. Guidelines Protocol Worksheet Salivary Stimulation Title of the Guideline The Use of Salivary Stimulants in Caries Prevention in Primary Sjögren s Patients Steering Committee Athena Papas, Chair; Ibtisam Al Hashimi Clinical Questions 1. In SS patients, does salivary stimulation compared to not stimulating saliva flow reduce the incidence, arrest or reverse coronal or root caries? Systematic Review Parameters Sample characteristics 18 and older Any sex, race, ethnicity, menopausal status Disease characteristics Primary Sjögren s; However, if insufficient evidence exists in primary Sjögren s, studies on secondary Sjögren s and other causes of xerostomia will be considered Any published criteria for Sjögren s Patients with flow rates consistent with Xerostomia from any cause Intervention/exposure Salivary stimulation agents 3

4 Comparisons RCTs are ideal, but other studies will be included in the literature search for consideration and review (study selection criteria to be refined further - after abstract review) Primary and secondary endpoints Primary: Reduction in the incidence, arrest or reverse coronal or root caries Secondary: Decreased s. mutans, lactobacillus, and plaque; remineralization; increased Unstimulated Whole Salivary Flow (UWSF) rate Publication type Published journal articles searched via PubMed and Cochrane. Study design/methods Specify study design(s): 2. Meta-analyses, systematic reviews, RCTs 3. Cohort studies 4. Case control studies Quality criteria other than design (e.g., sample size, follow-up period, validated and reliable measures, analyses): 5. Minimum length of study of 12 months (Note: studies of less than 12 months might be deemed acceptable for clinical trials using salagen and cevimeline) Other parameters Language: English only Year of publication: 1990 until <end date to be determined> Definitions for Quality Criteria (for Study Quality Assessment Tables) Provide definitions for quality criteria that pertain to particular topics and/or clinical questions (Categories and definitions below are adapted from AHRQ and Cochrane approaches.) The goal is to keep these as consistent as possible across groups. Make revisions, if necessary, below for your particular topic/clinical question(s). 11) Reproducible methodology: (e.g., study design and inclusion and exclusion criteria were clearly defined) 12) Adequate randomization: (e.g., methods used to randomize subjects to treatment were adequate) 13) Concealed allocation: (e.g., adequate method was used to conceal allocation to treatment arms) 14) Sufficient sample size: (e.g., sample size was sufficient to address relevant clinical question(s), power calculations provided) Minimum sample size of 50 15) Comparable groups: (e.g., groups' baseline characteristics and prognostic factors were similar) 16) Validated and reliable measures: (e.g., interventions and outcomes specified and clearly defined, outcomes assessed with standardized, valid, and reliable measures, reasonable uniformity in administration) Primary Outcome: Incidence, arrest or reversal of coronal or root caries Secondary Outcomes: Decreased s. mutans, lactobacillus, and plaque; remineralization; increased salivary flow 17) Adequate follow-up: (e.g., overall loss-to-follow-up and differential loss-to-follow-up assessed adequately and below defined threshold) Less than 20% loss to follow-up; Sufficient length of study - 12 months (or fewer months may be considered) 4

5 18) Appropriate analyses: (e.g., analyses appropriate and relevant to the nature of outcomes data, controlled for confounding, number of explanatory variables used in the analyses appropriate for the sample size, all subjects analyzed in originally allocated groups (i.e., ITT analysis), incomplete outcome data adequately addressed) 19) Accurate results: (e.g., results reported were thorough, clear, and with no discrepancies, conclusions were supported by results, with possible biases and limitations considered) Calibration of examiners; Adequate statistical power analysis/power calculation done a priori 20) Insignificant conflicts of interest: (e.g., conflicts of interest were reported and insignificant) Funding sources cited Limitations of the Literature Based on your preliminary assessment of the literature, do you feel there is enough evidence in the literature to make evidence-based recommendations? YES, an evidence-based recommendation will be feasible. We will assess the literature for studies in caries prevention in Sjögren s and other xerostomia patients, but we understand that the literature is limited, especially in Sjögren s, and that all recommendations largely will be expert consensus-based for caries prevention in Sjögren s. NO (OR) We should move directly to an expert consensus-based recommendation. Explain why a consensus-based recommendation is warranted: Study design criteria not met: (specify threshold for overall evidence) Overall study quality criteria: (specify threshold for overall evidence quality) Others (old data, out-of-date criteria for Sjögren s, too much heterogeneity) We should refer to another body of literature* to extrapolate to the Sjögren s population (e.g., lupus). Specify the non-sjögren s literature/population: any xerostomia population, including radiation for head and neck cancer; medication-induced; elderly Specify the justification for any extrapolations: Guidelines Protocol Worksheet Antimicrobials Title of the Guideline The Use of Antimicrobial Agents in Caries Prevention in Primary Sjögren s Patients Steering Committee Carol Stewart MS, DDS, MS, Chair; James Sciubba, DMD, PhD Clinical (PICO) Questions 1. In primary SS patients, does the use of antimicrobial agents compared to placebo reduce the incidence, arrest or reverse coronal or root caries? 5

6 Systematic Review Parameters Sample characteristics (e.g., age, sex, race, menopausal status, etc.): 18 yr Any sex, race, menopausal status Disease characteristics Primary Sjögren s; However, if insufficient evidence exists in primary Sjögren s, studies on secondary Sjögren s and other causes of xerostomia will be considered Any published criteria for Sjögren s Any published criteria for Sjögren s Patients with flow rates consistent with Xerostomia from any cause Intervention/exposure (e.g., agent or technology assessed, regimen, etc.): Antimicrobial agents Chlorhexidine, Cetylpyridinium, Nolvasan, Sebidin, Tubulicid, Cervitec, Chlorzoin, hibitane, Chlorhexidine-thymol Comparisons (e.g., is a control group needed? specify): RCTs are ideal, but other studies will be included in the literature search for consideration and review (study selection criteria to be refined further - after abstract review) Primary and secondary endpoints (e.g., DFS, OS, toxicity/aes, QOL): Primary Outcome: Reduction in the incidence, arrest or reversal of coronal or root caries Secondary Outcomes:Decreased S mutans, lactobacillus and plaque; Increased Unstimulated Whole Salivary Flow (UWSF) rate Added outcomes for information-gathering but not directly relevant to clinical question attachment loss, decreased bleeding upon probing, candidiasis, enamel staining Publication type (e.g., published journal articles, editorials/commentaries, meeting abstracts): Published journal articles searched via PubMed and Cochrane Study design/methods (e.g., placebo-controlled RCTs, prospective, retrospective, case-control, case series, case reports, meta-analyses, systematic reviews): Specify study design(s): Meta-analyses, systematic reviews, RCTs Cohort studies Case control studies Quality criteria other than design (e.g., sample size, follow-up period, validated and reliable measures, analyses): Minimum length of study of 12 months Other parameters Language: English only Year of publication: 1990 until <end date to be determined> 6

7 Definitions for Quality Criteria (for Study Quality Assessment Tables) Provide definitions for quality criteria that pertain to particular topics and/or clinical questions (Categories and definitions below are adapted from AHRQ and Cochrane approaches.) The goal is to keep these as consistent as possible across groups. Make revisions, if necessary, below for your particular topic/clinical question(s). 21) Reproducible methodology: (e.g., study design and inclusion and exclusion criteria were clearly defined) 22) Adequate randomization: (e.g., methods used to randomize subjects to treatment were adequate) 23) Concealed allocation: (e.g., adequate method was used to conceal allocation to treatment arms) 24) Sufficient sample size: (e.g., sample size was sufficient to address relevant clinical question(s), power calculations provided) Minimum sample size of 50 25) Comparable groups: (e.g., groups' baseline characteristics and prognostic factors were similar) 26) Validated and reliable measures: (e.g., interventions and outcomes specified and clearly defined, outcomes assessed with standardized, valid, and reliable measures, reasonable uniformity in administration) Primary Outcome: Incidence, arrest or reversal of coronal or root caries Secondary Outcomes: Decreased s. mutans, lactobacillus, and plaque; remineralization; increased salivary flow; Added for information-gathering but not directly relevant to clinical question attachment loss, decreased bleeding upon probing, candidiasis, enamel staining 27) Adequate follow-up: (e.g., overall loss-to-follow-up and differential loss-to-follow-up assessed adequately and below defined threshold) Less than 20% loss to follow-up; Sufficient length of study - 12 months 28) Appropriate analyses: (e.g., analyses appropriate and relevant to the nature of outcomes data, controlled for confounding, number of explanatory variables used in the analyses appropriate for the sample size, all subjects analyzed in originally allocated groups (i.e., ITT analysis), incomplete outcome data adequately addressed) 29) Accurate results: (e.g., results reported were thorough, clear, and with no discrepancies, conclusions were supported by results, with possible biases and limitations considered) Calibration of examiners; Adequate statistical power analysis/power calculation done a priori 30) Insignificant conflicts of interest: (e.g., conflicts of interest were reported and insignificant) Funding sources cited Limitations of the Literature Based on your preliminary assessment of the literature, do you feel there is enough evidence in the literature to make evidence-based recommendations? YES, an evidence-based recommendation will be feasible. We will assess the literature for studies in caries prevention in Sjögren s and other xerostomia patients, but we understand that the literature is limited, especially in Sjögren s, and that all recommendations largely will be expert consensus-based for caries prevention in Sjögren s. NO (OR) We should move directly to an expert consensus-based recommendation. Explain why a consensus-based recommendation is warranted: Study design criteria not met: (specify threshold for overall evidence) Overall study quality criteria: (specify threshold for overall evidence quality) Others (old data, out-of-date criteria for Sjögren s, too much heterogeneity) 7

8 We should refer to another body of literature* to extrapolate to the Sjögren s population (e.g., lupus). Specify the non-sjögren s literature/population: any xerostomia population, including radiation for head and neck cancer; medication-induced; elderly Specify the justification for any extrapolations: While we d prefer to have studies solely in Sjögren s, similarities are comparable with caries prevention strategies for all xerostomia patients. Guidelines Protocol Worksheet Non-Fluoride Remineralizing Agents Title of the Guideline The Use of Non-Fluoride Remineralizing Agents in Caries Prevention in Primary Sjögren s Patients Steering Committee Andres Pinto, Chair; Mahvash Navazesh, Nelson Rhodus Clinical (PICO) Questions 1. In primary Sjögren s patients, does the use of non-fluoride remineralization agents compared to placebo reduce the incidence, arrest or reverse coronal or root caries? 2. In primary Sjögren s patients, does the use of non-fluoride remineralization agents compared to the use of fluoride reduce the incidence, arrest or reverse coronal or root caries? Systematic Review Parameters Sample characteristics 18 and older Any sex, race, ethnicity, menopausal status Disease characteristics Primary Sjögren s; However, if insufficient evidence exists in primary Sjögren s, studies on secondary Sjögren s and other causes of xerostomia will be considered Any published criteria for Sjögren s Patients with flow rates consistent with Xerostomia from any cause Intervention/exposure Non-fluoride remineralization agents Comparisons RCTs are ideal, but other studies will be included in the literature search for consideration and review (study selection criteria to be refined further - after abstract review) Primary and secondary endpoints 8

9 Primary Outcome: Reduction in the incidence, arrest or reversal of coronal or root caries Secondary Outcomes: Decreased s mutans, lactobacillus, and plaque; Increased Unstimulated Whole Salivary Flow (UWSF) rate Publication type Published journal articles searched via PubMed and Cochrane Study design/methods Specify study design(s): Meta-analyses, systematic reviews, RCTs Cohort studies Case control studies Quality criteria other than design (e.g., sample size, follow-up period, validated and reliable measures, analyses): Minimum length of study of 12 months Other parameters Language: English only Year of publication: 1990 until <end date to be determined> Definitions for Quality Criteria (for Study Quality Assessment Tables) Provide definitions for quality criteria that pertain to particular topics and/or clinical questions (Categories and definitions below are adapted from AHRQ and Cochrane approaches.) The goal is to keep these as consistent as possible across groups. Make revisions, if necessary, below for your particular topic/clinical question(s). 31) Reproducible methodology: (e.g., study design and inclusion and exclusion criteria were clearly defined) 32) Adequate randomization: (e.g., methods used to randomize subjects to treatment were adequate) 33) Concealed allocation: (e.g., adequate method was used to conceal allocation to treatment arms) 34) Sufficient sample size: (e.g., sample size was sufficient to address relevant clinical question(s), power calculations provided) Minimum sample size of 50 35) Comparable groups: (e.g., groups' baseline characteristics and prognostic factors were similar) 36) Validated and reliable measures: (e.g., interventions and outcomes specified and clearly defined, outcomes assessed with standardized, valid, and reliable measures, reasonable uniformity in administration) Primary Outcome: Incidence, arrest or reversal of coronal or root caries Secondary Outcomes: Decreased s. mutans, lactobacillus, and plaque; remineralization; increased salivary flow 37) Adequate follow-up: (e.g., overall loss-to-follow-up and differential loss-to-follow-up assessed adequately and below defined threshold) Less than 20% loss to follow-up; Sufficient length of study - 12 months 38) Appropriate analyses: (e.g., analyses appropriate and relevant to the nature of outcomes data, controlled for confounding, number of explanatory variables used in the analyses appropriate for the sample size, all subjects analyzed in originally allocated groups (i.e., ITT analysis), incomplete outcome data adequately addressed) 39) Accurate results: (e.g., results reported were thorough, clear, and with no discrepancies, conclusions were supported by results, with possible biases and limitations considered) Calibration of examiners; Adequate statistical power analysis/power calculation done a priori 40) Insignificant conflicts of interest: (e.g., conflicts of interest were reported and insignificant) Funding sources cited 9

10 Limitations of the Literature Based on your preliminary assessment of the literature, do you feel there is enough evidence in the literature to make evidence-based recommendations? YES, an evidence-based recommendation will be feasible. We will assess the literature for studies in caries prevention in Sjögren s and other xerostomia patients, but we understand that the literature is limited, especially in Sjögren s, and that all recommendations largely will be expert consensus-based for caries prevention in Sjögren s. NO (OR) We should move directly to an expert consensus-based recommendation. Explain why a consensus-based recommendation is warranted: Study design criteria not met: (specify threshold for overall evidence) Overall study quality criteria: (specify threshold for overall evidence quality) Others (old data, out-of-date criteria for Sjögren s, too much heterogeneity) We should refer to another body of literature* to extrapolate to the Sjögren s population (e.g., lupus). Specify the non-sjögren s literature/population: any xerostomia population, including radiation for head and neck cancer; medication-induced; elderly Specify the justification for any extrapolations: 10

11 Appendix 2 Literature Search Terms for Caries Prevention 1. Fluoride: (Chair: D Zero; A Wu, M Singh) A. In SS patients, does the use of a topical fluoride compared to no topical fluoride reduce the incidence, arrest or reverse coronal or root caries? B. In SS patients, is one topical fluoride agent more effective than another in reducing the incidence, or to arrest or reverse coronal or root caries? 1: ("Sjögren s Syndrome"[Mesh] OR Sjögren s Syndrome OR head and neck radiation OR head and neck radiotherapy OR "Xerostomia"[Mesh]) 2: Dental Caries"[Mesh] 3: ("Prevalence"[Mesh] OR "Incidence"[Mesh] OR prevention OR arrest OR reversal OR reduction OR regression OR remineralize OR progression OR DMF Index[Mesh] OR ICDAS OR increment OR prevented fraction) 4: ("Fluorides, Topical"[Mesh] OR "Tin Fluorides"[Mesh] OR "Sodium Fluoride"[Mesh] OR AMF OR Amine F OR SMFP OR MFP OR Sodium monofluorophosphate OR varnish OR lacquer OR duraphat OR fluor protector OR gel OR foam OR "Dentifrices"[Mesh] OR "Mouthwashes"[Mesh] OR mouthrinse OR rinse) Amended to add quotation marks and text word phrases Search 1 = 16,654 Search 2 = 37,045 Search 3 = Search 4 = 433,319 Search with limits [publication date 5/1/2012 (6 months prior to previous search) to today (4/21/2015)] = 6 2. Salivary stimulation: (Chair: A Papas; I Al Hashimi) A. In SS patients, does salivary stimulation compared to not stimulating saliva flow reduce the incidence, arrest or reverse coronal or root caries? 1: ("Sjögren s Syndrome"[Mesh] OR Sjögren s Syndrome OR head and neck radiation OR head and neck radiotherapy OR "Xerostomia"[Mesh]) 2. "Dental Caries"[Mesh] 3. ("Prevalence"[Mesh] OR "Incidence"[Mesh] OR prevention OR arrest OR reversal OR reduction OR regression OR remineralize OR progression OR DMF Index[Mesh] OR ICDAS OR increment OR prevented fraction) 5. ( Chewing Gum [Mesh term] OR Lozenges OR Anhydrous crystalline maltose OR Pilocarpine [Mesh term] OR Salagen OR Cevimeline OR Evoxac OR Electric Stimulation [Mesh term] OR "Saliva, 11

12 Artificial"[Mesh] OR "Parasympathomimetics"[Mesh] OR "Physostigmine"[Mesh] OR Mucin OR "Carbachol"[Mesh] OR carbamoylcholine OR carbamann OR carbastat OR carbocholine OR miostat OR "Acetylcholine"[Mesh] OR "Muscarine"[Mesh] OR "Cholinesterase Inhibitors"[Mesh] OR "Cholinesterases"[Mesh] OR anti-cholinesterase OR anticholinesterase OR "Acetylcholinesterase"[Mesh] OR "Edrophonium"[Mesh] OR "Neostigmine"[Mesh] OR polstigmine OR proserine OR prostigmin OR prozerin OR synstigmin OR syntostigmine OR serine OR choline ester OR "Bethanechol"[Mesh OR methacholine OR distigmine OR "Pyridostigmine Bromide"[Mesh] OR "Ambenonium Chloride"[Mesh] OR demecarium OR cevimeline OR sialogogue OR Cholinergic Antagonists"[Mesh] OR anticholinergic OR anti-cholinergic OR "Electric Stimulation"[Mesh] OR neuroelectrostimulation OR masticatory stimulation OR intra-oral device OR "Acupuncture"[Mesh] OR "Hypnosis"[Mesh] OR "Hypnosis, Dental"[Mesh] OR autogenic train OR "Autosuggestion"[Mesh] OR "Edrophonium"[Mesh] OR "Neostigmine"[Mesh] OR polstigmine OR proserine OR prostigmin OR prozerin OR synstigmin OR syntostigmine OR eserine) Searches 1-3 same as PICO 1 Search 5 =153,797 Search with limits [publication date 5/1/2012 (6 months prior to previous search) to today (4/21/2015)] = 4 3. Antimicrobial agents: (Chair: C Stewart; J Sciubba) A. In SS patients, does the use of antimicrobial agents compared to placebo reduce the incidence, arrest or reverse coronal or root caries? 1. ("Sjögren s Syndrome"[Mesh] OR Sjögren s Syndrome OR head and neck radiation OR head and neck radiotherapy OR "Xerostomia"[Mesh]) 2. "Dental Caries"[Mesh] 3. ("Prevalence"[Mesh] OR "Incidence"[Mesh] OR prevention OR arrest OR reversal OR reduction OR regression OR remineralize OR progression OR DMF Index[Mesh] OR ICDAS OR increment OR prevented fraction) 6. ("Chlorhexidine"[Mesh] OR Nolvasan OR Novalsan OR Sebidin OR Tubulicid OR Cervitec OR Chlorzoin OR hibitane OR chlorhexidine-thymol OR "Anti-Infective Agents"[Mesh] OR "Cetylpyridinium"[Mesh]) Searches 1-3 same as PICO 1 Search 6 = 532,004 Search with limits [publication date 5/1/2012 (6 months prior to previous search) to today (4/21/2015)] = 3 4. Non-fluoride remineralizing agents: (Chair: A Pinto; M Navazesh, N Rhodus) A. In SS patients, does the use of non-fluoride remineralization agents compared to placebo reduce the incidence, arrest or reverse coronal or root caries? B. In SS patients, does the use of non-fluoride remineralization agents compared to the use of fluoride reduce the incidence, arrest or reverse coronal or root caries? 1. ("Sjögren s Syndrome"[Mesh] OR Sjögren s Syndrome OR head and neck radiation OR head and neck radiotherapy OR "Xerostomia"[Mesh]) 2. "Dental Caries"[Mesh] 3. ("Prevalence"[Mesh] OR "Incidence"[Mesh] OR prevention OR arrest OR reversal OR reduction OR regression OR remineralize OR progression OR DMF Index[Mesh] OR ICDAS OR increment OR prevented fraction) 12

13 7. ( casein phosphopeptide-amorphous calcium phosphate nanocomplex OR calcium phosphate OR casein phosphopeptides OR "Calcium"[Mesh] OR phosphate OR MI paste OR Tooth Mousse OR NovaMin OR calcium sodium phosphosilicate OR tri-calcium phosphate OR tricalcium phosphate OR CaviStat OR Caphosol OR Neutrasal OR Bioactive Glass OR Arginine Bicarbonate OR Calcium Carbonate OR fluoride) Searches 1-3 same as PICO 1 Search 7 = 566,100 Search with limits [publication date 5/1/2012 (6 months prior to previous search) to today (4/21/2015)] = 7 Merged Database removing duplicates: 10 citations from Medline One duplicate from prior search in 2012 (Yeh et al.) => total new = 9 Pubmed search for guidelines: "Sjögren s Syndrome"[Mesh] OR sjogren* with filter Practice Guideline. No new hits Cochrane Library: Search in title, abstract, keywords, all libraries 1. Sjogren* Syndrome or head and neck radiation or head and neck radiotherapy or xerostomia or dry mouth:ti,ab,kw (Word variations have been searched) = 5056 hits 2. MeSH descriptor: [Dental Caries] explode all trees = 1593 hits 3. #1 2 with limits [publication date 5/1/2012 (6 months prior to previous search) to today (4/21/2015)] = 0 hits Total (Pubmed searches 1-4; Pubmed guidelines filter; Cochrane Libraries) = 9 Primary outcomes The primary outcome measure is caries increment as measured by either: change from baseline in the decayed, (missing) and filled surface (D(M)FS) index, in all permanent teeth erupted at the start and erupting over the course of the study (dental caries is defined here as being clinically and radiologically recorded at the dentine level of diagnosis); change in the proportion developing new caries. 13