No consistent association found between dental caries and body mass index in children.

Data sourcesPubMed, Embase, the Cochrane Library and reference lists of identified studies.Study selectionObservational studies comparing dental caries and body mass index (BMI) where BMI was clearly defined were considered.Data extraction and synthesisTwo reviewers independently abstracted data using standard forms with study quality being assessed using a modified version of the Agency for Healthcare Research and Quality (AHRQ) methodology checklist for cross-sectional studies. The weighted mean differences and corresponding 95% confidence intervals for dental caries between children with abnormal weight and those with normal weight were analysed.ResultsFourteen cross-sectional studies including 43,860 children (boys: 23,299; girls: 20,561) were included. Only two studies were considered to be of high quality, eight of medium quality and four of low quality. Four main patterns of associations between dental caries and BMI were found: five studies showed no association, five studies found a positive association, three an inverse association and one found a U-shaped pattern, which meant that the deft score was significantly higher in underweight children and there was a higher DMFT score in overweight and obese children.ConclusionsThis meta-analysis showed no differences in dental caries between underweight and normal weight children. Further studies are recommended using suitable sample sizes, to unify the criteria for BMI categorisation and the dental caries index, and investigate the confounding factors that might influence dental caries and BMI.

Rubber dam may increase the survival time of dental restorations.

Data sourcesCochrane Oral Health's Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, LILACS, SciELO, Chinese BioMedical Literature Database, VIP, China National Knowledge Infrastructure, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, OpenGrey and Sciencepaper Online databases. Handsearches in a number of journals.Study selectionRandomised controlled trials, including split-mouth studies assessing the effects of rubber dam isolation for restorative treatments in dental patients.Data extraction and synthesisTwo review authors independently screened the results of the electronic searches, extracted data and assessed the risk of bias of the included studies.ResultsFour studies involving a total of 1,270 patients were included. The studies were at high risk of bias. One trial was excluded from the analysis due to inconsistencies in the presented data. Restorations had a significantly higher survival rate in the rubber dam isolation group compared to the cotton roll isolation group at six months in participants receiving composite restorative treatment of non-carious cervical lesions (risk ratio (RR) 1.19, 95% confidence interval (CI) 1.04 to 1.37, very low-quality evidence). The rubber dam group had a lower risk of failure at two years in children undergoing proximal atraumatic restorative treatment in primary molars (hazard ratio (HR) 0.80, 95% CI 0.66 to 0.97, very low-quality evidence). One trial reported limited data showing that rubber dam usage during fissure sealing might shorten the treatment time. None of the included studies mentioned adverse effects or reported the direct cost of the treatment, or the level of patient acceptance/satisfaction. There was also no evidence evaluating the effects of rubber dam usage on the quality of the restorations.ConclusionsWe found some very low-quality evidence, from single studies, suggesting that rubber dam usage in dental direct restorative treatments may lead to a lower failure rate of the restorations, compared with the failure rate for cotton roll usage. Further high quality research evaluating the effects of rubber dam usage on different types of restorative treatments is required.

Impact of smoking on tooth loss in adults.

DesignCohort studyCohort selectionParticipants were recruited between 1994 and 1998 from the general population with the preferred ages of 35 to 65 years in women and 40 to 65 years in men.Exposure measurementSmoking was assessed using a questionnaire from which pack years of smoking were calculated. Educational attainment, body mass index, hypertension, diabetes, alcohol consumption and vitamin or mineral supplements were assessed from measurements and questionnaires. Tooth loss was also assessed by questionnaire returned between 2004 and 2006. With the exception of the tooth loss data analysis was based on data collected at baseline.Data analysisThe 24,373 participants who returned the tooth loss questionnaire were analysed. Two hundred and eighty-six (1.2%) were excluded, as they did not respond to either of the tooth loss questions, and an additional 106 (0.4%) were excluded because they gave inconsistent responses to the questions on tooth loss. Four hundred and thirteen (1.7%) participants with missing data on cigarette smoking and 192 (0.8%) participants with missing data in any of the covariates were also excluded. The association between smoking and number of teeth at baseline was assessed using negative binomial regression models to obtain relative risks and 95% confidence intervals (CIs).ResultsThe sample of 23,376 included 9,032 men and 14,344 women of which 4,394 (19%) were current cigarette smokers, and 7,268 (31%) were cigarette smokers. 1,566 (6.7%) were edentulous at baseline. Compared with never smokers, current smokers were more likely to be male, less educated, more likely to be hypertensive, and less likely to take vitamins/mineral supplements, and they had higher alcohol consumption. Cigarette smoking was associated with higher prevalence of tooth loss at baseline as well as higher incidence of tooth loss during follow-up. The association between cigarette smoking and incident tooth loss during follow-up for the fully adjusted model (adjusted for age, sex, education, diabetes, body mass index, waist-to-hip ratio, hormone replacement therapy, contraception, intake of vitamin and mineral supplements, physical activity, alcohol intake, hypertension, and cardiovascular disease) is shown in the table.ConclusionsThere is a strong dose-dependent association between cigarette smoking and the risk of tooth loss. The risk declines after cessation of cigarette smoking; however, the risk may remain elevated for up to 20 years compared with never smokers. Efforts to improve the oral health of the population should include the prevention of smoking as well the promotion of smoking cessation.

Patients give meaning to changes in health complaints before, during and after the replacement of amalgam restorations.

DESIGN: Qualitative, explorative and reflexive thematic analysis. METHODS: Semi-structured in-depth interviews were carried out with 12 participants who had all taken part in a previous amalgam removal trial. Follow-up; three months and one, three and five years after amalgam restoration removal and replacement. Interviews were carried out by two researchers at a different location from clinical follow-up. Transcripts were analysed by reading through the written material to establish common themes. NVivo9 software was used to assist further organising themes. Themes were then refined and condensed into the presented findings, which included selected quotes. RESULTS: The authors found the following themes to be important to patients in giving meaning to health complaints before, during and after amalgam removal: Something is not working: betrayed by the body. You are out there on your own. Not being sure of the importance of amalgam removal. The relief experienced after amalgam is removed. To accept, to give up, or to continue the search. CONCLUSIONS: For this group of patients, it was important to remove dental amalgam restorations. However, it remains uncertain of how critical this actually was in relation to their experienced changes in health complaints, as they did not feel that they could credit all positive change to the amalgam removal. For some participants it meant this was no longer a source of worry and for others it helped them move towards accepting their health status.

Training and fairer payments would increase caries prevention in practice.

DATA SOURCES: PubMed, Embase, PsycoInfo, Scielo, Scopus, Web of Science, BBO, Lilacs and York databases supplemented by Google scholar. STUDY SELECTION: Qualitative studies with findings derived from individual or group interviews and structured questionnaires reporting factors that drove dentists towards or away from incorporating caries preventive measures were considered. Two reviewers conducted selection independently. DATA EXTRACTION AND SYNTHESIS: Data were abstracted independently by two reviewers and a qualitative metasummary carried out. This involves the extraction, grouping and formatting of findings and the calculation of frequency and intensity effect sizes in order to provide mixed research syntheses and to conduct a posteriori analyses of the relationship between reports and findings. RESULTS: Seven qualitative studies and 41 surveys (36,501 participants) were included. The reports were grouped together into six categories that were judged to be topically similar; education and training, personal beliefs, work conditions, remuneration, gender, place of residence and patients. Biologicism (27%), low remuneration (25%), length of time since graduation (22%) and male dentists (19%) were found to be the highest frequency effect size driving dentists away from using preventive approaches, and team work (21%), post-graduation (12%) and professional understanding of the benefits (12%) were identified as the main reasons for dentists' adherence to preventive measures. CONCLUSIONS: Despite the questionable quality of the included reports the evidence that emerged seems to indicate that further education and training coupled with a fairer pay scheme would be a reasonable approach to change the balance in favour of the provision of dental caries preventive measures by dentists. The results of this review could be of value in the planning and decision-making processes aimed at encouraging changes in professional dental practice that could result in the improvement of the oral health care provided to the population in general.

Ferritin trends do not predict changes in total body iron in patients with transfusional iron overload.

Ferritin levels and trends are widely used to manage iron overload and assess the efficacy of prescribed iron chelation in patients with transfusional iron loading. A retrospective cohort study was conducted in 134 patients with transfusion-dependent anemia, over a period of up to 9 years. To determine whether the trends in ferritin adequately reflect the changes in total body iron, changes in ferritin between consecutive liver iron measurements by magnetic resonance imaging (MRI) were compared to changes in liver iron concentrations (LIC), a measure of total body iron. The time period between two consecutive LIC measurements was defined as a segment. Trends in ferritin were considered to predict the change in LIC within a segment if the change in one parameter was less than twofold that of the other, and was in the same direction. Using the exclusion criteria detailed in methods, the trends in ferritin were compared to changes in LIC in 358 segments. An agreement between ferritin trends and LIC changes was found in only 38% of the 358 segments examined. Furthermore, the change in ferritin was in opposite direction to that of LIC in 26% of the segments. Trends in ferritin were a worse predictor of changes in LIC in sickle cell disease than in thalassemia (P < 0.01). While ferritin is a convenient measure of iron status; ferritin trends were unable to predict changes in LIC in individual patients. Ferritin trends need to be interpreted with caution and confirmed by direct measurement of LIC.

Barriers to providing dental care for older people.

DATA SOURCES: The Medline, Embase and CINAHL databases were searched together with the reference lists of selected publications. STUDY SELECTION: Studies published since January 1990 and published in English that looked at barriers, experienced by dentists, to delivering oral health care to people over the age of 65 were included. Study quality was assessed independently using criteria developed by the Dutch Cochrane Centre. DATA EXTRACTION AND SYNTHESIS: Study assessment and data extraction were carried out independently by two reviewers and a qualitative summary presented. RESULTS: Seven cross-sectional studies were included. The focus was primarily on dentists delivering oral health care to older people in care homes with only one focused on barriers experienced by dentists working in their own practice and delivering oral health care to community-dwelling older people. The most common barriers to delivering oral health care to older people were identified respectively as: the lack of adequate equipment in a care home and no area for treatment available (n = 4) and the lack of adequate reimbursement for working in a care home (n = 5). In addition, the inadequate training and experience in delivering oral health care to older care home residents (n = 2) were mentioned. Four publications indicated the loss of time from private practice as a barrier to delivering oral health care in a care home. CONCLUSIONS: Most articles retrieved described barriers experienced by dentists delivering oral health in care homes: much less is known about oral health care for community-dwelling older people. Therefore, we suggest that additional research should be initiated to investigate in more detail the barriers dentists experience in delivering oral health care to older people in their own dental practices.

Pain in thalassaemia: the effects of age on pain frequency and severity.

Pain is not a symptom generally associated with thalassaemia. However, providers have noted increasing patient reports of pain, creating an impetus for this prospective, observational assessment of pain in thalassaemia patients. The primary study goals were to assess pain prevalence, severity, location, and potential risk factors. This was a multicentre, prospective study of thalassaemia patients receiving care at 12 Thalassaemia Clinical Research Network sites. Pain was assessed using the Brief Pain Inventory. Two hundred and fifty-two thalassaemia patients ranging in age from 12 to 71 years (mean 28.8) were enrolled. Sixty-four per cent reported experiencing pain during the last 4 weeks, 22% of whom reported pain on a daily basis. Ordinal regression analysis of pain ratings demonstrated significant (P < 0.001) correlation of increased age with increased pain, irrespective of diagnosis, transfusion status, gender, bone density, chelator type or iron overload. Eighty-one per cent reported having pain for 1 year or longer and 31% reported pain for five or more years. Pain is a major cause of morbidity and an unrecognized problem for patients with thalassaemia. Age is the strongest predictor of frequency and severity. Little else is known about the aetiology and predictors of this pain syndrome.

Tissue iron evaluation in chronically transfused children shows significant levels of iron loading at a very young age.

Chronic blood transfusions start at a very young age in subjects with transfusion-dependent anemias, the majority of whom have hereditary anemias. To understand how rapidly iron overload develops, we retrospectively reviewed 308 MRIs for evaluation of liver, pancreatic, or cardiac iron in 125 subjects less than 10 years old. Median age at first MRI evaluation was 6.0 years. Median liver iron concentrations in patients less than 3.5 years old were 14 and 13 mg/g dry weight in thalassemia major (TM) and Diamond-Blackfan anemia (DBA) patients, respectively. At time of first MRI, pancreatic iron was markedly elevated (> 100 Hz) in DBA patients, and cardiac iron ( R2* >50 Hz) was present in 5/112 subjects (4.5%), including a 2.5 years old subject with DBA. Five of 14 patients (38%) with congenital dyserythropoietic anemia (CDA) developed excess cardiac iron before their 10th birthday. Thus, clinically significant hepatic and cardiac iron accumulation occurs at an early age in patients on chronic transfusions, particularly in those with ineffective or absent erythropoiesis, such as DBA, CDA, and TM, who are at higher risk for iron cardiomyopathy. Performing MRI for iron evaluation in the liver, heart, and pancreas as early as feasible, particularly in those conditions in which there is suppressed bone marrow activity is very important in the management of iron loaded children in order to prescribe appropriate chelation to prevent long-term sequelae. .

Pain over time and its effects on life in thalassemia.

Pain reports have become increasingly common and problematic in thalassemia. As patients are living longer,there is a growing need to study pain and to explore its impact on patient lives. The Brief Pain Inventory(BPI) was used quarterly to assess pain and pain interference in patients with thalassemia in North America.The Medical Outcomes Study 36-Item Short Form Health Survey and the Hospital Anxiety and Depression Scale were used to assess quality of life, anxiety and depression. Of the 252 participants, 56% reported pain at least once over the course of this study, with 32% reporting severe pain (≥7/10); 16% reported pain at all four visits. Increased pain severity significantly interfered with daily life (P< 0.001; regression analysis) and participants with more sites of pain showed an increase in the amount of daily activities affected by pain(P50.001). Participants reporting more visits with pain reported a significantly higher impact on affective and physical function (P< 0.001). Physical quality of life decreased with increasing numbers of visits with pain (P< 0.001). Those who reported one or more sites of pain showed increased symptoms of both depression(P< 0.001) and anxiety (P50.003). Participants reporting at least two visits with pain had higher symptoms of anxiety (P50.002) and those with at least three visits reported higher symptoms of depression(P50.003). Pain is prevalent in thalassemia and is often a chronic condition that interferes with life. The study highlights the significance of pain in thalassemia and its impact, which should be considered in future research and treatments.

Limited evidence for existing caries assessment systems.

DATA SOURCES: Data were sourced from the Cochrane Oral Health Groups Specialised Register, Cochrane Central Register of Controlled Trails, Medline, bibliographic references of identified systematic reviews, prospective cohort studies and clinical trials, textbooks and review articles. STUDY SELECTION: The studies included presented validating criteria for caries incidence/ increment and were limited to those with human subjects and natural carious lesions. Only studies published in peer reviewed journals were included. Excluded were studies which gave an incomplete description of sample selection, or of outcome, or had a small sample size. Studies which did not meet the Oxford Centre for Evidence Based Medicine prognosis category criteria for best evidence were also excluded. DATA EXTRACTION AND SYNTHESIS: Data were extracted by the first review author and were independently checked by a second author. The criteria reported in the ADA Clinical Recommendations Handbook(1) were used to assess the quality of the studies. Adjustments made for potential confounders were considered as a means to evaluate the internal validity of each study. RESULTS: One hundred and thirty-seven study reports remained for review following systematic strategic search and title review. Of these, six studies of existing caries risk assessment models were selected for inclusion. Of the six studies reviewed four were deemed 'fair' by the ADA criteria and two 'poor'. The authors found variation in the parameters used for caries risk assessment and the population groups studied. No study found the risk assessment systems to have reliable prediction utility in children. One prospective study found Cariogram to give good to moderate caries prediction in elderly adults and one retrospective study found the CAMBRA assessment to provide prediction for cavitated lesions, but only between low risk and extreme risk individuals over the age of six. CONCLUSIONS: This systematic review suggests that evidence available on the validity of a number of existing systems for caries risk assessment is limited and weak.

Possible role for arginine-containing toothpastes in managing dentine hypersensitivity.

DATA SOURCES: The Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase and LILACS databases were searched. Reference lists of eligible studies and systematic reviews were cross-checked to identify additional studies. STUDY SELECTION: Randomised and controlled clinical trials conducted in adults with at least two hypersensitive teeth confirmed by evaporative stimulus or tactile hypersensitivity assessment comparing arginine-containing desensitising toothpastes to non-arginine-containing control toothpastes were included. DATA EXTRACTION AND SYNTHESIS: Data abstraction and risk of bias assessment were conducted independently by two reviewers and a qualitative summary presented. RESULTS: Two randomised trials met the criteria; both showed a positive effect on dentine hypersensitivity in response to tactile and air-blast stimuli. No subjective measures of sensitivity were reported. CONCLUSIONS: Data identified indicate a potential role for arginine-containing toothpastes in managing dentine hypersensitivity. However, this conclusion is based on small sample sizes and the studies identified did not follow patients up in the medium to long term. The authors recommend that there is a need for well-designed RCTs to be conducted prior to any definitive recommendations being made.

Growth and adiposity in newborns study (GAINS): The influence of prenatal DHA supplementation protocol.

BACKGROUND: Obesity and central fat mass (FM) accrual drive disease development and are related to greater morbidity and mortality. Excessive gestational weight gain (GWG) increases fetal fat accretion resulting in greater offspring FM across the lifespan. Studies associate greater maternal docosahexaenoic acid (DHA) levels with lower offspring FM and lower visceral adipose tissue during childhood, however, most U.S. pregnant women do not consume an adequate amount of DHA. We will determine if prenatal DHA supplementation is protective for body composition changes during infancy and toddlerhood in offspring exposed to excessive GWG. METHODS AND DESIGN: Infants born to women who participated in the Assessment of DHA on Reducing Early Preterm Birth randomized controlled trial (ADORE; NCT02626299) will be invited to participate. Women were randomized to either a high 1000 mg or low 200 mg daily prenatal DHA supplement starting in the first trimester of pregnancy. Offspring body composition and adipose tissue distribution will be measured at 2 weeks, 6 months, 12 months, and 24 months using dual energy x-ray absorptiometry. Maternal GWG will be categorized as excessive or not excessive based on clinical guidelines. DISCUSSION: Effective strategies to prevent obesity development are lacking. Exposures during the prenatal period are important in the establishment of the offspring phenotype. However, it is largely unknown which exposures can be successfully targeted to have a meaningful impact. This study will determine if prenatal DHA supplementation modifies the relationship between maternal weight gain and offspring FM and FM distribution at 24 months of age. ETHICS AND DISSEMINATION: The University of Kansas Medical Center Institutional Review Board (IRB) approved the study protocol (STUDY00140895). The results of the trial will be disseminated at conferences and in peer reviewed publications. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03310983.

Methods for the drug effectiveness review project.

The Drug Effectiveness Review Project was initiated in 2003 in response to dramatic increases in the cost of pharmaceuticals, which lessened the purchasing power of state Medicaid budgets. A collaborative group of state Medicaid agencies and other organizations formed to commission high-quality comparative effectiveness reviews to inform evidence-based decisions about drugs that would be available to Medicaid recipients. The Project is coordinated by the Center for Evidence-based Policy (CEbP) at Oregon Health & Science University (OHSU), and the systematic reviews are undertaken by the Evidence-based Practice Centers (EPCs) at OHSU and at the University of North Carolina. The reviews adhere to high standards for comparative effectiveness reviews. Because the investigators have direct, regular communication with policy-makers, the reports have direct impact on policy and decision-making, unlike many systematic reviews. The Project was an innovator of methods to involve stakeholders and continues to develop its methods in conducting reviews that are highly relevant to policy-makers. The methods used for selecting topics, developing key questions, searching, determining eligibility of studies, assessing study quality, conducting qualitative and quantitative syntheses, rating the strength of evidence, and summarizing findings are described. In addition, our on-going interactions with the policy-makers that use the reports are described.

Use of electronic data collection to assess pain in thalassaemia: a feasibility study.

AIM: To assess the feasibility of collecting electronic pain data from thalassaemia patients, based on its acceptability and convenience to the participants and study team. METHODS: Participants in the Thalassemia Clinical Research Network Assessment of Pain Survey Study completed the Brief Pain Inventory (BPI) quarterly by paper or phone interview. Participants in a substudy completed the BPI Short Form daily over three non-consecutive transfusion cycles through an automated telephone system. RESULTS: The consent rate for the main study was 93%, with 93% retention. The substudy had 75% retention, with more than 75% of scheduled calls completed. Regular monitoring of enrollment, missed calls, data quality, and the performance of the subcontractor for the automated system was crucial to fulfillment of the study goals. CONCLUSIONS: Use of electronic data collection for patient-reported outcomes was convenient for both patients and study personnel but required human interactions beyond the automated system to maximise data quantity and quality.

We Can Dance If We Want To (with Safety Measures).

This work considers the spread of SARS-CoV-2 during a multiday intensive dance camp occurring from 26 December 2021 to 1 January 2022 in Asheville, North Carolina. Approximately 370 dancers and performers were in attendance, and the data presented are the result of an anonymous survey distributed 10 days following the event. While some transmission occurred during the time span of the event, it appears that the majority of transmission occurred either through the result of individual interactions or activities outside the formal dance event rather than due to a buildup of airborne viral particles in the event space.

Longitudinal analysis of heart and liver iron in thalassemia major.

High hepatic iron concentration (HIC) is associated with cardiac iron overload. However, simultaneous measurements of heart and liver iron often demonstrate no significant linear association. We postulated that slower rates of cardiac iron accumulation and clearance could reconcile these differences. To test this hypothesis, we examined the longitudinal evolution of cardiac and liver iron in 38 thalassemia major patients, using previously validated magnetic resonance imaging (MRI) techniques. On cross-sectional evaluation, cardiac iron was uncorrelated with liver iron, similar to previous studies. However, relative changes in heart and liver iron were compared with one another using a metric representing the temporal delay between them. Cardiac iron significantly lagged liver iron changes in almost half of the patients, implying a functional but delayed association. The degree of time lag correlated with initial HIC (r = 0.47, P < .003) and initial cardiac R2* (r = 0.57, P < .001), but not with patient age. Thus, longitudinal analysis confirms a lag in the loading and unloading of cardiac iron with respect to liver iron, and partially explains the weak cross-sectional association between these parameters. These data reconcile several prior studies and provide both mechanical and clinical insight into cardiac iron accumulation.

A documentation approach for faith community nursing.

Faith Community Nursing: Scope and Standards of Practice (American Nurses Association and Health Ministries Association, 2005) establishes the professional responsibility for documenting relevant data in a retrievable format that is both confidential and secure. Documentation systems used by faith community nurses (FCNs) need to be accurate, yet simple and concise. This article presents an approach to documenting FCN activities, the provided care, and outcomes of that care, while emphasizing the use of standardized nursing language.

Gabapentin versus tricyclic antidepressants for diabetic neuropathy and post-herpetic neuralgia: discrepancies between direct and indirect meta-analyses of randomized controlled trials.

BACKGROUND: Previous systematic reviews concluded that tricyclics antidepressants are superior to gabapentin for neuropathic pain, but were based on indirect comparisons from placebo-controlled trials. PURPOSE: To evaluate gabapentin versus tricyclic antidepressants for diabetic neuropathy and post-herpetic neuralgia, using direct and indirect comparisons. DATA SOURCES: MEDLINE (1966 to March Week 4 2008), the Cochrane central register of controlled trials (1st quarter 2008), and reference lists. STUDY SELECTION: We selected randomized trials directly comparing gabapentin versus tricyclic antidepressants or comparing either of these medications versus placebo. DATA EXTRACTION: Studies were reviewed, abstracted, and quality-rated by two independent investigators using predefined criteria. DATA SYNTHESIS: We performed a meta-analysis of head-to-head trials using a random effects model and compared the results to an adjusted indirect analysis of placebo-controlled trials. RESULTS: In three head-to-head trials, there was no difference between gabapentin and tricyclic antidepressants for achieving pain relief (RR 0.99, 95% CI 0.76 to 1.29). In adjusted indirect analyses, gabapentin was worse than tricyclic antidepressants for achieving pain relief (RR = 0.41, 95% CI 0.23 to 0.74). The discrepancy between direct and indirect analyses was statistically significant (p = 0.008). Placebo-controlled tricyclic trials were conducted earlier than the gabapentin trials, reported lower placebo response rates, had more methodological shortcomings, and were associated with funnel plot asymmetry. CONCLUSIONS: Though direct evidence is limited, we found no difference in likelihood of achieving pain relief between gabapentin and tricyclic antidepressants for diabetic neuropathy and post-herpetic neuralgia. Indirect analyses that combine data from sets of trials conducted in different eras can be unreliable.