Interpreting the results of patient reported outcome measures in clinical trials: The clinician's perspective

This article deals with the problem of interpreting health-related quality of life (HRQL) outcomes in clinical trials. First, we will briefly describe how dichotomization and item response theory can facilitate interpretation. Based on examples from the medical literature for the interpretation of HRQL scores we will show that dichotomies may help clinicians understand information provided by HRQL instruments in RCTs. They can choose thresholds to calculate proportions of patients benefiting based on absolute scores or change scores. For example, clinicians interpreting clinical trial results could consider the difference in the proportion of patients who achieve a mean score of 50 before and after an intervention on a scale from 1 to 100. For the change score approach, they could consider the proportion of patients who have changed by a score of 5 or more. Finally, they can calculate the proportion of patients benefiting and transform these numbers into a number needed to treat or natural frequencies. Second, we will describe in more detail an approach to the interpretation of HRQL scores based on the minimal important difference (MID) and proportions. The MID is the smallest difference in score in the outcome of interest that informed patients or informed proxies perceive as important, either beneficial or harmful, and that would lead the patient or clinician to consider a change in the management. Any change in management will depend on the downsides, including cost and inconvenience, associated with the intervention. Investigators can help with the interpretation of HRQL scores by determining the MID of an HRQL instrument and provide mean differences in relation to the MID. For instance, for an MID of 0.5 on a seven point scale investigators could provide the mean change on the instrument as well as the proportion of patients with scores greater than the MID. Thus, there are several steps investigators can take to facilitate this process to help bringing HRQL information closer to the bedside

Risk of thrombosis and bleeding in gynecologic noncancer surgery: systematic review and meta-analysis

Objective: This study aimed to provide procedure-specific estimates of the risk for symptomatic venous thromboembolism and major bleeding in noncancer gynecologic surgeries.Data sources: We conducted comprehensive searches on Embase, MEDLINE, Web of Science, and Google Scholar. Furthermore, we performed separate searches for randomized trials that addressed the effects of thromboprophylaxis.Study eligibility criteria: Eligible studies were observational studies that enrolled ≥50 adult patients who underwent noncancer gynecologic surgery procedures and that reported the absolute incidence of at least 1 of the following: symptomatic pulmonary embolism, symptomatic deep vein thrombosis, symptomatic venous thromboembolism, bleeding that required reintervention (including re-exploration and angioembolization), bleeding that led to transfusion, or postoperative hemoglobin level <70 g/L.Methods: A teams of 2 reviewers independently assessed eligibility, performed data extraction, and evaluated the risk of bias of the eligible articles. We adjusted the reported estimates for thromboprophylaxis and length of follow-up and used the median value from studies to determine the cumulative incidence at 4 weeks postsurgery stratified by patient venous thromboembolism risk factors and used the Grading of Recommendations Assessment, Development and Evaluation approach to rate the evidence certainty.Results: We included 131 studies (1,741,519 patients) that reported venous thromboembolism risk estimates for 50 gynecologic noncancer procedures and bleeding requiring reintervention estimates for 35 procedures. The evidence certainty was generally moderate or low for venous thromboembolism and low or very low for bleeding requiring reintervention. The risk for symptomatic venous thromboembolism varied from a median of <0.1% for several procedures (eg, transvaginal oocyte retrieval) to 1.5% for others (eg, minimally invasive sacrocolpopexy with hysterectomy, 1.2%-4.6% across patient venous thromboembolism risk groups). Venous thromboembolism risk was <0.5% for 30 (60%) of the procedures; 0.5% to 1.0% for 10 (20%) procedures; and >1.0% for 10 (20%) procedures. The risk for bleeding the require reintervention varied from <0.1% (transvaginal oocyte retrieval) to 4.0% (open myomectomy). The bleeding requiring reintervention risk was <0.5% in 17 (49%) procedures, 0.5% to 1.0% for 12 (34%) procedures, and >1.0% in 6 (17%) procedures.Conclusion: The risk for venous thromboembolism in gynecologic noncancer surgery varied between procedures and patients. Venous thromboembolism risks exceeded the bleeding risks only among selected patients and procedures. Although most of the evidence is of low certainty, the results nevertheless provide a compelling rationale for restricting pharmacologic thromboprophylaxis to a minority of patients who undergo gynecologic noncancer procedures

Development and evaluation of the Children's Experiences of Dental Anxiety Measure

Background Existing measures of children's dental anxiety have not been developed with children or based on a theoretical framework of dental anxiety. Aim To develop the children's experiences of dental anxiety measure (CEDAM) and evaluate the measure's properties. Design The measure was developed from interviews with dentally anxious children. Children recruited from a dental hospital and secondary school completed the CEDAM and Modified Child Dental Anxiety Scale (MCDAS). A subgroup of children completed the CEDAM before and after receiving an intervention to reduce dental anxiety to examine the measure's responsiveness. Rasch and Classical test analyses were undertaken. Results Children were aged between 9 and 16 years (N = 88 recruited from a dental hospital and N = 159 recruited from a school). Rasch analysis confirmed the measure's unidimensionality. The CEDAM correlated well with the MCDAS (rho = 0.67, P < 0.01) and had excellent internal consistency (Cronbach's alpha = 0.88) and test–retest reliability (ICC = 0.98). The CEDAM was also able to detect changes in dental anxiety following the intervention (baseline mean = 22.36, SD = 2.57 and follow-up mean = 18.88, SD = 2.42, t(df = 37) = 9.54, P < 0.01, Cohen's d = 1.39). Conclusions The results support the reliability, validity and responsiveness of the CEDAM. Initial findings indicate it has potential for use in future intervention trials or in clinical practice to monitor children's dental anxiety

Interventions for improving oral health in people after stroke

BACKGROUND: For people with physical, sensory and cognitive limitations due to stroke, the routine practice of oral health care (OHC) may become a challenge. Evidence‐based supported oral care intervention is essential for this patient group. OBJECTIVES: To compare the effectiveness of OHC interventions with usual care or other treatment options for ensuring oral health in people after a stroke. SEARCH METHODS: We searched the Cochrane Stroke Group and Cochrane Oral Health Group trials registers, CENTRAL, MEDLINE, Embase, and six other databases in February 2019. We scanned reference lists from relevant papers and contacted authors and researchers in the field. We handsearched the reference lists of relevant articles and contacted other researchers. There were no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that evaluated one or more interventions designed to improve the cleanliness and health of the mouth, tongue and teeth in people with a stroke who received assisted OHC led by healthcare staff. We included trials with a mixed population provided we could extract the stroke‐specific data. The primary outcomes were dental plaque or denture plaque. Secondary outcomes included presence of oral disease, presence of related infection and oral opportunistic pathogens related to OHC and pneumonia, stroke survivor and providers' knowledge and attitudes to OHC, and patient satisfaction and quality of life. DATA COLLECTION AND ANALYSIS: Two review authors independently screened abstracts and full‐text articles according to prespecified selection criteria, extracted data and assessed the methodological quality using the Cochrane 'Risk of bias' tool. We sought clarification from investigators when required. Where suitable statistical data were available, we combined the selected outcome data in pooled meta‐analyses. We used GRADE to assess the quality of evidence for each outcome. MAIN RESULTS: Fifteen RCTs (22 randomised comparisons) involving 3631 participants with data for 1546 people with stroke met the selection criteria. OHC interventions compared with usual care Seven trials (2865 participants, with data for 903 participants with stroke, 1028 healthcare providers, 94 informal carers) investigated OHC interventions compared with usual care. Multi‐component OHC interventions showed no evidence of a difference in the mean score (DMS) of dental plaque one month after the intervention was delivered (DMS –0.66, 95% CI –1.40 to 0.09; 2 trials, 83 participants; I(2) = 83%; P = 0.08; very low‐quality evidence). Stroke survivors had less plaque on their dentures when staff had access to the multi‐component OHC intervention (DMS –1.31, 95% CI –1.96 to –0.66; 1 trial, 38 participants; P < 0.0001; low‐quality evidence). There was no evidence of a difference in gingivitis (DMS –0.60, 95% CI –1.66 to 0.45; 2 trials, 83 participants; I(2) = 93%; P = 0.26: very low‐quality evidence) or denture‐induced stomatitis (DMS –0.33, 95% CI –0.92 to 0.26; 1 trial, 38 participants; P = 0.69; low‐quality evidence) among participants receiving the multi‐component OHC protocol compared with usual care one month after the intervention. There was no difference in the incidence of pneumonia in participants receiving a multi‐component OHC intervention (99 participants; 5 incidents of pneumonia) compared with those receiving usual care (105 participants; 1 incident of pneumonia) (OR 4.17, CI 95% 0.82 to 21.11; 1 trial, 204 participants; P = 0.08; low‐quality evidence). OHC training for stroke survivors and healthcare providers significantly improved their OHC knowledge at one month after training (SMD 0.70, 95% CI 0.06 to 1.35; 3 trials, 728 participants; I(2) = 94%; P = 0.03; very low‐quality evidence). Pooled data one month after training also showed evidence of a difference between stroke survivor and providers' oral health attitudes (SMD 0.28, 95% CI 0.01 to 0.54; 3 trials, 728 participants; I(2) = 65%; P = 0.06; very low‐quality evidence). OHC interventions compared with placebo Three trials (394 participants, with data for 271 participants with stroke) compared an OHC intervention with placebo. There were no data for primary outcomes. There was no evidence of a difference in the incidence of pneumonia in participants receiving an OHC intervention compared with placebo (OR 0.39, CI 95% 0.14 to 1.09; 2 trials, 242 participants; I(2) = 42%; P = 0.07; low‐quality evidence). However, decontamination gel reduced the incidence of pneumonia among the intervention group compared with placebo gel group (OR 0.20, 95% CI 0.05 to 0.84; 1 trial, 203 participants; P = 0.028). There was no difference in the incidence of pneumonia in participants treated with povidone‐iodine compared with a placebo (OR 0.81, 95% CI 0.18 to 3.51; 1 trial, 39 participants; P = 0.77). One OHC intervention compared with another OHC intervention Twelve trials (372 participants with stroke) compared one OHC intervention with another OHC intervention. There was no difference in dental plaque scores between those participants that received an enhanced multi‐component OHC intervention compared with conventional OHC interventions at three months (MD –0.04, 95% CI –0.33 to 0.25; 1 trial, 61 participants; P = 0.78; low‐quality evidence). There were no data for denture plaque. AUTHORS' CONCLUSIONS: We found low‐ to very low‐quality evidence suggesting that OHC interventions can improve the cleanliness of patient's dentures and stroke survivor and providers' knowledge and attitudes. There is limited low‐quality evidence that selective decontamination gel may be more beneficial than placebo at reducing the incidence of pneumonia. Improvements in the cleanliness of a patient's own teeth was limited. We judged the quality of the evidence included within meta‐analyses to be low or very low quality, and this limits our confidence in the results. We still lack high‐quality evidence of the optimal approach to providing OHC to people after stroke

Treatment outcomes for children with multidrug-resistant tuberculosis: a systematic review and meta-analysis

BACKGROUND: Paediatric multidrug-resistant (MDR) tuberculosis is a public health challenge of growing concern, accounting for an estimated 15% of all global cases of MDR tuberculosis. Clinical management is especially challenging, and recommendations are based on restricted evidence. We aimed to assess existing evidence for the treatment of MDR tuberculosis in children. METHODS: We did a systematic review and meta-analysis of published and unpublished studies reporting treatment outcomes for children with MDR tuberculosis. We searched PubMed, Ovid, Embase, Cochrane Library, PsychINFO, and BioMedCentral databases up to Oct 31, 2011. Eligible studies included five or more children (aged ≤16 years) with MDR tuberculosis within a defined treatment cohort. The primary outcome was treatment success, defined as a composite of cure and treatment completion. RESULTS: We identified eight studies, which reported treatment outcomes for a total of 315 patients. We recorded much variation in the characteristics of patients and programmes. Time to appropriate treatment varied from 2 days to 46 months. Average duration of treatment ranged from 6 months to 34 months, and duration of follow-up ranged from 12 months to 37 months. The pooled estimate for treatment success was 81·67% (95% CI 72·54-90·80). Across all studies, 5·9% (95% CI 1·3-10·5) died, 6·2% (2·3-10·2) defaulted, and 39·1% (28·7-49·4) had an adverse event. The most common drug-related adverse events were nausea and vomiting. Other serious adverse events were hearing loss, psychiatric effects, and hypothyroidism. INTERPRETATION: The treatment of paediatric MDR tuberculosis has been neglected, but when children are treated outcomes can be achieved that are at least as good as those reported for adults. Programmes should be encouraged to report outcomes in children to improve the knowledge base for care, especially as new drugs become available. FUNDING: None

Impact of maternal reproductive factors on cancer risks of offspring : a systematic review and meta-analysis of cohort studies

BackgroundA number of studies have reported on associations between reproductive factors, such as delivery methods, number of birth and breastfeeding, and incidence of cancer in children, but systematic reviews addressing this issue to date have important limitations, and no reviews have addressed the impact of reproductive factors on cancer over the full life course of offspring.MethodsWe performed a comprehensive search in MEDLINE, and Embase up to January 2020 and Web of Science up to 2018 July, including cohort studies reporting the association between maternal reproductive factors of age at birth, birth order, number of births, delivery methods, and breastfeeding duration and cancer in children. Teams of two reviewers independently extracted data and assessed risk of bias. We conducted random effects meta-analyses to estimate summary relative estimates, calculated absolute differences between those with and without risk factors, and used the GRADE approach to evaluate the certainty of evidence.ResultsFor most exposures and most cancers, we found no suggestion of a causal relation. We found low to very low certainty evidence of the following very small possible impact: higher maternal age at birth with adult multiple myeloma and lifetime uterine cervix cancer incidence; lower maternal age at birth with childhood overall cancer mortality (RR = 1.15, 95% CI = 1.01-1.30; AR/10,000 = 1, 95% CI = 0 to 2), adult leukemia and lifetime uterine cervix cancer incidence; higher birth order with adult melanoma, cervix uteri, corpus uteri, thyroid cancer incidence, lifetime lung, corpus uteri, prostate, testis, sarcoma, thyroid cancer incidence; larger number of birth with childhood brain (RR = 1.27, 95% CI = 1.06-1.52; AR/10,000 = 1, 95% CI = 0 to 2), leukemia (RR = 2.11, 95% CI = 1.62-2.75; AR/10,000 = 9, 95% CI = 5 to 14), lymphoma (RR = 4.66, 95% CI = 1.40-15.57; AR/10,000 = 11, 95% CI = 1 to 44) incidence, adult stomach, corpus uteri cancer incidence and lung cancer mortality, lifetime stomach, lung, uterine cervix, uterine corpus, multiple myeloma, testis cancer incidence; Caesarean delivery with childhood kidney cancer incidence (RR = 1.25, 95% CI = 1.01-1.55; AR/10,000 = 0, 95% CI = 0 to 1); and breastfeeding with adult colorectal cancer incidence.ConclusionVery small impacts existed between a number of reproductive factors and cancer incidence and mortality in children and the certainty of evidence was low to very low primarily due to observational design

Evaluation of a task-based community oriented teaching model in family medicine for undergraduate medical students in Iraq

BACKGROUND: The inclusion of family medicine in medical school curricula is essential for producing competent general practitioners. The aim of this study is to evaluate a task-based, community oriented teaching model of family medicine for undergraduate students in Iraqi medical schools. METHODS: An innovative training model in family medicine was developed based upon tasks regularly performed by family physicians providing health care services at the Primary Health Care Centre (PHCC) in Mosul, Iraq. Participants were medical students enrolled in their final clinical year. Students were assigned to one of two groups. The implementation group (28 students) was exposed to the experimental model and the control group (56 students) received the standard teaching curriculum. The study took place at the Mosul College of Medicine and at the Al-Hadba PHCC in Mosul, Iraq, during the academic year 1999–2000. Pre- and post-exposure evaluations comparing the intervention group with the control group were conducted using a variety of assessment tools. RESULTS: The primary endpoints were improvement in knowledge of family medicine and development of essential performance skills. Results showed that the implementation group experienced a significant increase in knowledge and performance skills after exposure to the model and in comparison with the control group. Assessment of the model by participating students revealed a high degree of satisfaction with the planning, organization, and implementation of the intervention activities. Students also highly rated the relevancy of the intervention for future work. CONCLUSION: A model on PHCC training in family medicine is essential for all Iraqi medical schools. The model is to be implemented by various relevant departments until Departments of Family medicine are established

The impact of illness in patients with moderate to severe gastro-esophageal reflux disease

BACKGROUND: Gastro-esophageal reflux disease (GERD) is a common disease. It impairs health related quality of life (HRQL). However, the impact on utility scores and work productivity in patients with moderate to severe GERD is not well known. METHODS: We analyzed data from 217 patients with moderate to severe GERD (mean age 50, SD 13.7) across 17 Canadian centers. Patients completed three utility instruments – the standard gamble (SG), the feeling thermometer (FT), and the Health Utilities Index 3 (HUI 3) – and several HRQL instruments, including Quality of Life in Reflux and Dyspepsia (QOLRAD) and the Medical Outcomes Short Form-36 (SF-36). All patients received a proton pump inhibitor, esomeprazole 40 mg daily, for four to six weeks. RESULTS: The mean scores on a scale from 0 (dead) to 1 (full health) obtained for the FT, SG, and HUI 3 were 0.67 (95% CI, 0.64 to 0.70), 0.76 (95% CI, 0.75 to 0.80), and 0.80 (95% CI, 0.77 to 0.82) respectively. The mean scores on the SF-36 were lower than the previously reported Canadian and US general population mean scores and work productivity was impaired. CONCLUSION: GERD has significant impact on utility scores, HRQL, and work productivity in patients with moderate to severe disease. Furthermore, the FT and HUI 3 provide more valid measurements of HRQL in GERD than the SG. After treatment with esomeprazole, patients showed improved HRQL

Ethnic differences in SARS-CoV-2 vaccine hesitancy in United Kingdom healthcare workers: Results from the UK-REACH prospective nationwide cohort study

Background: In most countries, healthcare workers (HCWs) represent a priority group for vaccination against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) due to their elevated risk of COVID-19 and potential contribution to nosocomial SARS-CoV-2 transmission. Concerns have been raised that HCWs from ethnic minority groups are more likely to be vaccine hesitant (defined by the World Health Organisation as refusing or delaying a vaccination) than those of White ethnicity, but there are limited data on SARS-CoV-2 vaccine hesitancy and its predictors in UK HCWs. Methods: Nationwide prospective cohort study and qualitative study in a multi-ethnic cohort of clinical and non-clinical UK HCWs. We analysed ethnic differences in SARS-CoV-2 vaccine hesitancy adjusting for demographics, vaccine trust, and perceived risk of COVID-19. We explored reasons for hesitancy in qualitative data using a framework analysis. Findings: 11,584 HCWs were included in the cohort analysis. 23% (2704) reported vaccine hesitancy. Compared to White British HCWs (21.3% hesitant), HCWs from Black Caribbean (54.2%), Mixed White and Black Caribbean (38.1%), Black African (34.4%), Chinese (33.1%), Pakistani (30.4%), and White Other (28.7%) ethnic groups were significantly more likely to be hesitant. In adjusted analysis, Black Caribbean (aOR 3.37, 95% CI 2.11 - 5.37), Black African (aOR 2.05, 95% CI 1.49 - 2.82), White Other ethnic groups (aOR 1.48, 95% CI 1.19 - 1.84) were significantly more likely to be hesitant. Other independent predictors of hesitancy were younger age, female sex, higher score on a COVID-19 conspiracy beliefs scale, lower trust in employer, lack of influenza vaccine uptake in the previous season, previous COVID-19, and pregnancy. Qualitative data from 99 participants identified the following contributors to hesitancy: lack of trust in government and employers, safety concerns due to the speed of vaccine development, lack of ethnic diversity in vaccine studies, and confusing and conflicting information. Participants felt uptake in ethnic minority communities might be improved through inclusive communication, involving HCWs in the vaccine rollout, and promoting vaccination through trusted networks. Interpretation: Despite increased risk of COVID-19, HCWs from some ethnic minority groups are more likely to be vaccine hesitant than their White British colleagues. Strategies to build trust and dispel myths surrounding the COVID-19 vaccine in these communities are urgently required. Emphasis should be placed on the safety and benefit of SARS-CoV-2 vaccination in pregnancy and in those with previous COVID-19. Public health communications should be inclusive, non-stigmatising and utilise trusted networks