World Health Organization Registry Research Articles

Vitamin D as an adjunct to antibiotics for the treatment of acute childhood pneumonia.

Children with acute pneumonia may be vitamin D deficient. Clinical trials have found that prophylactic vitamin D supplementation decreases children's risk of developing pneumonia. Data on the therapeutic effects of vitamin D in acute childhood pneumonia are limited. This is an update of a Cochrane Review first published in 2018. To evaluate the efficacy and safety of vitamin D supplementation as an adjunct to antibiotics for the treatment of acute childhood pneumonia. We searched CENTRAL, MEDLINE, Embase, and two trial registries on 28 December 2021. We applied no language restrictions. We included randomised controlled trials (RCTs) that compared vitamin D supplementation with placebo in children (aged one month to five years) hospitalised with acute community-acquired pneumonia, as defined by the World Health Organization (WHO) acute respiratory infection guidelines. For this update, we reappraised eligible trials according to research integrity criteria, excluding RCTs published from April 2018 that were not prospectively registered in a trials registry according to WHO or Clinical Trials Registry - India (CTRI) guidelines (it was not mandatory to register clinical trials in India before April 2018). Two review authors independently assessed trials for inclusion and extracted data. For dichotomous data, we extracted the number of participants experiencing the outcome and the total number of participants in each treatment group. For continuous data, we used the arithmetic mean and standard deviation (SD) for each treatment group together with number of participants in each group. We used standard methodological procedures expected by Cochrane. In this update, we included three new trials involving 468 children, bringing the total number of trials to seven, with 1601 children (631 with pneumonia and 970 with severe or very severe pneumonia). We categorised three previously included studies and three new studies as 'awaiting classification' based on the research integrity screen. Five trials used a single bolus dose of vitamin D (300,000 IU in one trial and 100,000 IU in four trials) at the onset of illness or within 24 hours of hospital admission; one used a daily dose of oral vitamin D (1000 IU for children aged up to one year and 2000 IU for children aged over one year) for five days; and one used variable doses (on day 1, 20,000 IU in children younger than six months, 50,000 IU in children aged six to 12 months, and 100,000 IU in children aged 13 to 59 months; followed by 10,000 IU/day for four days or until discharge). Three trials performed microbiological diagnosis of pneumonia, radiological diagnosis of pneumonia, or both. Vitamin D probably has little or no effect on the time to resolution of acute illness (mean difference (MD) -1.28 hours, 95% confidence interval (CI) -5.47 to 2.91; 5 trials, 1188 children; moderate-certainty evidence). We do not know if vitamin D has an effect on the duration of hospitalisation (MD 4.96 hours, 95% CI -8.28 to 18.21; 5 trials, 1023 children; very low-certainty evidence). We do not know if vitamin D has an effect on mortality rate (risk ratio (RR) 0.69, 95% CI 0.44 to 1.07; 3 trials, 584 children; low-certainty evidence). The trials reported no major adverse events. According to GRADE criteria, the evidence was of very low-to-moderate certainty for all outcomes, owing to serious trial limitations, inconsistency, indirectness, and imprecision. Three trials received funding: one from the New Zealand Aid Corporation, one from an institutional grant, and one from multigovernment organisations (Bangladesh, Sweden, and UK). The remaining four trials were unfunded. Based on the available evidence, we are uncertain whether vitamin D supplementation has important effects on outcomes of acute pneumonia when used as an adjunct to antibiotics. The trials reported no major adverse events. Uncertainty in the evidence is due to imprecision, risk of bias, inconsistency, and indirectness.

Smartphone Psychological Therapy During COVID-19: A Study on the Effectiveness of Five Popular Mental Health Apps for Anxiety and Depression

The aims of this study were to examine the effectiveness of a range of smartphone apps for managing symptoms of anxiety and depression and to assess the utility of a single-case research design for enhancing the evidence base for this mode of treatment delivery. The study was serendipitously impacted by the COVID-19 pandemic, which allowed for effectiveness to be additionally observed in the context of significant community distress. A pilot study was initially conducted using theSuperBetter app to evaluate the proposed methodology, which proved successful with the four finishing participants. In the main study, 39 participants commenced (27 females and 12 males,MAge = 34.04 years,SD = 12.20), with 29 finishing the intervention phase and completing post-intervention measures. At 6-month follow-up, a further three participants could not be contacted. This study used a digitally enhanced, multiple baseline across-individuals single-case research design. Participants were randomly assigned to the following apps:SuperBetter (n = 8),Smiling Mind (n = 7),MoodMission (n = 8),MindShift (n = 8), andDestressify (n = 8). Symptomatology and life functioning were measured at five different time points: pre-baseline/screening, baseline, intervention, 3-week post-intervention, and 6-month follow-up. Detailed individual perceptions and subjective ratings of the apps were also obtained from participants following the study’s completion. Data were analyzed using visual inspection, time-series analysis, and methods of statistical and clinical significance. Positive results were observed for all apps. Overall, more favorable outcomes were achieved by younger participants, those concurrently undertaking psychotherapy and/or psychotropic medication, those with anxiety and mixed anxiety and depression rather than stand-alone depression, and those with a shorter history of mental illness. Outcomes were generally maintained at 6-month follow-up. It was concluded that a diverse range of evidence-based therapies offered via apps can be effective in managing mental health and improving life functioning even during times of significant global unrest and, like all psychotherapies, are influenced by client features. Additionally, this single-case research design is a low-cost/high value means of assessing the effectiveness of mental health apps.Clinical Trial Registration: The study is registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR), which is a primary registry in the World Health Organization Registry Network, registration number ACTRN12619001302145p (http://www.ANZCTR.org.au/ACTRN12619001302145p.aspx).

Design and implementation of an intelligent monitoring system for household added salt consumption in China based on a real-world study: a randomized controlled trial

BackgroundA high intake of salt is a major risk factor for cardiovascular diseases. Despite decades of effort to reduce salt consumption, the salt intake in China is still considerably above the recommended level. Thus, this study aims to design and implement an intelligent household added salt monitoring system (SALTCHECKER) to monitor and control added salt consumption in Chinese households.MethodsA randomized controlled trial will be conducted among households to test the effect of a SALTCHECKER in Chongqing, China. The test modalities are the SALTCHECKER (with a smart salt checker and a salt-limiting WeChat mini programme) compared to a salt checker (with only a weighing function). The effectiveness of the system will be investigated by assessing the daily added salt intake of each household member and the salt consumption-related knowledge, attitude and practice (KAP) of the household’s main cook. Assessments will be performed at baseline and at 3 and 6 months.DiscussionThis study will be the first to explore the effect of the household added salt monitoring system on the reduction in salt intake in households. If the intelligent monitoring system is found to be effective in limiting household added salt consumption, it could provide scientific evidence on reducing salt consumption and preventing salt-related chronic diseases.Trial registrationChinese clinical trial registry (Primary registry in the World Health Organization registry network): ChiCTR1800018586. Date of registration: September 25, 2018.

Estimation of Absolute Risk of Colorectal Cancer Based on Healthy Lifestyle, Genetic Risk, and Colonoscopy Status in a Population-Based Study

Estimates of absolute risk of colorectal cancer (CRC) are needed to facilitate communication and better inform the public about the potentials and limits of cancer prevention. Using data from a large population-based case-control study in Germany (Darmkrebs: Chancen der Verhütung durch Screening [DACHS] study, which began in 2003) and population registry data, we calculated 30-year absolute risk estimates for development of CRC based on a healthy lifestyle score (derived from 5 modifiable lifestyle factors: smoking, alcohol consumption, diet, physical activity, and body fatness), a polygenic risk score (based on 90 single-nucleotide polymorphisms), and colonoscopy history. We analyzed data from 4220 patients with CRC and 3338 individuals without CRC. Adherence to a healthy lifestyle and colonoscopy in the preceding 10 years were associated with a reduced relative risk of CRC in men and women. We observed a higher CRC risk in participants with high or intermediate genetic risk scores. For 50-year-old men and women without a colonoscopy, the absolute risk of CRC varied according to the polygenic risk score and the healthy lifestyle score (men, 3.5%-13.4%; women, 2.5%-10.6%). For 50-year-old men and women with a colonoscopy, the absolute risk of developing CRC was much lower but still varied according to the polygenic risk score and the healthy lifestyle score (men, 1.2%-4.8%; women, 0.9%-4.2%). Among all risk factor profiles, the 30-year absolute risk estimates consistently decreased with adherence to a healthy lifestyle. In a population-based study, we found that a colonoscopy can drastically reduce the absolute risk of CRC and that the genetically predetermined risk of CRC can be further reduced by adherence to a healthy lifestyle. Our results show the magnitude of CRC prevention possible through colonoscopy and lifestyle at a predefined genetic risk. This observational study has been registered in the German Clinical Trials Register (DRKS00011793), which is a primary registry in the World Health Organization Registry Network.

LO42: Is point-of-care ultrasound a reliable predictor of outcome during atraumatic, non-shockable cardiac arrest? A systematic review and meta-analysis

Introduction: Point-of-Care Ultrasound (PoCUS) is being increasingly utilized during cardiac arrests for prognosis. Following the publication of recent studies, the goal of this study was to systematically review and analyze the literature to evaluate the accuracy of PoCUS in predicting return of spontaneous circulation (ROSC), survival to hospital admission (SHA), and survival to hospital discharge (SHD) in adult patients with non-traumatic, non- shockable out- of-hospital or emergency department cardiac arrest. Methods: A systematic review and meta-analysis was completed. A search of Medline, EMBASE, Cochrane, CINAHL, ClinicalTrials.gov and the World Health Organization Registry was completed from 1974 until August 24th 2018. Adult randomized controlled trials and observational studies were included. The QUADAS-2 tool was applied by two independent reviewers. Data analysis was completed according to PRISMA guidelines and with a random effects model for the meta-analysis. Heterogeneity was assessed using I-squared statistics. Results: Ten studies (1,485 participants) were included. Cardiac activity on PoCUS had a pooled sensitivity of 59.9% (95% confidence interval 36.5%-79.4%) and specificity of 91.5% (80.8%-96.5%) for ROSC; 74.7% (58.3%-86.2%) and 80.5% (71.7%-87.4%) for SHA; and 69.4% (45.5%-86.0%) and 74.6% (59.8%-85.3%) for SHD. The sensitivity of cardiac activity on PoCUS for predicting ROSC was 24.7%(6.8%-59.4%) in the asystole subgroup compared with 77% (59.4%-88.5%) within the PEA subgroup. Cardiac activity on PoCUS, compared to an absence had an odd ratio of 15.9 (5.9-42.5) for ROSC, 9.8 (4.9-19.4) for SHA and 5.7 (2.1-15.6) for SHD. Positive likelihood ratio (LR) was 6.65 (3.16-14.0) and negative LR was 0.27 (0.12-0.61) for ROSC. Conclusion: Cardiac activity on PoCUS was associated with improved odds for ROSC, SHA, and SHD among adults with non-traumatic asystole and PEA. We report lower sensitivity and higher negative likelihood ratio, but with greater heterogeneity compared to previous systematic reviews. PoCUS may provide valuable information in the management of non-traumatic PEA or asystole, but should not be viewed as the sole predictor in determining outcomes in these patients.

On-demand intermittent beclomethasone is effective for mild asthma in Brazil

BackgroundDaily inhaled corticosteroids are widely recommended for mild persistent asthma. This study aimed to assess the efficacy of the intermittent use of beclomethasone as an alternative treatment for mild persistent asthma.MethodsIn this 16-week trial, children aged 6–18 years were evaluated. Subjects in the continuous treatment arm of the study received 500 μg/day of beclomethasone, whereas the intermittent ones were given 1000 μg/day (250 μg every 6 h) in combination with albuterol for 7 days upon exacerbations or worsening of symptoms. Primary outcome (i.e., treatment failure) was the occurrence of any asthma exacerbation requiring prednisone, and co-secondary outcomes were the mean/median differences for both, (1) the pre-bronchodilator FEV1 (% predicted) and (2) asthma control test (ACT/cACT) scores, from randomization to the last follow-up visit, and beclomethasone and albuterol consumption.ResultsNinety-four subjects from each treatment arm were included. They were comparable regarding all baseline characteristics; prednisone was used by 10 (10.6%) and 7 (7.4%) patients, respectively (95% CI − 6.1 to 12.6%, for the difference; p = 0.47). Statistical analysis showed no statistically significant differences with respect to both FEV1 (p = 0.39) and ACT/cACT scores (p = 0.38). As assessed through canister weighting, children used from 0.5 to 0.7 and from 1.6 to 1.8 puffs per day of beclomethasone in the intermittent and continuous regimens, respectively. Regarding albuterol, received 0.3–0.4 (intermittent) and 0.1–0.2 (continuous) inhalations per day. There were no relevant clinical or functional differences between the two treatment regimens.ConclusionClinicians might consider intermittent inhaled steroid therapy as a therapeutic regimen for mild persistent asthma.Trial registration The Portuguese and English versions of the study protocol were submitted, approved, and registered in the Brazilian Network Platform for Clinical Trials (http://www.ensaiosclinicos.gov.br) under the primary identifier number “RBR-3gbyhk”. This platform is part of the Primary Registries in the World Health Organization Registry Network, where the trial is registered under the following Universal Trial Number: 1111-1149-4774

Prophylactic antibiotics before cord clamping in cesarean delivery: a systematic review.

The number of clinical trials investigating the optimal timing of prophylactic antibiotics in cesarean section has increased rapidly over the last few years. We conducted a systematic review to inform up-to-date evidence-based guidelines to prevent postpartum infectious morbidity in the mother and rule out any safety issues related to antepartum antibiotic exposure in infants. Four bibliographic databases were searched for published reports of trials. Ongoing or unpublished studies were searched in Clinicaltrials.gov and the World Health Organization registry platform. Randomized controlled trials comparing antibiotic prophylaxis before and after cord clamping in cesarean section were eligible. Maternal and neonatal outcomes were assessed, and certainty of evidence graded. In total, 18 randomized controlled trials met the inclusion criteria. Those women who received antibiotics preoperatively were 28% (relative risk 0.72, 95% confidence interval 0.56-0.92, nine studies, 4342 women, high quality of evidence) less likely to show infectious morbidity as compared with those who received antibiotics after cord clamping. The risk of endomyometritis and/or endometritis was reduced by 43% (relative risk 0.57, 95% confidence interval 0.40-0.82, 13 studies, 6250 women, high quality of evidence) and the risk of wound infection by 38% (relative risk 0.62, 95% confidence interval 0.47-0.81, 14 studies, 6450 women, high quality of evidence) in those who received antibiotics preoperatively as compared to those who received antibiotics after cord clamping. For other maternal infections no significant differences were identified. The risk for neonatal outcomes, such as deaths attributed to infection, sepsis, neonatal antibiotic treatment, intensive care unit admission or antibiotic-related adverse events, was not found to be different, either clinically or statistically, when antibiotics were given before or after cord clamping (moderate to low quality of evidence). The evidence in favor of prophylactic antibiotic administration before, in comparison with after, cord clamping for major maternal infections was of high quality, meaning that further research would be unlikely to change the confidence in these findings. However, we recommend additional research reflecting the precision of the effect estimates for neonatal outcomes.

Prolonged Excretion of Poliovirus among Individuals with Primary Immunodeficiency Disorder: An Analysis of the World Health Organization Registry.

Individuals with primary immunodeficiency disorder may excrete poliovirus for extended periods and will constitute the only remaining reservoir of virus after eradication and withdrawal of oral poliovirus vaccine. Here, we analyzed the epidemiology of prolonged and chronic immunodeficiency-related vaccine-derived poliovirus cases in a registry maintained by the World Health Organization, to identify risk factors and determine the length of excretion. Between 1962 and 2016, there were 101 cases, with 94/101 (93%) prolonged excretors and 7/101 (7%) chronic excretors. We documented an increase in incidence in recent decades, with a shift toward middle-income countries, and a predominance of poliovirus type 2 in 73/101 (72%) cases. The median length of excretion was 1.3 years (95% confidence interval: 1.0, 1.4) and 90% of individuals stopped excreting after 3.7 years. Common variable immunodeficiency syndrome and residence in high-income countries were risk factors for long-term excretion. The changing epidemiology of cases, manifested by the greater incidence in recent decades and a shift to from high- to middle-income countries, highlights the expanding risk of poliovirus transmission after oral poliovirus vaccine cessation. To better quantify and reduce this risk, more sensitive surveillance and effective antiviral therapies are needed.

Characteristics of clinical trial websites: information distribution between ClinicalTrials.gov and 13 primary registries in the WHO registry network

BackgroundIt is well known that information about clinical trials is not easily accessible by the public. In Japan, clinical trial information can be accessed by the general public through online registries; however, many people find these registries difficult to use. To improve current clinical trial registries, we propose that combining them with clinical information phrased in lay terms would be beneficial to other interested professionals such as journalists and clinicians, as well as the general public. Therefore, this study aimed to examine the current pattern of distribution of clinical trial information from the primary World Health Organization (WHO) registries. Based on the results of this assessment, we then aimed to build and evaluate a prototype of the Japan Primary Registries Network (JPRN) portal that would be easily accessible to patients and the public, while still remaining useful for professionals.MethodsWe assessed a total of 14 primary clinical trial registries listed on the WHO International Clinical Trials Registry Platform between January and February 2013. Website content was accessed and checked against a series of items that looked at usability, communication, design and accessibility of the sites. We excluded registries that were not active or were not on the approved WHO registry list at the time of our assessment. We also examined only the English versions of the websites as native-language registries may offer more functionality or different content than the English version of the same website.ResultsAll registries examined had a function allowing users to search the registry data and that displayed the related information from the search, including the clinical trial registration data. However, few websites were found to be user-friendly, and there was little integration with social media.ConclusionsWe confirmed that there are few websites providing useful clinical trial information to patients and their families. However, information gleaned from some of the more advanced online registries could be used to improve the content and functionality of the JPRN portal.

The Importance and Necessity of Establishing Technical Specifications for the Registration of Traditional Chinese Medicine Clinical Studies

Dear Editor: Registration of clinical trials can prevent bias and make their reporting transparent, thus also improving their quality. As an illustration, JAMA, New England Journal of Medicine, and The Lancet stipulate that researchers must register their clinical trials before they submit their articles. This is also supported by the World Health Organization (WHO) and is written in the declaration of Helsinki. We propose that registration provides an opportunity for Traditional Chinese Medicine (TCM) to solve some of the current problems in TCM clinical studies. As the number of TCM studies has increased greatly in recent years, their quality has been the focus of researchers' attention, with the finding that there is a large gap between the quantity and quality of TCM clinical studies. In the evaluation of 1452 randomized controlled trials (RCTs) of TCM, published between 1995 and 2005, it was reported that 103 (7.3%) had a correct randomization method and only 9 (0.6%) conformed to more than 50% of the items of the Consolidated Standards of Reporting Trials (CONSORT).1 Another report, based on searching the Chinese biomedical database and the Cochrane library, found that only 100 (3%) of 31,590 RCTs had appropriate randomizing, concealing, and blinding.2 Evidence-based medicine was introduced to TCM more than 20 years ago, and the quantity of systematic reviews has steadily increased. However, almost all systematic reviews conclude that there is insufficient evidence to draw conclusions and the studies are of poor quality. Similarly, in Chinese journals it has been found that international standards for methodological descriptions are not being met.3 Therefore, it is necessary when conducting RCTs for attention to be paid to improve the quality. In order to explore study protocols, we collected TCM clinical studies registered in primary registries in the WHO registry network and in ClinicalTrials.gov of the U.S. National Institutes of Health. Several problems were identified. Firstly, all these registers are designed for Western medicine clinical studies. However, such designs cannot accommodate TCM's theoretical system, which influences diagnosis and treatments. For example, treatment principles, TCM syndrome types, types of intervention (acupuncture, decoction, parenteral administration of medicine, Chinese preformulated medicine combinations), and TCM-specific outcome evaluation are all essential elements of TCM practice but cannot be included in the present format. Secondly, and most importantly, as yet no standard nomenclature exists for the registration of TCM clinical studies. This is particularly important for the correct identification of plant substances but also to understand concepts such as yin, yang, etc. In addition, we found examples of trials registered with ClinicalTrials.gov that after completion did not present the results and lacked details about the intervention. Furthermore, some content mentioned in protocols or registries differed from that which was finally published (e.g., NCT00741936). Currently there are only two internationally recognized reporting guidelines specific to TCM: CONSORT-TCM and Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA). Therefore, in order to prevent bias and promote transparency in TCM clinical studies, we propose, pending expert consensus on their final form, the following extensions to trial registers, such as ClinicalTrials.gov: • TCM studies should comply with current international standards and clinical study registration rules. • Additional items should be included: Specific details of interventions used, TCM treatment principles, and syndrome differentiation, TCM-specific outcome measures for symptoms and syndromes (including symptoms scores and quality-of-life measures). • Systematic analysis should be done of study registration details compared to postcompletion publications. As TCM clinical studies become more established within international medicine research, their scientific standard needs further improvements. These proposals to alterations in clinical study registers will enhance the credibility and reliability of evidence for TCM.

Law Ensures Public Access to Clinical Trial Disclosures

Law Ensures Public Access to Clinical Trial Disclosures

International Push Under Way To Improve Drug-Trials Data

International Push Under Way To Improve Drug-Trials Data