How to spot a statistical problem: advice for a non-statistical reviewer

Statistical analyses presented in general medical journals are becoming increasingly sophisticated. BMC Medicine relies on subject reviewers to indicate when a statistical review is required. We consider this policy and provide guidance on when to recommend a manuscript for statistical evaluation. Indicators for statistical review include insufficient detail in methods or results, some common statistical issues and interpretation not based on the presented evidence. Reviewers are required to ensure that the manuscript is methodologically sound and clearly written. Within that context, they are expected to provide constructive feedback and opinion on the statistical design, analysis, presentation and interpretation. If reviewers lack the appropriate background to positively confirm the appropriateness of any of the manuscript’s statistical aspects, they are encouraged to recommend it for expert statistical review

Stem cell transplantation in traumatic spinal cord injury:a systematic review and meta-analysis of animal studies

Spinal cord injury (SCI) is a devastating condition that causes substantial morbidity and mortality and for which no treatments are available. Stem cells offer some promise in the restoration of neurological function. We used systematic review, meta-analysis, and meta-regression to study the impact of stem cell biology and experimental design on motor and sensory outcomes following stem cell treatments in animal models of SCI. One hundred and fifty-six publications using 45 different stem cell preparations met our prespecified inclusion criteria. Only one publication used autologous stem cells. Overall, allogeneic stem cell treatment appears to improve both motor (effect size, 27.2%; 95% Confidence Interval [CI], 25.0%-29.4%; 312 comparisons in 5,628 animals) and sensory (effect size, 26.3%; 95% CI, 7.9%-44.7%; 23 comparisons in 473 animals) outcome. For sensory outcome, most heterogeneity between experiments was accounted for by facets of stem cell biology. Differentiation before implantation and intravenous route of delivery favoured better outcome. Stem cell implantation did not appear to improve sensory outcome in female animals and appeared to be enhanced by isoflurane anaesthesia. Biological plausibility was supported by the presence of a dose-response relationship. For motor outcome, facets of stem cell biology had little detectable effect. Instead most heterogeneity could be explained by the experimental modelling and the outcome measure used. The location of injury, method of injury induction, and presence of immunosuppression all had an impact. Reporting of measures to reduce bias was higher than has been seen in other neuroscience domains but were still suboptimal. Motor outcomes studies that did not report the blinded assessment of outcome gave inflated estimates of efficacy. Extensive recent preclinical literature suggests that stem-cell-based therapies may offer promise, however the impact of compromised internal validity and publication bias mean that efficacy is likely to be somewhat lower than reported here

Nine weeks of supplementation with a multi-nutrient product augments gains in lean mass, strength, and muscular performance in resistance trained men

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to compare the effects of supplementation with Gaspari Nutrition's SOmaxP Maximum Performance™ (SOmaxP) versus a comparator product (CP) containing an equal amount of creatine (4 g), carbohydrate (39 g maltodextrin), and protein (7 g whey protein hydrolysate) on muscular strength, muscular endurance, and body composition during nine weeks of intense resistance training.</p> <p>Methods</p> <p>Using a prospective, randomized, double-blind design, 20 healthy men (mean ± SD age, height, weight, % body fat: 22.9 ± 2.6 y, 178.4 ± 5.7 cm, 80.5 ± 6.6 kg, 16.6 ± 4.0%) were matched for age, body weight, resistance training history, bench press strength, bench press endurance, and percent body fat and then randomly assigned via the ABBA procedure to ingest 1/2 scoop (dissolved in 15 oz water) of SOmaxP or CP prior to, and another 1/2 scoop (dissolved in 15 oz water) during resistance exercise. Body composition (DEXA), muscular performance (1-RM bench press and repetitions to failure [RTF: 3 sets × baseline body weight, 60-sec rest between sets]), and clinical blood chemistries were measured at baseline and after nine weeks of supplementation and training. Subjects were required to maintain their normal dietary habits and follow a specific, progressive overload resistance training program (4-days/wk, upper body/lower body split) during the study. An intent-to-treat approach was used and data were analyzed via ANCOVA using baseline values as the covariate. Statistical significance was set <it>a priori </it>at p ≤ 0.05.</p> <p>Results</p> <p>When adjusted for initial differences, significant between group post-test means were noted in: 1-RM bench press (SOmaxP: 133.3 ± 1.3 kg [19.8% increase] vs. CP: 128.5 ± 1.3 kg [15.3% increase]; p < 0.019); lean mass (SOmaxP: 64.1 ± 0.4 kg [2.4% increase] vs. 62.8 ± 0.4 kg [0.27% increase], p < 0.049); RTF (SOmaxP: 33.3 ± 1.1 reps [44.8% increase] vs. 27.8 ± 1.1 reps [20.9% increase], p < 0.004); and fat mass (SOmaxP: 12.06 ± 0.53 kg [9.8% decrease] vs. 13.90 ± 0.53 kg [4.1% increase], p < 0.024). No statistically significant differences in vital signs (heart rate, systolic and diastolic blood pressures) or clinical blood chemistries were noted.</p> <p>Conclusions</p> <p>These data indicate that compared to CP, SOmaxP administration augments and increases gains in lean mass, bench press strength, and muscular performance during nine weeks of intense resistance training. Studies designed to confirm these results and clarify the molecular mechanisms by which SOmaxP exerts the observed salutary effects have begun. Both SOmaxP and the CP were well-tolerated, and no supplement safety issues were identified.</p

Using hospital discharge data for determining neonatal morbidity and mortality: a validation study

<p>Abstract</p> <p>Background</p> <p>Despite widespread use of neonatal hospital discharge data, there are few published reports on the accuracy of population health data with neonatal diagnostic or procedure codes. The aim of this study was to assess the accuracy of using routinely collected hospital discharge data in identifying neonatal morbidity during the birth admission compared with data from a statewide audit of selected neonatal intensive care (NICU) admissions.</p> <p>Methods</p> <p>Validation study of population-based linked hospital discharge/birth data against neonatal intensive care audit data from New South Wales, Australia for 2,432 babies admitted to NICUs, 1994–1996. Sensitivity, specificity and positive predictive values (PPV) with exact binomial confidence intervals were calculated for 12 diagnoses and 6 procedures.</p> <p>Results</p> <p>Sensitivities ranged from 37.0% for drainage of an air leak to 97.7% for very low birthweight, specificities all exceeded 85% and PPVs ranged from 70.9% to 100%. In-hospital mortality, low birthweight (≤1500 g), retinopathy of prematurity, respiratory distress syndrome, meconium aspiration, pneumonia, pulmonary hypertension, selected major anomalies, any mechanical ventilation (including CPAP), major surgery and surgery for patent ductus arteriosus or necrotizing enterocolitis were accurately identified with PPVs over 92%. Transient tachypnea of the newborn and drainage of an air leak had the lowest PPVs, 70.9% and 83.6% respectively.</p> <p>Conclusion</p> <p>Although under-ascertained, routinely collected hospital discharge data had high PPVs for most validated items and would be suitable for risk factor analyses of neonatal morbidity. Procedures tended to be more accurately recorded than diagnoses.</p

Comparing administrative and survey data for ascertaining cases of irritable bowel syndrome: a population-based investigation

<p>Abstract</p> <p>Background</p> <p>Administrative and survey data are two key data sources for population-based research about chronic disease. The objectives of this methodological paper are to: (1) estimate agreement between the two data sources for irritable bowel syndrome (IBS) and compare the results to those for inflammatory bowel disease (IBD); (2) compare the frequency of IBS-related diagnoses in administrative data for survey respondents with and without self-reported IBS, and (3) estimate IBS prevalence from both sources.</p> <p>Methods</p> <p>This retrospective cohort study used linked administrative and health survey data for 5,134 adults from the province of Manitoba, Canada. Diagnoses in hospital and physician administrative data were investigated for respondents with self-reported IBS, IBD, and no bowel disorder. Agreement between survey and administrative data was estimated using the κ statistic. The χ²statistic tested the association between the frequency of IBS-related diagnoses and self-reported IBS. Crude, sex-specific, and age-specific IBS prevalence estimates were calculated from both sources.</p> <p>Results</p> <p>Overall, 3.0% of the cohort had self-reported IBS, 0.8% had self-reported IBD, and 95.3% reported no bowel disorder. Agreement was poor to fair for IBS and substantially higher for IBD. The most frequent IBS-related diagnoses among the cohort were anxiety disorders (34.4%), symptoms of the abdomen and pelvis (26.9%), and diverticulitis of the intestine (10.6%). Crude IBS prevalence estimates from both sources were lower than those reported previously.</p> <p>Conclusions</p> <p>Poor agreement between administrative and survey data for IBS may account for differences in the results of health services and outcomes research using these sources. Further research is needed to identify the optimal method(s) to ascertain IBS cases in both data sources.</p

Food allergy knowledge, attitudes and beliefs: Focus groups of parents, physicians and the general public

<p>Abstract</p> <p>Background</p> <p>Food allergy prevalence is increasing in US children. Presently, the primary means of preventing potentially fatal reactions are avoidance of allergens, prompt recognition of food allergy reactions, and knowledge about food allergy reaction treatments. Focus groups were held as a preliminary step in the development of validated survey instruments to assess food allergy knowledge, attitudes, and beliefs of parents, physicians, and the general public.</p> <p>Methods</p> <p>Eight focus groups were conducted between January and July of 2006 in the Chicago area with parents of children with food allergy (3 groups), physicians (3 groups), and the general public (2 groups). A constant comparative method was used to identify the emerging themes which were then grouped into key domains of food allergy knowledge, attitudes, and beliefs.</p> <p>Results</p> <p>Parents of children with food allergy had solid fundamental knowledge but had concerns about primary care physicians' knowledge of food allergy, diagnostic approaches, and treatment practices. The considerable impact of children's food allergies on familial quality of life was articulated. Physicians had good basic knowledge of food allergy but differed in their approach to diagnosis and advice about starting solids and breastfeeding. The general public had wide variation in knowledge about food allergy with many misconceptions of key concepts related to prevalence, definition, and triggers of food allergy.</p> <p>Conclusion</p> <p>Appreciable food allergy knowledge gaps exist, especially among physicians and the general public. The quality of life for children with food allergy and their families is significantly affected.</p

mRNA vaccine boosting enhances antibody responses against SARS-CoV-2 Omicron variant in individuals with antibody deficiency syndromes

Individuals with primary antibody deficiency (PAD) syndromes have poor humoral immune responses requiring immunoglobulin replacement therapy. We followed individuals with PAD after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination by evaluating their immunoglobulin replacement products and serum for anti-spike binding, Fcγ receptor (FcγR) binding, and neutralizing activities. The immunoglobulin replacement products tested have low anti-spike and receptor-binding domain (RBD) titers and neutralizing activity. In coronavirus disease 2019 (COVID-19)-naive individuals with PAD, anti-spike and RBD titers increase after mRNA vaccination but wane by 90 days. Those vaccinated after SARS-CoV-2 infection develop higher and more sustained responses comparable with healthy donors. Most vaccinated individuals with PAD have serum-neutralizing antibody titers above an estimated correlate of protection against ancestral SARS-CoV-2 and Delta virus but not against Omicron virus, although this is improved by boosting. Thus, some immunoglobulin replacement products likely have limited protective activity, and immunization and boosting of individuals with PAD with mRNA vaccines should confer at least short-term immunity against SARS-CoV-2 variants, including Omicron

Immunoglobulin replacement products protect against SARS-CoV-2 infection in vivo despite poor neutralizing activity

Immunoglobulin (IG) replacement products are used routinely in patients with immune deficiency and other immune dysregulation disorders who have poor responses to vaccination and require passive immunity conferred by commercial antibody products. The binding, neutralizing, and protective activity of intravenously administered IG against SARS-CoV-2 emerging variants remains unknown. Here, we tested 198 different IG products manufactured from December 2019 to August 2022. We show that prepandemic IG had no appreciable cross-reactivity or neutralizing activity against SARS-CoV-2. Anti-spike antibody titers and neutralizing activity against SARS-CoV-2 WA1/2020 D614G increased gradually after the pandemic started and reached levels comparable to vaccinated healthy donors 18 months after the diagnosis of the first COVID-19 case in the United States in January 2020. The average time between production to infusion of IG products was 8 months, which resulted in poor neutralization of the variant strain circulating at the time of infusion. Despite limited neutralizing activity, IG prophylaxis with clinically relevant dosing protected susceptible K18-hACE2-transgenic mice against clinical disease, lung infection, and lung inflammation caused by the XBB.1.5 Omicron variant. Moreover, following IG prophylaxis, levels of XBB.1.5 infection in the lung were higher in FcγR-KO mice than in WT mice. Thus, IG replacement products with poor neutralizing activity against evolving SARS-CoV-2 variants likely confer protection to patients with immune deficiency disorders through Fc effector function mechanisms

SARS-CoV-2 booster vaccination rescues attenuated IgG1 memory B cell response in primary antibody deficiency patients

BACKGROUND: Although SARS-CoV-2 vaccines have proven effective in eliciting a protective immune response in healthy individuals, their ability to induce a durable immune response in immunocompromised individuals remains poorly understood. Primary antibody deficiency (PAD) syndromes are among the most common primary immunodeficiency disorders in adults and are characterized by hypogammaglobulinemia and impaired ability to mount robust antibody responses following infection or vaccination. METHODS: Here, we present an analysis of both the B and T cell response in a prospective cohort of 30 individuals with PAD up to 150 days following initial COVID-19 vaccination and 150 days post mRNA booster vaccination. RESULTS: After the primary vaccination series, many of the individuals with PAD syndromes mounted SARS-CoV-2 specific memory B and CD4 CONCLUSION: Together, these data indicate that SARS-CoV-2 vaccines elicit memory B and T cells in most PAD patients and highlights the importance of booster vaccination in immunodeficient individuals