Tag: pubmed

BMJ Evid Based Med. 2021 Sep 23:bmjebm-2020-111603. doi: 10.1136/bmjebm-2020-111603. Online ahead of print.

ABSTRACT

Commonly accepted statistical advice dictates that large-sample size and highly powered clinical trials generate more reliable evidence than trials with smaller sample sizes. This advice is generally sound: treatment effect estimates from larger trials tend to be more accurate, as witnessed by tighter confidence intervals in addition to reduced publication biases. Consider then two clinical trials testing the same treatment which result in the same p values, the trials being identical apart from differences in sample size. Assuming statistical significance, one might at first suspect that the larger trial offers stronger evidence that the treatment in question is truly effective. Yet, often precisely the opposite will be true. Here, we illustrate and explain this somewhat counterintuitive result and suggest some ramifications regarding interpretation and analysis of clinical trial results.

PMID:34556541 | DOI:10.1136/bmjebm-2020-111603

Thorax. 2021 Sep 23:thoraxjnl-2021-217594. doi: 10.1136/thoraxjnl-2021-217594. Online ahead of print.

ABSTRACT

INTRODUCTION: Recurrent pulmonary exacerbations lead to progressive lung damage in cystic fibrosis (CF). Inhaled medications (mucoactive agents and antibiotics) help prevent exacerbations, but objectively measured adherence is low. We investigated whether a multi-component (complex) self-management intervention to support adherence would reduce exacerbation rates over 12 months.

METHODS: Between October 2017 and May 2018, adults with CF (aged ≥16 years; 19 UK centres) were randomised to the intervention (data-logging nebulisers, a digital platform and behavioural change sessions with trained clinical interventionists) or usual care (data-logging nebulisers). Outcomes included pulmonary exacerbations (primary outcome), objectively measured adherence, body mass index (BMI), lung function (FEV₁) and Cystic Fibrosis Questionnaire-Revised (CFQ-R). Analyses were by intent to treat over 12 months.

RESULTS: Among intervention (n=304) and usual care (n=303) participants (51% female, median age 31 years), 88% completed 12-month follow-up. Mean exacerbation rate was 1.63/year with intervention and 1.77/year with usual care (adjusted ratio 0.96; 95% CI 0.83 to 1.12; p=0.64). Adjusted mean differences (95% CI) were in favour of the intervention versus usual care for objectively measured adherence (9.5% (8.6% to 10.4%)) and BMI (0.3 (0.1 to 0.6) kg/m²), with no difference for %FEV₁ (1.4 (-0.2 to 3.0)). Seven CFQ-R subscales showed no between-group difference, but treatment burden reduced for the intervention (3.9 (1.2 to 6.7) points). No intervention-related serious adverse events occurred.

CONCLUSIONS: While pulmonary exacerbations and FEV₁ did not show statistically significant differences, the intervention achieved higher objectively measured adherence versus usual care. The adherence difference might be inadequate to influence exacerbations, though higher BMI and lower perceived CF treatment burden were observed.

PMID:34556552 | DOI:10.1136/thoraxjnl-2021-217594

BMJ Evid Based Med. 2021 Sep 23:bmjebm-2021-111743. doi: 10.1136/bmjebm-2021-111743. Online ahead of print.

ABSTRACT

Survival analysis is routinely used to assess differences between groups in relapse prevention and treatment discontinuation studies involving people with long-term psychiatric conditions. The actual outcome in survival analysis is ‘time to event’, yet, in the mental health field, there has been little consideration of whether a temporary delay to relapse is clinically relevant in a condition that can last for decades. Moreover, in psychiatric drug trials, a pattern of elevated early relapses following randomisation to placebo or no treatment is common. This may be the result of the withdrawal of previous treatment leading to physiological withdrawal effects, which may be mistaken for relapse, or genuine relapse precipitated by the process of withdrawal. Such withdrawal effects typically produce converging survival curves eventually. They inevitably lead to differences in time to relapse, even when there is little or no difference in the cumulative risk of relapse at final follow-up. Therefore, statistical tests based on survival analyses can be misleading because they obscure these withdrawal effects. We illustrate these difficulties in a trial of antipsychotic reduction versus maintenance, and a trial of prophylactic esketamine in people with treatment-resistant depression. Both illustrate withdrawal-related effects that underline the importance of long-term follow-up and question the use of tests based on time to event. Further discussion of the most relevant outcome and appropriate approach to analysis, and research on patient and carer preferences is important to inform the design of future trials and interpretation of existing ones.

PMID:34556539 | DOI:10.1136/bmjebm-2021-111743

J Nucl Med. 2021 Sep 23:jnumed.121.262685. doi: 10.2967/jnumed.121.262685. Online ahead of print.

ABSTRACT

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are 4-repeat tauopathies with overlapping, but also morphologically distinct tau immunoreactive lesions that vary in count by brain region. ¹⁸F-flortaucipir positron emission tomography uptake has been reported to correlate with overall tau burden, and in one CBD case to have greater affinity to threads than tangles. We determine whether ¹⁸F-flortaucipir uptake is associated with histologic lesion type in 4-repeat tauopathies. Methods: We performed semi-quantitative regional lesion counts on pretangles/neurofibrillary tangles, threads, oligodendroglial coiled bodies, tufted astrocytes, and astrocytic plaques in 29 autopsied 4-repeat tauopathies (PSP = 16; CBD=13). Regression models were used for statistical analyses. Results: ¹⁸F-flortaucipir uptake marginally correlated with threads in the precentral cortex (P = 0.04) and with astrocytic lesions in the red nucleus (P = 0.05). Conclusion: The findings do not support ¹⁸F-flortaucipir having differential affinity to any 4-repeat tau lesion type.

PMID:34556525 | DOI:10.2967/jnumed.121.262685

Hosp Pediatr. 2021 Sep 23:hpeds.2020-003103. doi: 10.1542/hpeds.2020-003103. Online ahead of print.

ABSTRACT

OBJECTIVES: Insulin is a high-risk medication, and its dosing depends on the individualized clinical and nutritional needs of each patient. Our hospital implemented an insulin dose calculator (IDC) imbedded in the electronic medical record with the goal of decreasing average wait times in inpatient insulin ordering and administration. In this study, we evaluated whether implementation of an IDC decreased the average wait time for insulin administration for hospitalized pediatric patients.

METHODS: This pre- and postintervention cohort study measured wait times between point-of-care glucose testing and insulin administration. Patients admitted to the inpatient pediatric services who were treated with subcutaneous insulin during the study period were included. Additionally, nurses completed satisfaction surveys on the insulin administration process at our hospital pre- and post-IDC implementation. Descriptive statistics, χ², Fisher’s exact test, and Student t tests were used to compare groups. Statistical process control charts were used to analyze data trends.

RESULTS: The preintervention cohort included 79 insulin doses for admitted pediatric patients. The postimplementation cohort included 128 insulin doses ordered via the IDC. Post-IDC implementation, the average wait time between point-of-care glucose testing and insulin administration decreased from 37 to 25 minutes (P < .05). The statistical process control chart revealed a 5-month run below the established mean after implementation of the IDC. Before IDC implementation, 15.6% of nurses expressed satisfaction in the insulin-dosing process compared with 69.2% postimplementation (P < .05).

CONCLUSIONS: Implementation of an IDC reduced the average wait time in ordering and administration of rapid-acting insulin and improved nursing satisfaction with the process.

PMID:34556536 | DOI:10.1542/hpeds.2020-003103

BMJ Open. 2021 Sep 23;11(9):e052843. doi: 10.1136/bmjopen-2021-052843.

ABSTRACT

OBJECTIVES: Response rates to physician surveys are typically low. The objective of this study was to determine the effect of a prenotification letter on the response rate of a postal survey of emergency physicians.

DESIGN: This was a substudy of a national, cross-sectional postal survey sent to emergency physicians in Canada. We randomised participants to either receive a postal prenotification letter prior to the survey, or to no prenotification letter.

PARTICIPANTS: A random sample of 500 emergency physicians in Canada. Participants were selected from the Canadian Medical Directory, a national medical directory which lists more than 99% of practising physicians in Canada.

INTERVENTIONS: Using computer-generated randomisation, physicians were randomised in a concealed fashion to receive a prenotification letter approximately 1 week prior to the survey, or to not receive a prenotification letter. All physicians received an unconditional incentive of a $3 coffee card with the survey instrument. In both groups, non-respondents were sent reminder surveys approximately every 14 days and a special contact using Xpresspost during the final contact attempt.

OUTCOME: The primary outcome was the survey response rate.

RESULTS: 201 of 447 eligible physicians returned the survey (45.0%). Of 231 eligible physicians contacted in the prenotification group, 80 (34.6%) returned the survey and among 237 eligible physicians contacted in the no-prenotification group, 121 (51.1%) returned the survey (absolute difference in proportions 16.5%, 95% CI 2.5 to 30.5, p=0.01).

CONCLUSION: Inclusion of a prenotification letter resulted in a lower response rate in this postal survey of emergency physicians. Given the added costs, time and effort required to send a prenotification letter, this study suggests that it may be more effective to omit the prenotification letter in physician postal surveys.

PMID:34556517 | DOI:10.1136/bmjopen-2021-052843

BMJ Open. 2021 Sep 23;11(9):e049199. doi: 10.1136/bmjopen-2021-049199.

ABSTRACT

OBJECTIVES: To determine the association between participation of patients with breast cancer and patients with gynaecological cancer in their own multidisciplinary tumour conference (MTC) and their information needs with regard to their disease and treatment options.

METHODS: This is a prospective observational study that took place at six breast cancer and gynaecological cancer centres in North Rhine-Westphalia, Germany. Patient inclusion criteria included a minimum age of 18 years and at least one diagnosis of breast cancer or gynaecological cancer. Three surveys were administered. T0 (shortly before MTC), T1 (directly after MTC) and T2 (4 weeks after MTC). Patient information needs were measured using two three-item subscales of the Cancer Patients Information Needs scale. Analysis of change was done by one-way repeated measures analysis of variance (ANOVA). To control for sampling bias, a further one-way repeated measures analysis of covariance (ANCOVA) included a propensity score as a covariate.

RESULTS: Data from 81 patients in the participation group and 120 patients in the non-participation group were analysed. The patient groups did not differ in their levels of information needs at T0 or T2. From T0 to T2, information needs increased statistically significantly in both groups with regard to both disease-related information (η²=0.354) and treatment-related information (η²=0.250). The increase in both types of information needs lost its statistical significance when the propensity score was included as a covariate. Neither ANOVA nor ANCOVA revealed a statistically significant association between patients’ participation in the MTC and their self-reported information needs.

CONCLUSION AND CLINICAL IMPLICATIONS: As concerns patients’ information needs, findings do not support a general recommendation for or against the participation of patients in their MTCs. Future research should focus on the different ways of patients’ participation in their MTCs facilitated at different cancer centres. Further research should also aim to establish which patient and disease characteristics predispose patients to benefit from participating in their MTCs.

PMID:34556513 | DOI:10.1136/bmjopen-2021-049199

BMJ Open. 2021 Sep 23;11(9):e046713. doi: 10.1136/bmjopen-2020-046713.

ABSTRACT

The median age for total hip arthroplasty (THA) is over 70 years with the corollary that many individuals have multiple multimorbidities. Despite the predicted improvement in quality of life, THA might be denied even to those with low levels of multimorbidity.

OBJECTIVE: To evaluate how pre-existing levels of multimorbidity influence the likelihood and timing of THA.

SETTING: Longitudinal record linkage study of a UK sample linking their primary care to their secondary care records.

PARTICIPANTS: A total of 28 025 patients were included, based on the recording of the diagnosis of hip osteoarthritis in a national primary care register, Clinical Practice Research Datalink. Data were extracted from the database on background health and morbidity status using five different constructs: Charlson Comorbidity Index, Electronic Frailty Index and counts of chronic diseases (from list of 17), prescribed medications and number of primary care visits prior to recording of osteoarthritis.

OUTCOME MEASURES: The record of having received a THA as recorded in the primary care record and the linked secondary care database: Hospital Episode Statistics.

RESULTS: 40% had THA: median follow 10 months (range 1-17 years). Increased multimorbidity was associated with a decreased likelihood of undergoing THA, irrespective of the method of assessing multimorbidity although the impact varied by approach.

CONCLUSION: Markers of pre-existing ill health influence the decision for THA in the elderly with end-stage hip osteoarthritis, although these effects are modest for indices of multimorbidity other than eFI. There is evidence of this influence being present even in people with moderate decrements in their health, despite the balance of benefits to risk in these individuals being positive.

PMID:34556507 | DOI:10.1136/bmjopen-2020-046713

BMJ Open. 2021 Sep 23;11(9):e049026. doi: 10.1136/bmjopen-2021-049026.

ABSTRACT

BACKGROUND: The occurrence of depression in patients with schizophrenia (PWS) increases the risk of relapse, frequency and duration of hospitalisation, and decreases social and occupational functioning.

OBJECTIVE: This study aimed to assess prevalence of unrecognised comorbid depression and its determinants in PWS.

METHOD: A cross-sectional study was conducted from 1 to 30 March 2019 at Amanuel mental specialized hospital among 300 PWS. The 9-item Calgary Depression Scale for Schizophrenia was used to assess comorbid depression. Logistic regression was used to determine the association between outcome and explanatory variables. Statistical significance was declared at p value <0.05 with 95% CI.

RESULTS: The prevalence of unrecognised comorbid depression was found to be 30.3%. Living alone (adjusted OR (AOR)=3.49, 95% CI=0.45 to 8.36), having poor (AOR=4.43, 95% CI=1.45 to 13.58) and moderate (AOR=4.45, 95% CI=1.30 to 15.22) social support, non-adherence to medication (AOR=3.82, 95% CI=1.70 to 8.55), presenting with current negative symptoms such as asocialia (AOR=4.33, 95% CI=1.98 to 9.45) and loss of personal motivation (AOR=3.46, 95% CI=1.53 to 7.84), and having suicidal behaviour (AOR=6.83, 95% CI=3.24 to 14.41) were the significant predictors of comorbid depression in PWS.

CONCLUSION: This study revealed considerably a high prevalence of unrecognised comorbid depression among PWS. Therefore, clinicians consider timely screening and treating of comorbid depression in PWS.

PMID:34556512 | DOI:10.1136/bmjopen-2021-049026

BMJ Open. 2021 Sep 23;11(9):e046712. doi: 10.1136/bmjopen-2020-046712.

ABSTRACT

Total hip arthroplasty (THA) surgery for elderly people with multimorbidity increases the risk of serious health hazards including mortality. Whether such background morbidity reduces the clinical benefit is less clear.

OBJECTIVE: To evaluate how pre-existing health status, using multiple approaches, influences risks of, and quality of life benefits from, THA.

SETTING: Longitudinal record linkage study of a UK sample linking their primary care to their secondary care records.

PARTICIPANTS: A total of 6682 patients were included, based on the recording of the diagnosis of hip osteoarthritis in a national primary care register and the recording of the receipt of THA in a national secondary care register.Data were extracted from the primary care register on background health and morbidity status using five different constructs: Charlson Comorbidity Index, Electronic Frailty Index (eFI) and counts of comorbidity disorders (from list of 17), prescribed medications and number of primary care visits prior to recording of THA.

OUTCOME MEASURES: (1) Postoperative complications and mortality; (2) postoperative hip pain and function using the Oxford Hip Score (OHS) and health-related quality of life using the EuroQoL (EQ)-5D score.

RESULTS: Perioperative complication rate was 3.2% and mortality was 0.9%, both increased with worse preoperative health status although this relationship varied depending on the morbidity construct: the eFI showing the strongest relationship but number of visits having no predictive value. By contrast, the benefits were not reduced in those with worse preoperative health, and improvement in both OHS and EQ-5D was observed in all the morbidity categories.

CONCLUSIONS: Independent of preoperative morbidity, THA leads to similar substantial improvements in quality of life. These are offset by an increase in medical complications in some subgroups of patients with high morbidity, depending on the definition used. For most elderly people, their other health disorders should not be a barrier for THA.

PMID:34556506 | DOI:10.1136/bmjopen-2020-046712