Category: Statistics

Lancet Public Health. 2024 Jul;9(7):e432-e442. doi: 10.1016/S2468-2667(24)00100-2.

ABSTRACT

BACKGROUND: The COVID-19 pandemic disrupted health-care delivery, including difficulty accessing in-person care, which could have increased the need for strong pharmacological pain relief. Due to the risks associated with overprescribing of opioids, especially to vulnerable populations, we aimed to quantify changes to measures during the COVID-19 pandemic, overall, and by key subgroups.

METHODS: For this interrupted time-series analysis study conducted in England, with National Health Service England approval, we used routine clinical data from more than 20 million general practice adult patients in OpenSAFELY-TPP, which is a a secure software platform for analysis of electronic health records. We included all adults registered with a primary care practice using TPP-SystmOne software. Using interrupted time-series analysis, we quantified prevalent and new opioid prescribing before the COVID-19 pandemic (January, 2018-February, 2020), during the lockdown (March, 2020-March, 2021), and recovery periods (April, 2021-June, 2022), overall and stratified by demographics (age, sex, deprivation, ethnicity, and geographical region) and in people in care homes identified via an address-matching algorithm.

FINDINGS: There was little change in prevalent prescribing during the pandemic, except for a temporary increase in March, 2020. We observed a 9·8% (95% CI -14·5 to -6·5) reduction in new opioid prescribing from March, 2020, with a levelling of the downward trend, and rebounding slightly after April, 2021 (4·1%, 95% CI -0·9 to 9·4). Opioid prescribing rates varied by demographics, but we found a reduction in new prescribing for all subgroups except people aged 80 years or older. Among care home residents, in April, 2020, parenteral opioid prescribing increased by 186·3% (153·1 to 223·9).

INTERPRETATION: Opioid prescribing increased temporarily among older people and care home residents, likely reflecting use to treat end-of-life COVID-19 symptoms. Despite vulnerable populations being more affected by health-care disruptions, disparities in opioid prescribing by most demographic subgroups did not widen during the pandemic. Further research is needed to understand what is driving the changes in new opioid prescribing and its relation to changes to health-care provision during the pandemic.

FUNDING: The Wellcome Trust, Medical Research Council, The National Institute for Health and Care Research, UK Research and Innovation, and Health Data Research UK.

PMID:38942555 | DOI:10.1016/S2468-2667(24)00100-2

Lancet Public Health. 2024 Jul;9(7):e421-e431. doi: 10.1016/S2468-2667(24)00098-7.

ABSTRACT

BACKGROUND: Overdose is the leading cause of death for people released from prison, and opioid agonist treatment is associated with reductions in mortality after imprisonment. However, few studies have explored the interplay of the potential modifiable risk factors and protective factors for mortality after release from prison. We aimed to describe all-cause mortality and overdose mortality among individuals released from Norwegian prisons during 2000-22 and to identify pre-existing risk factors associated with both types of mortality among these individuals for 6 months.

METHODS: For this prospective analysis, we used data from the Norwegian Prison Release Study (nPRIS), which includes all people in prison in Norway between Jan 1, 2000, and Dec 31, 2022; the Norwegian Cause of Death Registry; the Norwegian Prison Registry; the Norwegian Patient Registry; and Statistics Norway. All prisons in Norway that were open during this period were included. People who did not have a Norwegian personal identification number or were serving their sentence outside of prison units were excluded from this analysis. To identify pre-existing risk factors associated with all-cause and overdose mortality among people released from prison, we left-censored the observation period on Jan 1, 2010, creating a subsample of individuals. We calculated crude mortality rates (CMRs) and corresponding 95% CIs as the number of deaths per 100 000 person-years for several time periods after release. The primary outcomes were all-cause mortality and overdose mortality according to the ICD-10, assessed in all participants and analysed via two separate Cox proportional-hazards models.

FINDINGS: The total nPRIS cohort included 112 877 individuals released from prison in Norway between 2000 and 2022, 11 995 (10·6%) of whom were female and 100 865 (89·4%) of whom were male. We identified 13 004 instances of all-cause mortality and 3085 instances of overdose mortality during the 1 463 035 person-years. The estimated CMR for all-cause mortality was 889 (95% CI 874-904) per 100 000 person-years and for overdose mortality was 211 (203-218) per 100 000 person-years. Among people diagnosed with opioid use disorder before entering prison during 2010-22 (n=6830), provision of opioid agonist treatment was estimated to be associated with reductions in both all-cause mortality (hazard ratio 0·58, 95% CI 0·39-0·85) and overdose mortality (0·51, 0·31-0·82) in the 6 months after leaving prison after adjustment for sociodemographic, prison-related, and clinical characteristics.

INTERPRETATION: In people diagnosed with opioid use disorder released from Norwegian prisons, opioid agonist treatment provided while in prison was a protective factor for both all-cause and overdose mortality at 6 months. Provision of opioid agonist treatment while in prison is crucial in reducing mortality for 6 months after release and should be available to all people in prison who have treatment needs.

FUNDING: South-Eastern Norway Regional Health Authority and the Research Council of Norway.

PMID:38942554 | DOI:10.1016/S2468-2667(24)00098-7

Lancet Public Health. 2024 Jul;9(7):e412-e413. doi: 10.1016/S2468-2667(24)00105-1.

NO ABSTRACT

PMID:38942547 | DOI:10.1016/S2468-2667(24)00105-1

PDA J Pharm Sci Technol. 2024 Jun 28:pdajpst.2023.012867. doi: 10.5731/pdajpst.2023.012867. Online ahead of print.

ABSTRACT

Vial and syringe filling by peristaltic pump has been widely implemented by contract manufacturing organizations and biopharmaceutical companies. Fill volume is commonly considered as critical quality attribute related in aseptic filling process and the variation needs to be well controlled to guarantee the safety, efficacy and consistency of drug products. However, the criteria for justifying the filling variation and underlying mechanisms that affect the variability are not fully revealed quantitatively in the literatures. This study selected filling accuracy, filling process capability and filling precision as three criteria for evaluating the filling process performance with four statistical indexes: Relative Error Mean, Critical Control Limit (Cpk ≥ 1.33), Relative Standard Deviation and Relative Moving Range Mean. The impact of liquid properties, pump tubing sizes and pump settings on above indexes were investigated using a bench-top system with a peristatic pump and a high-precision balance. The results showed that the viscosity, target fill volume, pump tubing size, pump speed, acceleration/deceleration rate and suck-back had statistical significance on the fill volume variability. Definitive Screening Design was further applied to clarify and visualize the priorities and interaction impact of above factors on fill volume variability. Stepwise approach for fill volume variability optimization and control based on predictive models was established and verified for drug product solution with viscosity between 1-23 cp and target fill volume between 0.2-2.0 mL.

PMID:38942483 | DOI:10.5731/pdajpst.2023.012867

Korean J Radiol. 2024 Jul;25(7):656-661. doi: 10.3348/kjr.2024.0049.

ABSTRACT

Evaluating the performance of a binary diagnostic test, including artificial intelligence classification algorithms, involves measuring sensitivity, specificity, positive predictive value, and negative predictive value. Particularly when comparing the performance of two diagnostic tests applied on the same set of patients, these metrics are crucial for identifying the more accurate test. However, comparing predictive values presents statistical challenges because their denominators depend on the test outcomes, unlike the comparison of sensitivities and specificities. This paper reviews existing methods for comparing predictive values and proposes using the permutation test. The permutation test is an intuitive, non-parametric method suitable for datasets with small sample sizes. We demonstrate each method using a dataset from MRI and combined modality of mammography and ultrasound in diagnosing breast cancer.

PMID:38942459 | DOI:10.3348/kjr.2024.0049

Korean J Radiol. 2024 Jul;25(7):634-643. doi: 10.3348/kjr.2023.1207.

ABSTRACT

OBJECTIVE: This study aimed to evaluate the diagnostic efficacy and safety of low-contrast-dose, dual-source dual-energy CT before transcatheter aortic valve replacement (TAVR) in patients with compromised renal function.

MATERIALS AND METHODS: A total of 54 consecutive patients (female:male, 26:38; 81.9 ± 7.3 years) with reduced renal function underwent pre-TAVR dual-energy CT with a 30-mL contrast agent between June 2022 and March 2023. Monochromatic (40- and 50-keV) and conventional (120-kVp) images were reconstructed and analyzed. The subjective quality score, vascular attenuation, contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) were compared among the imaging techniques using the Friedman test and post-hoc analysis. Interobserver reliability for aortic annular measurement was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. The procedural outcomes and incidence of post-contrast acute kidney injury (AKI) were assessed.

RESULTS: Monochromatic images achieved diagnostic quality in all patients. The 50-keV images achieved superior vascular attenuation and CNR (P < 0.001 in all) while maintaining a similar SNR compared to conventional CT. For aortic annular measurement, the 50-keV images showed higher interobserver reliability compared to conventional CT: ICC, 0.98 vs. 0.90 for area and 0.97 vs. 0.95 for perimeter; 95% limits of agreement width, 0.63 cm² vs. 0.92 cm² for area and 5.78 mm vs. 8.50 mm for perimeter. The size of the implanted device matched CT-measured values in all patients, achieving a procedural success rate of 92.6%. No patient experienced a serum creatinine increase of ≥ 1.5 times baseline in the 48-72 hours following CT. However, one patient had a procedural delay due to gradual renal function deterioration.

CONCLUSION: Low-contrast-dose imaging with 50-keV reconstruction enables precise pre-TAVR evaluation with improved image quality and minimal risk of post-contrast AKI. This approach may be an effective and safe option for pre-TAVR evaluation in patients with compromised renal function.

PMID:38942457 | DOI:10.3348/kjr.2023.1207

J Am Board Fam Med. 2024 Jun 28:jabfm.2023.230220R2. doi: 10.3122/jabfm.2023.230220R2. Online ahead of print.

ABSTRACT

BACKGROUND: The 2022 Centers for Disease Control’s “Clinical Practice Guidelines for Prescribing Opioids for Pain in United States” called for attention and action toward reducing disparities in untreated and undertreated pain among Black and Latino patients. There is growing evidence for controlled substance safety committees (CSSC) to change prescribing culture, but few have been examined through the lens of health equity. We examined the impact of a primary care CSSC on opioid prescribing, including by patients’ race and sex.

METHODS: We conducted a retrospective cohort study. Our primary outcome was a change in prescribed morphine milligram equivalents (MME) at baseline (2017) and follow-up (2021). We compared the differences in MME by race and sex. We also examined potential intersectional disparities. We used paired t test to compare changes in mean MME’s and logistic regression to determine associations between patient characteristics and MME changes.

RESULTS: Our cohort included 93 patients. The mean opioid dose decreased from nearly 200 MME to 136.1 MME, P < .0001. Thirty percent of patients had their dose reduced to under 90 MME by follow-up. The reduction rates by race or sex alone were not statistically significant. There was evidence of intersectional disparities at baseline. Black women were prescribed 88.5 fewer MME’s at baseline compared with their White men counterparts, P = .04.

DISCUSSION: Our findings add to the previously documented success of CSSCs in reducing opioid doses for chronic nonmalignant pain to safer levels. We highlight an opportunity for primary care based CSSCs to lead the efforts to identify and address chronic pain management inequities.

PMID:38942449 | DOI:10.3122/jabfm.2023.230220R2

J Am Board Fam Med. 2024 Jun 28:jabfm.2023.230289R1. doi: 10.3122/jabfm.2023.230289R1. Online ahead of print.

ABSTRACT

BACKGROUND: Social risk data collection is expanding in community health centers (CHCs). We explored clinicians’ practices of adjusting medical care based on their awareness of patients’ social risk factors-that is, changes they make to care plans to mitigate the potential impacts of social risk factors on their patients’ care and health outcomes-in a set of Texas CHCs.

METHODS: Convergent mixed methods. Surveys/interviews explored clinician perspectives on adjusting medical care based on patient social risk factors. Survey data were analyzed with descriptive statistics; interviews were analyzed using thematic analysis and inductive coding.

RESULTS: Across 4 CHCs, we conducted 15 clinician interviews and collected 97 surveys. Interviews and surveys overall indicated support for adjustment activities. Two main themes emerged: 1) clinicians reported making frequent adjustments to patient care plans based on their awareness of patients’ social contexts, while simultaneously expressing concerns about adjustment; and 2) awareness of patients’ social risk factors, and clinician time, training, and experience all influenced clinician adjustments.

CONCLUSIONS: Clinicians at participating CHCs described routinely adjusting patient care plans based on their patients’ social contexts. These adjustments were being made without specific guidelines or training. Standardization of adjustments may facilitate the contextualization of patient care through shared decision making to improve outcomes.

PMID:38942447 | DOI:10.3122/jabfm.2023.230289R1

Drug Metab Dispos. 2024 Jun 28:DMD-MR-2024-001735. doi: 10.1124/dmd.124.001735. Online ahead of print.

ABSTRACT

Recently, we have proposed simple methodology to derive clearance and rate constant equations, independent of differential equations, based on Kirchhoff’s Laws, a common methodology from physics used to describe rate-defining processes either in series or parallel. Our approach has been challenged in three recent publications, two published in this journal, but notably what is lacking is that none evaluate experimental pharmacokinetic data. As reviewed here, manuscripts from our laboratory have evaluated published experimental data, demonstrating that the Kirchhoff’s Laws approach explains (1) why all of the experimental perfused liver clearance data appear to fit the equation that was previously believed to be the well-stirred model, (2) why linear pharmacokinetic systemic bioavailability determinations can be greater than 1, (3) why renal clearance can be a function of drug input processes, and (4) why statistically different bioavailability measures may be found for urinary excretion versus systemic concentration measurements. Our most recent paper demonstrates (5) how the universally accepted steady-state clearance approach utilized by the field for the past 50 years leads to unrealistic outcomes concerning the relationship between liver-to-blood Kp_uu and hepatic availability F_H , highlighting the potential for errors in pharmacokinetic evaluations based on differential equations. The Kirchhoff’s Laws approach is applicable to all pharmacokinetic analyses of quality experimental data, those that were previously adequately explained with present pharmacokinetic theory, and those that were not. The publications that have attempted to rebut our position do not address unexplained experimental data, and we show here why their analyses are not valid. Significance Statement The Kirchhoff’s Laws approach to deriving clearance equations for linear systems in parallel or in series, independent of differential equations, successfully describes published pharmacokinetic data that has previously been unexplained. Three recent publications claim to refute our proposed methodology; these publications only make theoretical arguments, do not evaluate experimental data; never demonstrate that the Kirchhoff methodology provides incorrect interpretations of experimental pharmacokinetic data, including statistically significant data not explained by present pharmacokinetic theory. We demonstrate why these analyses are invalid.

PMID:38942444 | DOI:10.1124/dmd.124.001735

BMJ Open Qual. 2024 Jun 27;13(2):e002809. doi: 10.1136/bmjoq-2024-002809.

ABSTRACT

OBJECTIVES: Intravenous medication errors continue to significantly impact patient safety and outcomes. This study sought to clarify the complexity and risks of the intravenous administration process.

DESIGN: A qualitative focus group interview study.

SETTING: Focused interviews were conducted using process mapping with frontline nurses responsible for medication administration in September 2020.

PARTICIPANTS: Front line experiened nurses from a Japanese tertiary teaching hospital.

PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was to identify the mental models frontline nurses used during intravenous medication administration, which influence their interactions with patients, and secondarily, to examine the medication process gaps between the mental models nurses perceive and the actual defined medication administration process.

RESULTS: We found gaps between the perceived clinical administration process and the real process challenges with an emphasis on the importance of verifying to see if the drug was ordered for the patient immediately before its administration.

CONCLUSIONS: This novel and applied improvement approach can help nurses and managers better understand the process vulnerability of the infusion process and develop a deeper understanding of the administration steps useful for reliably improving the safety of intravenous medications.

PMID:38942437 | DOI:10.1136/bmjoq-2024-002809