Nevin Manimala

Drug Deliv. 2022 Dec;29(1):821-836. doi: 10.1080/10717544.2022.2048131.

ABSTRACT

This study aimed to illustrate the use of D-optimal mixture design (DOMD) for optimization of an enhancer containing Dapsone niosomal formula for acne topical treatment. Mixture components (MixCs) studied were: Span 20, Cholesterol, and Cremophor RH. Different responses were measured. Optimized formula (OF) was selected to minimize particle size and maximize absolute zeta potential and entrapment efficiency. Optimized formula gel (OF-gel) was prepared and characterized. OF-gel in vivo skin penetration using confocal laser scanning microscopy and activity against Cutibacterium acnes in acne mouse model were studied. Based on DOMD results analysis, adequate models were derived. Piepel and contour plots were plotted accordingly to explain how alteration in MixCs L-pseudo values affected studied responses and regions for different responses’ values. The OF had suitable predicted responses which were in good correlation with the actually measured ones. The OF-gel showed suitable characterization and in vivo skin penetration up to the dermis layer. In vivo acne mouse-model showed that OF-gel-treated group (OF-gel-T-gp) had significantly better recovery (healing) criteria than untreated (UT-gp) and Aknemycin^®-treated (A-T-gp) groups. This was evident in significantly higher reduction of inflammation percent observed in OF-gel-T-gp than both UT-gp and A-T-gp. Better healing in OF-gel-T-gp compared with other groups was also verified by histopathological examination. Moreover, OF-gel-T-gp and A-T-gp bacterial loads were non-significantly different from each other but significantly lower than UT-gp. Thus, DOMD was an adequate statistical tool for optimization of an appropriate enhancer containing Dapsone niosomal formula that proved to be promising for topical treatment of acne.

PMID:35266431 | DOI:10.1080/10717544.2022.2048131

J Health Soc Behav. 2022 Mar 10:221465221078313. doi: 10.1177/00221465221078313. Online ahead of print.

ABSTRACT

Postmortem diagnostic overshadowing-defined as inaccurately reporting a disability as the underlying cause of death-occurs for over half of adults with cerebral palsy. This practice obscures cause of death trends, reducing the effectiveness of efforts to reduce premature mortality among this marginalized health population. Using data from the National Vital Statistics System 2005 to 2017 U.S. Multiple Cause of Death files (N = 29,996), we identify factors (sociodemographic characteristics, aspects of the context and processing of death, and comorbidities) associated with the inaccurate reporting of cerebral palsy as the underlying cause of death. Results suggest that inaccurate reporting is associated with heightened contexts of clinical uncertainty, the false equivalence of disability and health, and potential racial-ethnic bias. Ending postmortem diagnostic overshadowing will require training on disability and health for those certifying death certificates and efforts to redress ableist death certification policies.

PMID:35266426 | DOI:10.1177/00221465221078313

Mult Scler. 2022 Mar 10:13524585221078825. doi: 10.1177/13524585221078825. Online ahead of print.

ABSTRACT

BACKGROUND: In the phase III ASCLEPIOS I and II trials, participants with relapsing multiple sclerosis receiving ofatumumab had significantly better clinical and magnetic resonance imaging (MRI) outcomes than those receiving teriflunomide.

OBJECTIVES: To assess the efficacy and safety of ofatumumab versus teriflunomide in recently diagnosed, treatment-naive (RDTN) participants from ASCLEPIOS.

METHODS: Participants were randomized to receive ofatumumab (20 mg subcutaneously every 4 weeks) or teriflunomide (14 mg orally once daily) for up to 30 months. Endpoints analysed post hoc in the protocol-defined RDTN population included annualized relapse rate (ARR), confirmed disability worsening (CDW), progression independent of relapse activity (PIRA) and adverse events.

RESULTS: Data were analysed from 615 RDTN participants (ofatumumab: n = 314; teriflunomide: n = 301). Compared with teriflunomide, ofatumumab reduced ARR by 50% (rate ratio (95% confidence interval (CI)): 0.50 (0.33, 0.74); p < 0.001), and delayed 6-month CDW by 46% (hazard ratio (HR; 95% CI): 0.54 (0.30, 0.98); p = 0.044) and 6-month PIRA by 56% (HR: 0.44 (0.20, 1.00); p = 0.049). Safety findings were manageable and consistent with those of the overall ASCLEPIOS population.

CONCLUSION: The favourable benefit-risk profile of ofatumumab versus teriflunomide supports its consideration as a first-line therapy in RDTN patients.ASCLEPIOS I and II are registered at ClinicalTrials.gov (NCT02792218 and NCT02792231).

PMID:35266417 | DOI:10.1177/13524585221078825

J Comp Eff Res. 2022 Mar 10. doi: 10.2217/cer-2021-0245. Online ahead of print.

ABSTRACT

Aim: To examine the economic impact of lives lost due to the coronavirus pandemic across California and Los Angeles (LA) County. Patients & methods: Years of potential life lost (YPLL) and the value of statistical life (VSL) were calculated using mortality data from the California Department of Public Health, the LA County Department of Public Health and the Social Security Administration websites. Results: In California and LA County, the average YPLL per person were 14.3 and 14.7 and the VSLs were approximately US$219.9 billion and $82.7 billion, respectively. YPLL and VSL were greatest for Latinos aged 50-64. Conclusion: The economic burden of lives lost due to the coronavirus across California and LA County is substantial. Latinos aged 50-64 were most affected.

PMID:35266408 | DOI:10.2217/cer-2021-0245

Anaesthesiol Intensive Ther. 2022 Mar 10:46530. doi: 10.5114/ait.2022.114203. Online ahead of print.

ABSTRACT

BACKGROUND: Modified radical mastectomy (MRM) and axillary lymph node dissection (AD) are the most commonly used surgical methods in breast cancer surgery, and they are characterized by moderate to severe pain. This study aimed to investigate the effect of ultrasound-guided serratus plane block (SPB) on postoperative acute and chronic pain in patients undergoing MRM and AD.

METHODS: After ethical approval, 60 patients, aged between 18-65 years, ASA I-III, underwent unilateral MRM, and AD was assigned into 2 groups. The SPB group received ultrasound-guided SPB with 30 mL 0.25% bupivacaine, and the control group received 2 mL saline injection subcutaneously. Postoperative analgesia was performed with intravenous patient-controlled analgesia and dexketoprofen trometamol. Pain scores, opioid consumption, and rescue analgesic requirements were recorded. Chronic pain and quality of life were evaluated with the Numerical Rating Scale (NRS), short form-36 (SF-36), and painDETECT.

RESULTS: Compared with the control group, the visual analogue scale scores were statistically lower in the SPB group during 4 postoperative hours in post-anaesthetic care unit PACU at 1st, 2nd (P < 0.001), and 4th hour (P = 0.014). Fentanyl consumption and rescue analgesics were lower in the SPB group than in the control group (0-4 h, P = 0.001; 4-8 h, 8-12 h, 24 h; total P < 0.001). The incidence of chronic pain was 11%, and there was no statistically significant difference between control and SPB groups in terms of SF-36, NRS, and painDETECT scores measured at the first and sixth months.

CONCLUSIONS: SPB demonstrated superiority versus the control group concerning acute postoperative pain parameters. However, SPB had no influence on the quality of life and did not prevent chronic postmastectomy pain.

PMID:35266378 | DOI:10.5114/ait.2022.114203

Anaesthesiol Intensive Ther. 2022 Mar 10:46499. doi: 10.5114/ait.2022.114048. Online ahead of print.

ABSTRACT

BACKGROUND: The Sequential Organ Failure Assessment (SOFA) score has been developed to score the severity of organ dysfunction in critically ill sepsis patients and has been proven to have a high predictive value for intensive care unit (ICU) mortality in severely ill patients. Our goal was to evaluate the prognostic value of the SOFA score as well as trends in SOFA score for ICU mortality in COVID-19 patients.

METHODS: All consecutive patients with confirmed COVID-19 pneumonia admitted to the ICU between March 13th, 2020, and October 17th, 2020 were included in this retrospective cohort study. The worst SOFA score was evaluated daily. Multiple logistic regression models were used to evaluate the predictive value of SOFA in ICU mortality.

RESULTS: 103 patients were included in this study. 30 patients (29%) died during their ICU stay and 73 (71%) patients were discharged alive. The ICU admission SOFA score was 5.2 ± 3.3 in ICU non-survivors vs. 4.3 ± 2.9 in ICU survivors (P = 0.15). The maximum SOFA score in ICU non-survivors was 11.7 ± 4.7 vs. 7.4 ± 4.3 in ICU survivors. SOFA scores increased the first week in both survivors and non-survivors, but the increase was less pronounced in survivors. In the multiple logistic regression models, neither admission SOFA score nor combination with delta SOFA in the first 48 hours was statistically significantly related to ICU mortality. Only the maximum SOFA score remained significant (OR = 1.23, 95% CI: 1.11-1.37, P < 0.001) in the multiple logistic models with an AUC of 0.91.

CONCLUSIONS: Evaluation of SOFA scores in the first 48 hours after ICU admission is not a good prognostic indicator in COVID-19 patients. Only the maximum SOFA score was predictive for ICU mortality.

PMID:35266376 | DOI:10.5114/ait.2022.114048

Eur J Pain. 2022 Mar 9. doi: 10.1002/ejp.1932. Online ahead of print.

ABSTRACT

BACKGROUND: With regard to attitudes towards pain, many questionnaires have been developed. Although undoubtedly useful, they were specifically designed for the use in chronic pain and are less suitable for the assessment in the general population. The purpose of the present paper was to develop a measure for the assessment of general attitudes towards pain applicable in the general population, regardless of clinical condition, and to test its psychometric properties.

METHODS: We developed the General Attitudes Towards Pain Inventory and conducted two studies in order to provide psychometric data: In a general population sample (N = 362, study one), participants were asked to complete a questionnaire battery. To assess test-retest reliability, participants were contacted again after four weeks (retest sample: N = 101). For the evaluation of criterion validity (study two), a sample with sadomasochistic sexual preference (N = 68) was additionally recruited.

RESULTS: Statistical analyses revealed, overall, acceptable internal consistencies and test-retest reliabilities. A ten-factor model showed acceptable fit and was superior to alternative models. The inventory demonstrated convergent and divergent validity. In this context, we found pain sensitivity to be associated with pain attitudes. Finally, compared to the general population sample, individuals with sadomasochistic sexual preference showed significantly higher scores on fascination-pleasure and challenge subscales.

CONCLUSIONS: In the present paper, we introduce a new and comprehensive instrument for pain research and provide evidence for its reliability and validity. In addition, we present new insights into how interindividual differences in pain sensitivity relate to pain attitudes.

PMID:35263817 | DOI:10.1002/ejp.1932

J Knee Surg. 2022 Mar 9. doi: 10.1055/s-0042-1743497. Online ahead of print.

ABSTRACT

Isolated lateral compartment knee osteoarthritis (OA) affects between 7 and 10% of patients with knee OA. Although lateral unicompartmental knee arthroplasty (UKA) is an accepted treatment to manage this condition, it is performed relatively infrequently. The aim of this study was to evaluate the mid-term survivorship, radiographic outcomes, and patient-reported outcome measures (PROMs). We performed a retrospective review of a prospectively maintained database of consecutive isolated lateral UKAs performed by a single surgeon at an academic institution between September 2007 and December 2015. Our primary outcome was failure defined as revision surgery to total knee arthroplasty (TKA). Secondary outcomes included any additional surgery for any other reason. Forty-nine consecutive patients (27 females) with median age of 54.7 years (45.2-82.2) met the inclusion criteria. The survival rate for the whole cohort was 86.1% (95% confidence interval [CI]: 73.2-99.0) at 10 years as defined by conversion to TKA. There were a total of four lateral UKAs (all mobile bearings) revised to TKAs. The entire cohort demonstrated statistically significant improvements from preoperative PROMs compared with the most recent postoperative PROMs including the Western Ontario and McMaster Universities Osteoarthritis Index, Knee injury and Osteoarthritis Outcome Score, and Tegner activity scale at a median 8.8 (1.7-12.2) years follow-up. Patients with mobile bearing underwent higher revision to TKA and reoperation for all indications compared with fixed-bearing lateral UKA. In this relatively young cohort, lateral UKA yielded acceptable long-term survival and satisfactory improvement in functional outcomes. Patients who had fixed-bearing implants had similar improvement and trended toward lower revision rates than those with mobile-bearing implants. Level III therapeutic: retrospective Study was performed.

PMID:35263794 | DOI:10.1055/s-0042-1743497

Rehabilitation (Stuttg). 2022 Mar 9. doi: 10.1055/a-1726-6845. Online ahead of print.

ABSTRACT

PURPOSE: There is little representative evidence for the German rehabilitation system on occupational reintegration after medical rehabilitation. For persons who have undergone rehabilitation on behalf of the German Pension Insurance (GPI) due to a neurological disease, it is therefore important to determine (a) what socio-medical risks exist prior to rehabilitation, (b) how well persons were able to participate in working life after rehabilitation, and (c) what conditions determine the work participation.

METHODS: The study is conducted on the basis of the GPI’s database of rehabilitation statistics. Included were all persons, who completed medical rehabilitation in 2016 due to a neurological disease. The analyses were carried out for the entire group and also in a differentiated manner for the 2 main diseases, cerebrovascular diseases (CD) and multiple sclerosis (MS). Work participation was operationalized both via a monthly status variable until 24 months after rehabilitation and as a rate of all persons who were employed at the 12 and 24 months follow up and in the 3 months before, respectively. To analyse the factors influencing stable work participation, multiple logistic regression models with stepwise inclusion were calculated separately for the rates after 12 and 24 months.

RESULTS: A total of 42,230 data sets were included in the analysis (CD: n=18,368, 44%; MS: n=6,343, 15%). Patients with neurological diseases were 50 years old on average, 43% were female. We found that approximately15% of patients reported no absenteeism, whereas 17% stated an absence leave of six months or more in the year prior to rehabilitation. Mental and cardiovascular comorbidity was documented in 31 and 44% of the cases respectively. Nearly 48% of patients with CD returned to work two years after rehabilitation. For MS patients, the percentage was slightly higher at 54%. The amount of sick leave of the rehabilitated individual, their gross/net income prior to rehabilitation as well their work capacity prior to admission were the three strongest influencing factors on their return to the labour market.

CONCLUSION: About half of all persons with neurological diseases return to sustainable work after medical rehabilitation in Germany. The amount of sick leave and the income before rehabilitation are determining factors as to whether the person will return to work. The analysis provides representative data on occupational reintegration after medical rehabilitation due to a neurological disease for the first time.

PMID:35263791 | DOI:10.1055/a-1726-6845

Am J Trop Med Hyg. 2022 Mar 9:tpmd211310. doi: 10.4269/ajtmh.21-1310. Online ahead of print.

ABSTRACT

Fluvoxamine is widely prescribed as an antidepressant. Recent studies show the drug may have a clinical benefit in treating COVID-19. We aimed to perform a meta-analysis of the existing randomized trials of fluvoxamine compared with placebo on the early treatment of COVID-19 patients. We included only randomized clinical trials enrolling ambulatory patients with early-stage disease (symptoms > 7 days) for the prevention of hospitalization. We searched MEDLINE, and clinicaltrials.gov databases to identify trials and extract data with clarifications from the study investigators. We performed a fixed-effects meta-analysis and sensitivity analyses via R to evaluate the pooled estimate of hospitalization. We included three randomized trials: STOP COVID 1 and 2, and the TOGETHER Trial. The studies included a total of 2,196 patients. The STOP COVID trials measured clinical deterioration whereas the TOGETHER Trial measured hospitalization as the primary outcome. All trials reported on hospitalization up to day 28. The meta-analysis results show that patients receiving fluvoxamine were 31% less likely to experience clinical deterioration or hospitalization compared with placebo (risk ratio, 0.69; 95% CI, 0.54-0.88). A sensitivity analysis using the definition of hospitalization resulted in a risk reduction of 21% (95% CI, 0.60-1.03). Data from three randomized controlled trials show that fluvoxamine was associated with a reduction in the primary outcome measure (either clinical deterioration or composite outcome of hospitalization or extended emergency setting observation), although analysis of hospitalization-only was not statistically significant. More evidence from future trials is still needed to support the findings of this meta-analysis.

PMID:35263710 | DOI:10.4269/ajtmh.21-1310