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Neutrophil gelatinase-associated lipocalin as a predictor of pre-eclampsia: A systematic review and meta-analysis

Int J Gynaecol Obstet. 2023 Apr 11. doi: 10.1002/ijgo.14777. Online ahead of print.

ABSTRACT

BACKGROUND: Protein neutrophil gelatinase-associated lipocalin (NGAL) has been associated with kidney injury and inflammatory conditions. In particular, several studies have found an association between maternal blood and urine levels and the development of pre-eclampsia.

OBJECTIVES: To examine whether maternal blood and urine levels of NGAL are good predictors of pre-eclampsia.

SEARCH STRATEGY: The authors searched MEDLINE databases via PubMed, Embase, Scopus, Scielo, Google Scholar, PROSPERO International Prospective Register of Systematic Reviews, and the Cochrane Central Register of Controlled Trials.

SELECTION CRITERIA: The authors included case-control observational clinical studies comparing protein levels of NGAL in serum and urine in women with pre-eclampsia with uncomplicated pregnancies. Only studies where the collection of blood or urine was peformed before the occurrence of pre-eclampsia were selected.

DATA COLLECTION AND ANALYSIS: The primary outcome was the difference in NGAL levels in blood or urine between women with and without pre-eclampsia.

RESULTS: Seven studies in total were included: five studies measuring NGAL in blood and two in urine. Regarding the serum studies, 315 patients were included as cases and 540 as controls. Higher NGAL in maternal blood during all three trimesters together was associated with pre-eclampsia; the standardized mean difference was 1.15 ng/mL (95% confidence interval, 0.92-1.39; P < 0.01). Regarding the urine studies, 39 patients were included as cases and 220 as controls. There was no statistically significant difference between patients with pre-eclampsia and controls regarding urine NGAL.

CONCLUSIONS: NGAL in maternal blood is higher in patients who later develop pre-eclampsia compared with controls and could be used as a potential predicting test in the routine clinical setting.

PMID:37040030 | DOI:10.1002/ijgo.14777

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Regulatory, health technology assessment and company interactions: the current landscape and future ecosystem for drug development, review and reimbursement

Int J Technol Assess Health Care. 2023 Apr 11;39(1):e20. doi: 10.1017/S0266462323000144.

ABSTRACT

BACKGROUND: Multi-stakeholder interactions have evolved at product and policy levels. There is a need to assess the current and future landscape of interactions between companies, and regulatory and HTA agencies to address challenges and identify areas for improvement.

OBJECTIVES: The aims of this study were to review the current interactions within and across regulatory and HTA agencies, and companies’ experiences in engaging in these activities; to assess the added value of interactions as well as limitations; to explore the future ecosystem for stakeholder interactions.

METHOD: Three separate questionnaires were developed for companies, regulators and HTA agencies, respectively, to assess their experiences and perceptions. The responses were analyzed using descriptive statistics and discussed at a multi-stakeholder workshop. Key outcomes from the surveys and workshop discussion were reported.

RESULTS: All seven regulators and seven HTA agencies in the survey indicated that they had stakeholder interactions. More formal collaboration occurred with regulators compared with HTA agencies. All nine companies have taken early advice but indicated the need for future prioritization. Success indicators can be built at the product and therapy levels, with the added value of faster patient access. Four principles were proposed for the future ecosystem: separate remit and functions between regulators and HTA; align processes; converge evidence requirements where possible; increase transparency.

CONCLUSIONS: This research brought together regulators, HTA agencies, companies to examine how they interact with one another. We propose measures of value and make recommendations on future evolution to enable better evidence generation and improve regulatory and HTA decision-making.

PMID:37039100 | DOI:10.1017/S0266462323000144

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Challenges in the combination of radiotherapy and immunotherapy for breast cancer

Expert Rev Anticancer Ther. 2023 Apr 11:1-9. doi: 10.1080/14737140.2023.2188196. Online ahead of print.

ABSTRACT

INTRODUCTION: Immunotherapy (IT) is showing promise in the treatment of breast cancer, but IT alone only benefits a minority of patients. Radiotherapy (RT) is usually included in the standard of care for breast cancer patients and is traditionally considered as a local form of treatment. The emerging knowledge of RT-induced systemic immune response, and the observation that the rare abscopal effect of RT on distant cancer metastases can be augmented by IT, have increased the enthusiasm for combinatorial immunoradiotherapy (IRT) for breast cancer patients. However, IRT largely follows the traditional sole RT and IT protocols and does not consider patient specificity, although patients’ responses to treatment remain heterogeneous.

AREAS COVERED: This review discusses the rationale of IRT for breast cancer, the current knowledge, challenges, and future directions.

EXPERT OPINION: The synergy between RT and the immune system has been observed but not well understood at the basic level. The optimal dosages, timing, target, and impact of biomarkers are largely unknown. There is an urgent need to design efficacious pre-clinical and clinical trials to optimize IRT for cancer patients, maximize the synergy of radiation and immune response, and explore the abscopal effect in depth, taking into account patients’ personal features.

PMID:37039098 | DOI:10.1080/14737140.2023.2188196

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The indirect effect of positive aspects of caregiving on the relationship between cognitive decline and dementia caregiver burden

Psychogeriatrics. 2023 Apr 11. doi: 10.1111/psyg.12966. Online ahead of print.

ABSTRACT

BACKGROUND: Research has linked increased cognitive decline in a dementia care recipient to worsening caregiver burden, but the presence of positive aspects of caregiving is associated with better outcomes. As cognitive decline worsens, a lack of positive caregiving experiences could lead to burden for the caregiver. This study investigated relationships among dementia caregiver burden, cognitive decline, and positive aspects of caregiving in dementia, predicting an indirect effect of positive aspects of caregiving.

METHODS: Data from 724 patients of an outpatient memory clinic in Ohio were examined and dyads included based on clinically supported patient diagnoses on the dementia spectrum. Caregivers completed the Zarit Burden Interview (ZBI) and Positive Aspects of Caregiving (PAC) measures. The Montreal Cognitive Assessment and Mini-Mental State Examination were used to estimate cognitive decline, standardized to create a single variable. Multiple potential covariates were considered for inclusion in the model. A cross-sectional mediation analysis using the Hayes PROCESS macro explored the presence of an indirect effect of PAC on the relationship between cognitive decline and ZBI using 5000 bootstrap samples.

RESULTS: Only the potential covariate caregiver age was correlated with any of the primary variables; this variable was controlled in analyses. Significant relationships emerged between cognitive decline and ZBI (r = -0.12, P < 0.001), between PAC and ZBI (r = -0.23, P < 0.001), and between cognitive decline and PAC (r = -0.07, P < 0.05). An indirect effect of positive aspects of caregiving on the relationship between cognitive decline and ZBI was statistically significant (B = 0.0092, 95% bias-corrected confidence interval: 0.0008, 0.0185), accounting for 14.4% of the variance in the model.

CONCLUSIONS: A lack of positive aspects of caregiving could be partially responsible for development of dementia caregiver burden as cognitive decline worsens. Longitudinal examination of these relationships is needed to understand causality fully. Findings may help healthcare providers tailor treatment to alleviate caregiver burden.

PMID:37039090 | DOI:10.1111/psyg.12966

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Apraxia and dementia severity in Alzheimer’s disease: a systematic review

J Clin Exp Neuropsychol. 2023 Apr 11:1-20. doi: 10.1080/13803395.2023.2199971. Online ahead of print.

ABSTRACT

INTRODUCTION: To investigate the role and influence of apraxia regarding dementia severity in Alzheimer’s disease (AD). In addition, to examine whether apraxia or its association to dementia severity show distinct characteristics between typical and atypical variants of AD, that commonly include frontal, logopenic, posterior, and Down’s syndrome variant.

METHOD: The search conducted on 4 December 2020 in the Cinahl, Ovid Medline, PsycArticles, PsycInfo, Scopus and Web of Science databases yielded 251 non-duplicate records published since 2000. Ten records examining the association between Clinical Dementia Rating (CDR) scores and apraxia in AD were included in the review.

RESULTS: Dementia severity was related to apraxia in AD, and the prevalence and severity of apraxia increased as dementia progressed. Constructional, ideomotor (imitation of meaningless gestures), orofacial, speech, gait, and total praxis, including constructional, ideomotor, and ideational praxis, tasks differentiated dementia severity in AD. In the atypical variants of AD apraxia occurred frequently but because of the small number of participants, no statistical analyses were available.

CONCLUSIONS: The results highlight the need for extensive assessment of AD severity, and praxis assessment throughout the disease course. Apraxia affects the independent functioning and communication of the patient, tool use, and the ability to perform activities of daily living. Apraxia occurs frequently in AD and other neurodegenerative diseases, and apraxia assessment has shown to differentiate AD from other neurodegenerative diseases, particularly frontotemporal dementia. Thus, apraxia assessment serves in recognizing the atypical variants of AD as well.

PMID:37039061 | DOI:10.1080/13803395.2023.2199971

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Use of procedural ultrasound for the insertion of peripheral intravenous catheters: A nationwide survey in acute care departments in Belgium

Acute Med. 2023;22(1):33-38. doi: 10.52964/AMJA.0931.

ABSTRACT

PURPOSE: Assessment of ultrasound use for peripheral intravenous cannulation among acute care nurses and physicians.

METHODS: Over a population of 17,437, the calculated sample size of respondents required was 376.

RESULTS: A total of 388 health professionals; 249 (64.2%) physicians and 139 (35.8%) nurses completed the entire questionnaire. 166 (45.2%) used ultrasound for intravenous cannulation. A statistically significant difference favored physicians’ ultrasound use (p<0.001). Respondents with less than 10 years of clinical practice used ultrasound significantly more (p<0.001). The main reported obstacle among users was the lack of time.

CONCLUSION: This survey revealed the gap between the current recommendations for ultrasound use for peripheral intravenous cannulation and the actual practices. Efforts should be made to develop specific training using ultrasound.

PMID:37039054 | DOI:10.52964/AMJA.0931

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Real-world effectiveness of systemic anticancer therapy for advanced melanoma in the west of Scotland from 2010 to 2018

Future Oncol. 2023 Apr 11. doi: 10.2217/fon-2022-0959. Online ahead of print.

ABSTRACT

Aim: Assess the real-world effectiveness of systemic anticancer therapy in advanced (unresectable or metastatic) melanoma. Methods: This was a retrospective cohort study linking routine healthcare data with systemic anticancer therapy prescriptions for patients starting immunotherapy or targeted treatments between 1 November 2010 and 31 December 2017 in the west of Scotland. Results: Among 362 patients identified, median overall survival varied between 18.5 months (95% CI: 14.4-not estimable) for ipilimumab/nivolumab combination and 5.6 months (95% CI: 4.5-7.3) for dabrafenib, but there were differences in the characteristics of each regimen cohort. Raised lactate dehydrogenase levels and Eastern Cooperative Oncology Group performance status ≥2 negatively impacted overall survival. Conclusion: The patients had a shorter median overall survival than those in pivotal trials. This was expected, given that this real-world cohort included patients with poorer prognostic indicators, typically excluded from trials.

PMID:37039001 | DOI:10.2217/fon-2022-0959

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Cancer mortality predictions for 2023 in Latin America with focus on stomach cancer

Eur J Cancer Prev. 2023 Apr 10. doi: 10.1097/CEJ.0000000000000806. Online ahead of print.

ABSTRACT

OBJECTIVE: We estimated cancer mortality statistics for the current year in seven major Latin American countries.

METHODS: We retrieved official death certification data and population figures from the WHO and the United Nations databases for the 1970-2020 calendar period. We considered mortality from all neoplasms combined and for 10 major cancer sites. We estimated the number of deaths and age-standardized mortality rates for the year 2023.

RESULTS: Age-standardized mortality rates for all cancers combined are predicted to decline in all countries, in both sexes, apart from Venezuelan women. The lowest predicted total cancer mortality rates are in Mexico, 69.8/100 000 men and 62.5/100 000 women. The highest rates are in Cuba with 133.4/100 000 men and 90.2/100 000 women. Stomach cancer is predicted to decline steadily in all countries considered, but remains the first-ranking site for men in Chile (14.3/100 000) and Colombia (11/100 000). Colorectal cancer rates also tended to decline but remain comparatively high in Argentina (14/100 000 men). Breast cancer rates were high in Argentinian women (16.5/100 000) though they tended to decline in all countries. Lung cancer mortality rates are also predicted to decline, however, rates remain exceedingly high in Cuba (30.5/100 000 men and 17.2/100 000 women) as opposed to Mexico (5.6/100 000 men and 3.2/10 000 women). Declines are also projected for cancer of the uterus, but rates remain high, particularly in Argentina and Cuba (10/100 000 women), and Venezuela (13/100 000 women) due to inadequate screening and cervical cancer control.

CONCLUSION: Certified cancer mortality remains generally lower in Latin America (apart from Cuba), as compared to North America and Europe; this may be partly due to death certification validity.

PMID:37038996 | DOI:10.1097/CEJ.0000000000000806

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Validation of the Antifungal National Antimicrobial Prescribing Survey (AF-NAPS) quality assessment tool

J Antimicrob Chemother. 2023 Apr 11:dkad085. doi: 10.1093/jac/dkad085. Online ahead of print.

ABSTRACT

BACKGROUND: The Antifungal National Antimicrobial Prescribing Survey (AF-NAPS) was developed to undertake streamlined quality audits of antifungal prescribing. The validity and reliability of such tools is not characterized.

OBJECTIVES: To assess the validity and reliability of the AF-NAPS quality assessment tool.

METHODS: Case vignettes describing antifungal prescribing were prepared. A steering group was assembled to determine gold-standard classifications for appropriateness and guideline compliance. Infectious diseases physicians, antimicrobial stewardship (AMS) and specialist pharmacists undertook a survey to classify appropriateness and guideline compliance of prescriptions utilizing the AF-NAPS tool. Validity was measured as accuracy, sensitivity and specificity compared with gold standard. Inter-rater reliability was measured using Fleiss’ kappa statistics. Assessors’ responses and comments were thematically analysed to determine reasons for incorrect classification.

RESULTS: Twenty-eight clinicians assessed 59 antifungal prescriptions. Overall accuracy of appropriateness assessment was 77.0% (sensitivity 85.3%, specificity 68.0%). Highest accuracy was seen amongst specialist (81%) and AMS pharmacists (79%). Prescriptions with lowest accuracy were in the haematology setting (69%), use of echinocandins (73%), mould-active azoles (75%) and for prophylaxis (71%). Inter-rater reliability was fair overall (0.3906), with moderate reliability amongst specialist pharmacists (0.5304). Barriers to accurate classification were incorrect use of the appropriateness matrix, knowledge gaps and lack of guidelines for some indications.

CONCLUSIONS: The AF-NAPS is a valid tool, assisting assessors to correctly classify appropriate prescriptions more accurately than inappropriate prescriptions. Specialist and AMS pharmacists had similar performance, providing confidence that both can undertake AF-NAPS audits to a high standard. Identified reasons for incorrect classification will be targeted in the online tool and educational materials.

PMID:37038993 | DOI:10.1093/jac/dkad085

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Multilevel Calibration procedure for the oral health national multicentre survey in primary teeth

Int J Paediatr Dent. 2023 Apr 11. doi: 10.1111/ipd.13072. Online ahead of print.

ABSTRACT

BACKGROUND: Early childhood caries (ECC) requires systematically collected and standardized data.

AIM: To describe a novel multilevel calibration procedure in primary dentition.

DESIGN: Calibration method involved two calibration levels: the first (L1 ) involved inter-examiner agreement between three main investigators, the group leaders (GLs) in the following level; the second level (L2 ) involved three groups of 11 pediatric dentists and inter-examiner agreement assessment according to the GLs in each group. The study sample consisted of 650 primary teeth surfaces in eight children (mean age 6.56±2.22 years). Surface-by-surface percent agreement, tooth-by-tooth percentage agreement, Cohen’s kappa and Fleiss Kappa statistics were used to calculate inter-examiner reliability. Statistical analysis was performed with SPSS 27.0.

RESULTS: Surface-by-surface agreement regarding ICDASepi -merged revealed almost perfect agreement (>90.00%) both on L1 and L2 . Kappa values and ranges showed good agreement both at L1 (Overall Kappa=0.95) and L2 (Overall Kappa=0.98) and almost perfect consistency was detected between GLs at L1 (>91.30%) and substantial agreement at L2 (>85.00%). All examiner at L2 showed almost perfect positive agreement (sensitivity=96.77-100%) when detecting presence of dental plaque.

CONCLUSIONS: The calibration procedure appeared feasible prior to organizing multicenter epidemiological oral health survey in large population groups of preschool children, with higher number of examiners.

PMID:37038983 | DOI:10.1111/ipd.13072