Tag: pubmed

Adv Exp Med Biol. 2023;1430:41-58. doi: 10.1007/978-3-031-34567-8_3.

ABSTRACT

This chapter describes the regulation of cell and gene therapy products (CGTPs) in Switzerland and its legal basis. The Swiss Agency for Therapeutic Products, Swissmedic, is the lead Regulatory Authority and its ATMP Division is responsible for the regulation of these products at the level of clinical trials and marketing authorization. CGTPs are regulated similarly to medicinal products. The legal basis is set by the Therapeutic Product Act, the Transplantation Act, the Human Research Act, and associated ordinances. The ATMP Division is involved in processes such as scientific advice meetings, presubmission advice meetings, pharmacovigilance, market surveillance, import/export approvals, manufacturing license approval, and inspections. In Switzerland, guidance documents relevant for cell and gene therapy provided by PIC/S, OECD, ICH, Ph.Eur., EMA, or FDA are considered. In order to harmonize requirements for CGTPs, the ATMP Division is in constant exchange of information with foreign Regulatory Authorities and part of working groups of ICH, IPRP, and Ph.Eur. As CGTPs are biologically and technically complex, a risk-based approach is applied on a case-by-case basis for the evaluation of clinical trial and marketing applications. A substantial part of this chapter will provide requirements with respect to the manufacturing and quality, nonclinical and clinical evaluation of CGTPs. Furthermore, information will be provided regarding the use of real-world evidence in evaluation of clinical long-term efficacy and safety in case of rare diseases where the numbers of patients are too small for statistically meaningful analysis during clinical trials. Finally, the chapter will provide information on a health technology assessment (HTA) program that was launched in 2015 in Switzerland by the federal authorities.

PMID:37526841 | DOI:10.1007/978-3-031-34567-8_3

J Gen Intern Med. 2023 Aug 1. doi: 10.1007/s11606-023-08328-8. Online ahead of print.

ABSTRACT

BACKGROUND: High-need, high-cost Medicare patients can have difficulties accessing office-based primary care. Home-based primary care (HBPC) can reduce access barriers and allow a clinician to obtain valuable information not obtained during office visit, possibly leading to reductions in hospital use.

OBJECTIVE: To determine whether HBPC for high-need, high-cost patients reduces hospitalizations and Medicare inpatient expenditures.

DESIGN: We conducted a matched retrospective cohort study using a difference-in-differences analysis to examine patients 2 years before and 2 years after their first home visit (HBPC group).

PARTICIPANTS: The study included high-need, high-cost fee-for-service Medicare patients without prior HBPC use, of which 55,303 were new HBPC recipients and 156,142 were matched comparison patients.

INTERVENTION: Receipt of at least two HBPC visits and, within 6 months of the index HBPC visit, a majority of a patient’s primary care visits in the home.

MAIN MEASURES: Total and potentially avoidable hospitalizations and Medicare inpatient expenditures.

KEY RESULTS: HBPC reduced total hospitalization rates, but the marginal effects were not statistically significant: a reduction of 11 total hospitalizations per 1000 patients in the first year (- 0.6%, p = 0.19) and 14 in the second year (- 0.7%, p = 0.16). However, HBPC reduced potentially avoidable hospitalization rates in the second year. The estimated marginal effect was a reduction of 6 potentially avoidable hospitalizations per 1000 patients in the first year (- 1.6%, p = 0.16) and 11 in the second (- 3.1%, p = 0.01). The estimated effect of HBPC was a small decrease in inpatient expenditures of $24 per patient per month (- 1.1%, p = 0.10) in the first year and $0 (0.0%, p = 0.99) in the second.

CONCLUSIONS: After high-need, high-cost patients started receiving HBPC, they did not experience fewer total hospitalizations or lower inpatient spending but may have had lower rates of potentially avoidable hospitalizations after 2 years.

PMID:37526814 | DOI:10.1007/s11606-023-08328-8

Sports Med. 2023 Aug 1. doi: 10.1007/s40279-023-01892-3. Online ahead of print.

ABSTRACT

BACKGROUND: Hyperthermia (and associated health and performance implications) can be a significant problem for athletes and teams involved in intermittent sports. Quantifying the highest thermal strain (i.e. peak core body temperature [peak T_c]) from a range of intermittent sports would enhance our understanding of the thermal requirements of sport and assist in making informed decisions about training or match-day interventions to reduce thermally induced harm and/or performance decline.

OBJECTIVE: The objective of this systematic review was to synthesise and characterise the available thermal strain data collected in competition from intermittent sport athletes.

METHODS: A systematic literature search was performed on Web of Science, MEDLINE, and SPORTDiscus to identify studies up to 17 April 2023. Electronic databases were searched using a text mining method to provide a partially automated and systematic search strategy retrieving terms related to core body temperature measurement and intermittent sport. Records were eligible if they included core body temperature measurement during competition, without experimental intervention that may influence thermal strain (e.g. cooling), in healthy, adult, intermittent sport athletes at any level. Due to the lack of an available tool that specifically includes potential sources of bias for physiological responses in descriptive studies, a methodological evaluation checklist was developed and used to document important methodological considerations. Data were not meta-analysed given the methodological heterogeneity between studies and therefore were presented descriptively in tabular and graphical format.

RESULTS: A total of 34 studies were selected for review; 27 were observational, 5 were experimental (2 parallel group and 3 repeated measures randomised controlled trials), and 2 were quasi-experimental (1 parallel group and 1 repeated measures non-randomised controlled trial). Across all included studies, 386 participants (plus participant numbers not reported in two studies) were recruited after accounting for shared data between studies. A total of 4 studies (~ 12%) found no evidence of hyperthermia, 24 (~ 71%) found evidence of ‘modest’ hyperthermia (peak T_c between 38.5 and 39.5 °C), and 6 (~ 18%) found evidence of ‘marked’ hyperthermia (peak T_c of 39.5 °C or greater) during intermittent sports competition.

CONCLUSIONS: Practitioners and coaches supporting intermittent sport athletes are justified to seek interventions aimed at mitigating the high heat strain observed in competition. More research is required to determine the most effective interventions for this population that are practically viable in intermittent sports settings (often constrained by many competing demands). Greater statistical power and homogeneity among studies are required to quantify the independent effects of wet bulb globe temperature, competition duration, sport and level of competition on peak T_c, all of which are likely to be key modulators of the thermal strain experienced by competing athletes.

REGISTRATION: This systematic review was registered on the Open Science Framework ( https://osf.io/vfb4s ; https://doi.org/10.17605/OSF.IO/EZYFA , 4 January 2021).

PMID:37526813 | DOI:10.1007/s40279-023-01892-3

Odontology. 2023 Aug 1. doi: 10.1007/s10266-023-00839-4. Online ahead of print.

ABSTRACT

Trace- and macro-chemical elements are crucial for cellular physiological functioning, and their alterations in biological fluids might be associated with an underlying pathological state. Hence, this study aimed to examine and summarize the published literature concerning the application of salivary ionomics for caries diagnosis. An extensive search of studies was conducted using PubMed, EMBASE, Web of Science, and Scopus, without any language and year restriction for answering the following PECO question: “In subjects (i.e., children, adolescents, or adults) with good systematic health, are there any variations in the salivary concentrations of trace- or macro-elements between caries-free (CF) individuals and caries-active (CA) subjects?” A modified version of the QUADOMICS tool was used to assess the quality of the included studies. The Review Manager Version 5.4.1. was used for data analyses. The analysis of salivary chemical elements that significantly differed between CF and CA subjects was also performed. Thirty-four studies were included, involving 2299 CA and 1669 CF subjects, having an age range from 3 to 64 years in over 16 countries. The meta-analysis revealed a statistically significant difference (p < 0.05) in the salivary levels of calcium, phosphorus, chloride, magnesium, potassium, sodium, and zinc between CA and CF subjects, suggesting higher levels of calcium, phosphorus, potassium, and sodium in CF subjects while higher levels of chloride, magnesium, and zinc in CA patients. Half of the included studies (17/34) were considered high quality, while the remaining half were considered medium quality. Only zinc and chloride ions were found to be higher significantly and consistent in CF and CA subjects, respectively. Conflicting outcomes were observed for all other salivary chemical elements including aluminum, bromine, calcium, copper, fluoride, iron, potassium, magnesium, manganese, sodium, ammonia, nitrite, nitrate, phosphorus, lead, selenium, and sulfate ions.

PMID:37526792 | DOI:10.1007/s10266-023-00839-4

Lasers Med Sci. 2023 Aug 1;38(1):172. doi: 10.1007/s10103-023-03837-8.

ABSTRACT

This study aimed to evaluate the efficacy of fluoride-free remineralizing agents in initial enamel caries, with and without combined Er,Cr:YSGG laser application. The remineralization effect of various agents and their combinations on artificial initial caries was investigated using 10 experimental groups (n = 7): NC, negative control; PC, positive control; TM, calcium-phosphate compounds (CPP-ACP); TD, theobromine-containing toothpaste; RG, ROCS® remineralizing gel; L, Er,Cr:YSGG laser (2780 nm; 0.25 W; repetition rate, 20 Hz; pulse duration, 140 μs; tip diameter, 600 μm; without air/water cooling); L + fluoride toothpaste; L + TM; L + TD; and L + RG. The demineralized bovine enamel specimens were subjected to an 8-day pH cycle by daily application of the remineralizing agents and laser therapy once prior to the pH cycle and paste application. The enamel samples underwent the Vickers surface microhardness test, and one sample per group was analyzed with scanning electron microscopy. The Kruskal Wallis test was used to compare the microhardness recovery percentage (SMHR%) for each group, and multiple comparisons were made with the Dunn test. Groups L (p = 0.003), RG (p = 0.019), L + TM (p < 0.001), L + fluoride toothpaste (p = 0.001),and L + RG (p = 0.036) exhibited significant increase in SMHR%. The tested remineralizing agents exhibited no statistically significant difference in effect when used alone and in combination with Er,Cr:YSGG laser. Combined application of Er,Cr:YSGG laser and ROCS® remineralization gel effectively promoted enamel remineralization, while use of CPP-ACP and fluoride toothpaste alone was ineffective. Theobromine-containing toothpaste exhibited the least SMHR%. Long-term evaluation of these agents is recommended.

PMID:37526766 | DOI:10.1007/s10103-023-03837-8

Lasers Med Sci. 2023 Aug 1;38(1):171. doi: 10.1007/s10103-023-03774-6.

ABSTRACT

The effects of low-level laser on the wound healing and burn injuries have been previously examined to demonstrate some satisfactory results. Despite there are a few articles available to study photobiomodulation (PBM) effects on the pain relief of cesarean sectioned wound, however no systematic examination has been carried out so far regarding its healing. Here, the aim of this clinical study was to evaluate PBM effect on the cesarean-sectioned wound healing. PBM effects of semiconductor lasers are investigated at 658 and 660 nm with 100, 150 and 350 mW output powers on 40 patients. Due to the global increasing number of cesarean sections, we have decided to investigate the effect of laser as a reliable technique to recover the wounds fast. We considered women as the target group who had their first delivery giving the birth of their children by cesarean section. We selected patients are who treated by laser therapy using indium gallium aluminum phosphide (InGaAlP) semiconductor linear scanning type with beam cross section of 12 cm² and the output power of 100 mW at 658 nm exposing a therapeutic dose of 2 J/cm². The purpose is to accelerate the healing process of the wounds after delivery as an intervention group against the people who chose the conventional methods (using ointments, pills, etc.) to heal their cesarean sectioned wounds as the control group. Regarding the wounds of these two groups, the questionnaires were filled by patients to assess the severity of pain from visual analogue scale (VAS) based on the healing of wounds from redness, edema, ecchymosis, discharge, and distance between the two edges of the wound (REEDA) scale in the early hours after surgery and the post-treatment follow-up on the third, seventh, and the tenth days. The data collected by these questionnaires were analyzed using statistical package for social science)SPSS( as a statistical software to give out the comparative histograms. This study reports a clinical examination of PBM under intervention group of 40 patients ranging 18-40 years old with body mass index (BMI) of 29-36, during post-cesarean surgery to elucidate successful healing of the wounds and scars against conventional methods which considered as control group. Comparison of mean REEDA scores on the third day (p = 0.035), seventh day (p = 0.03), and tenth day (p = 0.02) after delivery exhibits that the two groups benefit a statistically significant difference with each other. For instance, the mean wound healing score in the intervention group was almost half of the mean wound healing score on the tenth day in the control group (1.09 ± 0.586 vs. 2.25 ± 0.422). The post-cesarean follow-up indicates that the patients treated by the laser therapy (intervention group) encounter better recovery than the control group.

PMID:37526765 | DOI:10.1007/s10103-023-03774-6

Int J Biometeorol. 2023 Aug 1. doi: 10.1007/s00484-023-02510-7. Online ahead of print.

ABSTRACT

Many studies have reported that the impact of high temperatures affects physiology, welfare, health, and productivity of farm animals, and among these, the dairy cattle farming is one of the livestock sectors that suffers the greatest effects. The temperature-humidity index (THI) represents the state of the art in the evaluation of heat stress conditions in dairy cattle but often its measurement is not carried out in sheds. For this reason, the aim of this study was the monitoring of the THI in three dairy cattle farms in Mugello (Tuscany) to understand its influence on dairy cows. THI values were calculated using meteorological data from direct observation in sheds and outdoor environments. Data relating to the animal’s behavior were collected using radio collars. The Pearson test and Mann-Kendall test were used for statistical analysis. The results highlighted a significant (P < 0.001) upward trend in THImax during the last 30 years both in Low Mugello (+ 1.1 every 10 years) and in High Mugello (+ 0.9 every 10 years). In Low Mugello sheds, during the period 2020-2022, more than 70% of daytime hours during the summer period were characterized by heat risk conditions (THI > 72) for livestock. On average the animals showed a significant (P < 0.001) decrease in time spent to feeding and rumination, both during the day and the night, with a significant (P < 0.001) increase in inactivity. This study fits into the growing demand for knowledge of the micro-climatic conditions within farms in order to support resilience actions for protecting both animal welfare and farm productivity from the effects of climate change. This could also be carried out thanks to estimation models which, based on the meteorological conditions forecast, could implement the thermal stress indicator (THI) directly from the high-resolution meteorological model, allowing to get a prediction of the farm’s potential productivity loss based on the expected THI.

PMID:37526764 | DOI:10.1007/s00484-023-02510-7

Acta Diabetol. 2023 Aug 1. doi: 10.1007/s00592-023-02155-3. Online ahead of print.

ABSTRACT

AIMS: The target of metabolic control (HbA1c < 7% or 53 mmol/mol) recommended by the ADA and ISPAD is attained by 30% of children with Type 1 Diabetes (T1D). Advances in technologies for T1D aim to improve metabolic outcomes and reduce complications. This observational study assesses the long-term outcomes of advanced technologies for treatment of T1D compared to conventional approach started at onset in a group of very young children with T1D.

METHODS: 54 patients with less 4 years old at onset of T1D were enrolled and followed for up to 9 years after diagnosis. 24 subjects started continuous subcutaneous insulin (CSII) treatment and 30 subjects received MDI therapy from onset. Auxological data, HbA1c and total daily insulin dose (TDD/kg) have been collected at admission and every 4 months. HbA1cAUC>6%, rates of acute complications, glycemic variability indices and glucometrics were also recorded.

RESULTS: Patients with CSII therapy had significantly lower mean HbA1c values compared to subjects receiving MDI treatment. CSII approach also recorded lower mean HbA1cAUC>6% and TDD/kg than MDI therapy. At the last download data, the time in range (TIR) was higher in patients with CSII and hyperglycemia events were lower. Better glycemic variability indices have been described during CSII therapy, including mean glycemia, standard deviation, coefficient of variation (CV), glycemia risk index (GRI) and high blood glucose index (HBGI). There was no statistically significant difference between frequency of severe hypoglycemia and ketoacidosis episodes between groups.

CONCLUSIONS: Early initiation of diabetes technologies is safe and able to determine a better long term glycemic control in young children with T1D. It also allows to flatten the trajectory of HbA1c, probably reducing microvascular, macrovascular and neurological complications of diabetes in this very peculiar age group.

PMID:37526745 | DOI:10.1007/s00592-023-02155-3

J Math Biol. 2023 Aug 1;87(2):35. doi: 10.1007/s00285-023-01958-w.

ABSTRACT

Renewal equations are a popular approach used in modelling the number of new infections, i.e., incidence, in an outbreak. We develop a stochastic model of an outbreak based on a time-varying variant of the Crump-Mode-Jagers branching process. This model accommodates a time-varying reproduction number and a time-varying distribution for the generation interval. We then derive renewal-like integral equations for incidence, cumulative incidence and prevalence under this model. We show that the equations for incidence and prevalence are consistent with the so-called back-calculation relationship. We analyse two particular cases of these integral equations, one that arises from a Bellman-Harris process and one that arises from an inhomogeneous Poisson process model of transmission. We also show that the incidence integral equations that arise from both of these specific models agree with the renewal equation used ubiquitously in infectious disease modelling. We present a numerical discretisation scheme to solve these equations, and use this scheme to estimate rates of transmission from serological prevalence of SARS-CoV-2 in the UK and historical incidence data on Influenza, Measles, SARS and Smallpox.

PMID:37526739 | DOI:10.1007/s00285-023-01958-w

Arch Orthop Trauma Surg. 2023 Aug 1. doi: 10.1007/s00402-023-05003-9. Online ahead of print.

ABSTRACT

INTRODUCTION: Scaphoid is the most fractured carpal bone, with a 5-10% nonunion rate. Treatment challenges include choosing the implant and graft that best corrects humpback deformity and carpal malalignment with higher chances of bony healing.

OBJECTIVE: Compare cortico-cancellous and cancellous grafts between two groups of patients treating scaphoid nonunion with locking plates using autologous bone graft and evaluate bone healing rates and radiographic, tomographic, and functional parameters before and after surgery.

METHODS: Non-randomized prospective study including 20 cases of scaphoid nonunion. Groups were divided into Group A (ten patients treated with cortico-cancellous iliac graft) and Group B (ten patients treated with cancellous iliac graft). Patients underwent pre- and postoperative radiographs, computed tomography, and functional evaluation.

RESULTS: In postoperative analysis, Group A showed a statistically significant difference in intrascaphoid angle (p = 0.002) and scapholunate angle (p = 0.011) correction when comparing the pre- and postoperative periods. Group B showed a statistically significant difference in intrascaphoid angle (p = 0.002) and scapholunate angle correction (p = 0.0018), grip strength (p = 0.002), and tip pinch strength (p = 0.001) when comparing the pre- and postoperative periods. By comparing both groups, Group B showed a statistically significant difference in intrascaphoid angle correction (p = 0.002), grip strength (p = 0.002), tip pinch strength (p = 0.002), and radial deviation (p = 0.0003). There was no statistical difference when comparing bony healing between groups.

CONCLUSION: Scaphoid nonunion treatment with a locking plate was effective, showing a high bony healing rate and improved carpal alignment in imaging tests for both graft types. However, results for intrascaphoid angle correction, grip strength, tip pinch strength, and radial deviation were better in Group B.

LEVEL OF EVIDENCE: IV, case series.

PMID:37526738 | DOI:10.1007/s00402-023-05003-9