Category: Statistics

J Prosthodont. 2024 May 12. doi: 10.1111/jopr.13865. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the fracture resistance of zirconia overlays, considering various preparation designs and the presence of endodontic access.

MATERIALS AND METHODS: Ninety translucent zirconia (5Y-PSZ) overlay restorations were divided into six groups (n = 15/group) based on different preparation designs, with and without endodontic access: chamfer margin 4 mm above the gingival level without (group 1) and with endodontic access (group 2); margin 2 mm above the gingival level without (group 3) and with endodontic access (group 4); overlay with no chamfer margin without (group 5) and with endodontic access (group 6). Restorations were bonded to mandibular first molar resin dies, and the groups with endodontic access were sealed with flowable resin composite. All restorations underwent 100,000 cycles of thermal cycling between 5°C and 55°C, followed by loading until fracture. Maximum load and fracture resistance were recorded. ANOVA with Tukey post-hoc tests were used for statistical comparison (α < 0.05).

RESULTS: Fracture resistance significantly varied among overlay designs with and without endodontic access (p < 0.001), except for the no-margin overlays (groups 5 and 6). Overlays with a 2 mm margin above the gingival margin with endodontic access (group 4) exhibited significantly higher fracture resistance compared to both the 4-mm supragingival (group 2) and no-margin (group 6) designs, even when compared to their respective intact groups (groups 1 and 5). There were no significant differences between the no-margin and 4-mm supragingival overlays.

CONCLUSION: The more extensive zirconia overlay for mandibular molars is the first choice since the 2 mm margin above the gingival level design withstood considerable loads even after undergoing endodontic access. A no-margin overlay is preferred over the 4-mm supragingival design as it preserves more tooth structure and there was no outcome difference, irrespective of endodontic access. Caution is warranted in interpreting these findings due to the in vitro nature of the study.

PMID:38734932 | DOI:10.1111/jopr.13865

Hum Reprod. 2024 May 11:deae085. doi: 10.1093/humrep/deae085. Online ahead of print.

ABSTRACT

STUDY QUESTION: To what extent and via what mechanism does the concomitant administration of rapamycin (a follicle activation pathway inhibitor and antitumour agent) and cyclophosphamide (a highly toxic ovarian anticancer agent) prevent cyclophosphamide-induced ovarian reserve loss and inhibit tumour proliferation in a breast cancer xenograft mouse model?

SUMMARY ANSWER: Daily concomitant administration of rapamycin and a cyclic regimen of cyclophosphamide, which has sufficient antitumour effects as a single agent, suppressed cyclophosphamide-induced primordial follicle loss by inhibiting primordial follicle activation in a breast cancer xenograft mouse model, suggesting the potential of an additive inhibitory effect against tumour proliferation.

WHAT IS KNOWN ALREADY: Cyclophosphamide stimulates primordial follicles by activating the mammalian target of the rapamycin (mTOR) pathway, resulting in the accumulation of primary follicles, most of which undergo apoptosis. Rapamycin, an mTOR inhibitor, regulates primordial follicle activation and exhibits potential inhibitory effects against breast cancer cell proliferation.

STUDY DESIGN, SIZE, DURATION: To assess ovarian follicular apoptosis, 3 weeks after administering breast cancer cells, 8-week-old mice were randomized into three treatment groups: control, cyclophosphamide, and cyclophosphamide + rapamycin (Cy + Rap) (n = 5 or 6 mice/group). Mice were treated with rapamycin or vehicle control for 1 week, followed by a single dose of cyclophosphamide or vehicle control. Subsequently, the ovaries were resected 24 h after cyclophosphamide administration (short-term treatment groups). To evaluate follicle abundance and the mTOR pathway in ovaries, as well as the antitumour effects and impact on the mTOR pathway in tumours, 8-week-old xenograft breast cancer transplanted mice were randomized into three treatment groups: vehicle control, Cy, and Cy + Rap (n = 6 or 7 mice/group). Rapamycin (5 mg/kg) or the vehicle was administered daily for 29 days. Cyclophosphamide (120 mg/kg) or the vehicle was administered thrice weekly (long-term treatment groups). The tumour diameter was measured weekly. Seven days after the last cyclophosphamide treatment, the ovaries were harvested, fixed, and sectioned (for follicle counting) or frozen (for further analysis). Similarly, the tumours were resected and fixed or frozen.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) was performed to examine ovarian follicular apoptosis in the short-term treatment groups. All subsequent experiments were conducted in the long-term treatment groups. Tumour growth was evaluated using the tumour volume index. The tumour volume index indicates the relative volume, compared to the volume 3 weeks after tumour cell injection (at treatment initiation) set to 100%. Tumour cell proliferation was evaluated by Ki-67 immunostaining. Activation of the mTOR pathway in tumours was assessed using the protein extracts from tumours and analysed by western blotting. Haematoxylin and eosin staining of ovaries was used to perform differential follicle counts for primordial, primary, secondary, antral, and atretic follicles. Activation of the mTOR pathway in ovaries was assessed using protein extracts from whole ovaries and analysed by western blotting. Localization of mTOR pathway activation within ovaries was assessed by performing anti-phospho-S6 kinase (downstream of mTOR pathway) immunohistochemistry.

MAIN RESULTS AND THE ROLE OF CHANCE: Ovaries of the short-term treatment groups were resected 24 h after cyclophosphamide administration and subjected to TUNEL staining of apoptotic cells. No TUNEL-positive primordial follicles were detected in the control, Cy, and Cy + Rap groups. Conversely, many granulosa cells of growing follicles were TUNEL positive in the Cy group but negative in the control and Cy + Rap groups. All subsequent experimental results were obtained from the long-term treatment groups. The tumour volume index stabilized at a mean of 160-200% in the Cy group and 130% in the Cy + Rap group throughout the treatment period. In contrast, tumours in the vehicle control group grew continuously with a mean tumour volume index of 600%, significantly greater than that of the two treatment groups. Based on the western blot analysis of tumours, the mTOR pathway was activated in the vehicle control group and downregulated in the Cy + Rap group when compared with the control and Cy groups. Ki-67 immunostaining of tumours showed significant inhibition of cell proliferation in the Cy + Rap group when compared with that in the control and Cy groups. The ovarian follicle count revealed that the Cy group had significantly fewer primordial follicles (P < 0.001) than the control group, whereas the Cy + Rap group had significantly higher number of primordial follicles (P < 0.001, 2.5 times) than the Cy group. The ratio of primary to primordial follicles was twice as high in the Cy group than in the control group; however, no significant difference was observed between the control group and the Cy + Rap group. Western blot analysis of ovaries revealed that the mTOR pathway was activated by cyclophosphamide and inhibited by rapamycin. The phospho-S6 kinase (pS6K)-positive primordial follicle rate was 2.7 times higher in the Cy group than in the control group. However, this effect was suppressed to a level similar to the control group in the Cy + Rap group.

LARGE SCALE DATA: None.

LIMITATIONS, REASONS FOR CAUTION: The combinatorial treatment of breast cancer tumours with rapamycin and cyclophosphamide elicited inhibitory effects on cell proliferative potential compared to cyclophosphamide monotherapy. However, no statistically significant additive effect was observed on tumour volume. Thus, the beneficial antitumour effect afforded by rapamycin administration on breast cancer could not be definitively proven. Although rapamycin has ovarian-protective effects, it does not fully counteract the ovarian toxicity of cyclophosphamide. Nevertheless, rapamycin is advantageous as an ovarian protective agent as it can be used in combination with other ovarian protective agents, such as hormonal therapy. Hence, in combination with other agents, mTOR inhibitors may be sufficiently ovario-protective against high-dose and cyclic cyclophosphamide regimens.

WIDER IMPLICATIONS OF THE FINDINGS: Compared with a cyclic cyclophosphamide regimen that replicates human clinical practice under breast cancer-bearing conditions, the combination with rapamycin mitigates the ovarian follicle loss of cyclophosphamide without interfering with the anticipated antitumour effects. Hence, rapamycin may represent a new non-invasive treatment option for cyclophosphamide-induced ovarian dysfunction in breast cancer patients.

STUDY FUNDING/COMPETING INTEREST(S): This work was not financially supported. The authors declare that they have no conflict of interest.

PMID:38734930 | DOI:10.1093/humrep/deae085

Rev Gastroenterol Peru. 2024 Jan-Mar;44(1):35-40.

ABSTRACT

OBJECTIVE: To determine the prevalence and genotypic characteristics of anal papillomaviruses in HIV-positive men who have sex with men (MSM).

MATERIALS AND METHODS: This is a prospective cross-sectional observational study of HIV-positive MSM at Almenara General Hospital between September 2017 and December 2018. HPV detection and typing was performed using a polymerase chain reaction technique that evaluated 21 genotypes stratified according to oncogenic risk into six low-risk and fifteen high-risk.

RESULTS: we evaluated 214 HIV-positive MSM. The overall prevalence of anal infection by papillomavirus infection was 70% (150/214). 86% (129/150) were caused by high-risk genotypes, 79% (102/129) of them were affected by a two or more-papillomavirus genotype. The most frequent high-risk genotypes were HPV-16, 31% (46/150); HPV-52, 22% (33/150); HPV-33, 21% (31/150); HPV-58, 21% (31/150) and HPV-31, 20% (30/150). In addition, HPV-18 reached 7% (10/150). The most frequent low-risk genotypes were HPV-6, 30% (45/150) and HPV-11, 29% (44/150).

CONCLUSIONS: Prevalence of anal papillomavirus infection in HIV-positive MSM is very high in the hospital investigated. Most of these infections occurs with high-risk oncogenic genotypes. Papillomavirus 16 was the most frequent high-risk genotype.

PMID:38734910

J Orthop Res. 2024 May 11. doi: 10.1002/jor.25876. Online ahead of print.

ABSTRACT

Primary total knee arthroplasty (TKA) is one of the most successful procedures for end-stage knee osteoarthritis. To determine the effect of preoperative knee joint function on postoperative quality of life in patients undergoing primary TKA. This descriptive cross-sectional study was conducted with a total of 208 patients in the orthopedics and traumatology clinic. Data were gathered with a personal information form, the Oxford Knee Score (OKS), and the EQ-5D-5L Quality Of Life Scale in the preoperative period, at postoperative 6th week, and at postoperative 3rd month. The data were analyzed using descriptive statistics, one-way analysis of variance (ANOVA), correlation analysis, and simple linear regression analysis. The mean age of the patients was 65.65 ± 7.01 years. Most patients (86.1%) were women, and 51.4% underwent left TKA. OKS scores indicated poor knee function preoperatively and gradually increased at postoperative 6th week and 3rd month. Preoperative OKS was a significant predictor of postoperative knee joint function and quality of life. This study shows that preoperative knee joint function significantly affects postoperative knee joint function and quality of life. These results demonstrate the importance of the surgery timing and suggest that performing surgery earlier in functional decline may be associated with a better outcome.

PMID:38734879 | DOI:10.1002/jor.25876

Int J Clin Pharm. 2024 May 11. doi: 10.1007/s11096-024-01742-w. Online ahead of print.

ABSTRACT

BACKGROUND: Medication errors significantly compromise patient safety in emergency departments. Although previous studies have investigated the prevalence of these errors in this setting, results have varied widely.

AIM: The aim was to report pooled data on the prevalence and severity of medication errors in emergency departments, as well as the proportion of patients affected by these errors.

METHOD: Systematic searches were conducted in Embase, PubMed, and the Cochrane Library from database inception until June 2023. Studies provided numerical data on medication errors within emergency departments were eligible for inclusion. Random-effects meta-analysis was employed to pool the prevalence of medication errors, the proportion of patients experiencing these errors, and the error severity levels. Heterogeneity among studies was assessed using the I² statistic and Cochran’s Q test.

RESULTS: Twenty-four studies met the inclusion criteria. The meta-analysis gave a pooled prevalence of medication errors in emergency departments of 22.6% (95% Confidence Interval [CI] 19.2-25.9%, I² = 99.9%, p < 0.001). The estimated proportion of patients experiencing medication errors was 36.3% (95% CI 28.3-44.3%, I² = 99.8%, p < 0.001). Of these errors, 42.6% (95% CI 5.0-80.1%) were potentially harmful but not life-threatening, while no-harm errors accounted for 57.3% (95% CI 14.1-100.0%).

CONCLUSION: The prevalence of medication errors, particularly those potentially harmful, underscores potential safety issues in emergency departments. It is imperative to develop and implement effective interventions aimed at reducing medication errors and enhancing patient safety in this setting.

PMID:38734867 | DOI:10.1007/s11096-024-01742-w

Int J Clin Pharm. 2024 May 11. doi: 10.1007/s11096-024-01739-5. Online ahead of print.

ABSTRACT

BACKGROUND: Patient satisfaction has been positively associated with adherence which is expected to impact outcomes. Although vital for successful implementation of biosimilar medicines, little is known about the patient perspective of transition.

AIM: The aim of this study was to investigate clinical outcomes and patient experience of transitioning between reference adalimumab and a biosimilar (SB5).

METHOD: iBaSS is a phase IV single-centre, prospective, randomised, single-blind, cross-over study in adult subjects with Crohn’s disease. Participants, stable on adalimumab before consent, received 24 weeks of treatment with both reference adalimumab and SB5. The primary outcome was the proportion of patients maintaining baseline clinical status throughout each treatment period, with patients’ perspective of disease control and treatment satisfaction assessed as secondary outcomes.

RESULTS: A total of 112 participants, representative of the heterogeneous patient populations encountered in routine clinical practice, were enrolled. A similar proportion of participants maintained baseline clinical status through each treatment period: 81.8% with reference adalimumab and 79.5% with SB5. Patient reported outcomes (IBD-Control questionnaire (SB5: 15.5; reference adalimumab 15) and TSQM), adverse events and therapeutic drug monitoring remained consistent through both treatment periods, although a higher median injection pain VAS score was noted with SB5 (53/100 versus 6/100 with reference adalimumab). The number of switches undertaken in the study did not impact serum drug concentration or immunogenicity.

CONCLUSION: This study, mimicking real world adalimumab transition, demonstrates that patients undertaking brand transition can be expected to have consistent clinical and satisfaction outcomes.

CLINICAL TRIAL REGISTERED WITH EUDRACT: Number 2018-004967-30.

PMID:38734866 | DOI:10.1007/s11096-024-01739-5

Arch Dermatol Res. 2024 May 11;316(5):159. doi: 10.1007/s00403-024-02882-9.

ABSTRACT

As an increasing number of women pursue careers in dermatology, the structure and culture of training must reflect the evolving needs of dermatology residents. To examine perceived barriers to and perceptions of family planning amongst dermatology residents capable of becoming pregnant, evidence-based principles were employed to develop a 40-question survey for dermatology residents in ACGME-accredited training programs. A pilot study was conducted with the Harvard Combined Dermatology Residency Training Program residents before full-scale national electronic survey distribution from April to June 2023. Information was collected regarding factors influencing attitudes towards becoming pregnant during residency, as well as information regarding residency program family leave, fertility preservation, and lactation policies. Ultimately, 95 dermatology residents capable of becoming pregnant completed the survey. The majority (77.9%) of respondents reported intentionally delaying having children because of their careers, and 73.7% believed there is a negative stigma attached to being pregnant or having children during dermatology residency. Of respondents who had not yet attempted to become pregnant, 75.3% were concerned about the possibility of future infertility. Of the 60% of respondents considering fertility preservation options, 84.6% noted concerns about these procedures being cost-prohibitive on a resident salary. Only 2% of respondents reported that cryopreservation was fully covered through their residency benefits, while 20% reported partial coverage. Reported program parental leave policies varied considerably with 54.9%, 25.4%, 1.4%, and 18.3% of residents reporting 4-6 weeks, 7-8 weeks, 9-10 weeks, and 11 + weeks of available leave, respectively. Notably, 53.5% of respondents reported that vacation or sick days must be used for parental leave. Respondents reported lactation policies and on-site childcare at 49.5% and 8.4% of residency programs, respectively. The trends noted in the survey responses signal concerning aspects of family planning and fertility for dermatology residents capable of becoming pregnant. Residency family planning policies, benefits, and resources should evolve and homogenize across programs to fully support trainees.

PMID:38734865 | DOI:10.1007/s00403-024-02882-9

Mol Biol Rep. 2024 May 11;51(1):651. doi: 10.1007/s11033-024-09605-3.

ABSTRACT

BACKGROUND: Canine atopic dermatitis (CAD) is a common genetically predisposed, inflammatory, and pruritic skin disorder that affects dogs globally. To date, there are no specific biomarkers available to diagnose CAD, and the current diagnosis is based on a combination of criteria including patient history, clinical signs, and exclusion of other relevant differential diagnoses.

METHODS AND RESULTS: We examined the gene expression of phosphodiesterase 4D (PDE4D) in peripheral blood mononuclear cells (PBMCs), as well as miR-203 and miR-483 in plasma, in three groups: healthy dogs, CAD dogs, and other inflammatory pruritic skin diseases (OIPSD) such as pemphigus foliaceus, scabies, cutaneous lymphoma, and dermatophytosis. Our results showed that PDE4D gene expression in the CAD group is statistically higher compared to those in the healthy and OIPSD groups, suggesting PDE4D may be a specific marker for CAD. Nevertheless, no correlation was found between PDE4D gene expression levels and the lesion severity gauged by CAD severity index-4 (CADESI-4). We also showed that miR-203 is a generic marker for clinical dermatitis and differentiates both CAD and OIPSD inflammatory conditions from healthy controls.

CONCLUSIONS: We show that PDE4D is a potential marker to differentiate CAD from non-atopic healthy and OIPSD while miR-203 may be a potential marker for general dermatologic inflammation. Future study of PDE4D and miR-203 on a larger scale is warranted.

PMID:38734860 | DOI:10.1007/s11033-024-09605-3

Insights Imaging. 2024 May 11;15(1):113. doi: 10.1186/s13244-024-01695-8.

ABSTRACT

OBJECTIVE: To investigate the structural alterations, neovascularity, and elasticity of tendons and the relationship between elasticity and the Patient Rated Tennis Elbow Evaluation score after undergoing US-guided fenestration or surgery in patients with chronic lateral elbow tendinopathy.

METHODS: Participants from the per-protocol population of a randomized trial conducted between October 2016 and June 2020 were included. The surgery and fenestration groups included 24 (mean age, 50 ± 7 years [standard deviation], 10 men) and 29 (47 ± 8 years, 18 men) participants, respectively. Ultrasound exams were performed at baseline, 6 months, and 12 months. Statistical analyses included linear mixed effects and generalized equation estimation models.

RESULTS: Fenestration had no significant impact on tendon thickness (p = 0.46). Conversely, surgery significantly increased tendon thickness at 6 months (p < 0.0001) and remained elevated at 12 months (p = 0.04). Tendon echostructure exhibited a group effect (p = 0.03), indicating a higher proportion of pathological scores in the surgery group post-intervention compared to the fenestration group. Both groups showed a similar reduction in neovascularity from 6 to 12 months postintervention (p = 0.006). Shear-wave velocity increased in the fenestration group at 6 months (p = 0.04), while the surgery group experienced a nonsignificant decrease at 6 months, with some improvement at 12 months (p = 0.08). Changes in shear-wave velocity did not correlate with clinical outcome.

CONCLUSIONS: Fenestration and surgery reduced tendon neovascularity over time. Unlike surgery, fenestration did not impact tendon size while improving tendon echostructure and elasticity.

CRITICAL RELEVANCE STATEMENT: Fenestration and surgery equally alleviated symptoms and decreased tendon neovascularity in lateral elbow tendinopathy; however, fenestration did not alter tendon thickness and improved echostructure and shear-wave velocity, suggesting shear-wave velocity’s potential for quantitatively monitoring tendon elasticity during healing.

KEY POINTS: Reliable markers for monitoring healing response and informing treatment protocols in elbow tendinopathy are lacking. Fenestration and surgery reduced tendon neovascularity, while fenestration improved tendon echostructure and shear-wave velocity. Shear-wave velocity may provide quantitative measures to monitor tendon elasticity in response to treatment.

PMID:38734857 | DOI:10.1186/s13244-024-01695-8

Arch Dermatol Res. 2024 May 11;316(5):168. doi: 10.1007/s00403-024-02907-3.

NO ABSTRACT

PMID:38734853 | DOI:10.1007/s00403-024-02907-3