Surgical and/ or conservative treatment improves quality of life (EHP-30) in patients with endometriosis.

AIM: To investigate the quality of life of women with endometriosis before treatment and 3 months after the start of surgical and/or conservative treatment. SAMPLE AND METHODOLOGY: The sample comprised of 38 patients, of whom 26 underwent surgical treatment, 6 had pharmacological treatment, and 6 had both surgical and pharmacological treatment. The Endometriosis Health Profile (EHP-30) questionnaire in the Czech version and the Numeric Rating Scale (NRS) were used to assess quality of life. The questionnaires were completed before treatment and 3 months into the treatment. RESULTS AND DISCUSSION: When comparing quality of life with the EHP-30 questionnaire, 3 months after the start of treatment, significantly better quality of life scores were found in all domains except the domain "Infertility." Statistically significant improvement was observed in the domains of "Control and powerlessness," "Emotional well-being," and "Pain" (P < 0.0001). Pain assessment using NRS showed subjective improvement in pain during menstruation, outside menstruation, during intercourse, micturition, and defecation. Statistically significant improvement was reported in pain during menstruation and outside menstruation (P < 0.0001). CONCLUSION: Treatment of endometriosis improves the quality of life and also leads to a subjective reduction of pain intensity as one of the main symptoms of the disease.

Canadian Regulatory Framework and Regulatory Requirements for Cell and Gene Therapy Products.

Health Canada regulates gene therapy products and many cell therapy products as biological drugs under the Canadian Food and Drugs Act and its attendant regulations. Cellular products that meet certain criteria, including minimal manipulation and homologous use, may be subjected to a standards-based approach under the Safety of Human Cells, Tissues and Organs for Transplantation Regulations. The manufacture and clinical testing of cell and gene therapy products (CGTP) presents many challenges beyond those for protein biologics. Cells cannot be subjected to pathogen removal or inactivation procedures and must frequently be administered shortly after final formulation. Viral vector design and manufacturing control are critically important to overall product quality and linked to safety and efficacy in patients through concerns such as replication competence, vector integration, and vector shedding. In addition, for many CGTP, the value of nonclinical studies is largely limited to providing proof of concept, and the first meaningful data relating to appropriate dosing, safety parameters, and validity of surrogate or true determinants of efficacy must come from carefully designed clinical trials in patients. Addressing these numerous challenges requires application of various risk mitigation strategies and meeting regulatory expectations specifically adapted to the product types. Regulatory cooperation and harmonization at an international level are essential for progress in the development and commercialization of these products. However, particularly in the area of cell therapy, new regulatory paradigms may be needed to harness the benefits of clinical progress in situations where the resources and motivation to pursue a typical drug product approval pathway may be lacking. This chapter is dedicated to provide an overview of Health Canada regulatory oversight of CGTP.

Acute recurrent pancreatitis during 3rd trimester of pregnancy.

OBJECTIVE: We present an unusual case report of a pregnant patient with recurrent attacks of acute pancreatitis due to cholecystolithiasis. CONCLUSION: Acute pancreatitis in pregnancy is a rare disease. Unlike the non-pregnant population, it is characterized by a high recurrence rate. Acute pancreatitis during pregnancy has a negative effect on both the mother and the fetus. The treatment is modified depending on the trimester of pregnancy.

Do age-targeted messages increase cervical screening intentions in women aged 50-64 years with weak positive intentions? A randomised control trial in Great Britain.

Over 20% of women aged 50-64 in Britain have not attended cervical screening within the recommended 5-year interval. The aim of the present study was to investigate the impact of five messages, informed using strategies from the Behaviour Change Wheel, on strength of intention to attend cervical screening in women aged 50-64 with weak positive intentions to be screened when next invited. Women were randomised (2:2:1), into one of two intervention groups or a control group. The control group saw basic information about cervical screening. Intervention group 1 saw a social norms message and an outcome expectancy message. Intervention group 2 saw a risk reduction message and a response efficacy message. There was further randomisation within the two intervention groups (1:1) to test the effectiveness of message framing and age-targeted information. Lastly, both intervention groups were randomised (1:1) to see a message acknowledging the possible discomfort associated with screening and offering support, or the support message only. Data were included from 475 women, collected using an online survey in March 2022. Adjusting for baseline intention, social norms (p = .84), outcome expectancy (p = .51), risk reduction (p = .19), response efficacy (p = .23) and discomfort acknowledgement messages (p = .71) had no effect on intention strength. However, there was a significant increase in intention after reading multiple messages. These results suggest that although no single message has a significant impact on intentions, when combined, they may act together to increase intention strength. Further research will understand the impact of these messages when combined in information materials.

Multilevel musculo-fascial defect magnetic resonance study of female pelvic floor: retrospective case control study in women with pelvic floor dysfunction after the first vaginal delivery.

INTRODUCTION: Magnetic resonance imaging (MRI) provides a detailed display of the pelvic floor structures responsible for normal pelvic floor anatomy. The aim of the study is to assess the appearance of musculo-fascial defects in women with pelvic floor dysfunction following first vaginal delivery. MATERIAL AND METHODS: Analysis of axial T3 (Tesla 3) MRI scans from a case control study of symptomatic (n = 149) and asymptomatic (n = 60) women after first vaginal delivery. Presence and severity of pelvic organ support and attachment system defects in three axial pelvic planes were assessed. RESULTS: In the symptomatic group, major muscular defects were found in 67.1% (for pubovisceral muscle complex) and 87.9% (for iliococcygeal muscle). Only 6.7% of major pubovisceral and 35.0% of major iliococcygeal defects were identified in the controls (p = 0.000). Prolapse patients had an odds ratio (OR) of 22.1 (95% CI 8.94-54.67) to have major pubovisceral muscle complex defect and OR of 4.9 (95% CI 1.51-15.71) to have major iliococcygeal muscle defect. Fascial defects were found in 60.4% and 83.2% the symptomatic group, respectively. Those with prolapse had an OR of 29.1 (95% CI 9.77-86.31) to have facial defect at the level of pubovisceral muscle complex and an OR of 16.9 (95% CI 7.62-37.69) to have fascial defect at the level of iliococcygeal muscle. Uterosacral ligaments detachment was associated with prolapse with an OR of 10.1 (95% CI 4.01-25.29). For the model based on combination on all MRI markers, the area under the receiver operating characteristic curve is 0.921. CONCLUSIONS: This study provides comprehensive data about first vaginal delivery-induced changes in the levator ani muscle and endopelvic fascial attachment system. These changes are seen also in asymptomatic controls, but they are significantly less expressed.

Relationship between urethrovesical junction mobility changes and postoperative progression of stress urinary incontinence following sacrospinous ligament fixation - a subanalysis of a multicentre randomized study.

OBJECTIVES: The study aimed to assess the relationship between urethrovesical junction (UVJ) descent and development of de novo stress urinary incontinence (SUI) and postoperative progression of preexisting SUI following surgery for pelvic organ floor prolapse using the method of sacrospinal fixation (SSF). This was a secondary analysis of the SAME prospective randomized multicentre study (reg. no. NCT03053479) comparing three approaches to surgery for apical defects - sacropexy, SSF and transvaginal mesh. METHODS: The subanalysis included 81 patients with apical defects managed by SSF, either right-sided (N = 14, 17.3%) or bilateral (N = 67, 82.7%). Postoperative follow-up was assessed at 3 months (N = 59), 12 months (N = 47) and 24 months (N = 30). UVJ mobility at rest and with maximum effort, the Valsalva manoeuvre was determined using a standardized 3D/ 4D transperineal ultrasound protocol proposed by Dietz et al. De novo SUI and postoperative progression of preexisting SUI were ascertained from history. RESULTS: Preoperative demographic data (N = 81) were as follows: BMI 27.3 kg/ m2 (16.8-44.5), age 67.0 years (31-85), and parity 2 (1-6). Concomitant anterior repair was performed in 65.4%. Postoperative progression of SUI was 45.8% at 3 months, 21.3% at 12 months, and 23.3% at 24 months. There were significant differences between preoperative and postoperative UVJ descent values at 3, 12 and 24 months (P < 0.0001). Correlations between UVJ descent at 3, 12 and 24 months postoperatively and de novo SUI or progression of preexisting SUI at 3, 12 and 24 months postoperatively were not statistically significant (P = 0.051-0.883). Correlations between differences (preoperative UVJ descent minus UVJ descent at 3, 12 and 24 months postoperatively) and de novo SUI or progression of preexisting SUI at 3, 12 and 24 months postoperatively were not statistically significant (P = 0.691-0.779). CONCLUSIONS: The study showed significant changes in UVJ descent values preoperatively and at 3, 12 and 24 months after SSF. There were no significant correlations between UVJ descent and de novo SUI and postoperative progression of preexisting SUI following surgery for pelvic organ floor prolapse at 3-, 12- and 24-month follow-up. There were no signifi cant correlations between differences (preoperative UVJ descent minus UVJ descent at 3, 12 and 24 months postoperatively and de novo SUI and postoperative progression of preexisting SUI following surgery for pelvic organ floor prolapse at 3-, 12- and 24-month follow-up.

Review of the current use and evaluation of cell substrates for producing biologicals in selected countries.

In 2010, the WHO guidance document for the evaluation of cell substrates for producing biologicals was replaced with updated recommendations and in May 2013 an implementation workshop on the new recommendations was held in Beijing, China. As part of this workshop, a survey of the use and evaluation of cell substrates for producing biologicals was undertaken and the information obtained was updated in June 2014. The purpose of survey was to capture the status of national requirements related to cell substrates in various countries with particular emphasis on whether or not the updated WHO recommendations had been, or were to be, incorporated into national requirements. This paper reports the outcome of the survey and is based on information provided by regulators in eleven countries. Since the publication of the updated WHO recommendations, several activities such as the implementation workshop and publications have been undertaken by the WHO. The aim of these activities, including the publication of this article, is to contribute to the implementation of WHO recommendations so as to reduce regulatory gaps between national requirements and globally agreed expectations.

The impact of age-relevant and generic infographics on knowledge, attitudes and intention to attend cervical screening: A randomized controlled trial.

OBJECTIVES: Cervical screening uptake in England is falling. Infographics could strengthen intention to attend, increase positive attitudes and improve knowledge. Age targeting could improve these outcomes further. We tested the impact of generic and age-targeted infographics. DESIGN: A randomized controlled trial using an age-stratified, parallel-group design. METHODS: Women aged 25-64 (n = 2095) were recruited through an online panel and randomized to see one of the three infographics. We tested: (i) impact of a generic cervical screening infographic compared to a control infographic on an unrelated topic with all screening age women and (ii) impact of an age-targeted infographic compared to a generic cervical screening infographic with older women (50-64 years). Intentions, knowledge and attitudes were measured. RESULTS: Women aged 25-64 years who viewed the generic infographic had significantly higher intentions [F(1, 1513) = 6.14, p = .013, η p 2 = .004], more accurate beliefs about the timeline of cervical cancer development (OR: 5.18, 95% CI: 3.86-6.95), more accurate social norms (OR: 3.03, 95% CI: 2.38-3.87) and more positive beliefs about screening benefits (OR: 2.23, 95% CI: 1.52-3.28) than those viewing the control infographic. In the older age group, there was no significant difference in intention between those viewing the generic versus age-targeted versions [F(1, 607) = .03, p = .853, η p 2 < .001], but the age-targeted version was more engaging [F(1, 608) = 9.41, p = .002, η p 2 = .015]. CONCLUSIONS: A cervical screening infographic can result in more positive attitudes and better knowledge and may have a small impact on intentions. Although age targeting did not affect intention, it had a positive impact on engagement and may therefore be useful in encouraging women to read and process materials.

Prediabetes/early diabetes-associated neuropathy predominantly involves sensory small fibres.

The aim of this study was to investigate the characteristics of prediabetes (preDM) and early (<3 years) diabetes mellitus type 2 (eDM2)-associated neuropathy and the value of recently proposed diagnostic criteria for diabetic sensorimotor polyneuropathy (DSPN). A prospective case-control study in a group of 48 consecutive patients with eDM2, 16 preDM patients and 40 age- and sex-matched normoglycaemic controls was performed. Clinical and laboratory diagnostic tests were used to detect neuropathic abnormalities; these were further classified in terms of recent diagnostic criteria. Criteria for confirmed DSPN based on abnormal nerve conduction (NC) studies were met in 7 (14.6%) eDM2 patients compared to no control (p < 0.05), and the proportion significantly increased to 37.5% compared to 2.5% controls (p < 0.001), if intraepidermal nerve fibre density (IENFD) was used as an alternative criterion in addition to NC. The subclinical DSPN criteria based on NC abnormalities were met in 4.2% eDM2 patients, while the proportion of preDM and eDM2 cases with subclinical sensory small-fibre involvement documented by IENFD reached 12.5% and 22.9% compared with 2.5% controls (p = 0.005 for eDM2). The absolute IENFD values from distal leg were significantly lower in both eDM2 (p < 0.0001) and preDM patients (p = 0.005) compared to controls. Neuropathy associated with preDM/eDM2 predominantly involves sensory small fibres.

Testing key messages about extending cervical screening intervals.

OBJECTIVES: We tested the impact of different messages about the rationale for extended cervical screening intervals on acceptability of an extension. METHODS: Women in England aged 25-49 years (n = 2931) were randomised to a control group or one of 5 groups given different messages about extending cervical screening intervals from 3 to 5 years. Outcome measures were general acceptability and six components from the Theoretical Framework of Acceptability (TFA). RESULTS: The groups who saw additional messages (47-63%) were more likely to find the change acceptable than controls (43%). Messages about interval safety, test accuracy and speed of cell changes resulted in more positive affective-attitudes, higher ethicality beliefs, a better understanding of the reasons for extended intervals and greater belief in the safety of 5-year intervals. Being up-to-date with screening and previous abnormal results were associated with finding 5-yearly screening unacceptable. CONCLUSIONS: Emphasising the slow development of cell changes following an HPV negative result and the safety of longer intervals, alongside the accuracy of HPV primary screening is important. PRACTICAL IMPLICATIONS: Campaigns explaining the rationale for extended cervical screening intervals are likely to improve acceptability. Though women who feel at increased risk, may remain worried even when the rationale is explained.

Acceptability of extending HPV-based cervical screening intervals from 3 to 5 years: an interview study with women in England.

OBJECTIVES: The introduction of primary Human Papillomavirus (HPV) testing in the National Health Service (NHS) Cervical Screening Programme in England means the screening interval for 25-49 years can be extended from 3 to 5 years. We explored women's responses to the proposed interval extension. METHODS: We conducted semi-structured phone/video interviews with 22 women aged 25-49 years. Participants were selected to vary in age, socioeconomics and screening history. We explored attitudes to the current 3-year interval, then acceptability of a 5-year interval. Interviews were transcribed verbatim and analysed using framework analysis. RESULTS: Attitudes to the current 3-year interval varied; some wanted more frequent screening, believing cancer develops quickly. Some participants worried about the proposed change; others trusted it was evidence based. Frequent questions concerned the rationale and safety of longer intervals, speed of cancer development, the possibility of HPV being missed or cell changes occurring between screens. Many participants felt reassured when the interval change was explained alongside the move to HPV primary screening, of which most had previously been unaware. CONCLUSIONS: Communication of the interval change should be done in the context of broader information about HPV primary screening, emphasising that people who test negative for HPV are at lower risk of cell changes so can safely be screened every 5 years. The long time needed for HPV to develop into cervical cancer provides reassurance about safety, but it is important to be transparent that no screening test is perfect.

Testing the content for a targeted age-relevant intervention to promote cervical screening uptake in women aged 50-64 years.

OBJECTIVES: Low uptake of cervical screening in women in their 50s and 60s leaves them at elevated risk of cancer in older age. An age-targeted intervention could be an effective way to motivate older women to attend cervical screening. Our primary objective was to test the impact of different candidate messages on cervical screening intention strength. DESIGN: A cross-sectional online survey with randomized exposure to different candidate messages. METHODS: Women aged 50-64 years who were not intending to be screened when next invited were recruited through an online panel. Those meeting the inclusion criteria (n = 825) were randomized to one of three groups: (1) control group, (2) intervention group 1, (3) intervention group 2. Each intervention group saw three candidate messages. These included a descriptive social norms message, a diagram illustrating the likelihood of each possible screening outcome, a response efficacy message, a risk reduction message and an acknowledgement of the potential for screening discomfort. We tested age-targeted versions (vs. generic) of some messages. The primary outcome was screening intention strength. RESULTS: After adjusting for baseline intention, social norms (p = .425), outcome expectancy (p = .367), risk reduction (p = .090), response efficacy (p = .136) and discomfort acknowledgement messages (p = .181) had no effect on intention strength. Age-targeted messages did not result in greater intention than generic ones. CONCLUSIONS: There was no evidence that a single message used to convey social norms, outcome expectancy, risk reduction or response efficacy had an impact on intention strength for older women who did not plan to be screened in future.

Are subjects with spondylotic cervical cord encroachment at increased risk of cervical spinal cord injury after minor trauma?

The aim of the study was to analyse the risk of symptomatic myelopathy after minor trauma in patients with asymptomatic spondylotic cervical spinal cord encroachment (ASCCE). In a cohort of 199 patients with ASCCE, previously followed prospectively in a study investigating progression into symptomatic myelopathy, the authors looked retrospectively for traumatic episodes that may have involved injury to the cervical spine. A questionnaire and data file analysis were employed to highlight whatever hypothetical relationship might emerge with the development of symptomatic myelopathy. Fourteen traumatic episodes in the course of a follow-up of 44 months (median) were recorded in our group (who had been instructed to avoid risky activities), with no significant association with the development of symptomatic myelopathy (found in 45 cases). Only three minor traumatic events without fracture of the cervical spine were found among the symptomatic myelopathy cases, with no chronological relationship between trauma and myelopathy. Furthermore, 56 traumatic spinal cord events were found before the diagnosis of cervical cord encroachment was established, with no correlation to either type of compression (discogenic vs osteophytic). In conclusion, the risk of spinal cord injury after minor trauma of the cervical spine in patients with ASCCE appeared to be low in our cohort provided risky activities in these individuals are restricted. Implementation of preventive surgical decompression surgery into clinical practice in these individuals should be postponed until better-designed studies provide proof enough for it to take precedence over a conservative approach.

Maximising the acceptability of extended time intervals between screens in the NHS Cervical Screening Programme: An online experimental study.

OBJECTIVE: The NHS Cervical Screening Programme plans to increase the screening interval from 3 to 5 years for women aged 25-49 who test negative for human papillomavirus (HPV). This exploratory cross-sectional online survey tested the impact of different levels of information about the proposed change on acceptability of a longer interval. METHODS: Women aged 18-45 (n = 585) were individually randomised to one of three information exposure groups differing in the level of information provided about the screening interval change: (1) basic information; (2) basic information with additional detail about timeline of HPV infection; (3) as (2) but with the addition of a diagram. Acceptability of the change (favourable and unfavourable attitudes) was assessed post-exposure alongside HPV timeline beliefs. We used ANOVA and regression analyses to test for between-group differences. RESULTS: Women in Group 3 had higher scores on the favourable attitudes sub-scale compared with Group 1. Women in Groups 2 and 3 had more accurate timeline beliefs than those in Group 1. There were no between-group differences in unfavourable attitudes. After adjusting for demographic factors, a higher favourable attitudes score was independently predicted by being in Group 3 compared to Group 1, more accurate HPV timeline beliefs, and previous irregular or non-attendance at screening. CONCLUSIONS: Overall, acceptability of an increased screening interval was moderate, but providing women with information about the safety and rationale for this change may improve acceptability. In particular, communicating the long timeline from HPV exposure to cervical cancer may reassure women about the safety of the proposed changes.

Spinal Cord MR Diffusion Properties in Patients with Degenerative Cervical Cord Compression.

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) has previously been used as a biomarker of myelopathy in patients with degenerative cervical cord compression (DCCC). However, many factors may affect the diffusion properties of the spinal cord. This prospective study seeks to identify sources of variability in spinal cord DTI parameters in both DCCC patients and healthy subjects. METHODS: The study group included 130 patients with DCCC confirmed by magnetic resonance imaging and 71 control subjects without signs of DCCC. DTI data of the cervical spine were acquired in all subjects. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were measured at different levels of the spinal cord (SCLs). Statistical data analysis was then used to determine diffusion parameters in terms of age, sex, SCL, and spinal cord compression. RESULTS: Significant variations in FA and ADC values emerged when several spinal cord levels were mutually compared in the control group. FA values correlated significantly with age in the DCCC group and sex had a significant influence on ADC values in both groups. The two diffusion parameters in the DCCC group differed significantly between patients with clinical signs of mild-to-moderate myelopathy compared with asymptomatic patients, and correlated with measurements of spinal canal morphology. CONCLUSIONS: Diffusion parameters of the cervical spinal cord were thus shown to respond significantly to spinal cord compression, but were subject to interaction with several other factors including sex, age, and SCL. These findings may be important to the interpretation of DTI measurements in individual patients.

Prevalence and Imaging Characteristics of Nonmyelopathic and Myelopathic Spondylotic Cervical Cord Compression.

STUDY DESIGN: Cross-sectional population-based observational study. OBJECTIVE: To estimate the prevalence of nonmyelopathic spondylotic cervical cord compression (NMSCCC) and cervical spondylotic myelopathy (CSM) in a population older than 40 years and to evaluate the magnetic resonance imaging (MRI) characteristics of these conditions. SUMMARY OF BACKGROUND DATA: The prevalence of neither NMSCCC nor CSM is known and there exists no commonly accepted quantitative MRI definition of cervical cord compression. METHODS: A group of 183 randomly recruited volunteers, 93 women, median age 66 years, range 40-80 years, underwent MRI examination of the cervical spine and spinal cord on a 1.5 T device using conventional sequences from disc levels C2/C3 to C6/C7. The imaging criterion for cervical cord compression was defined as a change in spinal cord contour at the level of an intervertebral disc on axial or sagittal MRI scan. RESULTS: MRI signs of cervical cord compression were found in 108 individuals (59.0%; 95% CI: 51.5%-66.2%); their numbers increased with age from 31.6% in the fifth decade to 66.8% in the eighth. Clinical signs of symptomatic CSM were found in two cases (1.1%), and 75 cases (41.0%) were without compression. An anteroposterior cervical canal diameter at the level of intervertebral disc (CDdisc) of less than 9.9 mm was associated with the highest probability of NMSCCC-odds ratio (OR) = 32.5, followed by a compression ratio of ≤0.5: OR = 11.1. CONCLUSION: The prevalence of NMSCCC in a population older than 40 years is higher than previously reported and increases with age. CDdisc and compression ratio had the highest capacity to discriminate between subjects with and without asymptomatic compression, and their cut-off values could be used to objectify criteria for cervical cord compression. LEVEL OF EVIDENCE: 2.

Expression of growth-associated protein 43 in the skin nerve fibers of patients with type 2 diabetes mellitus.

The growth-associated protein 43 (GAP-43) is known as a marker of regenerating nerve fibers and their continuous remodeling in the adult human skin. The purpose of this pilot study was to investigate a possible role for GAP-43 in the detection of the early stages of small-fiber neuropathy in patients with type 2 diabetes mellitus (DM2) as compared with a well- established and validated parameter - intra-epidermal nerve fiber density (IENFD) of protein gene product 9.5 (PGP 9.5) immunoreactive intra-epidermal C fibers. In a group of 21 patients with DM2 within three years of diagnosis (13 men, 8 women; mean age 53.9±12.8; range 30-74) and a group of 17 healthy volunteers (8 men, 9 women; mean age 55.8±8.5; range 45-70 years), skin punch biopsies were taken from a distal calf and double immunostained with both PGP 9.5 and GAP-43. In healthy controls, 96.8% of 629 PGP 9.5 immunoreactive fibers were immunostained with GAP-43; the proportion of PGP 9.5 intra-epidermal nerve fibers immunoreactive for GAP-43 in control subjects ranged from 86.5 to 100%. In DM2 patients, IENFD was significantly lower compared to controls (median, 1.5 vs. 11.2/mm; p<0.001). The proportion of GAP-43 immunoreactive intraepidermal nerve fibers was significantly lower in DM2 patients compared to healthy controls (73.6% of 337 PGP 9.5 positive fibers; p<0.001); ranged from 0 to 98.1%. In conclusion, these results show that impaired regeneration of intra-epidermal C fibers in the early stages of type 2 diabetes mellitus, as indicated by GAP-43, might be a marker of incipient diabetic neuropathy.