Does dual oocyte retrieval with continuous FSH administration increase the number of mature oocytes in low responders? An open-label randomized controlled trial.

STUDY QUESTION: Is there an increase in the total number of metaphase II (MII) oocytes between a conventional ovarian stimulation (OS) and a double uninterrupted stimulation? SUMMARY ANSWER: There is no increase in the total number of MII oocytes when comparing one conventional OS to a continuous stimulation with double oocyte aspiration. WHAT IS KNOWN ALREADY: Based on the concept of multiple follicular waves, the combination of two stimulations in the same ovarian cycle has gained interest in patients with a low ovarian reserve. This so-called dual stimulation approach is usually characterized by a discontinuation of FSH administration for ∼5 days and appears to have a favourable impact on the number of retrieved oocytes without affecting the embryo quality or ploidy status. The outcomes of dual uninterrupted OS have not yet been studied. STUDY DESIGN, SIZE, DURATION: This was an open-label randomized controlled trial (RCT) with superiority design, performed in a single tertiary centre. Subjects were randomized with a 1:1 allocation into two groups between October 2019 and September 2021. All patients underwent a conventional stimulation with recombinant FSH. When two or more follicles of 17 mm were present, the final inclusion criterion was assessed; randomization occurred only in the presence of ≤9 follicles of ≥11 mm. In Group A, ovulation was triggered with hCG, and oocyte retrieval (OR) was performed 34-36 h later, followed by a fresh single or double embryo transfer (SET or DET) on Day 3/5. In Group B, ovulation was triggered with GnRH agonist, followed by another OS, without discontinuation of the FSH administration. In the presence of one or more follicles of ≥17 mm, the second stimulation was completed with hCG. A freeze-all strategy (Day 3/5) was applied for both retrievals, followed by transfer of one or two embryos in an artificially prepared frozen-thawed cycle. In the absence of one or more follicles of ≥17 mm after 13 additional days of stimulation, the second cycle was cancelled. All ORs were executed by a senior fertility specialist who was blinded for the first treatment, and all follicles >10 mm were aspirated, according to routine clinical practice. The primary outcome was the total number of MII oocytes. Patients were followed up until all embryos were transferred, or until live birth was achieved. Other secondary outcomes included the number of cumulus-oocyte complexes (COCs), the number of good quality embryos (Day 3/5), the ongoing pregnancy rate, and gonadotropin consumption. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients between 25 and 40 years old, with an anti-Müllerian hormone level of ≤1.5 ng/ml, antral follicle count of ≤6, or ≤5 oocytes after a previous stimulation, were included. At the start, 70 patients were eligible for participation in the trial, of whom 48 patients fulfilled the final inclusion criterium and were randomized. After drop-out of two patients, 23 patients were randomized to a single round of OS (Group A), and 23 patients were randomized to two uninterrupted rounds of OS (Group B). MAIN RESULTS AND THE ROLE OF CHANCE: Baseline characteristics were similar between both groups. The cumulative number of COCs and MII oocytes after completion of the second OR was similar in Group A and Group B [5.3 ± 2.7 versus 5.3 ± 3.0 (P = 0.95); 4.1 ± 2.4 versus 4.3 ± 2.7 (P = 0.77)]. Likewise, a comparable number of excellent and good quality embryos was available on Day 3 (3.0 ± 2.0 versus 2.7 ± 2.0; P = 0.63). In Group B, the cancellation rate due to insufficient response to the second round of stimulation was 39.1% (9/23). When focusing on the first stimulation in both groups, there were no significant differences regarding basal FSH, gonadotropin consumption, and the number of preovulatory follicles. After the first OR, the mean number of COC and MII oocytes was significantly higher in Group A (who had hCG triggering), compared to Group B (who had GnRH agonist triggering) [5.3 ± 2.7 versus 3.3 ± 2.2; difference 95% CI (0.54 to 3.45), P = 0.004 and 4.1 ± 2.4 versus 3.0 ± 2.2; difference 95% CI (-0.15 to 2.6), P = 0.05, respectively]. Likewise, the number of excellent and good quality embryos on Day 3 was significantly higher (3.0 ± 2.0 versus 1.9 ± 1.7; P = 0.02) in Group A. LIMITATIONS, REASONS FOR CAUTION: This study was powered to demonstrate superiority for the number of MII oocytes after dual stimulation. Investigating the impact of dual stimulation on pregnancy rates would have required a larger sample size. Furthermore, the heterogeneity in embryo vitrification and transfer policies precluded a correct comparison of embryologic outcomes between both groups. WIDER IMPLICATIONS OF THE FINDINGS: This is the first RCT investigating the role of continuous stimulation with double aspiration in low responders. Our results show no statistically significant differences in the cumulative number of MII oocytes between one conventional stimulation with fresh ET and two consecutive stimulations with a freeze-only approach. Furthermore, the observed suboptimal oocyte yield after agonist ovulation triggering in low responders in the dual uninterrupted OS group is a reason for concern and further scrutiny, given that previous RCTs have shown similar outcomes in normal and high responders after hCG and GnRH agonist triggers. STUDY FUNDING/COMPETING INTEREST(S): This work was supported in part by a research grant from Organon. H.T. received honoraria for lectures and presentations from Abbott, Cooper Surgical, Gedeon-Richter, Cook, Goodlife, and Ferring. L.B. received fees for lectures from Merck & Organon and support for attending ESHRE 2023. M.D.V. reports fees for lectures from Ferring, Merck, Organon, IBSA, Gedeon Richter, and Cooper Surgical and support for attending ASRM 2023. S.M. received honoraria for lectures and presentations from Abbott, Cooper Surgical, Gedeon-Richter, IBSA, and Merck. C.B. was on the Advisory board and received consulting fees from Theramex and received honoraria for lectures and presentations from Abbott, Ferring, Gedeon-Richter, IBSA, and Merck. TRIAL REGISTRATION NUMBER: NCT03846544. TRIAL REGISTRATION DATE: 19 February 2019. DATE OF FIRST PATIENT'S ENROLMENT: 28 October 2019.

Enzymatic tissue processing after testicular biopsy in non-obstructive azoospermia enhances sperm retrieval.

STUDY QUESTION: What is the added value of enzymatic processing of testicular biopsies on testicular sperm retrieval (SR) rates for patients with non-obstructive azoospermia (NOA)? SUMMARY ANSWER: In addition to mechanical mincing, enzymatic digestion increased SR rates in testicular biopsies of NOA patients. WHAT IS KNOWN ALREADY: Many studies focus on the surgical approach to optimize recovery of testicular sperm in NOA, and in spite of that, controversy still exists about whether the type of surgery makes any difference as long as multiple biopsies are taken. Few studies, however, focus on the role of the IVF laboratory and the benefit of additional lab procedures, e.g. enzymatic digestion, in order to optimize SR rates. STUDY DESIGN SIZE DURATION: This retrospective single-center cohort study included all patients who underwent their first testicular sperm extraction (TESE) by open multiple-biopsy method between January 2004 and July 2022. Only patients with a normal karyotype, absence of Y-q deletions and a diagnosis of NOA based on histology were included. The primary outcome was SR rate after mincing and/or enzymes. The secondary outcome was cumulative live birth (CLB) after ICSI with fresh TESE and subsequent ICSI cycles with frozen TESE. PARTICIPANTS/MATERIALS SETTING METHODS: Multiple biopsies were obtained from the testis, unilaterally or bilaterally, on the day of oocyte retrieval. Upon mechanical mincing, biopsies were investigated for 30 min; when no or insufficient numbers of spermatozoa were observed, enzymatic treatment was performed using Collagenase type IV. Multivariable regression analysis was performed to predict CLB per TESE by adjusting for the following confounding factors: male FSH level, female age, and requirement of enzymatic digestion to find sperm. MAIN RESULTS AND THE ROLE OF CHANCE: We included 118 patients, of whom 72 (61.0%) had successful SR eventually. Spermatozoa were retrieved after mechanical mincing for 28 patients (23.7%; 28/118) or after additional enzymatic digestion for another 44 patients (37.2%; 44/118). Thus, of the 90 patients requiring enzymatic digestion, sperm were retrieved for 44 (48.9%). Male characteristics were not different between patients with SR after mincing or enzymatic digestion, in regard to mean age (34.5 vs 34.5 years), testis volume (10.2 vs 10.6 ml), FSH (17.8 vs 16.9 IU/l), cryptorchidism (21.4 vs 34.1%), varicocele (3.6 vs 4.6%), or histological diagnosis (Sertoli-cell only 53.6 vs 47.7%, maturation arrest 21.4 vs 38.6%, sclerosis/atrophy 25.0 vs 13.6%).Of the 72 patients with sperm available for ICSI, 23/72 (31.9%) achieved a live birth (LB) after the injection with fresh testicular sperm (and fresh or frozen embryo transfers). Of the remaining 49 patients without LB, 34 (69.4%) had supernumerary testicular sperm frozen. Of these 34 patients, 19 (55.9%) continued ICSI with frozen testicular sperm, and 9/19 (47.4%) had achieved an LB after ICSI with frozen testicular sperm. Thus, the total CLB was 32/118 (27.1%) per TESE or 32/72 (44.4%) per TESE with sperm retrieved.Of the female characteristics (couples with sperm available), only female age (30.3 vs 32.7 years; P = 0.042) was significantly lower in the group with a LB, compared to those without.The CLB with testicular sperm obtained after enzymatic digestion was 31.8% (14/44), while the CLB with sperm obtained after mincing alone was 64.3% (18/28). Multivariable logistic regression analysis showed that when enzymatic digestion was required, it was associated with a significant decrease in CLB per TESE (OR: 0.23 (0.08-0.7); P = 0.01). LIMITATIONS REASONS FOR CAUTION: Limitations of the study are related to the retrospective design. However, the selection of only patients with NOA, and specific characteristics (normal karyotype and absence Y-q deletion) and having their first TESE, strengthens our findings. WIDER IMPLICATIONS OF THE FINDINGS: Enzymatic processing increases the SR rate from testicular biopsies of NOA patients compared to mechanical mincing only, demonstrating the importance of an appropriate laboratory protocol. However, NOA patients should be counseled that when sperm have been found after enzymatic digestion, their chances to father a genetically own child may be lower compared to those not requiring enzymatic digestion. STUDY FUNDING/COMPETING INTERESTS: None reported. TRIAL REGISTRATION NUMBER: N/A.

A global perspective on bacterial diversity in the terrestrial deep subsurface.

While recent efforts to catalogue Earth's microbial diversity have focused upon surface and marine habitats, 12-20 % of Earth's biomass is suggested to exist in the terrestrial deep subsurface, compared to ~1.8 % in the deep subseafloor. Metagenomic studies of the terrestrial deep subsurface have yielded a trove of divergent and functionally important microbiomes from a range of localities. However, a wider perspective of microbial diversity and its relationship to environmental conditions within the terrestrial deep subsurface is still required. Our meta-analysis reveals that terrestrial deep subsurface microbiota are dominated by Betaproteobacteria, Gammaproteobacteria and Firmicutes, probably as a function of the diverse metabolic strategies of these taxa. Evidence was also found for a common small consortium of prevalent Betaproteobacteria and Gammaproteobacteria operational taxonomic units across the localities. This implies a core terrestrial deep subsurface community, irrespective of aquifer lithology, depth and other variables, that may play an important role in colonizing and sustaining microbial habitats in the deep terrestrial subsurface. An in silico contamination-aware approach to analysing this dataset underscores the importance of downstream methods for assuring that robust conclusions can be reached from deep subsurface-derived sequencing data. Understanding the global panorama of microbial diversity and ecological dynamics in the deep terrestrial subsurface provides a first step towards understanding the role of microbes in global subsurface element and nutrient cycling.

The effect of ventilation rate on outcome in adults receiving cardiopulmonary resuscitation.

AIM: To investigate whether a ventilation rate ≤10 breaths min-1 in adult cardiac arrest patients treated with tracheal intubation and chest compressions in a prehospital setting is associated with improved Return of Spontaneous Circulation (ROSC), survival to hospital discharge and one-year survival with favourable neurological outcome, compared to a ventilation rate >10 breaths min-1. METHODS: In this retrospective study, prospectively acquired data were analysed. Ventilation rates were measured with end-tidal CO2 and ventilation pressures. Analyses were corrected for age, sex, compression rate, compression depth, initial heart rhythm and cause of cardiac arrest. RESULTS: 337 of 652 patients met the inclusion criteria. Hyperventilation was common, with 85% of the patients ventilated >10 breaths min-1. The mean ventilation rate was 15.3 breaths min-1. The corrected odds ratio (OR) of ventilating >10 breaths min-1 for achieving ROSC was 0.91 (95% CI: 0.49 - 1.71, p = 0.78), the uncorrected OR of ventilating >10 breaths min-1 for survival to hospital discharge was 0.91 (95% CI: 0.30 - 2.77, p = 0.78), and the uncorrected OR of ventilating >10 breaths min1 for one-year survival with a favourable neurological outcome was 0.59 (95% CI: 0.19 - 1.87, p = 0.32). A logistic regression with continuous ventilation rate showed no significant relation with ROSC, and a ROC curve for ROSC showed a poor predictive performance (AUC: 0.52, 95% CI: 0.46 - 0.58), suggesting no other adequate cut-off value for ventilation rate. CONCLUSION: A ventilation rate ≤10 breaths min-1 was not associated with significantly improved outcomes compared to a ventilation rate >10 breaths min-1. No other adequate cut-off value could be proposed.

Plant-based sterols and stanols in health & disease: "Consequences of human development in a plant-based environment?"

Dietary plant sterols and stanols as present in our diet and in functional foods are well-known for their inhibitory effects on intestinal cholesterol absorption, which translates into lower low-density lipoprotein cholesterol concentrations. However, emerging evidence suggests that plant sterols and stanols have numerous additional health effects, which are largely unnoticed in the current scientific literature. Therefore, in this review we pose the intriguing question "What would have occurred if plant sterols and stanols had been discovered and embraced by disciplines such as immunology, hepatology, pulmonology or gastroenterology before being positioned as cholesterol-lowering molecules?" What would then have been the main benefits and fields of application of plant sterols and stanols today? We here discuss potential effects ranging from its presence and function intrauterine and in breast milk towards a potential role in the development of non-alcoholic steatohepatitis (NASH), cardiovascular disease (CVD), inflammatory bowel diseases (IBD) and allergic asthma. Interestingly, effects clearly depend on the route of entrance as observed in intestinal-failure associated liver disease (IFALD) during parenteral nutrition regimens. It is only until recently that effects beyond lowering of cholesterol concentrations are being explored systematically. Thus, there is a clear need to understand the full health effects of plant sterols and stanols.

Case series on acute HCV in HIV-negative men in regular clinical practice: a call for action.

BACKGROUND: The evidence that HIV treatment as prevention (TasP) and HIV pre-exposure prophylaxis (PrEP) reduces the risk of HIV transmission is overwhelming. But as PrEP and TasP can lead to increased sexual mixing between HIV positive and negative men who have sex with men (MSM), sexually transmitted infections such as acute hepatitis C (HCV), which were thought to be limited to HIV-infected MSM, could become more frequent in HIV uninfected MSM as well. The objective of this study was to describe a series of cases of sexually transmitted HCV infections in HIV-uninfected MSM in the Netherlands and Belgium. METHODS: Through the Dutch Acute HCV in HIV Study (a Dutch-Belgian prospective multicentre study on the treatment of acute HCV infection, NCT02600325) and the Be-PrEP-ared study (a PrEP project in Antwerp, EudraCT2015-000054-37) several acute HCV infections were detected in HIV-negative men. RESULTS: A newly acquired HCV infection was diagnosed in ten HIV-negative MSM. HCV was diagnosed at a sexually transmitted infection (STI) clinic (n = 2), by their general practitioner (n = 2), by their HIV physician (n = 1) or at a PrEP clinic (n = 5). Ten patients reported unprotected anal intercourse and four had a concomitant STI at the time of HCV diagnosis. Six patients reported using drugs during sex. CONCLUSIONS: Our observation calls for a larger nationwide epidemiological study on the prevalence, incidence and risk factors of HCV infection in HIV-uninfected MSM. In the changing landscape of TasP and PrEP, reliable and up-to-date epidemiological data on HCV among HIV-uninfected MSM are needed and will help in developing evidence-based testing policies.

Abdominal subcutaneous and visceral adipocyte size, lipolysis and inflammation relate to insulin resistance in male obese humans.

Obesity is associated with a disturbed adipose tissue (AT) function characterized by adipocyte hypertrophy, an impaired lipolysis and pro-inflammatory phenotype, which contributes to insulin resistance (IR). We investigated whether AT phenotype in different AT depots of obese individuals with and without type 2 diabetes mellitus (T2DM) is associated with whole-body IR. Subcutaneous (SC) and visceral (V) AT biopsies from 18 lean, 17 obese and 8 obese T2DM men were collected. AT phenotype was characterized by ex vivo measurement of basal and stimulated lipolysis (mature adipocytes), adipocyte size distribution (AT tissue sections) and AT immune cells (flow cytometry). In VAT, mean adipocyte size, CD45+ leukocytes and M1 macrophages were significantly increased in both obese groups compared to lean individuals. In SCAT, despite adipocyte hypertrophy, no significant differences in immune cell populations between groups were found. In SCAT, multiple linear regression analysis showed that none of the AT phenotype markers independently contributed to HOMA-IR while in VAT, mean adipocyte size was significantly related to HOMA-IR. In conclusion, beside adipocyte hypertrophy in VAT, M1 macrophage- or B-cell-mediated inflammation, may contribute to IR, while inflammation in hypertrophic SCAT does not seem to play a major role in IR.

NDRG4, an early detection marker for colorectal cancer, is specifically expressed in enteric neurons.

BACKGROUND: Promoter methylation of N-myc Downstream-Regulated Gene 4 (NDRG4) in fecal DNA is an established early detection marker for colorectal cancer (CRC). Despite its connection to CRC, NDRG4 is predominantly studied in brain and heart, with little to no knowledge about its expression or role in other organs. In this study, we aimed to determine the whole-body expression of NDRG4, with a focus on the intestinal tract. METHODS: We investigated NDRG4 expression throughout the body by immunohistochemistry, Western Blotting and in situ mRNA hybridization using tissues from NDRG4 wild-type, heterozygous and knockout mice and humans. In addition, we explored cell-specific expression of NDRG4 in murine whole-mount gut preparations using immunofluorescence and confocal microscopy. KEY RESULTS: NDRG4 is specifically expressed within nervous system structures throughout the body. In the intestinal tract of both mouse and man, NDRG4 immunoreactivity was restricted to the enteric nervous system (ENS), where it labeled cell bodies of the myenteric and submucosal plexuses and interconnecting nerve fibers. More precisely, NDRG4 expression was limited to neurons, as NDRG4 always co-localized with HuC/D (pan-neuronal marker) but never with GFAP (an enteric glial cell marker). Furthermore, NDRG4 was expressed in various neuropeptide Y positive neurons, but was only found in a minority (~10%) of neurons expressing neuronal nitric oxide synthase. CONCLUSIONS AND INFERENCES: NDRG4 is exclusively expressed by central, peripheral and enteric neurons/nerves, suggesting a neuronal-specific role of this protein. Our findings raise the question whether NDRG4, via the ENS, an understudied component of the tumor microenvironment, supports CRC development and/or progression.

Impact of childhood trauma on course of panic disorder: contribution of clinical and personality characteristics.

OBJECTIVE: To investigate the impact of childhood trauma on the clinical course of panic disorder and possible contributing factors. METHOD: Longitudinal data of 539 participants with a current panic disorder were collected from the Netherlands Study of Depression and Anxiety (NESDA). Childhood trauma was assessed with a structured interview and clinical course after 2 years with a DSM-IV-based diagnostic interview and the Life Chart Interview. RESULTS: At baseline, 54.5% reported childhood trauma, but this was not predictive of persistence of panic disorder. Emotional neglect and psychological abuse were associated with higher occurrence of anxiety disorders other than panic disorder (social phobia) and with higher chronicity of general anxiety symptoms (anxiety attacks or episodes and avoidance). Baseline clinical features (duration and severity of anxiety and depressive symptoms) and personality traits (neuroticism and extraversion) accounted for roughly 30-60% of the total effect of childhood trauma on chronicity of anxiety symptoms and on occurrence of other anxiety disorders. CONCLUSION: After two years, childhood trauma is associated with chronicity of anxiety symptoms and occurrence of social phobia, rather than persistence of panic disorder. These relationships are partially accounted for by duration and severity of anxiety and depressive symptoms, and neuroticism and extraversion.

Changes in Swallowing-related Quality of Life After Endoscopic Treatment For Zenker's Diverticulum Using SWAL-QOL Questionnaire.

Dysphagia affects the most cardinal of human functions: the ability to eat and drink. The aim of this prospective study was to evaluate swallowing dysfunction in patients diagnosed with Zenker's diverticulum using the Swallowing Quality of Life (SWAL-QOL) questionnaire preoperatively. In addition, SWAL-QOL was used to assess changes in the outcome of swallowing function after endoscopic treatment of Zenker's diverticulum compared to baseline. Pre- and postoperative SWAL-QOL data were analyzed in 25 patients who underwent endoscopic treatment of Zenker's diverticulum between January 2011 and December 2013. Patients were treated by different endoscopic techniques, depending on the size of the diverticulum: CO2 laser technique or stapler technique, or the combination of both techniques used in larger diverticula. Their mean age was 69 years, and 28% of patients were female. The mean interval between endoscopic surgery and completion of the postoperative SWAL-QOL was 85 days. The median (min-max) preoperative total SWAL-QOL score was 621 (226-925) out of 1100, indicating the perception of oropharyngeal dysphagia and diminished quality of life. Following endoscopic treatment of Zenker's diverticulum, significant improvement was demonstrated in the postoperative total SWAL-QOL score of 865 (406-1072) out of 1100 (p < 0.001). On the majority of subscales of SWAL-QOL there was significant improvement between pre- and postoperative scores. To the authors' knowledge, this is the first report in the literature on the changes in pre- and postoperative SWAL-QOL scores for patients with Zenker's diverticulum before and after treatment. The results of this study indicate that endoscopic treatment of Zenker's diverticulum leads to significant symptom relief as documented by significant changes in the majority of the SWAL-QOL domains.

Coblation® intracapsular tonsillectomy (tonsillotomy) in children: A prospective study of 500 consecutive cases with long-term follow-up.

OBJECTIVES: Intracapsular tonsillectomy (tonsillotomy) has been used internationally, mainly in the management of obstructive sleep apnoea, rather than recurrent tonsillitis, with few published data evaluating its use for this latter indication. We present long-term prospective data from 500 paediatric cases undergoing Coblation® intracapsular tonsillectomy, for both obstructive and infective indications. DESIGN: Prospective case series, March 2013-January 2016, all with completed follow-up. SETTING: Tertiary paediatric otolaryngological practice. PARTICIPANTS: A total of 500 consecutive patients (6 months to 18 years, mean 5.1 years) undergoing Coblation® intracapsular tonsillectomy (with or without adenoidectomy), for obstructive and/ or infective indications, almost exclusively under the care of the senior author (DJT). MAIN OUTCOME MEASURES: Validated parent-reported T-14 tonsil symptom questionnaires were used in all cases pre- and postoperatively, including in the long term. Parents also recorded duration of analgesia, time to return to school, any complications and whether they would recommend the procedure. RESULTS: With a mean follow-up 7.4 months, symptom control has been excellent (mean total T-14 score (/70) 31.01 preoperatively, 2.68 postoperatively, P<.0000001), with similar trends for obstructive and infective domains. Two small secondary haemorrhages required readmission and observation only (0.4%); otherwise, no complications, delayed discharges or readmissions occurred; 12/500 (2.4%) have since undergone revision tonsil surgery, 10 for obstructive and 2 for infective symptoms, the majority in very young children, with revision adenoidectomy at the same time. More than 99% of parents would recommend the surgery. CONCLUSIONS: Our experience of this technique has been very positive, with excellent control of both obstructive and infective symptoms, and exceptionally low rates of complications. Further work will be required to allow conclusive demonstration of its advantages over extracapsular tonsillectomy.

SolCos model-based individual reminiscence for older adults with mild to moderate dementia in nursing homes: a randomized controlled intervention study.

WHAT IS KNOWN ON THE SUBJECT?: To stimulate reminiscence of older adults with dementia performed individually or through group sessions is a well-known practice in nursing homes resulting in effects on behaviour and well-being as an alternative for medication. Robust scientific proof of the effectiveness of individual reminiscence therapy performed in nursing homes is sparse. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: We have provided individual standardized reminiscence therapy to residents with dementia. The therapy was developed and tested in a previous study and performed in this study by trained nursing home volunteers. In comparison with a control group who received usual care, residents who received the reminiscence therapy showed significant less depressive symptoms. Moreover, residents were, in general, attentive, open and collaborative during the sessions and volunteers experienced the sessions as useful and pleasant. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Individual reminiscence therapy can be learned and used by nursing home volunteers to improve care in nursing homes. ABSTRACT: Aim To investigate the effect of a standardized individualized intervention based on the SolCos transformational reminiscence model on depressive symptoms (primary outcome), cognition and behaviour (secondary outcomes) for older people with mild to moderate dementia, performed by trained nursing home volunteers as facilitators. Background Because of limited pharmacological treatment options for older adults with dementia relevant physical, sensory, psychological or social interventions offer alternative opportunities. Method Randomized controlled trial (ISRCTN74355073) was set up in two nursing homes with 29 and 31 residents in the intervention and the control groups respectively. Eighteen nursing home volunteers were trained to perform the reminiscence therapy. Various assessment scales were measured pre- and post-sessions. Results Linear regression analysis showed an impact on depressive symptoms. However, no impact was identified on cognition and behaviour. Facilitators experienced the sessions as useful and pleasant, and study participants were, in general, attentive, open and collaborative. Discussion Study results showed that organizing standardized individual reminiscence therapy with nursing home volunteers was feasible and study participants' attention and participation were overall good. Further study initiatives to explore the potential of individual reminiscence therapy within a person-centred framework are recommended in order to improve care in nursing homes.

Quality assessment of colonoscopy in Flanders: a voluntary survey among Flemish gastroenterologist.

Colonoscopy is an important endoscopic examination for the diagnosis and treatment of pathological conditions of the colon, like polyps and colorectal cancer. However, several factors determine the quality of colonoscopy and thus the quality of polyp and colorectal cancer detection. The Flemish Society of Gastroenterology (VVGE) performed a voluntary on-line registry among its members to identify quality of colonoscopy in Flanders, Belgium. 64 gastroenterologists voluntarily registered 4276 consecutive colonoscopies performed during a 3 month study period. Colonoscopy quality indicators were prospectively collected and analysed. Results showed a low voluntary participation rate (17%), acceptable overall adenoma detection rate of 20,5% and colorectal cancer interval rate of 5,4%. Complications were low (perforation 0,1% and major bleeding 1,5%). The current study showed that in Flanders, Belgium on-line registration of colonoscopy quality indicators is feasible and that quality of colonoscopy in daily practice meets the expectations of (inter)national guidelines. However, further improvement of the registry and an open debate on the quality control of colonoscopy in Flanders is warranted (Belgian Registry B30020096548).

Direct comparison of conventional radiography and cone-beam CT in small bone and joint trauma.

OBJECTIVE: To compare the diagnostic value of cone-beam computed tomography (CBCT) and conventional radiography (CR) after acute small bone or joint trauma. MATERIALS AND METHODS: Between March 2013 and January 2014, 231 patients with recent small bone or joint trauma underwent CR and subsequent CBCT. CR and CBCT examinations were independently assessed by two readers, blinded to the result of the other modality. The total number of fractures as well as the number of complex fractures were compared, and inter- and intraobserver agreement for CBCT was calculated. In addition, radiation doses and evaluation times for both modalities were noted and statistically compared. RESULTS: Fracture detection on CBCT increased by 35% and 37% for reader 1 and reader 2, respectively, and identification of complex fractures increased by 236% and 185%. Interobserver agreement for CBCT was almost perfect, as was intraobserver agreement for reader 1. The intraobserver agreement for reader 2 was substantial. Radiation doses and evaluation time were significantly higher for CBCT. CONCLUSION: CBCT detects significantly more small bone and joint fractures, in particular complex fractures, than CR. In the majority of cases, the clinical implication of the additionally detected fractures is limited, but in some patients (e.g., fracture-dislocations), the management is significantly influenced by these findings. As the radiation dose for CBCT substantially exceeds that of CR, we suggest adhering to CR as the first-line examination after small bone and joint trauma and keeping CBCT for patients with clinical-radiographic discordance or suspected complex fractures in need of further (preoperative) assessment.

Prevalence of residual excessive sleepiness during effective oral appliance therapy for sleep-disordered breathing.

BACKGROUND: Oral appliance therapy with a mandibular advancement device (OAm) can yield to complete therapeutic response (apnea-hypopnea index [AHI]<5 events/h), though some patients show little or no improvement in daytime sleepiness. The prevalence of residual excessive sleepiness (RES) despite effective treatment with OAm therapy is unknown. We aimed to determine the prevalence of RES in patients treated with a titratable custom-made duobloc OAm. METHODS: A prevalence study was performed, collecting data from 185 patients with an established diagnosis of sleep-disordered breathing (SDB) under OAm therapy with a titratable custom-made duobloc device (baseline data were male:female ratio, 129:56; age, 48±9 years; body mass index [BMI], 27±4 kg/m2; Epworth Sleepiness Scale [ESS] score, 10±5; and AHI, 19±12 events/h). A full-night polysomnography was performed at baseline and after 3 months of OAm therapy. Daytime sleepiness was assessed using the ESS with RES defined as an ESS score of 11 or higher out of 24, despite complete therapeutic response. RESULTS: Out of 185 patients, 84 patients (45%) showed a complete therapeutic response with an AHI of <5 events per hour after 3 months of OAm therapy. Despite this normalization of AHI, 27 out of these 84 patients (32%) showed RES and had a significantly higher baseline ESS (15±4 vs. 9±4; P<.001) and were younger (43±9 vs. 47±9; P=.028) compared to patients without RES. CONCLUSION: RES under OAm therapy showed a prevalence of up to 32% in SDB patients effectively treated with respect to AHI. Patients with RES were younger and had higher baseline daytime sleepiness.

Validation and translation of the Dutch tinnitus functional index.

OBJECTIVES: Several questionnaires are used to survey how tinnitus affects quality of life, making comparisons across studies difficult. The questionnaires also are used to measure treatment outcome but were not designed for this purpose. To address these issues, a new questionnaire has been suggested, the tinnitus functional index (TFI), which is highly responsive to treatment-related change. The current study aim was to translate and validate the TFI for a Dutch-speaking population. Factor analysis was performed to characterize the TFI profile in a large tinnitus population. METHODS: The questionnaire was translated using a translation-back translation procedure, and 263 patients in the ENT department of Antwerp University Hospital with tinnitus-related complaints completed it. Factor structure was assessed using exploratory analysis with oblique rotation and compared with the original questionnaire. Internal consistency was measured using Cronbach's alpha coefficient. Spearman correlations with the percentage of time aware of the tinnitus and the visual analogue scales (VAS) for maximum tinnitus loudness and mean tinnitus loudness were calculated to investigate convergent validity. RESULTS: The original eight-factor structure could be confirmed in the Dutch version of the TFI. Internal consistency (a=0.96) and convergent validity showed good results. Statistically significant correlations were found with the VAS for maximum loudness (r=0.59; p<0.001), VAS for mean loudness (r=0.66; p<0.001), and percentage of time aware of tinnitus (r=0.58; p<0.001). CONCLUSIONS: The Dutch version of the TFI is suitable for measuring in clinical and research settings how tinnitus affects daily life, with psychometric properties in line with the original version.

Prospective observational study of treatment pattern, effectiveness and safety of zoledronic acid therapy beyond 24 months in patients with multiple myeloma or bone metastases from solid tumors.

PURPOSE: To study the treatment patterns, effectiveness and safety of zoledronic acid (ZOL) beyond 2 years of therapy, given the paucity of data on long-term treatment in daily clinical practice. METHODS: Patients with multiple myeloma (MM) or solid tumor bone metastases (STM) and at least 24 months of regular q3-4w ZOL therapy were followed prospectively for an additional 18 months beyond the 24 months required for study entry. End-points included ZOL exposure, incidence of skeletal related events (SRE), and safety. RESULTS: In all, 298 evaluable patients were enrolled. The mean continuation rate of ZOL was 90.6%. Exposure to ZOL decreased with time in all patients, but was lower (50.0% vs. 67.6%; p<0.001) and with higher discontinuation rates (incidence rate ratio [IRR]=1.95; p=0.002) in MM compared to the STM group. ZOL suppressed the rate of SREs similarly during the study as compared to before inclusion (0.12 vs. 0.13 events per person-year; p=0.7). At 18 months, 84.5% remained SRE-free. In STM patients, persistent ZOL therapy was associated with lower SRE risk (hazard ratio [HR]=0.42; p=0.01), but not in MM. Renal deterioration occurred in 3.7% and osteonecrosis of the jaw (ONJ) developed in 6.0%, with dental trauma increasing ONJ risk (HR=4.67; p=0.002). CONCLUSIONS: Beyond 2 years of therapy, treatment patterns of ZOL were heterogeneous and SRE rates were low. The safety profile of ZOL was acceptable, and interrupting ZOL in patients with solid tumors was associated with a higher risk of SREs.

Using conventional HIV tests on oral fluid.

There is need for more evaluations of non-invasive tests in order to broaden the reach of testing programs and to perform large scale epidemiological studies. In this study, three different human immunodeficiency virus (HIV) enzyme linked immunosorbent assays (ELISAs) and one line immunoassay were evaluated to detect HIV antibodies in oral fluid samples. Specimens were collected, after informed consent was obtained, with the Oracol (MMD, Worcester, England) device. A total IgG quantitation test was performed to demonstrate the quality of the sample. Assessment of a modified protocol of the Vironostika HIV Ag/Ab, Enzygnost Anti-HIV 1/2 Plus Genscreen HIV-1/2 Version 2 and a line immune confirmatory assay the INNO-LIA HIV I/II score was done, using oral fluid specimens of 325 HIV positive and negative individuals. For the ELISAs, the addition of an extra internal oral fluid control was evaluated as well as different cut-offs, time between sampling and testing and the effect of drinking water just before sampling. Finally, the confirmatory test and some testing algorithms and combination of tests were discussed. The results obtained from the oral fluid specimens were compared with the gold standard on paired serum specimens. Firstly, there was no significant difference observed between the use of the kit controls and the oral fluid controls. New protocols and calculation of cut-offs were defined for two of the three ELISAs. High sensitivities and specificities were obtained with all three ELISAs without any statistical difference between the three tests. Secondly, no statistically significant difference was observed when samples were stored for different time periods between sampling and testing, meaning that a period of seven days at room temperature before testing is still acceptable. Thirdly, drinking water before sample collection did not interfere with the testing, although lower optical densities were observed. None of the positive samples were missed. In addition, the line immunoassay INNO-LIA HIV I/II score test is a promising test for confirmation of reactive oral fluid specimen, but more samples need to be validated in order to adapt the interpretation rules specifically for oral fluid specimens. Different choices/algorithms adapted for the purpose of testing can be proposed. In conclusion, it can be said that the commercial ELISAs with adapted protocol and cut-off values are suitable tools for making HIV test performance accessible to people. With this non-invasive sampling method, more eligible individuals can and will be selected for further HIV test on blood.

Work engagement supports nurse workforce stability and quality of care: nursing team-level analysis in psychiatric hospitals.

Research in healthcare settings reveals important links between work environment factors, burnout and organizational outcomes. Recently, research focuses on work engagement, the opposite (positive) pole from burnout. The current study investigated the relationship of nurse practice environment aspects and work engagement (vigour, dedication and absorption) to job outcomes and nurse-reported quality of care variables within teams using a multilevel design in psychiatric inpatient settings. Validated survey instruments were used in a cross-sectional design. Team-level analyses were performed with staff members (n = 357) from 32 clinical units in two psychiatric hospitals in Belgium. Favourable nurse practice environment aspects were associated with work engagement dimensions, and in turn work engagement was associated with job satisfaction, intention to stay in the profession and favourable nurse-reported quality of care variables. The strongest multivariate models suggested that dedication predicted positive job outcomes whereas nurse management predicted perceptions of quality of care. In addition, reports of quality of care by the interdisciplinary team were predicted by dedication, absorption, nurse-physician relations and nurse management. The study findings suggest that differences in vigour, dedication and absorption across teams associated with practice environment characteristics impact nurse job satisfaction, intention to stay and perceptions of quality of care.