Randomized trial: treatment of genitourinary syndrome of menopause using radiofrequency.

OBJECTIVE: A randomized controlled study was conducted to evaluate the safety and efficacy of radiofrequency treatment in postmenopausal women not willing to use or presenting a contraindication for menopause hormone therapy (MHT) and suffering from genitourinary syndrome of menopause (GSM). METHODS: A prospective randomized open study evaluated the effect of radiofrequency treatment versus a gel (control group) in postmenopausal women suffering from GSM. Patients were assessed at baseline and after 10-12 weeks of treatment for severity of vulvovaginal atrophy, dyspareunia, pH, vaginal smear maturation index, Vaginal Health Index and Female Sexual Function Index. The difference at baseline and after 10-12 weeks of treatment and the difference in improvement were tested between groups by a two-sample t-test and the Mann-Whitney test. RESULTS: Due to the COVID-19 pandemic, we were only able to treat 48 patients (24 patients using radiofrequency and 24 patients using a gel). Globally, at the end of the study, there were no differences in changes of the measured outcomes between the group of women treated with radiofrequency and the control group. CONCLUSION: Radiofrequency treatment was found to be safe, but was not superior to a gel, although the study lacked power. The study was registered at ClinicalTrials.gov (NCT03857893).

Determining clinically important differences in health-related quality of life in older patients with cancer undergoing chemotherapy or surgery.

PURPOSE: Using the EORTC Global Health Status (GHS) scale, we aimed to determine minimal clinically important differences (MCID) in health-related quality of life (HRQOL) changes for older cancer patients with a geriatric risk profile, as defined by the geriatric 8 (G8) health screening tool, undergoing treatment. Simultaneously, we assessed baseline patient characteristics prognostic for HRQOL changes. METHODS: Our analysis included 1424 (G8 ≤ 14) older patients with cancer scheduled to receive chemotherapy (n = 683) or surgery (n = 741). Anchor-based methods, linking the GHS score to clinical indicators, were used to determine MCID between baseline and follow-up at 3 months. A threshold of 0.2 standard deviation (SD) was used to exclude MCID estimates too small for interpretation. Logistic regressions analysed baseline patient characteristics prognostic for HRQOL changes. RESULTS: The 15-item Geriatric Depression Scale (GDS15), Visual Analogue Scale (VAS) for Fatigue and ECOG Performance Status (PS) were selected as clinical anchors. In the surgery group, MCID estimates for improvement and deterioration were ECOG PS (5*, 11*), GDS15 (5*, 2) and VAS Fatigue (3, 9*). In the chemotherapy group, MCID estimates for improvement and deterioration were ECOG PS (8*, 7*), GDS15 (5, 4) and VAS Fatigue (5, 5*). Estimates with * were > 0.2 SD threshold. Patients experiencing pain or malnutrition (surgery group) or fatigue (chemotherapy group) at baseline showed a significantly stable or improved HRQOL (p < 0.05) after their treatment. CONCLUSION: The reported MCID for improvement and deterioration depended on the anchor used and treatment received. The estimates can be used to evaluate significant changes in HRQOL and to determine sample sizes in clinical trials.

[A rare case of hepatotoxicity in geriatrics]. / Un cas rare d'hépatotoxicité en gériatrie.

We report a case of hepatotoxicity following the introduction of two drugs to treat a 81 years old man. The presence of liver alterations following the introduction of a new drug must suggest an adverse drug reaction. Manifestations of adverse drug reactions are often non-specific. Thus, the most important problem in assessing adverse drug reactions is establishing whether there is a causal association between the suspected drug and the untoward clinical event. The use of the Naranjo score could help the clinician to assess the probability of a causal relationship between a drug and the suspected adverse drug reaction.

Nous présentons le cas d'un patient de 81 ans qui développe une hépatotoxité après l'introduction de deux médicaments dans son traitement. La présence d'une perturbation du bilan hépatique à l'introduction d'un nouveau médicament doit faire évoquer une hépatotoxicité médicamenteuse. Les manifestations des effets secondaires médicamenteux ne sont généralement pas spécifiques. Dans ce contexte, le problème le plus important pour le clinicien est d'établir la probabilité d'une relation causale entre l'effet et le médicament suspecté. Le calcul du score de Naranjo permet d'aider le clinicien dans l'évaluation de la probabilité d'une relation causale entre un médicament et la suspicion de l'apparition d'un effet secondaire.

Adherence to geriatric assessment-based recommendations in older patients with cancer: a multicenter prospective cohort study in Belgium.

Background: In the general older population, geriatric assessment (GA)-guided treatment plans can improve overall survival, quality of life and functional status (FS). In GA-related research in geriatric oncology, studies mainly focused on geriatric screening and GA but not on geriatric recommendations, interventions and follow-up. The aim of this study was to investigate the adherence to geriatric recommendations and subsequent actions undertaken in older patients with cancer. Patient and methods: A prospective Belgian multicenter (N = 22) cohort study included patients ≥70 years with a malignant tumor upon oncologic treatment decision. Patients with an abnormal result on the geriatric screening (G8 ≤14/17) underwent GA. Geriatric recommendations were formulated based on GA results. At follow-up the adherence to geriatric recommendations was documented including a description of actions undertaken. Results: From November 2012 till February 2015, G8 screening was carried out in 8451 patients, of which 5838 patients had an abnormal result. Geriatric recommendations data were available for 5631 patients. Geriatric recommendations were made for 4459 patients. Geriatric interventions data were available for 4167 patients. A total of 12 384 geriatric recommendations were made. At least one different geriatric recommendation was implemented in 2874 patients. A dietician, social worker and geriatrician intervened most frequently for problems detected on the nutritional, social and functional domain. A total of 7569 actions were undertaken for a total of 5725 geriatric interventions, most frequently nutritional support and supplements, extended home care and psychological support. Conclusions: This large-scale Belgian study focuses on the adherence to geriatric recommendations and subsequent actions undertaken and contributes to the optimal management of older patients with cancer. We identified the domains for which geriatric recommendations are most frequently made and adhered to, and which referrals to other health care workers and facilities are frequently applied in the multidisciplinary approach of older patients with cancer.

A Belgian Survey on Geriatric Assessment in Oncology Focusing on Large-Scale Implementation and Related Barriers and Facilitators.

OBJECTIVES: The aim of this study is to describe a large-scale, Belgian implementation project about geriatric assessment (=GA) in daily oncology practice and to identify barriers and facilitators for implementing GA in this setting. Design / setting / participants: The principal investigator of every participating hospital (n=22) was invited to complete a newly developed questionnaire with closed- and open-ended questions. The closed-ended questions surveyed how GA was implemented. The open-ended questions identified barriers and facilitators for the implementation of GA in daily oncology practice. Descriptive statistics and conventional content analysis were performed as appropriate. RESULTS: Qualifying criteria (e.g. disease status and cancer type) for GA varied substantially between hospitals. Thirteen hospitals (59.1%) succeeded to screen more than half of eligible patients. Most hospitals reported that GA data and follow-up data had been collected in almost all screened patients. Implementing geriatric recommendations and formulating new geriatric recommendations at the time of follow-up are important opportunities for improvement. The majority of identified barriers were organizational, with high workload, lack of time or financial/staffing problems as most cited. The most cited facilitators were all related to collaboration. CONCLUSION: Interventions to improve the implementation of GA in older patients with cancer need to address a wide range of factors, with organization and collaboration as key elements. All stakeholders, seeking to improve the implementation of GA in older patients with cancer, should consider and address the identified barriers and facilitators.

[Appropriate use of psychotropic drugs in institutionalized elderly presenting acute confusional state (delirium)]. / Usage adéquat des psychotropes chez les personnes âgées institutionnalisées en cas d'état confusionnel aigu (delirium).

Delirium (acute confusion) is a common, morbid, and costly geriatric syndrome that affects onethird of hospitalized older adults. As evidence mounts that delirium may persist for weeks to months, concern about delirium can no longer be restricted to acute hospitals. We present a review about non-pharmacologic and pharmacologic management of delirium in institution.

Le " Delirium " (état confusionnel) est un syndrome gériatrique fréquent et coûteux qui affecte un tiers des personnes âgées hospitalisées ; sa prévalence en institution est mal connue. Il apparaît que ce syndrome peut persister pendant des semaines à des mois, et n'est donc pas limité aux hospitalisations aiguës. Nous présentons une revue de la littérature sur la prise en charge du delirium en institution suivie d'une proposition d'algorithme définissant l'approche pharmacologique et non pharmacologique de ce syndrome gériatrique.

Diffusion kurtosis imaging probes cortical alterations and white matter pathology following cuprizone induced demyelination and spontaneous remyelination.

Although MRI is the gold standard for the diagnosis and monitoring of multiple sclerosis (MS), current conventional MRI techniques often fail to detect cortical alterations and provide little information about gliosis, axonal damage and myelin status of lesioned areas. Diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) provide sensitive and complementary measures of the neural tissue microstructure. Additionally, specific white matter tract integrity (WMTI) metrics modelling the diffusion in white matter were recently derived. In the current study we used the well-characterized cuprizone mouse model of central nervous system demyelination to assess the temporal evolution of diffusion tensor (DT), diffusion kurtosis tensor (DK) and WMTI-derived metrics following acute inflammatory demyelination and spontaneous remyelination. While DT-derived metrics were unable to detect cuprizone induced cortical alterations, the mean kurtosis (MK) and radial kurtosis (RK) were found decreased under cuprizone administration, as compared to age-matched controls, in both the motor and somatosensory cortices. The MK remained decreased in the motor cortices at the end of the recovery period, reflecting long lasting impairment of myelination. In white matter, DT, DK and WMTI-derived metrics enabled the detection of cuprizone induced changes differentially according to the stage and the severity of the lesion. More specifically, the MK, the RK and the axonal water fraction (AWF) were the most sensitive for the detection of cuprizone induced changes in the genu of the corpus callosum, a region less affected by cuprizone administration. Additionally, microgliosis was associated with an increase of MK and RK during the acute inflammatory demyelination phase. In regions undergoing severe demyelination, namely the body and splenium of the corpus callosum, DT-derived metrics, notably the mean diffusion (MD) and radial diffusion (RD), were among the best discriminators between cuprizone and control groups, hence highlighting their ability to detect both acute and long lasting changes. Interestingly, WMTI-derived metrics showed the aptitude to distinguish between the different stages of the disease. Both the intra-axonal diffusivity (Da) and the AWF were found to be decreased in the cuprizone treated group, Da specifically decreased during the acute inflammatory demyelinating phase whereas the AWF decrease was associated to the spontaneous remyelination and the recovery period. Altogether our results demonstrate that DKI is sensitive to alterations of cortical areas and provides, along with WMTI metrics, information that is complementary to DT-derived metrics for the characterization of demyelination in both white and grey matter and subsequent inflammatory processes associated with a demyelinating event.

Correlates of fractures in elderly, diabetic outpatients.

It is widely recognized that patients presenting diabetes are at increased risk for fractures. In a retrospective case-control study, 101 cases were selected from medical charts of outpatients older than 70 with diabetes mellitus and a fracture within the past 5 years. Glycosylated hemoglobin (HbA1c) had been measured within 4 months around the assessment. Each case was matched for sex and age with one control, diabetic patient with no fracture. HbA1c level was similar in both groups. Patients with fractures presented significantly lower BMIs than controls, and had a higher rate of declared osteoporosis and comorbidity. A small number of cases were using vitamin D supplements while more were treated with benzodiazepine, opiates and Selective serotonin reuptake inhibitors (SSRI). This study suggests that, rather than the tight control of blood glucose, other factors such as medication and comorbidity could be associated with fracture risk in elderly diabetics.

Optimization and diagnostic performance of a single multiparameter lineblot in the serological workup of systemic sclerosis.

INTRODUCTION: Detection of systemic sclerosis-associated antibodies (SSc-Ab) in routine clinical practice is mostly restricted to anti-centromere and anti-topoisomerase-I antibodies. However, also other SSc-Ab (e.g. anti-RNA-polymerase-III, anti-PM/Scl, anti-fibrillarin and anti-Th/To) have been shown to be valuable diagnostic and prognostic markers for the disease, but testing methodologies for their detection are laborious and time-consuming. This study aimed to optimize interpretational criteria of a multiparameter lineblot (LB) for the parallel detection of SSc-Ab. We also assessed its global diagnostic value as an alternative for combined conventional techniques (CCT) in the serological workup of systemic sclerosis (SSc) patients. METHODS: The presence of SSc-Ab (anti-centromere, anti-topoisomerase-I, anti-RNA-polymerase-III, anti-PM/Scl, anti-fibrillarin and anti-Th/To) was identified by LB on 145 consecutive SSc patients and on 277 disease controls. Diagnostic sensitivity and specificity were calculated for both individual reactivities and the global LB. Cohen's kappa coefficient was used to examine agreement between LB and CCT and guided the definition of final interpretational criteria for LB. RESULTS: Applying the optimal cut-off values and interpretational criteria, LB identified SSc-Ab in 110 SSc patients (sensitivity=76%) and in 19 disease controls (specificity=93%). Globally, there was a substantial agreement between CCT and LB (κ=0.787, concordance 92.4%). LB and CCT showed a very good correlation (κ>0.800) for most SSc-Ab (anti-centromere, anti-topoisomerase-I, anti-RNA-polymerase-III and anti-PM/Scl). The best agreement for anti-RNA-polymerase-III and anti-PM/Scl was achieved when positivity for both components was taken as a criterion. CONCLUSIONS: LB is a reliable alternative for the laborious and time-consuming conventional techniques in the diagnostic workup of SSc, especially for the detection of anti-centromere, anti-topoisomerase-I, anti-RNA-polymerase-III and anti-PM/Scl.

Rituximab in diffuse cutaneous systemic sclerosis: an open-label clinical and histopathological study.

OBJECTIVES: The safety and potential efficacy of rituximab was examined in diffuse cutaneous systemic sclerosis (dc-SSc). METHODS: A 24 week open-label study in which eight patients with dc-SSc received an infusion of 1000 mg rituximab administered at baseline and day 15, together with 100 mg methylprednisolone at each infusion. Assessment included CD19+ peripheral blood lymphocyte number, skin sclerosis score, indices of internal organ functioning, the health assessment questionnaire disability index, the 36-item Short Form health survey and histopathological evaluation of the skin. RESULTS: Ritixumab induced effective B-cell depletion in all patients (<5 CD19+ cells/microl blood). There was a significant change in skin score at week 24 (p<0.001). Also, significant improvements were measured in the dermal hyalinised collagen content (p = 0.014) and dermal myofibroblast numbers (p = 0.011). Two serious adverse events occurred, which were thought to be unrelated to the rituximab treatment. CONCLUSIONS: Rituximab appears to be well tolerated and may have potential efficacy for skin disease in dc-SSc.

Validation of a new screening strategy for anti-extractable nuclear antigen antibodies.

OBJECTIVE: Although indirect immunofluorescence (IIF) is the most widely applied screening test for antinuclear antibodies (ANA), it lacks specificity for the identification of specific diseases or antigen reactivities. The aim of the present study was to validate an anti-extractable nuclear antigen (ENA) screening strategy encompassing a three-step cascade whereby an ELISA with pooled specific ENA is positioned between the IIF and the final anti-ENA identification. METHODS: Sera from 4 populations were tested for anti-ENA using an automated ELISA (EliA Symphony) and a line immunoassay (INNO-LIA ANA update). RESULTS: At the manufacturer's cut-off, a 96% sensitivity (95% CI 94%-98%) and 96% specificity (95% CI 94%-98%) of EliA Symphony for anti-ENA was obtained in a consecutive selection of 328 IIF positive serum samples referred for ANA testing. In addition, a high sensitivity was demonstrated for anti-ENA reactivities in patients with SLE (99%, 95% CI 97%-101%) and SSc (100%), and for anti-ENA monoreactivities. CONCLUSION: The EliA Symphony test was shown to be a sensitive second-line screening test for anti-ENA antibodies. In the context of a high clinical suspicion of connective tissue disease or autoreactivities not included in the EliA Symphony assay, third-line testing may be useful, even if the anti-ENA screening is negative.

Over-representation of construction-related occupations in male patients with systemic sclerosis.

AIMS: Based on preliminary observations, we tested the hypothesis that construction-related occupations are associated with systemic sclerosis (SSc). METHODS: The professional occupation of 91 patients with SSc (71 females and 20 males) was recorded. Categorisation into construction-related and other professions was performed. A double definition was used for construction-related occupations. The first (limited) definition was based upon categories of the Belgian National Institute of Statistics (NIS) occupational list. The following occupations were considered construction-related: electricians, joiners, masons and tilers, plumbers and pipefitters. The use of this list also allows us to compare the distribution of professions in these patients with that in the general population. As the NIS occupational list is limitative and leaves out some "real-life" construction-related occupations, a second and broader interpretation was given to the concept of construction-related occupations. RESULTS: The prevalence of construction-related professions in males with SSc, according to the limited definition, was 10-fold higher than in the general working population (50% vs 5%; p<0.001). Interestingly, most of the patients with construction-related occupations were electricians. In the broader interpretation, 75% of the men with SSc fell into the category of construction-related occupations. CONCLUSIONS: The data show an association between SSc and professional occupation.

Do all anti-citrullinated protein/peptide antibody tests measure the same? Evaluation of discrepancy between anti-citrullinated protein/peptide antibody tests in patients with and without rheumatoid arthritis.

BACKGROUND: Different methods exist to demonstrate anti-citrullinated protein/peptide antibodies (ACPA). AIMS: To evaluate discrepancy between four ACPA tests. PATIENTS AND METHODS: Population 1 consisted of patients with a new diagnostic problem, including 86 patients with rheumatoid arthritis (RA) and 450 patients without RA. Population 2 consisted of 155 patients with RA who had long-standing disease. Population 3 consisted of 188 patients with psoriatic arthritis and in population 4 there were 192 patients with systemic lupus erythematosus. Populations 1 and 2 were tested with the anti-human fibrinogen antibody (AhfibA) test, anti-CCP2 from Eurodiagnostica (CCP2-euro), anti-CCP2 from Pharmacia (CCP2-phar) and anti-CCP3 test by Inova (CCP3). Samples were annotated as discrepant if positive in one and negative in at least one other test. Each discrepant sample was re-analysed in a different run. Populations 3 and 4 were analysed in the CCP2-euro and AhFibA test. RESULTS: In population 1, ACPA positivity was found in 17 of 450 (3.8%) patients without RA; 14 (82%) of these 17 samples were discrepant. In contrast, 61 of 86 (70.9%) patients with RA were ACPA positive of whom 18 of 61 (29.5%) were discrepant (70.9% vs. 29.5%, p<0.001). The discrepancies between tests could be partly attributed to borderline results, inter-assay discrepancy and inter-test variability. They were more prevalent in patients with systemic lupus erythematosus who were ACPA positive than in those with psoriatic arthritis who were ACPA positive. CONCLUSIONS: Discrepancy between different ACPA tests was observed attributable to the occurrence of borderline results, inter-assay variability and mainly to inter-test variability. The lowest inter-test discrepancy is observed between tests that use the same substrate.

[Sézary syndrome with ascitis: case report and review of the literature]. / Ascite associée a un syndrome de Sézary: cas clinique et revue de la littérature.

This case report describes the evolution of a mycosis fungoides into a Sézary syndrome. The originality of the case consists in the appearance of ascitis with Sézary cells during the leukemic phase. It is the second report of a such case. Mycosis fungoides and its leukemic variant, the Sézary syndrome, are primary cutaneous T-cell lymphomas. Their incidence is low. The treatments are topical in the early stages and systemic during the advanced stages. New immunomodulating treatments are in development. The existing therapeutic agents unfortunately do not improve the prognosis of the disease today.

Venous pooling during nitrate-stimulated tilt testing in patients with vasovagal syncope.

AIMS: To investigate the importance of venous pooling and variation in venous tone during nitrate-stimulated tilt testing in patients. METHODS: Ten patients with a history of vasovagal syncope underwent an upright tilt test after an injection of 99mTc-labelled albumin. A gamma camera was positioned at the level of the lower legs. The patients were tilted to 90 degrees for 30 min or until symptoms developed. In those subjects who did not show any symptoms before the end of the 30-min period, isosorbide dinitrate (ISDN) 5 mg was given sublingually and the test was prolonged for a maximum of 15 min. RESULTS: Nine of 10 patients needed nitrate stimulation to develop symptoms, and one patient remained symptom free following ISDN administration. Measurement of radioactivity revealed no significant increase in calf volume after nitrate stimulation (the mean volume increase was 77% before ISDN stimulation and a further 0.9% afterwards). CONCLUSIONS: The higher sensitivity for vasovagal syncope during upright tilt testing after administration of sublingual ISDN is not due to an increase in venous pooling in the lower extremities.

Comparative study of the intestinal absorption of three salts of calcium in young and elderly women.

A daily ingestion of 1000 to 1500 mg elemental calcium associated with vitamin D supplement is presently considered to be the adequate and least expensive therapy for senile osteoporosis. There exists only scarce data about calcium absorption with available calcium salts in elderly patients. We have compared the digestive absorption of calcium (Ca) citrate in soluble and solid form and calcium gluconolactate-carbonate in 15 young and 20 elderly, healthy women using the oral calcium loading test. The subjects were divided into two groups. In the first group, the absorption of solid Ca citrate (1000 mg Ca element) was compared to the absorption of Ca gluconolactate-carbonate (1000 mg Ca element) both in young (n = 7) and elderly women (n = 10). In the second group, the absorption of soluble Ca citrate (1000 mg Ca element) was compared to the absorption of Ca gluconolactate-carbonate (1000 mg Ca element) in young (n = 8) and elderly (n = 10) women. In the preload phase, basal calciuria was increased in elderly women (p < 0.01) although basal calcemia was similar in young and elderly women. After oral administration of the calcium salts, an increase in plasma Ca was observed in both groups which was greater for soluble Ca citrate and Ca gluconolactate than for solid Ca citrate. In young women, the increase in plasma calcium was significantly higher with soluble Ca citrate compared to Ca gluconolactate (p < 0.05). In elderly women, the postload calciuria was significantly higher for soluble Ca citrate (p < 0.05) and Ca gluconolactate (p < 0.05) compared to solid Ca citrate. A similar pattern was observed in young women, although it was not significant. In conclusion, an oral load of 1000 mg soluble Ca citrate and Ca gluconolactate-carbonate induces significant biochemical changes suggesting a better digestive absorption compared to Ca citrate in solid form, both in young and elderly women. We did not observe different response, between young and old patients.

[Physiopathology of bedsores]. / Physiopathologie des escarres.

Pressure is the primary pathogenic factor in the development of decubitus ulcers. Other major factors are shearing forces, friction and moisture. Significant intrinsic risk factors are immobility, age-related diseases, nutritional status, medications and smoking. The morbidity and mortality related to the complications of pressure sores are quite significant. Prevention is essential and is best achieved by identification of high risk patients. The therapeutic approach is based on the grade of pressure ulcer.