Just and inclusive end-of-life decision-making for long-term care home residents with dementia: a qualitative study protocol.

BACKGROUND: Many people living with dementia eventually require care services and spend the remainder of their lives in long-term care (LTC) homes. Yet, many residents with dementia do not receive coordinated, quality palliative care. The stigma associated with dementia leads to an assumption that people living in the advanced stages of dementia are unable to express their end-of-life needs. As a result, people with dementia have fewer choices and limited access to palliative care. The purpose of this paper is to describe the protocol for a qualitative study that explores end-of-life decision-making processes for LTC home residents with dementia. METHODS/DESIGN: This study is informed by two theoretical concepts. First, it draws on a relational model of citizenship. The model recognizes the pre-reflective dimensions of agency as fundamental to being human (irrespective of cognitive impairment) and thereby necessitates that we cultivate an environment that supports these dimensions. This study also draws from Smith's critical feminist lens to foreground the influence of gender relations in decision-making processes towards palliative care goals for people with dementia and reveal the discursive mediums of power that legitimize and sanction social relations. This study employs a critical ethnographic methodology. Through data collection strategies of interview, observation, and document review, this study examines decision-making for LTC home residents with dementia and their paid (LTC home workers) and unpaid (family members) care partners. DISCUSSION: This research will expose the embedded structures and organizational factors that shape relationships and interactions in decision-making. This study may reveal new ways to promote equitable decision-making towards palliative care goals for LTC home residents with dementia and their care partners and help to improve their access to palliative care.

[Impact of luteal phase support by human chorionic gonadotropin (hCG) in intrauterine inseminations]. / Impact du soutien de la phase lutéale par Human Chorionic Gonadotropine (hCG) dans les inséminations intra-utérines.

OBJECTIVES: The objective of our study is to evaluate the impact of luteal phase support by hCG in intrauterine inseminations preceded by ovarian gonadotropin stimulation. METHODS: A retrospective study was conducted at the CHU of Nice between March 1, 2016 and October 31, 2017. During this period, 300 intrauterine inseminations were included in data analysis. Ovarian stimulation was performed by gonadotropins and a GnRH antagonist was added, if needed. Following a modification of standard operative procedure in the department, patients who performed an intrauterine insemination from December 1, 2016 received luteal phase support with two injections of hCG 1500 IU, performed at three days of interval. Pregnancy and ovarian hyperstimulation syndrome were the primary and secondary study endpoints, respectively. RESULTS: Out of 300 inseminations included in the analysis, 144 were performed with luteal phase support and 156 without support. No statistically significant difference in pregnancy rate was observed between these two groups (19.4% of pregnancy in the luteal phase support group and 15.38% in the group without luteal phase support, P=0.353). No ovarian hyperstimulation syndrome occurred over the course of the study. CONCLUSION: Our study shows a slight improvement of pregnancy rate in the group subjected to luteal phase support by hCG after intrauterine insemination, but the benefit was not significant. A randomised prospective study based on a large cohort could help to assess the effect of luteal phase support during intrauterine inseminations.

Feasibility of a tapering opioids prescription program for trauma patients at high risk of chronic consumption (TOPP-trauma): protocol for a pilot randomized controlled trial.

BACKGROUND: Opioid use disorder (OUD) and deaths related to the chronic use of opioids have increased significantly over the last two decades. Chronic consumption of opioids has been documented in many patients with traumatic injuries. Preliminary research findings have shown that interventions using cognitive-behavioral strategies were a promising adjunct in decreasing the burden associated with opioid consumption. Accordingly, the Tapering Opioids Prescription Program in Trauma (TOPP-Trauma) was developed. PURPOSE: To assess the feasibility of the TOPP-Trauma intervention and its research methods; and explore the potential efficacy of TOPP-Trauma in reducing opioid consumption. METHODS: A 2-arm pilot randomized controlled trial (RCT) will be conducted in patients presenting a high risk for chronic opioid consumption. Fifty participants at high risk for chronic consumption of opioid will receive either TOPP-Trauma or an educational pamphlet. The feasibility assessment of TOPP-Trauma will be based on the ability to provide its components as initially planned. Several parameters will be evaluated to determine the feasibility of the research methods, including the adequacy of the sampling pool, the dropout rate, and the ease of data collection. The morphine equivalent dose (MED) per day between both groups will be measured at 6 and 12 weeks. Pain intensity and pain interference with activities will also be evaluated at the same time points. DISCUSSION: This study will provide evidence on the feasibility of a preventive program aimed at reducing chronic opioid use in high risk trauma patients. Information will also be gathered on the methods that should be used to test the efficacy of such programs. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 40263056. Registered 26 May 2018.

[Barriers to the use of emergency contraception in a population consulting for an abortion]. / Évaluation lors d'une IVG des freins à l'utilisation de la contraception d'urgence.

OBJECTIVES: In France, one pregnancy out of three is unplanned. Half of those pregnancies lead to abortion. However, the use of emergency contraception is far from systematic. It is therefore relevant to question the reasons and factors linked to the low rate of use of emergency contraception. METHODS: A retrospective observational study was conducted in the orthogenic service of the University hospital Center of Nice, over a six weeks period. Patients were consulting in the context of voluntary termination of pregnancy and were subjected to a questionnaire during a semi-structured interview. The collected data were: age, degree of education, profession, size of their home town municipality, legal status, obstetrical history, contraception used at the time of unplanned pregnancy, emergency contraception background and justification for not using an emergency contraception. RESULTS: A total of one hundred and five questionnaires were studied. The absence of emergency contraception was due to an underestimation of the risk of pregnancy in 81% of cases. Among characteristic variables of the studied population, none was related to the non-use of emergency contraception. CONCLUSIONS: Independently of the patient profile, underestimation of the risk of pregnancy is the main cause of non-use of emergency contraception. It seems crucial to inform women with childbearing age and their families about their fertility and the basic mechanisms of fertility in order to reduce the number of unplanned pregnancies in France.

Utility of the QuantiFERON-TB Gold In-Tube assay for the diagnosis of tuberculosis in Moroccan children.

SETTING: The utility of interferon-gamma release assays (IGRAs), such as the QuantiFERON-TB Gold In-Tube (QFT-GIT) test, in diagnosing active tuberculosis (TB) in children is unclear and depends on the epidemiological setting. OBJECTIVE: To evaluate the performance of QFT-GIT for TB diagnosis in children living in Morocco, an intermediate TB incidence country with high bacille Calmette-Gurin vaccination coverage. DESIGN: We prospectively recruited 109 Moroccan children hospitalised for clinically suspected TB, all of whom were tested using QFT-GIT. RESULTS: For 81 of the 109 children, the final diagnosis was TB. The remaining 28 children did not have TB. QFT-GIT had a sensitivity of 66% (95%CI 5277) for the diagnosis of TB, and a specificity of 100% (95%CI 88100). The tuberculin skin test (TST) had lower sensitivity, at 46% (95%CI 3360), and its concordance with QFT-GIT was limited (69%). Combining QFT-GIT and TST results increased sensitivity to 83% (95%CI 6992). CONCLUSION: In epidemiological settings such as those found in Morocco, QFT-GIT is more sensitive than the TST for active TB diagnosis in children. Combining the TST and QFT-GIT would be useful for the diagnosis of active TB in children, in combination with clinical, radiological and laboratory data.

A genome-wide association study of pulmonary tuberculosis in Morocco.

Although epidemiological evidence suggests a human genetic basis of pulmonary tuberculosis (PTB) susceptibility, the identification of specific genes and alleles influencing PTB risk has proven to be difficult. Previous genome-wide association (GWA) studies have identified only three novel loci with modest effect sizes in sub-Saharan African and Russian populations. We performed a GWA study of 550,352 autosomal SNPs in a family-based discovery Moroccan sample (on the full population and on the subset with PTB diagnosis at <25 years), which identified 143 SNPs with p < 1 × 10(-4). The replication study in an independent case/control sample identified four SNPs displaying a p < 0.01 implicating the same risk allele. In the combined sample including 556 PTB subjects and 650 controls these four SNPs showed suggestive association (2 × 10(-6) < p < 4 × 10(-5)): rs358793 and rs17590261 were intergenic, while rs6786408 and rs916943 were located in introns of FOXP1 and AGMO, respectively. Both genes are involved in the function of macrophages, which are the site of latency and reactivation of Mycobacterium tuberculosis. The most significant finding (p = 2 × 10(-6)) was obtained for the AGMO SNP in an early (<25 years) age-at-onset subset, confirming the importance of considering age-at-onset to decipher the genetic basis of PTB. Although only suggestive, these findings highlight several avenues for future research in the human genetics of PTB.

Pott's disease in Moroccan children: clinical features and investigation of the interleukin-12/interferon-γ pathway.

SETTING: Tuberculosis spondylodiscitis (TS), or Pott's disease, an extra-pulmonary form of tuberculosis (TB), is rare and difficult to diagnose in children. Some cases of severe TB in children were recently explained by inborn errors of immunity affecting the interleukin-12/interferon-gamma (IL-12/IFN-γ) axis. OBJECTIVE: To analyse clinical data on Moroccan children with TS, and to perform immunological and genetic explorations of the IL-12/IFN-γ axis. DESIGN: We studied nine children with TS diagnosed between 2012 and 2014. We investigated the IL-12/IFN-γ circuit by both whole-blood assays and sequencing of the coding regions of 14 core genes of this pathway. RESULTS: A diagnosis of TS was based on a combination of clinical, biological, histological and radiological data. QuantiFERON(®)-TB Gold In-Tube results were positive in 75% of patients. Whole-blood assays showed normal IL-12 and IFN-γ production in all but one patient, who displayed impaired decreased response to IL-12. No candidate disease-causing mutations were detected in the exonic regions of the 14 genes. CONCLUSIONS: TS diagnosis in children remains challenging, and is based largely on imaging. Further investigations of TS in children are required to determine the role of genetic defects in pathways that may or may not be related to the IL-12/IFN-γ axis.

Pineal germinoma in a child with interferon-γ receptor 1 deficiency. case report and literature review.

Interferon-γ receptor 1 (IFN-γR1) deficiency is one of the primary immunodeficiencies conferring Mendelian Susceptibility to Mycobacterial Disease (MSMD). Some cases of neoplasms have been recently reported in patients with MSMD, underlying the already known link between immunodeficiency and carcinogenesis. We report the first case of intracranial tumour, i.e. pineal germinoma, in a 11-year-old patient with complete IFN-γR1 deficiency. The first clinical presentation of the genetic immunodeficiency dates back to when the child was aged 2 y and 10 mo, when he presented a multi-focal osteomyelitis caused by Mycobacterium scrofulaceum. The diagnosis of IFN-γR1 deficiency (523delT/523delT in IFNGR1 gene) was subsequently made. The child responded to antibiotic therapy and remained in stable clinical condition until the age of 11 years, when he started complaining of frontal, chronic headache. MRI revealed a solid pineal region mass lesion measuring 20 × 29 × 36 mm. Histological findings revealed a diagnosis of pineal germinoma. The patient received chemotherapy followed by local whole ventricular irradiation with boost on pineal site, experiencing complete remission, and to date he is tumor-free at four years follow-up. Four other cases of tumors have been reported in patients affected by MSMD in our knowledge: a case of Kaposi sarcoma, a case of B-cell lymphoma, a case of cutaneous squamous cell carcinoma and a case of oesophageal squamous cell carcinoma. In conclusion, in patients with MSMD, not only the surveillance of infectious diseases, but also that of tumors is important.

Corticosteroids in the management of brain-dead potential organ donors: a systematic review.

Summary Current guidelines recommend the administration of hormonal combination therapy including immunosuppressive doses of corticosteroids to donors with low left ventricular ejection fractions and to consider hormonal therapy administration to all donors. However, these recommendations are largely based on observational data. The aim of this systematic review (SR) was to assess the clinical efficacy and safety of corticosteroids in brain-dead potential organ donors. MEDLINE and EMBASE were searched from the earliest accessible date up to March 2013 with a qualified librarian. Studies comparing the effects of any corticosteroid with those of placebo, standard treatment, or another active comparator were sought. Two independent reviewers evaluated each citation retrieved and selected studies independently and in duplicate. A third independent reviewer resolved any disagreement. Outcomes included donor haemodynamics and oxygenation, organ procurement, recipient survival, and graft survival. This review included 11 randomized controlled trials (RCTs) and 14 observational studies. The majority used methylprednisolone and often combined it with other hormonal therapies. Ten out of the 11 RCTs yielded neutral results. However, in observational studies, use of corticosteroids generally resulted in improved donor haemodynamics and oxygenation status, increased organ procurement, and improved recipient and graft survival. Overall quality of included studies was poor, as most of them presented high risks of confounding. This SR highlights the low quality and conflicting evidence supporting the routine use of corticosteroids in the management of organ donors. A large trial evaluating the effect of corticosteroids on outcomes such as organ recovery and graft survival is warranted.

[Human genetics of tuberculosis]. / Génétique humaine de la tuberculose.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a major public health problem worldwide, resulting in 8.7 million new cases and 1.4 million deaths each year. One third of the world's population is exposed to M. tuberculosis and, after exposure, most, but not all, individuals become infected. Among infected subjects, only a minority (∼10%) will eventually develop clinical disease, which is typically either a primary, often extra-pulmonary, TB in children, or a reactivation, pulmonary TB in adults. Considerable genetic epidemiological evidence has accumulated to support a major role for human genetic factors in the development of TB. Numerous association studies with various candidate genes have been conducted in pulmonary TB, with very few consistent results. Recent genome-wide association studies revealed only a modest role for two inter-genic polymorphisms. However, a first major locus for pulmonary TB was mapped to chromosome 8q12-q13 in a Moroccan population after a genome-wide linkage screen. Using a similar strategy, two other major loci controlling TB infection were recently identified. While the precise identification of these major genes is ongoing, the other fascinating observation of these last years was the demonstration that TB can also reflect a Mendelian predisposition. Following the findings obtained in the syndrome of Mendelian susceptibility to mycobacterial diseases, several children with complete IL-12Rß1 deficiency, were found to have severe TB as their sole phenotype. Overall, these recent findings provide the proof of concept that the human genetics of TB involves a continuous spectrum from Mendelian to complex predisposition with intermediate major gene involvement. The understanding of the molecular genetic basis of TB will have fundamental immunological and medical implications, in particular for the development of new vaccines and treatments.

Bacille Calmette-Guérin lymphadenitis and recurrent oral candidiasis in an infant with a new mutation leading to interleukin-12 receptor beta-1 deficiency.

Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare syndrome characterized by predisposition to infections caused by weakly virulent mycobacteria, such as those in bacille Calmette-Guérin (BCG) vaccine and environmental mycobacteria. Salmonellosis has been reported in almost half of affected patients. Patients are also vulnerable to Mycobacterium tuberculosis infection. Several other infectious diseases may occur, albeit rarely. Mucocutaneous candidiasis is more common. Interleukin-12 receptor beta1 (IL-12Rbeta1) deficiency is the most frequent genetic cause of MSMD. Here, we describe an infant with a single episode of BCG lymphadenitis who also suffered from recurrent oral candidiasis. Genetic analysis revealed a new homozygous mutation (64+1G>T) in the IL12RB1 gene that caused complete IL-12R1beta1 deficiency. IL-12Rbeta1 deficiency should be considered in patients with BCG infection, even in those who experience a single episode of BCG lymphadenitis or recurrent mucocutaneous candidiasis. Every attempt should be made to heighten awareness in countries where BCG vaccination is performed.

[Introduction of a bar coding pharmacy stock replenishment system in a prehospital emergency medical unit: economical impact]. / Mise en place d'un système de gestion informatique de la pharmacie au sein d'un service médical d'urgence et de réanimation: impact sur les dépenses.

OBJECTIVE: To assess economical impact after introduction of a bar coding pharmacy stock replenishment system in a prehospital emergency medical unit. STUDY DESIGN: Observational before and after study. METHODS: A computer system using specific software and bare-code technology was introduced in the pre hospital emergency medical unit (Smur). Overall activity and costs related to pharmacy were recorded annually during two periods: the first 2 years period before computer system introduction and the second one during the 4 years following this system installation. RESULTS: The overall clinical activity increased by 10% between the two periods whereas pharmacy related costs continuously decreased after the start of pharmacy management computer system use. Pharmacy stock management was easier after introduction of the new stock replenishment system. The mean pharmacy related cost of one patient management was 13 Euros before and 9 Euros after the introduction of the system. The overall cost savings during the studied period was calculated to reach 134,000 Euros. CONCLUSION: The introduction of a specific pharmacy management computer system allowed to do important costs savings in a prehospital emergency medical unit.

[Childhood cancer incidence and survival rates in the Rhône-Alpes regional paediatric registry 1987-1999]. / Les cancers de l'enfant de la région Rhône-Alpes: incidence et survie 1987-1999.

UNLABELLED: Cancer is rare in children, and pediatric malignancies represent only 1% of all cancers. OBJECTIVES: The cure rate is high and increasing, and ongoing data collection is therefore warranted. MATERIALS AND METHODS: Here we report the incidence and survival rates of childhood cancers between 1987 and 1999 in the Rhône-Alpes region of France. RESULTS: A total of 1945 cases were recorded during the study period, with an average of 149.6 new cases per year. The approximate incidence rate was 134.1/10(6) per year and the age-standardized incidence rate was 139.2/10(6) per year. The histological distribution and 5-year survival rates were respectively 30.2 and 73% for leukemia, 12.3 and 91.6% for lymphoma, 24.7 and 60.1% for CNS tumors, 9.1 and 71.1% for neuroblastoma, 2.5 and 94.1% for retinoblastoma, 5.8% and 89.9% for renal tumors, 1 and 75% for liver tumors, 6.1 and 60.9% for bone tumors, 4.1 and 58.6% for soft-tissue tumors, 1.1 and 71% for germ cell tumors, and 2.4 and 85.1% for carcinomas. CONCLUSION: The overall survival rate was 75%. Long-term treatment complications warrant further studies of children who survive into adulthood.

[Gastric trichobezoar in an adolescent presenting with anemia: ultrasound and MRI findings]. / Trichobézoard gastrique révélé par une anémie chez une adolescente: association échographie--imagerie par résonance magnétique (IRM).

Trichobezoars are rare and composed of ingested hair or fibers. Diagnosis is usually made by plain radiographs and barium meal. The usefulness of computed tomography has been reported in the preoperative period. In the pediatric population the authors propose, based on a recent case report, a non invasive and non irradiating protocol using sonography and T1W and T2W MR imaging.

Rapid upregulation of telomerase activity in human leukemia HL-60 cells treated with clinical doses of the DNA-damaging drug etoposide.

The enzyme telomerase is implicated in cellular resistance to apoptosis, but the mechanism for this resistance remains to be elucidated. The ability of telomerase to synthesize new DNA at telomeres suggests that this enzyme might function in the repair of double-stranded DNA breaks. To distinguish the effects of double-stranded DNA break damage and apoptosis on human telomerase activity, we treated the HL-60 human hematopoietic cancer cell line with clinical doses of the chemotherapeutic drug etoposide (0.5 to 5 microM), which allowed us to distinguish between events associated with DNA damage-induced cell cycle arrest, and events associated with apoptosis. Large (three- to seven-fold) upregulation of telomerase activity occurred soon after etoposide treatment (3 h) in S/G2/M-arresting populations; this upregulation was abolished at onset of apoptotic cell death. No upregulation of telomerase activity was observed in cells treated with a larger dose of etoposide (5 microM) that caused cells to undergo rapid apoptosis without intervening cell cycle arrests. These observations are consistent with a possible role for telomerase upregulation during the DNA damage response.

Inherited disorders of IL-12- and IFNgamma-mediated immunity: a molecular genetics update.

In the last 6 years, considerable advances have been made in the molecular analysis of a rare clinical syndrome: Mendelian susceptibility to mycobacterial disease (MSMD). Infection with poorly virulent environmental non-tuberculous mycobacteria (NTM) or vaccination with bacillus Calmette-Guerin (BCG) may cause disseminating and even fatal disease in individuals suffering from this syndrome. Mutations in five genes (IFNGR1, IFNGR2, STAT1, IL12B and IL12RB1) have been shown to be responsible for MSMD and further allelic heterogeneity accounts for the existence of nine distinct inherited disorders. All of these disorders are caused by impaired IFNgamma-mediated immunity. These results have important medical and biological implications. In this report, we update the disease-causing mutations reported in the literature.

Role of clathrin in the regulated secretory pathway of pancreatic beta-cells.

The role of clathrin in the sorting of proinsulin to secretory granules, the formation of immature granules and their subsequent maturation is not known. To this end, primary rat pancreatic beta-cells were infected with a recombinant adenovirus co-expressing the Hub fragment, a dominant-negative peptide of the clathrin heavy chain and enhanced green fluorescent protein (EGFP as a marker of infected cells). A population of cells expressing the highest levels of EGFP (and thus Hub) was obtained using a fluorescence-activated cell sorter (FACS). Control cells were infected with an adenovirus expressing EGFP alone. By immunofluorescence, control cells showed intense staining for both clathrin light chain and proinsulin in a perinuclear region. In cells expressing high levels of Hub, the clathrin light-chain signal was faint and diffuse in keeping with its displacement from membranes. There was, however, no detectable effect of Hub expression on proinsulin staining or disposition within the cell. Proinsulin sorting and conversion, and the fate (release and/or degradation) of insulin and C-peptide, was studied by pulse-chase and quantitative reverse phase HPLC. In both Hub-expressing and control cells, >99% of all newly synthesized proinsulin was sorted to the regulated pathway and there was no effect of Hub on proinsulin conversion to insulin. In presence of Hub there was, however, a significant increase in the percentage of C-peptide truncated to des-(27-31)-C-peptide at early times of chase as well as more extensive degradation of C-peptide thereafter. It is concluded that clathrin is not implicated in the sorting or processing of proinsulin or in regulated exocytosis of secretory granules. These results confirm a role for clathrin in the removal of proteases from maturing granules, thus explaining the increased truncation and degradation of C-peptide in cells expressing Hub.

[T-cell-depleted HLA non-identical bone marrow transplantation in the child: prevention of graft-versus-host reaction by administration of donor T lymphocytes alloreactive against the recipient]. / Greffe de moelle osseuse T déplétée HLA non géno-identique chez l'enfant: prévention de la réaction du greffon contre l'hôte par adjonction de lymphocytes T du donneur dépourvus d'alloréactivité vis-à-vis du receveur.

The success of HSCT from HLA partially disparate donors depends on the development of new strategies able to efficiently prevent GVHD and to protect patients from infections and relapse. Using an immunotoxin (IT) directed against the alpha-chain (p55) of the human IL-2r (RFT5-SMPT-dgA), we have previously shown that it is possible to kill mature T cells activated towards a specific HLA complex by a one-way MLR. We designed a clinical trial assessing the effect of infusing increasing doses of T lymphocytes in the setting of children recipients of non HLA genetically identical HSCT. Thirteen patients have been enrolled from September 1998 to April 2000 and fourteen HSCT have been realized in 13 patients (pts). Donors were MUD in 3 cases and familial HLA partially disparate in the remaining cases. Allodepleted donor T cells were injected between day +14 and day +30 provided that ATG was undetectable in the serum and blood PMN counts was > 500/microliter. The mean age of these patients was 17 months (range 1 to 42). Diagnosis included immune deficient and malignant hemopathies. Three patients received 1 x 10(5) allodepleted T cell/kg, 7 patients received 4 x 10(5)/kg and 4 patients received 6 x 10(5)/kg allodepleted T cells. Full inhibition of MLR was achieved in 12 out of 14 cases. In two cases, a residual T cell reactivity to the recipient was observed (4 to 5%) and patients developed grade II aGVHD. aGVHD occurred in 4 out of 11 grafted patients (all grade II). No chronic GVHD has developed, so far. Three patients died from severe VOD or PHT at day +34, day 51 and day +166, while one infected patient by VZV, CMV and EBV before HSCT died 6 months after transplantation from meningoencephalitis and another patient died from relapse at day +291. The patient for which there was no engraftment died at day +48 from staphylococcus infection. Overall survival is 54%, with a median follow up of 8 months; the mean time to reach a blood lymphocyte count > 500 was 41 days, to reach a CD3 count > 300 microliters 63 days (20-111), CD4 > 200 microliters 97 days and positive mitogen-induced proliferation 90 days. In three patients, a tetanus-toxoid positive proliferation was detected before immunization. From this intermediate analysis, we conclude that 1) specific allodepletion is an effective approach to prevent aGVHD in a haploincompatible setting, 2) data on immunological reconstitution suggest that infused T cells do survive and expand. A higher number of patients must be enrolled to determine the optimal number of T cells to infuse.