Chronic Granulomatous Disease (CGD) is a rare primary immunodeficiency due to a defect in one of the NADPH oxidase complex subunits; 70 % of cases are X-linked, due to a
CYBB
mutation, resulting in ...defective production of gp91
PHOX
. Female carriers of X-linked CGD have previously been considered to be unaffected. It is increasingly recognized that they may suffer from similar problems to CGD patients. This review will examine the literature about clinical manifestations of disease in X-linked carriers of CGD.
Pregnancy loss is exceptionally common, yet there exist few interventions for clinical providers to assist parents who are expecting again. Perhaps even less prevalent are practice models for parents ...who have terminated a pregnancy due to fetal anomaly (TOPFA). In this article, we present the "Double Rainbow" acronym, which provides evidence-supported guidance for counseling people experiencing a subsequent pregnancy after TOPFA.
Using prompts of: Remember; Rehearse & Anticipate; Attach & Internalize; Interrogate decision; Neutralize; Normalize; Bond; Breathe & Observe; Optimize health; Weave and Whole story, we tie intervention techniques to evidence-based treatments and clinical practice examples.
Filling a gap for guidance for effective intervention with people during subsequent pregnancies after termination of pregnancy due to fetal anomaly, we aim to improve such treatment while also encouraging evaluation of the approach, encouraging evaluation of its use with broader populations.
The double RAINBOW approach weaves together evidence-based therapies while also attending to the work of distinguishing past losses and promoting parental attachment and caregiving systems in clients who have terminated a pregnancy due to fetal anomaly.
Healthcare workers (HCWs) have been disproportionately affected by coronavirus disease 2019 (COVID-19), which may be driven, in part, by nosocomial exposure. If HCW exposure is predominantly ...nosocomial, HCWs in paediatric facilities, where few patients are admitted with COVID-19, may lack antibodies to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and be at increased risk during the current resurgence.
To compare the seroprevalence of SARS-CoV-2 amongst HCWs in paediatric facilities in seven European countries and South Africa (N=8).
All categories of paediatric HCWs were invited to participate in the study, irrespective of previous symptoms. A single blood sample was taken and data about previous symptoms were documented. Serum was shipped to a central laboratory in London where SARS-CoV-2 immunoglobulin G was measured.
In total, 4114 HCWs were recruited between 1st May and mid-July 2020. The range of seroprevalence was 0–16.93%. The highest seroprevalence was found in London (16.93%), followed by Cape Town, South Africa (10.36%). There were no positive HCWs in the Austrian, Estonian and Latvian cohorts; 2/300 0.66%, 95% confidence interval (CI) 0.18–2.4 HCWs tested positive in Lithuania; 1/124 (0.81%, 95% CI 0.14–4.3) HCWs tested positive in Romania; and 1/76 (1.3%, 95% CI 0.23–7.0) HCWs tested positive in Greece.
Overall seroprevalence amongst paediatric HCWs is similar to their national populations and linked to the national COVID-19 burden. Staff working in paediatric facilities in low-burden countries have very low seroprevalence rates and thus are likely to be susceptible to COVID-19. Their susceptibility to infection may affect their ability to provide care in the face of increasing cases of COVID-19, and this highlights the need for appropriate preventative strategies in paediatric healthcare settings.
There are no epidemiological studies from the British Isles of chronic granulomatous disease, characterized by recurrent, life-threatening bacterial and fungal infections and inflammatory sequelae. ...Patients were enrolled in a national registry and medical records were analysed. Of 94 subjects, 69 had X-linked disease, 16 had autosomal recessive disease and nine were unknown. Prevalence was 7·5/million for 1990-99 and 8·5/million for 1980-89. Suppurative adenitis, abscesses and pneumonia presented commonly. Twenty-three of 30 patients who underwent high resolution computerized tomography had chronic respiratory disease. Inflammatory sequelae included bowel stricture and urogenital tract granulomata. Growth failure was common; 75% of those measured were below the population mean. All patients received prophylactic antibiotics and 93% anti-fungal prophylaxis. Interferon gamma was used to treat infection, but rarely as prophylaxis. Despite prophylaxis, estimated survival was 88% at 10 years but 55% at age 30 years. Morbidity remains significant, severe infectious complications common. Curative treatments including stem cell transplantation should be considered for patients with frequent or serious complications.
Streptococcus pneumoniae is one of the most common bacterial pathogens of infants and young children. Antibody responses against the pneumococcal polysaccharide capsule are the basis of ...vaccine-mediated protection. We examined the relationship between the dose of polysaccharide in pneumococcal conjugate vaccines (PCVs) and immunogenicity.
A systematic search of English publications that evaluated the immunogenicity of varying doses of pneumococcal conjugate vaccines was performed in Medline and Embase (Ovid Sp) databases in August 2019. We included only articles that involved administration of pneumococcal conjugate vaccine in humans and assessed the immunogenicity of more than one serotype-specific saccharide dose. Results were synthesised descriptively due to the heterogeneity of product valency, product content and vaccine schedule.
We identified 1691 articles after de-duplication; 9 studies met our inclusion criteria; 2 in adults, 6 in children and 1 in both. Doses of polysaccharide evaluated ranged from 0.44 mcg to 17.6 mcg. In infants, all doses tested elicited IgG geometric mean concentrations (GMCs) above the established correlate of protection (COP; 0.35 mcg/ml). A month after completion of the administered vaccine schedule, 95% confidence intervals of only three out of all the doses evaluated had GMCs that crossed below the COP. In the adult studies, all adults achieved GMCs that would be considered protective in children who have received 3 standard vaccine doses.
For some products, the mean antibody concentrations induced against some pneumococcal serotypes increased with increasing doses of the polysaccharide conjugate, but for other serotypes, there were no clear dose–response relationships or the dose response curves were negative. Fractional doses of polysaccharide which contain less than is included in currently distributed formulations may be useful in the development of higher valency vaccines, or dose-sparing delivery for paediatric use.
The objective of this study was to determine the utility of anti-nuclear antibody (ANA) testing in the investigation of cutaneous and other lupus symptoms in female carriers of X-linked chronic ...granulomatous disease (CGD). We undertook a prospective study of 19 carrier mothers attending our institution, with direct questioning of carriers concerning symptoms and testing for anti-nuclear and anti-phospholipid antibodies. A total of 58% reported significant photosensitive skin rashes, 42% reported mouth ulcers and 37% complained of joint pains that could not be attributed to other known causes. Anti-nuclear antibody (ANA) testing was negative in 73% of all carriers. The five positive ANAs were of low titre (maximum 1 : 320 on Hep 2 cells in two women) and only one weak positive double-stranded DNA antibody and no extractable nuclear antibodies were found. Several of the mothers, despite negative serology, benefited from referral to a specialist, and in some cases to specific treatment. A history of skin rashes, joint pain, fatigue and mouth ulcers should be sought actively in the female relatives of X-CGD patients but negative lupus serology should not preclude referral to appropriate dermatology or rheumatology services. as symptoms may respond well to appropriate treatment.
Increased advocacy for the informed consent model of transgender health care specifies that patients should be in control of access to receiving medical interventions such as hormone therapy or ...surgery. However, in practice, mental health clinicians, including clinical social workers, are increasingly called upon by medical providers to serve as gatekeepers for these processes. It is frequently the role of social workers to assess transgender clients' baseline mental health and their understanding of the consequences of treatment, and to forward recommendations to medical providers regarding the readiness of patients to transition. Therefore, social workers assisting transgender clients must be aware of the ethical standards that are particularly pertinent to their work with this marginalized and oppressed population. They must also be prepared to address unique ethical dilemmas that may be especially challenging to resolve. In this article we apply the most commonly utilized bioethical framework known as Principlism to describe the ethical standards and values that are particularly important to consider when working with transgender clients, namely autonomy; beneficence; nonmaleficence; and social justice. Because clinical social workers are frequently in the position of balancing client self-determination with their role as gatekeepers, a framework for resolving resulting ethical dilemmas is described (I CARE) and applied to three case examples.
All culture-positive tuberculosis (TB) isolates in Israel.
To outline the magnitude of drug-resistant TB in Israel, describe treatment outcomes and identify risk factors.
Retrospective study of ...laboratory data of all strains of adult TB patients tested for resistance to first- and second-line anti-tuberculosis drugs between 1999 and 2010.
Of 4652 reported TB cases, 3552 (76.3%) underwent culture (annual range 73-81%); 445 (12.5%) were resistant to one or more first-line drugs, while 207 (5.8%) had multidrug-resistant TB (MDR-TB). Risk factors for MDR-TB included being male, age 30-59 years, migrants (mainly from the former Soviet Union FSU) who had stayed in Israel >2 years, and having pulmonary TB, human immunodeficiency virus (HIV) infection and sputum smear positivity. Of all MDR-TB patients, 71.0% achieved treatment success, while 19.8% died. Twelve Israeli citizens had extensively drug-resistant TB (5.8% of MDR-TB cases). All had emigrated from the FSU and had pulmonary TB; 1 was HIV-infected. Seven (58.4%) achieved treatment success and 5 (41.6%) died.
Drug-resistant TB in Israel is influenced by migration, especially from the FSU, where the patients were probably infected. Rapid sputum sampling performed in the early stages of the disease, patient isolation and drug susceptibility testing should be the standard of care to avoid further transmission and improve TB control.
Opsonophagocytic assays (OPAs) are routinely used for assessing the immunogenicity of pneumococcal vaccines, with OPA data often being utilized for licensure of new vaccine formulations. However, no ...reference serum for pneumococcal OPAs is available, making evaluation of data among different laboratories difficult. This international collaboration was initiated to (i) assign consensus opsonic indexes (OIs) to FDA pneumococcal reference serum lot 007sp (here referred to as 007sp) and a panel of serum samples used for calibration of the OPA and (ii) determine if the normalization of the OPA results obtained with test samples to those obtained with 007sp decreases the variability in OPA results among laboratories. To meet these goals, six participating laboratories tested a panel of serum samples in five runs for 13 serotypes. For each serum sample, consensus OIs were obtained using a mixed-effects analysis of variance model. For the calibration serum samples, normalized consensus values were also determined on the basis of the results obtained with 007sp. For each serotype, the overall reduction in interlaboratory variability was calculated by comparing the coefficients of variation of the unadjusted and the normalized values. Normalization of the results substantially reduced the interlaboratory variability, ranging from a 15% reduction in variability for serotype 9V to a 64% reduction for serotype 7F. Normalization also increased the proportion of data within 2-fold of the consensus value from approximately 70% (average for all serotypes) to >90%. On the basis of the data obtained in this study, pneumococcal reference standard lot 007sp will likely be a useful reagent for the normalization of pneumococcal OPA results from different laboratories. The data also support the use of the 16 FDA serum samples used for calibration of the OPA as part of the initial evaluation of new assays or periodic assessment of established assays.
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