Economic impact of informal caring for a person with arthritis in Australia from 2015 to 2030: a microsimulation approach using national survey data.

OBJECTIVES: To estimate the economic burden of informal caregivers not in the labour force (NILF) due to caring for a person with arthritis in Australia, with projections of these costs from 2015 to 2030. DESIGN: Static microsimulation modelling using national survey data. SETTING: Australia nationwide survey. PARTICIPANTS: Participants include respondents to the Survey of Disability, Ageing and Carers who are informal carers of a person who has arthritis as their main chronic condition and non-carers. OUTCOME MEASURES: Estimating the economic impact and national aggregated costs of informal carers NILF to care for a person with arthritis and projecting these costs from 2015 to 2030 in 5-year intervals. RESULTS: On a per-person basis, when adjusted for age, sex and highest education attained, the difference in average weekly total income between informal carers and non-carers employed in the labour force is $A1051 (95% CI: $A927 to $A1204) in 2015 and projected to increase by up to 22% by 2030. When aggregated, the total national annual loss of income to informal carers NILF is estimated at $A388.2 million (95% CI: $A324.3 to $A461.9 million) in 2015, increasing to $A576.9 million (95% CI: $A489.2 to $A681.8 million) by 2030. The national annual tax revenue lost to the government of the informal carers NILF is estimated at $A99 million (95% CI: $A77.9 to $A126.4 million) in 2015 and is projected to increase 49% by 2030. CONCLUSION: Informal carers NILF are economically worse off than employed non-carers, and the aggregated national annual costs are substantial. The future economic impact of informal carers NILF to care for a person with arthritis in Australia is projected to increase, with the estimated differences in income between informal carers and employed non-carers increasing by 22% from 2015 to 2030.

The Healthcare and Societal Costs of Familial Intellectual Disability.

Most of the studies on the cost of intellectual disability are limited to a healthcare perspective or cohorts composed of individuals where the etiology of the condition is a mixture of genetic and non-genetic factors. When used in policy development, these can impact the decisions made on the optimal allocation of resources. In our study, we have developed a static microsimulation model to estimate the healthcare, societal, and lifetime cost of individuals with familial intellectual disability, an inheritable form of the condition, to families and government. The results from our modeling show that the societal costs outweighed the health costs (approximately 89.2% and 10.8%, respectively). The lifetime cost of familial intellectual disability is approximately AUD 7 million per person and AUD 10.8 million per household. The lifetime costs to families are second to those of the Australian Commonwealth government (AUD 4.2 million and AUD 9.3 million per household, respectively). These findings suggest that familial intellectual disability is a very expensive condition, representing a significant cost to families and government. Understanding the drivers of familial intellectual disability, especially societal, can assist us in the development of policies aimed at improving health outcomes and greater access to social care for affected individuals and their families.

Family Caregivers' Role in Navigating Diet: Perspectives from Caregivers of Older Asian Americans.

Family caregivers uphold significant healthcare responsibilities including language translation and diet management. This study sought to understand family caregivers' experiences and challenges navigating and managing their older Asian American relative's diet. We conducted an exploratory sequential mixed-methods study with family caregivers involving (1) qualitative interviews (n = 40) and (2) a nationwide survey (n = 100). Interviewees discussed their role and challenges with (a) applying American/Western clinical dietary recommendations to their relative's traditional meal preferences and (b) managing misalignment between their relative's traditional dietary preferences and the food offered in hospitals and long-term care environments. Survey responses triangulated; almost 65% of family caregivers prepared and brought traditional meals to healthcare facilities upon observing a lack of culturally relevant food options. Culturally relevant nutrition training for family caregivers can help them support their relative in community settings. Creating an inclusive healthcare system requires transforming the food environment within healthcare facilities.

Diversity-oriented synthesis encoded by deoxyoligonucleotides.

Diversity-oriented synthesis (DOS) is a powerful strategy to prepare molecules with underrepresented features in commercial screening collections, resulting in the elucidation of novel biological mechanisms. In parallel to the development of DOS, DNA-encoded libraries (DELs) have emerged as an effective, efficient screening strategy to identify protein binders. Despite recent advancements in this field, most DEL syntheses are limited by the presence of sensitive DNA-based constructs. Here, we describe the design, synthesis, and validation experiments performed for a 3.7 million-member DEL, generated using diverse skeleton architectures with varying exit vectors and derived from DOS, to achieve structural diversity beyond what is possible by varying appendages alone. We also show screening results for three diverse protein targets. We will make this DEL available to the academic scientific community to increase access to novel structural features and accelerate early-phase drug discovery.

Linear IgA bullous dermatosis and elevated bullous interleukin-6 levels: Responsive to treatment with Anti-IL-6 receptor monoclonals.

Linear IgA bullous dermatosis (LABD) is  a rare autoimmune/inflammatory skin condition. Here, we report on a patient who developed treatment resistant LABD. At diagnosis, elevations of IL-6 and C-reactive protein in the blood and extreme elevations of IL-6 in LABD bullous fluid were seen. The patient responded well to tocilizumab (anti-IL-6 receptor) treatment.

Novel small molecules that increase the susceptibility of Neisseria gonorrhoeae to cationic antimicrobial peptides by inhibiting lipid A phosphoethanolamine transferase.

OBJECTIVES: Neisseria gonorrhoeae is an exclusively human pathogen that commonly infects the urogenital tract resulting in gonorrhoea. Empirical treatment of gonorrhoea with antibiotics has led to multidrug resistance and the need for new therapeutics. Inactivation of lipooligosaccharide phosphoethanolamine transferase A (EptA), which attaches phosphoethanolamine to lipid A, results in attenuation of the pathogen in infection models. Small molecules that inhibit EptA are predicted to enhance natural clearance of gonococci via the human innate immune response. METHODS: A library of small-fragment compounds was tested for the ability to enhance susceptibility of the reference strain N. gonorrhoeae FA1090 to polymyxin B. The effect of these compounds on lipid A synthesis and viability in models of infection were tested. RESULTS: Three compounds, 135, 136 and 137, enhanced susceptibility of strain FA1090 to polymyxin B by 4-fold. Pre-treatment of bacterial cells with all three compounds resulted in enhanced killing by macrophages. Only lipid A from bacterial cells exposed to compound 137 showed a 17% reduction in the level of decoration of lipid A with phosphoethanolamine by MALDI-TOF MS analysis and reduced stimulation of cytokine responses in THP-1 cells. Binding of 137 occurred with higher affinity to purified EptA than the starting material, as determined by 1D saturation transfer difference NMR. Treatment of eight MDR strains with 137 increased susceptibility to polymyxin B in all cases. CONCLUSIONS: Small molecules have been designed that bind to EptA, inhibit addition of phosphoethanolamine to lipid A and can sensitize N. gonorrhoeae to killing by macrophages.

Machine Learning on DNA-Encoded Library Count Data Using an Uncertainty-Aware Probabilistic Loss Function.

DNA-encoded library (DEL) screening and quantitative structure-activity relationship (QSAR) modeling are two techniques used in drug discovery to find novel small molecules that bind a protein target. Applying QSAR modeling to DEL selection data can facilitate the selection of compounds for off-DNA synthesis and evaluation. Such a combined approach has been done recently by training binary classifiers to learn DEL enrichments of aggregated "disynthons" in order to accommodate the sparse and noisy nature of DEL data. However, a binary classification model cannot distinguish between different levels of enrichment, and information is potentially lost during disynthon aggregation. Here, we demonstrate a regression approach to learning DEL enrichments of individual molecules, using a custom negative-log-likelihood loss function that effectively denoises DEL data and introduces opportunities for visualization of learned structure-activity relationships. Our approach explicitly models the Poisson statistics of the sequencing process used in the DEL experimental workflow under a frequentist view. We illustrate this approach on a DEL dataset of 108,528 compounds screened against carbonic anhydrase (CAIX), and a dataset of 5,655,000 compounds screened against soluble epoxide hydrolase (sEH) and SIRT2. Due to the treatment of uncertainty in the data through the negative-log-likelihood loss used during training, the models can ignore low-confidence outliers. While our approach does not demonstrate a benefit for extrapolation to novel structures, we expect our denoising and visualization pipeline to be useful in identifying structure-activity trends and highly enriched pharmacophores in DEL data. Further, this approach to uncertainty-aware regression modeling is applicable to other sparse or noisy datasets where the nature of stochasticity is known or can be modeled; in particular, the Poisson enrichment ratio metric we use can apply to other settings that compare sequencing count data between two experimental conditions.

α-Amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor and RNA processing gene dysregulation are early determinants of selective motor neuron vulnerability in a mouse model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis is a late-onset adult neurodegenerative disease, although there is mounting electrophysiological and pathological evidence from patients and animal models for a protracted preclinical period of motor neuron susceptibility and dysfunction, long before clinical diagnosis. The key molecular mechanisms linked to motor neuron vulnerability in amyotrophic lateral sclerosis have been extensively studied using transcriptional profiling in motor neurons isolated from adult mutant superoxide dismutase 1 mice. However, neonatal and embryonic motor neurons from mutant superoxide dismutase 1 mice show abnormal morphology and hyperexcitability, suggesting preceding transcriptional dysregulation. Here, we used RNA sequencing on motor neurons isolated from embryonic superoxide dismutase 1G93A mice to determine the earliest molecular mechanisms conferring neuronal susceptibility and dysfunction known in a mouse model of amyotrophic lateral sclerosis. Transgenic superoxide dismutase 1G93A mice expressing the spinal motor neuron homeobox HB9:green fluorescent protein reporter allowed unambiguous identification and isolation of motor neurons using fluorescence-activated cell sorting. Gene expression profiling of isolated motor neurons revealed transcriptional dysregulation in superoxide dismutase 1G93A mice as early as embryonic Day 12.5 with the majority of differentially expressed genes involved in RNA processing and α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate-mediated glutamate receptor signalling. We confirmed dysregulation of the α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor Subunit 2, at transcript and protein levels, in embryonic superoxide dismutase 1G93A mouse motor neurons and human motor neurons derived from amyotrophic lateral sclerosis patient induced pluripotent stem cells harbouring pathogenic superoxide dismutase 1 mutations. Mutant superoxide dismutase 1 induced pluripotent stem cell-derived motor neurons showed greater vulnerability to α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate-mediated excitotoxicity, consistent with α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor Subunit 2 downregulation. Thus, α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor Subunit 2 deficiency leading to enhanced α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor signalling, calcium influx, hyperexcitability, and chronic excitotoxicity is a very early and intrinsic property of spinal motor neurons that may trigger amyotrophic lateral sclerosis pathogenesis later in life. This study reinforces the concept of therapeutic targeting of hyperexcitability and excitotoxicity as potential disease-modifying approaches for amyotrophic lateral sclerosis.

Conformational flexibility of EptA driven by an interdomain helix provides insights for enzyme-substrate recognition.

Many pathogenic gram-negative bacteria have developed mechanisms to increase resistance to cationic antimicrobial peptides by modifying the lipid A moiety. One modification is the addition of phospho-ethano-lamine to lipid A by the enzyme phospho-ethano-lamine transferase (EptA). Previously we reported the structure of EptA from Neisseria, revealing a two-domain architecture consisting of a periplasmic facing soluble domain and a transmembrane domain, linked together by a bridging helix. Here, the conformational flexibility of EptA in different detergent environments is probed by solution scattering and intrinsic fluorescence-quenching studies. The solution scattering studies reveal the enzyme in a more compact state with the two domains positioned close together in an n-do-decyl-ß-d-maltoside micelle environment and an open extended structure in an n-do-decyl-phospho-choline micelle environment. Intrinsic fluorescence quenching studies localize the domain movements to the bridging helix. These results provide important insights into substrate binding and the molecular mechanism of endotoxin modification by EptA.

The association between bacteria colonizing the upper respiratory tract and lower respiratory tract infection in young children: a systematic review and meta-analysis.

BACKGROUND: Bacteria colonizing the upper respiratory tract (URT) of young children play a key role in the pathogenesis of lower respiratory tract infection (LRTI). OBJECTIVES: To systematically review the literature on the association between bacteria colonizing the URT and LRTI among young children. DATA SOURCES: MEDLINE, Academic Search Premier, Africa-Wide Information and CINAHL, Scopus and Web of Science. STUDY ELIGIBILITY CRITERIA: Studies published between 1923 and 2020, investigating URT bacteria from LRTI cases and controls. PARTICIPANTS: Children under 5 years with and without acute LRTI. METHODS: Three reviewers independently screened titles, abstracts and full texts. Meta-analysis was done using Mantel-Haenszel fixed- or random-effects models. RESULTS: Most eligible studies (41/50) tested nasopharyngeal specimens when investigating URT bacteria. Most studies were of cross-sectional design (44/50). Twenty-four studies were performed in children in lower- or lower-middle-income countries (LMICs). There was higher prevalence of Haemophilus influenzae (pooled OR 1.60; 95% CI 1.23-2.07) and Klebsiella spp. (pooled OR 2.04; 95% CI 1.17-3.55) from URT specimens of cases versus controls. We observed a positive association between the detection of Streptococcus pneumoniae from URT specimens and LRTI after excluding studies where there was more antibiotic treatment prior to sampling in cases vs. controls (pooled OR 1.41; 95% CI 1.04-1.90). High density colonization with S. pneumoniae (>6.9 log10 copies/mL) was associated with an increased risk for LRTI. The associations between both Streptococcus and Haemophilus URT detection and LRTI were supported, at genus level, by 16S rRNA sequencing. Evidence for the role of Moraxella catarrhalis and Staphylococcus aureus was inconclusive. CONCLUSIONS: Detection of H. influenzae or Klebsiella spp. in the URT was associated with LRTI, while evidence for association with S. pneumoniae was less conclusive. Longitudinal studies assessing URT microbial communities, together with environmental and host factors are needed to better understand pathogenesis of childhood LRTI.

Validity and reliability of the English and translated Chinese versions of the Integrated Palliative care Outcome Scale (IPOS) in Singapore.

CONTEXT: Measurement of patient-centred outcomes enables clinicians to focus on patient and family priorities and enables quality of palliative care to be assessed. OBJECTIVES: This study aimed to evaluate the validity and reliability of the English and translated Chinese versions of the Integrated Palliative care Outcome Scale (IPOS) among advanced cancer patients in Singapore. METHODS: IPOS was forward and backward translated from English into Chinese. Structural validity was assessed by confirmatory factor analysis; known-group validity by comparing inpatients and community patients; construct validity by correlating IPOS with Edmonton Symptom Assessment System-revised (ESAS-r) and Functional Assessment of Cancer Therapy-General (FACT-G); internal consistency by Cronbach's alpha; inter-rater reliability between patient and staff responses; test-retest reliability of patient responses between two timepoints. RESULTS: One hundred eleven English-responding and 109 Chinese-responding patients participated. The three-factor structure (Physical Symptoms, Emotional Symptoms and Communication and Practical Issues) was confirmed with Comparative Fit Index and Tucker-Lewis-Index > 0.9 and Root Mean Square Error of Approximation < 0.08. Inpatients scored higher than outpatients as hypothesised. Construct validity (Pearson's correlation coefficient, r ≥ |0.608|) was shown between the related subscales of IPOS and FACT-G and ESAS-r. Internal consistency was confirmed for total and subscale scores (Cronbach's alpha≥0.84), except for the Communication and Practical Issues subscale (Cronbach's alpha = 0.29-0.65). Inter-rater reliability (Intra-class correlation coefficient [ICC] ≤ 0.43) between patient and staff responses was insufficient. Test-retest reliability was confirmed with Intra-class correlation coefficient ICC = 0.80 (English) and 0.88 (Chinese) for IPOS Total. CONCLUSION: IPOS in English and Chinese showed good validity, good internal consistency, and good test-retest reliability, except for the Communication and Practical Issues subscale. There was poor inter-rater reliability between patients and staff.

Anti-Virulence Therapeutic Approaches for Neisseria gonorrhoeae.

While antimicrobial resistance (AMR) is seen in both Neisseria gonorrhoeae and Neisseria meningitidis, the former has become resistant to commonly available over-the-counter antibiotic treatments. It is imperative then to develop new therapies that combat current AMR isolates whilst also circumventing the pathways leading to the development of AMR. This review highlights the growing research interest in developing anti-virulence therapies (AVTs) which are directed towards inhibiting virulence factors to prevent infection. By targeting virulence factors that are not essential for gonococcal survival, it is hypothesized that this will impart a smaller selective pressure for the emergence of resistance in the pathogen and in the microbiome, thus avoiding AMR development to the anti-infective. This review summates the current basis of numerous anti-virulence strategies being explored for N. gonorrhoeae.

Derivation of phenotypically diverse neural culture from hESC by combining adherent and dissociation methods.

BACKGROUND: Differentiation of human embryonic stem cells (hESCs) into distinct neural lineages has been widely studied. However, preparation of mixed yet neurochemically mature populations, for the study of neurological diseases involving mixed cell types has received less attention. NEW METHOD: We combined two commonly used differentiation methods to provide robust and reproducible cultures in which a mixture of primarily GABAergic and Glutamatergic neurons was obtained. Detailed characterisation by immunocytochemistry (ICC) and quantitative real-time PCR (qPCR) assessed the neurochemical phenotype, and the maturation state of these neurons. RESULTS: We found that once neurospheres (NSs) had attached to the culture plates, proliferation of neural stem cell was suppressed. Neuronal differentiation and synaptic development then occurred after 21 days in vitro (DIV). By 49DIV, there were large numbers of neurochemically and structurally mature neurons. The qPCR studies indicated that expression of GABAergic genes increased the most (93.3-fold increase), followed by glutamatergic (51-fold increase), along with smaller changes in expression of cholinergic (3-fold increase) and dopaminergic genes (6-fold increase), as well as a small change in glial cell marker expression (5-fold increase). COMPARISON WITH EXISTING METHOD (S): Existing methods isolate hESC-derived neural progenitors for onward differentiation to mature neurons using either migration or dissociative paradigms. These give poor survival or yield. By combining these approaches, we obtain high yields of morphologically and neurochemically mature neurons. These can be maintained in culture for extended periods. CONCLUSION: Our method provides a novel, effective and robust neural culture system with structurally and neurochemically mature cell populations and neural networks, suitable for studying a range of neurological diseases from a human perspective.

Effect of gastroretentive gabapentin (Gralise) on postmastectomy pain syndrome: a proof-of-principle open-label study.

INTRODUCTION: Chronic pain is a common and debilitating complication following breast surgery. One of the most challenging for treatment is the neuropathic pain condition, postmastectomy pain syndrome (PMPS). Gabapentin is a pharmacotherapy for neuropathic pain disorders; however, its once-daily, gastroretentive formulation, Gralise, has not been evaluated in PMPS. OBJECTIVE: To evaluate the safety and effectiveness of Gralise in patients with moderate-to-severe PMPS. METHODS: The primary effectiveness endpoint was a change in the worst pain intensity score from baseline to completion of 8 weeks of Gralise therapy. The secondary endpoints included the change in mood, coping behavior, sleep, and function. Sensitivity to experimental stimuli was tested before and after treatment via quantitative sensory testing. The incidence and type of adverse event were used to evaluate the safety and tolerability of Gralise. RESULTS: Twenty-one patients with confirmed moderate-to-severe PMPS were enrolled. Nineteen of 21 (90.5%) patients completed the 8-week treatment with Gralise. A significant positive change was found in pain intensity, pain impact, and sleep. There was no change in sensory testing scores. Of total, 63.16% of patients reported reduction in present pain, 78.95% in average pain, 89.47% in worst pain, and 84.21% in overall pain severity at posttreatment visit. No significant adverse effects were noted in the study. LIMITATIONS: Variation in type of breast surgery, small sample size, lack of placebo control. CONCLUSION: There was a significant improvement in pain and sleep, and Gralise was well tolerated in patients with PMPS. Further investigation is warranted.

Malignant melanoma in solid transplant recipients: collection of database cases and comparison with surveillance, epidemiology, and end results data for outcome analysis.

OBJECTIVE: To determine malignant melanoma cause-specific and overall survival among patients with melanoma diagnosed after organ transplantation compared with a national sample with malignant melanoma. DESIGN: Retrospective review. SETTING: Mayo Clinic sites. PATIENTS: Immunosuppressed organ transplant recipients with malignant melanoma identified from surgical and medical databases at Mayo Clinic (1978-2007), the Organ Procurement and Transplantation Network/United Network for Organ Sharing database (1999-2006), and the Israel Penn International Transplant Tumor Registry (1967-2007). MAIN OUTCOME MEASURES: Prognostic analyses by Breslow thickness and Clark level of overall and melanoma cause-specific survival. Expected survival rates were estimated by applying the age-, sex-, and calendar year-specific survival rates of patients with malignant melanoma cases reported in the Surveillance, Epidemiology, and End Results Program to the study cohort. RESULTS: Malignant melanoma was diagnosed in 638 patients (724 cases) after transplantation. Breslow thickness was available for 123 patients; Clark level, for 175. Three-year overall survival rates for patients stratified by Breslow thickness (≤ 0.75, 0.76-1.50, 1.51-3.00, and >3.00 mm) were 88.2%, 80.8%, 51.2%, and 55.3%, respectively, and 3-year cause-specific survival rates (95% confidence intervals) were 97.8% (93.7%-100%), 89.4% (76.5%-100%), 73.2% (53.2%-100%), and 73.9% (56.4%-96.6%), respectively. Three-year cause-specific survival rates (95% confidence intervals) for patients stratified by Clark level (I-IV) were 100%, 97.4% (92.4%-100%), 82.8% (65.3%-100%), and 65.8% (51.8%-83.7%), respectively. For patients with Breslow thickness of 1.51 to 3.00 mm and Clark level III or IV, the cause-specific survival rate in the study sample was significantly different from the expected estimates for patients with the same Breslow thickness or Clark level. CONCLUSIONS: Compared with the expected survival rates derived from malignant melanoma cases reported in the Surveillance, Epidemiology, and End Results Program, immunosuppressed organ transplant recipients with thicker melanomas (ie, with a Clark level of III or IV or a Breslow thickness of 1.51 to 3.00 mm) had a significantly poorer malignant melanoma cause-specific survival rate. The overall survival rate was worse among patients with a prior history of transplantation, regardless of Breslow thickness or Clark level.

Factors leading to the biopsy of 1547 pigmented lesions at Mayo Clinic, Scottsdale, Arizona, in 2005.

BACKGROUND: Both physician-driven and patient-driven factors influence biopsy decisions. We sought to determine the ratio of benign to malignant melanocytic biopsy findings in our general dermatology practice and to characterize the reasons for biopsy. METHODS: A retrospective review of institutional records (1 January to 31 December 2005) was undertaken. RESULTS: We identified 1398 nevi, 147 invasive and in situ melanomas, and two lesions interpreted as atypical melanocytic proliferations. Prior histories of melanoma, atypical nevi, or nonmelanoma skin cancer were common. Patient concerns about changes or symptoms drove about one-third of the biopsies. Physician concerns more commonly drove biopsies in men and older patients (> 60 years). Physician-directed biopsies more commonly yielded atypical nevi, but there was no difference in the likelihood of melanoma. The ratio of removed nevi to melanomas was 9.2 : 1. CONCLUSIONS: Both patient-driven and physician-driven indications lead to skin biopsies. We found no standard method of documentation of dermoscopic evaluation, which prevented us from making definitive conclusions about the role of dermoscopy in this cohort.

Treatment of basal cell carcinoma with curettage alone.

BACKGROUND: Although curettage and electrodesiccation (C&E) is widely used to treat basal cell carcinoma, whether electrodesiccation improves outcome is unknown. OBJECTIVE: We sought to compare cure rates of curettage alone with those of C&E. METHODS: We conducted a retrospective records review of patients treated with curettage alone at 5-year follow-up or longer that extracted data about tumor location, size, histologic subtype, biopsy specimen margin involvement, and recurrence, as well as data about the medical history of patients treated in a dermatology clinic in a tertiary-care academic medical institution. RESULTS: Biopsy-proven tumors (302) amenable to treatment with C&E and treated by a single investigator with curettage alone had a 5-year cure rate of 96.03%, with minimal complications (hypopigmentation, scarring). Tumors involving more than 50% of the deep edge of the shave biopsy specimen had an increased risk of recurrence. LIMITATIONS: This is a retrospective study based on historic controls. CONCLUSION: For nonaggressive basal cell carcinoma, curettage alone has a cure rate similar to the published rates for C&E.

Sweet syndrome (acute febrile neutrophilic dermatosis) associated with pulmonary coccidioidomycosis.

BACKGROUND: Sweet syndrome (acute febrile neutrophilic dermatosis) may arise in association with a variety of underlying systemic diseases. Only 1 case of coccidioidomycosis-associated Sweet syndrome has previously been reported. OBSERVATIONS: We describe 2 patients who developed Sweet syndrome during the onset of acute pulmonary coccidioidomycosis. Systemic antifungal therapy was given in both cases. Respiratory symptoms and skin lesions resolved within 5 weeks. CONCLUSIONS: Sweet syndrome may be a presenting feature of coccidioidomycosis. Recognition of the underlying pulmonary infection is important so that inappropriate treatment with systemic corticosteroids can be avoided.

Comparison of mohs micrographic surgery and wide excision for extramammary Paget's disease.

BACKGROUND: Extramammary Paget's disease is a rare cutaneous adenocarcinoma that occurs in an apocrine gland distribution mainly in the anogenital region. OBJECTIVE: To formulate treatment recommendations for this rare disease, we examined clinical and follow-up data of patients with it. METHODS: A retrospective review is given about the treatment and outcome for 95 patients at Mayo Clinic, Rochester, Minnesota, and Scottsdale, Arizona, between 1976 and 2001. The literature regarding diagnosis and treatment of this disease is also reviewed. RESULTS: Of the 95 patients, 86 had primary disease and 9 had recurrent disease. At mean follow-up (wide excision, 65 months; Mohs surgery, 24 months), disease had recurred in 18 of 83 (22%) who underwent standard wide excision, compared with recurrence in 1 of 12 (8%) who had the Mohs micrographic excision. CONCLUSION: Mohs micrographic surgery compares favorably with wide excision. Intraoperative immunostaining with cytokeratin 7 is helpful in delineating disease, as are preoperative scouting biopsies and photodynamic diagnosis.