Clinical Surveillance Program Research Articles

Nationwide lung function monitoring from infancy in newborn-screened children with cystic fibrosis.

Cystic fibrosis (CF) lung disease starts in infancy and can be assessed for structural lung abnormalities using computed tomography or magnetic resonance scans, or for lung function impairment using multiple breath washout (MBW). However, in infancy these two methods are not well correlated. Trajectories of CF lung disease assessed by MBW in infants and toddlers remain poorly described, which is why we aimed to 1) describe the trajectory of lung function, 2) explore risk factors for progression and 3) explore the real-life effect of lumacaftor/ivacaftor. This was a nationwide observational cohort study (2018-2021) using data collected as part of the routine clinical surveillance programme (including MBW and monthly endo-laryngeal suction sampling for bacterial pathogens) in children born after implementation of newborn screening for CF (May 2016). Lumacaftor/ivacaftor commenced from age 2 years in children homozygous for F508del. Ventilation distribution efficiency (VDE), recently described to have advantages over lung clearance index (LCI), was reported as the primary MBW outcome after z-score calculations based on published reference data. Mixed effect linear regression models were the main statistical analyses performed in this study. 59 children, aged 2-45 months, contributed with 211 MBW occasions (median (interquartile range (IQR)) 3 (2-5) MBW occasions per child) with a median (IQR) follow-up time of 10.8 (5.2-22.3) months. An overall mean annual deterioration rate of -0.50 (95% CI -0.78- -0.22) z-VDE was observed, starting from an estimated mean z-VDE of -1.68 (95% CI -2.15- -1.22) at age 0.0 years (intercept). Pseudomonas aeruginosa "ever" (n=14, MBWs 50) had a significantly worse z-VDE trajectory versus P. aeruginosa "never" (mean difference 0.53 (95% CI 0.16-0.89) per year; p=0.0047) and lumacaftor/ivacaftor treatment (n=22, MBWs 46) significantly improved the trajectory of z-VDE (mean difference 1.72 (95% CI 0.79-2.66) per year; p=0.0004), leading to a stable mean z-VDE trajectory after start of treatment. Infants and toddlers with CF demonstrated progressive deterioration in z-VDE over the first years of life. P. aeruginosa isolation "ever" was associated with an accelerated deterioration in lung function, while lumacaftor/ivacaftor therapy significantly improved and stabilised the trajectory.

Somatic mutational landscape of hereditary hematopoietic malignancies caused by germline variants in RUNX1, GATA2, and DDX41

AbstractIndividuals with germ line variants associated with hereditary hematopoietic malignancies (HHMs) have a highly variable risk for leukemogenesis. Gaps in our understanding of premalignant states in HHMs have hampered efforts to design effective clinical surveillance programs, provide personalized preemptive treatments, and inform appropriate counseling for patients. We used the largest known comparative international cohort of germline RUNX1, GATA2, or DDX41 variant carriers without and with hematopoietic malignancies (HMs) to identify patterns of genetic drivers that are unique to each HHM syndrome before and after leukemogenesis. These patterns included striking heterogeneity in rates of early-onset clonal hematopoiesis (CH), with a high prevalence of CH in RUNX1 and GATA2 variant carriers who did not have malignancies (carriers-without HM). We observed a paucity of CH in DDX41 carriers-without HM. In RUNX1 carriers-without HM with CH, we detected variants in TET2, PHF6, and, most frequently, BCOR. These genes were recurrently mutated in RUNX1-driven malignancies, suggesting CH is a direct precursor to malignancy in RUNX1-driven HHMs. Leukemogenesis in RUNX1 and DDX41 carriers was often driven by second hits in RUNX1 and DDX41, respectively. This study may inform the development of HHM-specific clinical trials and gene-specific approaches to clinical monitoring. For example, trials investigating the potential benefits of monitoring DDX41 carriers-without HM for low-frequency second hits in DDX41 may now be beneficial. Similarly, trials monitoring carriers-without HM with RUNX1 germ line variants for the acquisition of somatic variants in BCOR, PHF6, and TET2 and second hits in RUNX1 are warranted.

Dr. Ani John (1950-2007): An exemplary dental educator and administrator and the first female President of the Indian Academy of Oral Medicine and Radiology.

Dr. Ani John (1950-2007): An exemplary dental educator and administrator and the first female President of the Indian Academy of Oral Medicine and Radiology.

Alcoholic liver disease in relation to cancer incidence and mortality: Findings from a large, matched cohort study in South Korea.

To estimate the risk of cancer incidence and mortality among patients with alcoholic liver disease in South Korea. A matched cohort study was conducted, including 1,042,185 men (alcoholic liver disease cases: 208,437; controls: 833,748) and 100,400 women (alcoholic liver disease cases: 20,080; controls: 80,320), matched for sex, age, smoking, alcohol consumption, and body mass index at a 1:4 ratio. The risk of cancer incidence and mortality in the alcoholic liver disease group was assessed using Cox proportional hazards regression models. Both men and women with alcoholic liver disease had an elevated risk of all-cancer and liver cancer incidence and mortality in comparison with the control group. In men, alcoholic liver disease was associated with a significantly higher risk of development of 10 cancer types, including lip, oral cavity, and pharynx; esophagus; liver; gallbladder and biliary tract; pancreas; larynx; lung; kidney; thyroid gland; and leukemia. Subgroup analysis by hepatitis B and C infection showed increased hazard ratios of all cancer incidences and mortality in the alcoholic liver disease group, regardless of hepatitis B or C infection status. In both sexes, a higher number and more years of hospital or clinic visits for alcoholic liver disease were associated with an increased risk of incidence and mortality from all cancers and liver cancer. A more profound dose-response relationship between alcoholic liver disease and alcohol consumption was observed in women than in men. Our findings emphasize the need for a clinical surveillance program and the early detection of cancer in patients with alcoholic liver disease.

Linking digital surveillance and in-depth virology to study clinical patterns of viral respiratory infections in vulnerable patient populations

SummaryTo improve the identification and management of viral respiratory infections, we established a clinical and virologic surveillance program for pediatric patients fulfilling pre-defined case criteria of influenza-like illness and viral respiratory infections. The program resulted in a cohort comprising 6,073 patients (56% male, median age 1.6 years, range 0–18.8 years), where every patient was assessed with a validated disease severity score at the point-of-care using the ViVI ScoreApp. We used machine learning and agnostic feature selection to identify characteristic clinical patterns. We tested all patients for human adenoviruses, 571 (9%) were positive. Adenovirus infections were particularly common and mild in children ≥1 month of age but rare and potentially severe in neonates: with lower airway involvement, disseminated disease, and a 50% mortality rate (n = 2/4). In one fatal case, we discovered a novel virus: HAdV-80. Standardized surveillance leveraging digital technology helps to identify characteristic clinical patterns, risk factors, and emerging pathogens.

338. Multicenter Evaluation of Superinfection Occurrence and Impact on Clinical Outcomes in Patients with COVID-19

BackgroundThe coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), spread globally throughout late 2019. During this pandemic, concern for bacterial and fungal superinfections has been present during the treatment of these patients. MethodsHospitalized, adult patients with laboratory confirmed and symptomatic COVID-19 disease admitted between March 12, 2020 and May 31, 2020 were eligible for inclusion in this study. Data was obtained from electronic medical records and the hospital system’s clinical surveillance program including demographics, comorbidities, hospitalization dates, laboratory values, mechanical ventilation, positive blood and respiratory cultures, treatment administration for COVID-19 as defined by the system’s fluid treatment algorithm, and discharge disposition. Outcomes of this analysis include overall bacterial and fungal superinfection occurrence rate within 28 days of admission, patient characteristics that correlate with a higher risk of a superinfection, and the effect on 28-day mortality.Patient Population Flow diagram of patient inclusion.ResultsA total of 404 patients were included in the study analyses of which 56 (13.9%) had a documented superinfection within 28-days from admission. The most common superinfection organisms observed were Staphylococcus spp. (36.9%), Candida spp. (16.7%), and Klebsiella spp. (13.1%). Mortality was significantly higher in patients with superinfections (12.1% vs 5.8%, p < 0.001). To best assess characteristics that place patients at a higher risk of superinfection, a backwards, stepwise, multivariable logistic regression was performed. Black ethnicity, chronic kidney disease, intensive care unit (ICU) upon admission, lymphocytopenia, and receipt of tocilizumab were found to more likely have a superinfection within 28-days from admission. Baseline Characteristics Comparison and analysis of baseline characteristics in patients with or without superinfection present.28-day Mortality Day-28 mortality comparison in patients with or without superinfection. Mortality was observed in 7/58 patients with a superinfection versus 20/346 patients without superinfection present (p < 0.001). Multivariable analysis results for increased superinfection risk. All baseline characteristics with univariate analysis resulting in a p value of < 0.2 were included in the backwards, stepwise logistic regression model.ConclusionIn conclusion, our retrospective cohort study reports a superinfection rate of 13.9%. Presence of a superinfection significantly increases the likelihood of mortality within 28-days from admission. Characteristics that have a significant correlation to increased risk of superinfections include Black ethnicity, chronic kidney disease, ICU upon admission, and receipt of tocilizumab. Disclosures Kevin W. Garey, Pharm.D., M.S., FASHP, Summit Therapeutics (Research Grant or Support)

Early disease surveillance in young children with cystic fibrosis: A qualitative analysis of parent experiences

Background. Sensitive measures of early lung disease are being integrated into therapeutic trials and clinical practice in cystic fibrosis (CF). The impact of early disease surveillance (EDS) using these novel and often intensive techniques on young children and their families is not well researched.Methods. The Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) has operated a combined clinical and research early disease surveillance program, based around annual chest CT scan, bronchoscopy and lung function from newborn screening diagnosis until age 6 years, for over two-decades. To explore parental experiences of EDS in their child, a qualitative study was conducted using audio-recorded, semi-structured interviews in n=46 mothers and n=21 fathers of children (aged 3-months to six years) attending CF centres in Perth and Melbourne, Australia. Themes were developed iteratively using thematic analysis and assessed for validity and confirmability.Results. Parents’ experiences were positive overall; affording a sense of control over CF, disease knowledge, and belief that EDS was in the best interests of their child. Challenges included poor understanding about EDS measures leading to anxiety and distress, self-blame surrounding adverse findings, and emotional burden of surveillance visits. Tailored information regarding the practical and psychosocial aspects of EDS were endorsed.Conclusion. While experiences were generally positive there is need for information and psychosocial support for parents to mitigate anxiety and develop positive coping strategies surrounding surveillance procedures and results. Managing expectations regarding risks and benefits of disease surveillance in clinical and research settings are important aspects of care.

Nosocomial Infections at Three Regional Tertiary Hospitals in Trinidad and Tobago

Objective: The main objectives of this research were to conduct and provide accurate and original findings related to the epidemiological study of nosocomial infections at three regional tertiary hospitals in Trinidad and Tobago. Specifically, the researcher determined; the frequency of nosocomial infections (NI), the frequency of multiple drug resistance among bacterial organisms associated with NI, infection control measures practiced at the research hospitals and the cost of such NI in terms of morbidity and mortality Synopsis: This study estimated the rate of nosocomial infections (NI) among patients at three major regional hospitals in Trinidad and Tobago and evaluated the frequency of pathogens associated with nosocomial infections. Approximately 450 of 126, 668 patients had nosocomial infections and the most frequent type of nosocomial pathogens were: Staphylococcus sp. (22.5%), Pseudomonas aeruginosa sp. (12.7%), Acinetobacter (11.8%) and Klebsiella sp. (11.6%). Methods: A one-year prospective cross-sectional study was carried out. The nosocomial pathogens were retrieved from the microbiology laboratory. Antimicrobial susceptibility test by the disk diffusion method were done on all bacterial isolates. Data was analysed using SPSS version 20.0. Results: This research revealed that 450 inpatients suffered nosocomial infections, with thirty (30) mortalities during the twelve (12) months that the study lasted (June 2013 to May 2014) at three regional hospitals of Trinidad and Tobago. The incidence of nosocomial infections was 5.8% and the nosocomial infection rate was 3.6 per 1000 (450/126,668). The highest rate (30.1%) was observed in the Intensive Care Unit (82/272 admissions). The most frequent type of nosocomial infection was Skin and Soft Tissue Infections 168 (37.3%). Staphylococcus sp. (22.5%), Pseudomonas aeruginosa sp. (12.7%), Acinetobacter (11.8%) and Klebsiella sp. (11.6%) were the most frequently occurring nosocomial pathogens. Conclusion: Consistency in performing good hygiene practices is vital for reducing the high nosocomial rate found at the research sites. Prediction of these infections is very important as a part of clinical surveillance programs to take preventive measures in advance. The antimicrobial susceptibility pattern rate (ASPR) showed that only 8.3 % (5/60) of the isolates were antibiotic-susceptible strains.

867-P: Ongoing Manufacturer-Led Clinical Surveillance of Two Blood Glucose Monitoring Test Strip Systems

There are no requirements for manufacturers of blood glucose monitoring systems (BGMS) to ensure their products continue to meet accuracy claims post-launch. Reported here is an on-going manufacturer-initiated clinical surveillance programme for two globally distributed BGMS: OneTouch Verio and OneTouch Select Plus, launched in 2009 and 2015 respectively. Test strip batches were randomly and routinely sampled from the manufacturer’s (LifeScan Inc.) finished product and tested in clinic using capillary blood from subjects with diabetes (testing performed by professional staff). BGMS accuracy was determined against a reference instrument (results in Table). A small number of ’control’ batches were also sent to clinic on a repeat basis for on-going assessment of test variability (data not included in analysis). Both products met clinical accuracy requirements for all years as defined by EN ISO 15197:2015 (min. 95% of all BGMS values within ±15 mg/dL of reference at blood glucose (BG) &amp;lt;100 mg/dL or ±15% at BG ≥100 mg/dL). Furthermore, the OneTouch Verio product, available in U.S. markets, met the clinical accuracy criterion as proposed in current FDA guidance (min. 95% of all BGMS values within ±15% of reference at all BG levels). The manufacturer advocates that all manufacturers of glucose monitoring systems for diabetes patients adopt and maintain a similarly robust surveillance program. Disclosure S.J. Setford: Employee; Self; LifeScan Scotland. L.B. Katz: Employee; Self; LifeScan, Inc. M. Grady: Employee; Self; LifeScan, Inc. K. Macleod: Employee; Self; LifeScan Scotland. H. Cameron: None.

Australian National Enterovirus Reference Laboratory annual report, 2015.

Australia conducts surveillance for cases of acute flaccid paralysis (AFP) in children less than 15 years as recommended by the World Health Organization (WHO) as the main method to monitor its polio-free status. Cases of AFP in children are notified to the Australian Paediatric Surveillance Unit or the Paediatric Active Enhanced Disease Surveillance System and faecal specimens are referred for virological investigation to the National Enterovirus Reference Laboratory. In 2015, no cases of poliomyelitis were reported from clinical surveillance and Australia reported 1.2 non-polio AFP cases per 100,000 children, meeting the WHO performance criterion for a sensitive surveillance system. Two non-polio enteroviruses, enterovirus A71 and coxsackievirus B3, were identified from clinical specimens collected from AFP cases. Australia complements the clinical surveillance program with enterovirus and environmental surveillance for poliovirus. Two Sabin-like polioviruses were isolated from sewage collected in Melbourne in 2015, which would have been imported from a country that uses the oral polio vaccine. The global eradication of wild poliovirus type 2 was certified in 2015 and Sabin poliovirus type 2 will be withdrawn from oral polio vaccine in April 2016. Laboratory containment of all remaining wild and vaccine strains of poliovirus type 2 will occur in 2016 and the National Enterovirus Reference Laboratory was designated as a polio essential facility. Globally, in 2015, 74 cases of polio were reported, only in the two remaining countries endemic for wild poliovirus: Afghanistan and Pakistan. This is the lowest number reported since the global polio eradication program was initiated.

Predictors of Beta-Hexachlorocyclohexane blood levels among people living close to a chemical plant and an illegal dumping site

BackgroundHexachlorocyclohexane is a synthetic chemical with several isomers, including β-Hexachlorocyclohexane (β-HCH). In 2005, a large contamination of crude milk from some bovine farms along the Sacco River (Central Italy) was detected; it was related to the illegal disposal of large quantities of processing waste by a chemical industry of the area. A biomonitoring study, conducted in 2007 on a sample of the residing population, found high values of β-HCH in people living close to the river. These results led to the establishment of a clinical and epidemiological surveillance program on all the exposed population.The aim of the study was to evaluate the determinants of β-HCH blood levels in people living within 1 Km of the Sacco River, focusing on the role of specific foods, body mass index and risk factors not yet identified.MethodsThe program involved all people living within 1 km of the river. A descriptive analysis of β-HCH blood levels was done in relation to the potential determinants including specific foods. Regression analysis was used to study the association between potential determinants and (natural log) β-HCH haematic concentration. The results were expressed as geometric mean ratios (GMR). To take into account similarities within the families we adjusted for family clustering.ResultsA total of 602 subjects (87.2%) agreed to participate in the surveillance. The β-HCH geometric mean serum concentration was 72 ng/g lipid. The regression analysis showed that being female (GMR: 1.32, 95%CI: 1.14–1.53), elderly (GMR> 70yy: 10.04, 95%CI: 6.65–15.15), obese (GMR: 1.63, 95%CI: 1.28–2.08), eating food of local/own production (GMR 1.47, 95%CI: 1.15–1.88) and using water from private wells (GMRdrink:1.47, 95%CI: 1.00–2.14 and GMRwash: 1.48, 95%CI: 1.17–1.87) were associated with higher β-HCH values. There was inverse association with breastfeeding (GMR: 0.64, 95%CI: 0.47–0.86). The focus on specific foods showed that the most important factors were eggs and beef.ConclusionsThe study indicated a greater contamination for older people, and those drinking and washing with water from private wells and consuming locally produced food, especially eggs and beef.

The clinical benefit of instituting a prospective clinical community-acquired respiratory virus surveillance program in allogeneic hematopoietic stem cell transplantation

BackgroundThere is a lack of studies comparing clinical outcomes among retrospective versus prospective cohorts of allogeneic stem cell transplant (allo-HCT) recipients with community acquired respiratory virus (CARV) infections. MethodsWe compare outcomes in two consecutive cohorts of allo-HCT recipients with CARV infections. The retrospective cohort included 63 allo-HCT recipients with 108 CARV infections from January 2013 to April 2016 who were screened and managed following standard clinical practice based on influenza and respiratory syncytial virus rapid antigen detection methods. The prospective cohort was comprised of 144 consecutive recipients with 297 CARV episodes included in a prospective interventional clinical surveillance program (ProClinCarvSur-P) based on syndromic multiplex PCR as first-line test from May 2016 to December 2018 at a single transplant center. ResultsCARV infections in the retrospective cohort showed more severe clinical features at the time of diagnosis compared to the prospective cohort (fever 83% vs. 57%, hospital admission 69% vs. 28% and lower respiratory tract 58% vs. 31%, respectively, p ≤ 0.002 for all comparisons). Antiviral therapy was more commonly prescribed in the prospective cohort (69 vs. 43 treated CARV episodes), particularly at the upper respiratory tract disease stage (34 vs. 12 treated CARV episodes). Three-month all-cause mortality was significantly higher in the retrospective cohort (n = 23, 37% vs. n = 10, 7%, p < 0.0001). Multivariate logistic regression analysis showed that recipients included in ProClinCarvSur-P had lower mortality rate [odds ratio 0.31, 95% confidence interval 0.12–0.7, p = 0.01]. ConclusionThis study report on outcome differences when reporting retrospective vs. prospective CARV infections after allo-HCT. Recipients included in a ProClinCarvSur-P had lower mortality.

Enzyme replacement therapy initiated in adulthood: Findings from the mucopolysaccharidosis VI Clinical Surveillance Program

ObjectiveTo evaluate the impact of galsulfase enzyme replacement therapy (ERT) when initiated in adulthood for patients with mucopolysaccharidosis (MPS) VI. MethodsIn 2005, the multi-national, MPS VI Clinical Surveillance Program (CSP) was established to collect long-term observational data from routine clinical and laboratory assessments. A sub-analysis was performed in patients who started ERT at ≥16 years of age and had received galsulfase for ≥6 months. Urinary glycosaminoglycans (uGAG), 6-min walk test (6MWT), 3-min stair climb test (3MSCT), pulmonary function measures, cardiac function, ophthalmology measures, liver and spleen sizes, and safety were evaluated. ResultsOf 223 patients enrolled in the CSP, 51 were included in the sub-analysis. Patients were between 16 and 63 years of age at first infusion. From pre-treatment baseline, uGAG level decreased by a mean (±standard deviation [SD]) of 66 (±45)% (N = 29) after a median follow-up of 7.2 years. 6MWT distance decreased slightly by a mean of 17 (±107) meters (N = 23) after 6.6 years. Stairs/min in the 3MSCT increased by a mean of 26 (±33) (N = 14) after 2.8 years. Pulmonary function measures, forced expiratory volume in 1 second and forced vital capacity, increased by a mean of 0.06 (±0.21) L after 7.3 years and 0.05 (±0.28) L after 7.2 years, respectively (N = 19 for both measures). Overall, galsulfase was well tolerated, with most adverse events reported being MPS-related clinical manifestations and not related to galsulfase. ConclusionsResults of this sub-analysis of the CSP suggest that initiation of galsulfase in adulthood is well tolerated and can possibly stabilize MPS VI in the long term.

Enzyme replacement therapy outcomes across the disease spectrum: Findings from the mucopolysaccharidosis VI Clinical Surveillance Program.

The impact of galsulfase enzyme replacement therapy in patients with mucopolysaccharidosis (MPS) VI with phenotypes at either end of the disease spectrum was evaluated. The MPS VI Clinical Surveillance Program (CSP) was established to collect long-term observational data from routine clinical and laboratory assessments. A subanalysis of the CSP was performed in patients with pretreatment urinary glycosaminoglycan (uGAG) levels <100 μg/mg and ≥200 μg/mg creatinine (low- and high-uGAG) who had received galsulfase for ≥6 months. uGAG, 6-minute walk test (6MWT), 3-minute stair climb test (3MSCT), pulmonary function measures, height/growth, cardiac function, and safety were evaluated. Patients with a high-uGAG level at pre-treatment baseline (N = 68) showed greater impairments in endurance and pulmonary function than those with low-baseline uGAG levels (N = 39). From pre-treatment baseline, the distance walked on the 6MWT in the low- and high-uGAG groups increased by a mean (±SD) of 49 (±151) meters and 42 (±165) meters (median follow-up 5.5 and 7.7 years), respectively. The number of stairs/min climbed in the 3MSCT in the low- and high-uGAG groups increased by a mean of 18 (±33) and 30 (±45) (median follow-up 2.8 and 3.5 years), respectively. Overall, pulmonary function remained unchanged for both groups. No impact was seen on cardiac function. Galsulfase was generally well tolerated in both groups, with most adverse events being MPS-related complications unrelated to galsulfase. Results of this CSP sub-analysis suggest that galsulfase stabilizes MPS VI in the long-term and has an acceptable safety profile, regardless of baseline disease severity.

Evidence From a Long-Term, Systematic Post-Market Surveillance Program: Clinical Performance of a Hematocrit-Insensitive Blood Glucose Test Strip.

Described is a manufacturer's systematic post-market evaluation of the long-term clinical accuracy of a commercially available blood glucose monitoring (BGM) test strip product. Production batches of test strips were routinely and regularly sampled and evaluated in a clinical setting to assess product accuracy. Evaluations were performed on capillary blood samples from a minimum of 100 subjects with diabetes, by clinical staff according to instructions for use. Readings were compared against capillary blood samples collected at the same time and measured by a standard laboratory reference method. Clinical accuracy was calculated according to EN ISO 15197:2015. A total of 21 115 paired results were obtained, equating to 209 production batches over the >3-year period since test strip launch. Of the results, 97.6% met the accuracy criterion (range: 97.1-98.1% by year), with 98.1% of values presenting zero risk as defined by the surveillance error grid. At the <5th (21.0-33.8%) and >95th (48.3-59.4%) percentile extremes of hematocrit distribution, 97.9% and 96.4% of values were clinically accurate. The product also demonstrated clinical accuracy across all seven glucose ranges ("bins") as defined by the standard. Under conditions of combined hematocrit and glucose (<80 mg/dL and ≥300 mg/dL) extremes, 97.7% of values were clinically accurate. Methodologies and results from a manufacturer's self-imposed clinical accuracy surveillance program of a BGM product is presented. Given the publication of sometimes-conflicting data presented within ad hoc BGM clinical accuracy evaluations, usually of limited size, it is advocated that BGM manufacturers adopt similarly robust and systematic surveillance programs to safeguard patients.

Surveillance results and bone effects in the Gulf War depleted uranium-exposed cohort

ABSTRACTA small group of Gulf War I veterans wounded in depleted uranium (DU) friendly-fire incidents have been monitored in a clinical surveillance program since 1993. During the spring of 2017, 42 members of the cohort were evaluated with a protocol which includes exposure monitoring for total and isotopic uranium concentrations in urine and a comprehensive assessment of health outcomes including measures of bone metabolism, and for participants >50 years, bone mineral density (BMD) determination. Elevated urine U concentrations were observed in cohort members with retained DU shrapnel fragments. Only the mean serum estradiol concentration, a marker of bone metabolism, was found to be significantly different for lower-vs- higher urine U (uU) cohort sub-groups. For the first time, a significant deficit in BMD was observed in the over age 50, high uU sub-group. After more than 25 years since first exposure to DU, an aging cohort of military veterans continues to exhibit few U-related adverse health effects in known target organs of U toxicity. The new finding of reduced BMD in older cohort members, while biologically plausible, was not suggested by other measures of bone metabolism in the full (all ages) cohort, as these were predominantly within normal limits over time. Only estradiol was recently found to display a difference as a function of uU grouping. As BMD is further impacted by aging and the U-burden from fragment absorption accrues in this cohort, a U effect may be clarified in future surveillance visits.

Satisfaction and Impact on Quality of Life of Clinical and Instrumental Surveillance and Prophylactic Surgery in BRCA-mutation Carriers

IntroductionBRCA 1 and 2 mutation carriers are invited to follow intensive clinical and instrumental surveillance programs or are offered prophylactic breast and ovarian surgery. These recommendations impact many aspects of their life. This study aims to evaluate the satisfaction with surveillance and prophylactic surgery and the impact of these procedures on the quality of life. Patients and MethodsAn anonymous questionnaire was administered to 174 BRCA1-2 mutation carriers. ResultsA total of 95% of women comply with the scheduled checks every 6 months. Periodic examinations are considered useful for early diagnosis of breast/ovarian cancer by 91.5% of responders. Among those women who received prophylactic breast surgery, 95% believe that this procedure can reduce cancer risk, but only 65% were completely satisfied by the cosmetic outcome. Among women who underwent prophylactic ovarian surgery, 90.5% would choose it again, mainly owing to a lower degree of concern about ovarian cancer risk. The early onset of menopausal symptoms was the most frequently reported side effects, but only 21% of patients use any treatment to relieve them. ConclusionWomen who follow a surveillance program show a good level of satisfaction, thanks to the lowering of concerns of cancer risk. The degree of satisfaction about the prophylactic surgery is generally high. Risk-reducing mastectomy is usually well-accepted, despite the fact that cosmetic results are not entirely satisfactory. Bilateral salpingo-oophorectomy may impact on quality of life because of the symptoms associated with early surgical menopause, even if it can be treated with hormonal replacement therapies.

Mucopolysaccharidosis type VI enzyme replacement therapy outcomes across the disease spectrum: findings from the MPS VI clinical surveillance program

Mucopolysaccharidosis type VI enzyme replacement therapy outcomes across the disease spectrum: findings from the MPS VI clinical surveillance program

Mucopolysaccharidosis type VI enzyme replacement therapy initiated in adulthood: Findings from the MPS VI clinical surveillance program

Mucopolysaccharidosis type VI enzyme replacement therapy initiated in adulthood: Findings from the MPS VI clinical surveillance program

Evaluation of pregnancy outcomes in patients with multiple sclerosis after fingolimod exposure.

Background and Methods:Limited data are available on the safety of fingolimod in pregnant women. We estimated the risk of adverse pregnancy outcomes in women with multiple sclerosis (MS) exposed to fingolimod either shortly before or during pregnancy in prospectively collected cases from clinical trials, observational studies, surveillance programs, and spontaneous reports.Results:The prevalence of major malformations among live births does not appear to be significantly higher than those in the general population and the unexposed MS population. Similarly, the prevalence of cardiac malformations observed in this analysis was not significantly different from that of the general population. Proportions of miscarriage were in line with those of the general and unexposed MS population and no specific pattern of birth defects was identified.Conclusions:These data can help inform healthcare professionals and women with MS exposed to fingolimod during conception.