To the Editor:
We share the concern of Chastain and colleagues (Aug. 27 issue)
1
that racial and ethnic minorities affected by social and structural health disparities in the United States should ...have equitable access to Covid-19 trials. However, we disagree with their conclusion about the SIMPLE-Severe (GS-U.S.-540-5773)
2
and SIMPLE-Moderate (GS-U.S.-540-5774)
3
trials of remdesivir, since their comparison of overall race and ethnicity data from these trials involving patients from 12 countries with those of a nonrepresentative sample of the U.S. population is misleading. The SIMPLE trials completed enrollment for their primary analysis populations by mid-April 2020, and between them they included . . .
The incidence and severity of dengue in Latin America has increased substantially in recent decades and data from Puerto Rico suggests an increase in severe cases. Successful clinical management of ...severe dengue requires early recognition and supportive care.
Fatal cases were identified among suspected dengue cases reported to two disease surveillance systems and from death certificates. To be included, fatal cases had to have specimen submitted for dengue diagnostic testing including nucleic acid amplification for dengue virus (DENV) in serum or tissue, immunohistochemical testing of tissue, and immunoassay detection of anti-DENV IgM from serum. Medical records from laboratory-positive dengue fatal case-patients were reviewed to identify possible determinants for death.
Among 10,576 reported dengue cases, 40 suspect fatal cases were identified, of which 11 were laboratory-positive, 14 were laboratory-negative, and 15 laboratory-indeterminate. The median age of laboratory-positive case-patients was 26 years (range 5 months to 78 years), including five children aged < 15 years; 7 sought medical care at least once prior to hospital admission, 9 were admitted to hospital and 2 died upon arrival. The nine hospitalized case-patients stayed a mean of 15 hours (range: 3-48 hours) in the emergency department (ED) before inpatient admission. Five of the nine case-patients received intravenous methylprednisolone and four received non-isotonic saline while in shock. Eight case-patients died in the hospital; five had their terminal event on the inpatient ward and six died during a weekend. Dengue was listed on the death certificate in only 5 instances.
During a dengue epidemic in an endemic area, none of the 11 laboratory-positive case-patients who died were managed according to current WHO Guidelines. Management issues identified in this case-series included failure to recognize warning signs for severe dengue and shock, prolonged ED stays, and infrequent patient monitoring.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Accidental suffocation and strangulation in bed, a subgroup of sudden, unexpected infant deaths, is a leading mechanism of injury-related infant deaths. We explored trends and characteristics of ...these potentially preventable deaths.
In this descriptive study, we analyzed US infant mortality data from 1984 through 2004. To explore trends in accidental suffocation and strangulation in bed and other sudden, unexpected infant deaths, we calculated cause-specific infant mortality rates and estimated proportionate mortality. Sudden, unexpected infant death was defined as a combination of all deaths attributed to accidental suffocation and strangulation in bed, sudden infant death syndrome, and unknown causes. Finally, we examined factors that were reported as contributing to these accidental suffocation and strangulation in bed deaths.
Between 1984 and 2004, infant mortality rates attributed to accidental suffocation and strangulation in bed increased from 2.8 to 12.5 deaths per 100000 live births. These rates remained relatively stagnant between 1984 and 1992 and increased between 1992 and 2004; the most dramatic increase occurred between 1996 and 2004 (14% average annual increase). In contrast, total sudden, unexpected infant death rates remained stagnant between 1996 and 2004, whereas the proportion of deaths attributed to sudden infant death syndrome declined and to unknown cause increased. Black male infants <4 months of age were disproportionately affected by accidental suffocation and strangulation in bed. Beds, cribs, and couches were reported as places where deaths attributed to accidental suffocation and strangulation in bed occurred.
Infant mortality rates attributable to accidental suffocation and strangulation in bed have quadrupled since 1984. The reason for this increase is unknown. Prevention efforts should target those at highest risk and focus on helping parents and caregivers provide safer sleep environments.
Chikungunya, a mosquito-borne viral, acute febrile illness (AFI) is associated with polyarthralgia and polyarthritis. Differentiation from other AFI is difficult due to the non-specific presentation ...and limited availability of diagnostics. This 3-year study identified independent clinical predictors by day post-illness onset (DPO) at presentation and age-group that distinguish chikungunya cases from two groups: other AFI and dengue. Specimens collected from participants with fever ≤7 days were tested for chikungunya, dengue viruses 1-4, and 20 other pathogens. Of 8,996 participants, 18.2% had chikungunya, and 10.8% had dengue. Chikungunya cases were more likely than other groups to be older, report a chronic condition, and present <3 DPO. Regardless of timing of presentation, significant positive predictors for chikungunya versus other AFI were: joint pain, muscle, bone or back pain, skin rash, and red conjunctiva; with dengue as the comparator, red swollen joints (arthritis), joint pain, skin rash, any bleeding, and irritability were predictors. Chikungunya cases were less likely than AFI and dengue to present with thrombocytopenia, signs of poor circulation, diarrhea, headache, and cough. Among participants presenting <3 DPO, predictors for chikungunya versus other AFI included: joint pain, skin rash, and muscle, bone or back pain, and absence of thrombocytopenia, poor circulation and respiratory or gastrointestinal symptoms; when the comparator was dengue, joint pain and arthritis, and absence of thrombocytopenia, leukopenia, and nausea were early predictors. Among all groups presenting 3-5 DPO, pruritic skin became a predictor for chikungunya, joint, muscle, bone or back pain were no longer predictive, while arthritis became predictive in all age-groups. Absence of thrombocytopenia was a significant predictor regardless of DPO or comparison group. This study identified robust clinical indicators such as joint pain, skin rash and absence of thrombocytopenia that can allow early identification of and accurate differentiation between patients with chikungunya and other common causes of AFI.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BACKGROUND:Despite the absence of adequate safety or efficacy data, clindamycin is widely prescribed in the neonatal intensive care unit. We evaluated the association between clindamycin exposure and ...adverse events, as well as antibiotic effectiveness in infants.
METHODS:This was a retrospective cohort study of infants receiving clindamycin before postnatal day 121 who were discharged from a Pediatrix Medical Group neonatal intensive care unit (1997–2015). Using a previously developed pharmacokinetic model, we performed simulations to predict clindamycin exposure based on available dosing data. We used multivariable logistic regression to evaluate the association between clindamycin exposure and safety outcomes during and after clindamycin therapy. We reported the proportion of infants with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and clearance of MRSA bacteremia.
RESULTS:A total of 4089 infants received clindamycin at a median (25th–75th percentile) dose of 15 mg/kg/d (12–16). Clearance increased with older gestational age. Infants with the highest total clindamycin exposure had marginally increased odds of necrotizing enterocolitis within 7 days (adjusted odds ratio = 1.95 1.04–3.63), but exposure was not associated with death, sepsis, seizures, intestinal perforation or intestinal strictures. Of 25 infants who had MRSA bacteremia, 19 (76%) cleared the infection by the end of the clindamycin course.
CONCLUSIONS:Higher clindamycin exposure was not associated with increased odds of death or nonlaboratory adverse events. The use of pharmacokinetic models combined with available electronic health record data offers a valuable, cost-effective approach to analyzing the safety and effectiveness of drugs in infants when large-scale trials are not feasible.
Dengue is major public health problem, globally. Timely verification of suspected dengue outbreaks allows for public health response, leading to the initiation of appropriate clinical care. Because ...the clinical presentation of dengue is nonspecific, dengue diagnosis would benefit from a sensitive rapid diagnostic test (RDT). We evaluated the diagnostic performance of an RDT that detects dengue virus (DENV) nonstructural protein 1 (NS1) and anti-DENV IgM during suspected acute febrile illness (AFI) outbreaks in four countries. Real-time reverse transcription-PCR and anti-DENV IgM enzyme-linked immunosorbent assay were used to verify RDT results. Anti-DENV IgM RDT sensitivity and specificity ranged from 55.3 to 91.7% and 85.3 to 98.5%, respectively, and NS1 sensitivity and specificity ranged from 49.7 to 92.9% and 22.2 to 89.0%, respectively. Sensitivity varied by timing of specimen collection and DENV serotype. Combined test results moderately improved the sensitivity. The use of RDTs identified dengue as the cause of AFI outbreaks where reference diagnostic testing was limited or unavailable.
Understanding how late preterm infants (34-36 completed weeks’ gestation) are affected by discharge policies created for term infants (37-41 completed weeks’ gestation) is essential for preventing ...postdischarge neonatal morbidity among late preterm infants. We analyzed linked birth certificate and hospital discharge data for Massachusetts between 1998 and 2002 to evaluate the risk of neonatal morbidity (defined as hospital readmission, observational stay, or both) between all vaginally delivered, live-born singleton late preterm and term infants. All infants were born at a Massachusetts hospital to a state resident and were discharged home early (<2-night hospital stay). We calculated crude and adjusted risk ratios using a modified Poisson regression and compared the timing and principal discharge diagnoses for those neonates who needed hospital readmission. Of the 1004 late preterm and 24,320 term infants in our study, 4.3% and 2.7% of infants, respectively, were either readmitted or had an observational stay. Late preterm infants were 1.5 times more likely to require hospital-related care and 1.8 times more likely to be readmitted than term infants. Among infants who were breastfed, late preterm infants were 1.8 times more likely than term infants to require hospital-related care and 2.2 times more likely to be readmitted. In contrast, no differences were found between late preterm and term infants who were not breastfed. Jaundice and infection accounted for the majority of readmissions. Our findings suggest that late preterm infants discharged early experience significantly more neonatal morbidity than term infants discharged early; however, this may be true only for breastfed infants. Evidence-based recommendations for appropriate discharge timing and postdischarge follow-up for these late preterm infants are needed to prevent neonatal morbidity.
BACKGROUND
In the absence of active blood donation screening, dengue viruses (DENV) have been implicated in only a limited number of transfusion transmissions worldwide. This study attempted to ...identify if blood from donors testing negative by an NS1‐antigen (Ag) enzyme‐linked immunosorbent assay (ELISA) but confirmed positive for DENV RNA caused DENV‐related disease in recipients during the epidemic years of 2010 to 2012 in Puerto Rico.
STUDY DESIGN AND METHODS
Donation aliquots testing negative by an investigational NS1‐Ag ELISA were stored frozen and retested retrospectively using a research transcription‐mediated amplification assay (TMA) detecting DENV RNA. All RNA‐reactive donations were subject to confirmatory RNA and antibody testing. Recipient tracing was conducted for all components manufactured from TMA‐reactive components. Medical chart review, recipient interview, and follow‐up sampling occurred for 42 recipients transfused with TMA‐reactive components.
RESULTS
Six of 42 recipients developed new‐onset fever in the 2 weeks posttransfusion; three (50%) received RNA confirmed‐positive, NS1‐Ag–negative red blood cell (RBC) units. One recipient of a high‐titer unit (7 × 107 DENV‐4 RNA copies/mL) developed severe dengue, and a second recipient had only fever recorded but had a negative sepsis work‐up. New fever attributable to DENV infection in a third recipient was confounded by fever potentially attributable to posttransfusion sepsis.
CONCLUSIONS
In our retrospective study, NS1‐Ag detected 20% of all RNA confirmed‐positive donations demonstrating limitations of NS1‐Ag ELISA for blood donation screening. We identified one recipient with a clinical syndrome compatible with severe dengue who had received an NS1‐Ag–negative but RNA confirmed‐positive RBC unit. This investigation illustrates the difficulty in confirming transfusion transmission in dengue‐endemic areas among severely ill transfusion recipients.
BACKGROUND: Dengue is endemic in Puerto Rico and causes periodic outbreaks involving thousands of persons. Seroprevalence studies among blood donors can provide useful data on the immune status of ...the adult population. The objective of this study was to determine the prevalence of anti‐dengue immunoglobulin (Ig)G antibodies in a random sample of blood donors to the American Red Cross (ARC) in Puerto Rico.
STUDY DESIGN AND METHODS: Three‐hundred randomly selected blood donations collected by the ARC from February 1 to March 31, 2006, were tested using an anti‐dengue IgG enzyme‐linked immunosorbent assay. One‐third of the positive specimens were randomly selected and tested by a microneutralization test (MNT) to determine the serotypes of previous dengue infections.
RESULTS: Most (84%) blood donors were male, and the mean age was 44.6 years (range, 18‐80 years). The prevalence (95% confidence interval) of anti‐dengue IgG antibodies was 92% (89%‐95%). Of the 92 specimens tested by the MNT, reactivity to all four dengue serotypes was observed and 96% were secondary infections. The predominant serotype with the highest neutralization titers, as identified by at least a fourfold higher titer compared to any other serotype tested, was identified in 32 specimens; the most common predominant serotypes identified by the MNT were DENV‐3 and DENV‐2 (63%). Recent infection with DENV‐1 was detected but, in 2005, routine surveillance did not detect any cases of this serotype.
CONCLUSION: Supplementary serologic testing of donated blood can potentially provide information on the silent circulation or introduction of dengue serotypes.
Dengue is a potentially fatal acute febrile illness caused by four mosquito-transmitted dengue viruses (DENV-1-4). Although dengue outbreaks regularly occur in many regions of the Pacific, little is ...known about dengue in the Republic of the Marshall Islands (RMI). To better understand dengue in RMI, we investigated an explosive outbreak that began in October 2011. Suspected cases were reported to the Ministry of Health, serum specimens were tested with a dengue rapid diagnostic test (RDT), and confirmatory testing was performed using RT-PCR and IgM ELISA. Laboratory-positive cases were defined by detection of DENV nonstructural protein 1 by RDT, DENV nucleic acid by RT-PCR, or anti-DENV IgM antibody by RDT or ELISA. Secondary infection was defined by detection of anti-DENV IgG antibody by ELISA in a laboratory-positive acute specimen. During the four months of the outbreak, 1,603 suspected dengue cases (3% of the RMI population) were reported. Of 867 (54%) laboratory-positive cases, 209 (24%) had dengue with warning signs, six (0.7%) had severe dengue, and none died. Dengue incidence was highest in residents of Majuro and individuals aged 10-29 years, and ∼95% of dengue cases were experiencing secondary infection. Only DENV-4 was detected by RT-PCR, which phylogenetic analysis demonstrated was most closely related to a virus previously identified in Southeast Asia. Cases of vertical DENV transmission, and DENV/Salmonella Typhi and DENV/Mycobacterium leprae co-infection were identified. Entomological surveys implicated water storage containers and discarded tires as the most important development sites for Aedes aegypti and Ae. albopictus, respectively. Although this is the first documented dengue outbreak in RMI, the age groups of cases and high prevalence of secondary infection demonstrate prior DENV circulation. Dengue surveillance should continue to be strengthened in RMI and throughout the Pacific to identify and rapidly respond to future outbreaks.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
