Shigella in Africa: New Insights From the Vaccine Impact on Diarrhea in Africa (VIDA) Study.

BACKGROUND: We evaluated the burden of Shigella spp from children aged 0-59 months with medically attended moderate-to-severe diarrhea and matched controls at sites in Mali, The Gambia, and Kenya participating in the Vaccine Impact on Diarrhea in Africa (VIDA) study from 2015 to 2018. METHODS: Shigella spp were identified using coprocultures and serotyping in addition to quantitative polymerase chain reaction (qPCR). Episode-specific attributable fractions (AFe) for Shigella were calculated using Shigella DNA quantity; cases with AFe ≥0.5 were considered to have shigellosis. RESULTS: The prevalence of Shigella was determined to be 359 of 4840 (7.4%) cases and 83 of 6213 (1.3%) controls by culture, and 1641 of 4836 (33.9%) cases and 1084 of 4846 (22.4%) controls by qPCR (cycle threshold <35); shigellosis was higher in The Gambia (30.8%) than in Mali (9.3%) and Kenya (18.7%). Bloody diarrhea attributed to Shigella was more common in 24- to 59-month-old children (50.1%) than 0- to 11-month-old infants (39.5%). The Shigella flexneri serogroup predominated among cases (67.6% of isolates), followed by Shigella sonnei (18.2%), Shigella boydii (11.8%), and Shigella dysenteriae (2.3%). The most frequent S. flexneri serotypes were 2a (40.6%), 1b (18.8%), 6 (17.5%), 3a (9.0%), and 4a (5.1%). Drug-specific resistance among 353 (98.3%) Shigella cases with AMR data was as follows: trimethoprim-sulfamethoxazole (94.9%), ampicillin (48.4%), nalidixic acid (1.7%), ceftriaxone (0.3%), azithromycin (0.3%), and ciprofloxacin (0.0%). CONCLUSIONS: A high prevalence of shigellosis continues in sub-Saharan Africa. Strains are highly resistant to commonly used antibiotics while remaining susceptible to ciprofloxacin, ceftriaxone, and azithromycin.

Hymenoptera venom skin testing: Adopting an accelerated test protocol.

BACKGROUND: The standard method of Hymenoptera venom intradermal skin test is performed at a starting concentration of 0.001 to 0.01 µg/mL and increased by 10-fold concentrations until positive or a maximum concentration of 1 µg/mL. Accelerated methods that start at higher concentrations have been reported as safe; however, many institutions have not adopted this approach. OBJECTIVE: To compare the outcome and safety of standard and accelerated venom skin test protocols. METHODS: This was a retrospective chart review of patients with suspected venom allergy who underwent skin testing at 4 allergy clinics within a single health care system from 2012 to 2022. Demographic data, test protocol (standard vs accelerated), test results, and adverse reactions were reviewed. RESULTS: Of 134 patients who underwent standard venom skin test, 2 (1.5%) experienced an adverse reaction, whereas none of the 77 patients who underwent accelerated venom skin test experienced an adverse reaction. One patient, with a history of chronic urticaria, experienced urticaria. The other experienced anaphylaxis requiring an epinephrine although had tested negative to all venom concentrations. Within the standard testing protocol, more than 75% of the positive results occurred at concentrations of 0.1 or 1 µg/mL. Within the accelerated testing protocol, more than 60% of the positive results occurred at 1 µg/mL. CONCLUSION: The study underscores the overall safety of venom intradermal skin test. Most of the positive results occurred at 0.1 or 1 µg/mL. Adopting an accelerated approach would reduce time and cost associated with testing.

Effect of ultrasonic vibration on the presence of voids in core build-up materials.

The core build-up procedure is utilized to restore teeth with limited remaining coronal tooth structure. However, voids have been observed radiographically within composite resin- and glass ionomer-based core build-ups, potentially compromising the mechanical strength of a fully restored tooth and requiring build-up replacement before a final restoration can be delivered. The purpose of this in vitro study was to determine whether applying ultrasonic vibration during core build-up placement reduces the presence of radiographically detectable voids. A total of 120 acrylic resin mandibular premolar analogs were fabricated using a 3-dimensional printer and randomly allocated into 4 groups (n = 30). Dual-cured composite resin or glass ionomer core build-ups were placed with or without vibration. The final build-ups were assessed radiographically and rated by 3 independent calibrated clinicians based on a 4-category scale for the severity of voids. In an ordinal logistic regression model with the void severity rating as the outcome, a significant interaction was found for glass ionomer, composite resin, and the use of ultrasonic vibration (P = 0.03). Vibration was associated with worse void severity ratings in glass ionomer specimens (P < 0.01). No effect of vibration was found in the composite resin specimens. The Fleiss kappa score (κ = 0.36) indicated fair agreement in all severity ratings among the 3 raters. These results suggest that the application of ultrasonic vibration during core build-up placement may not be clinically advantageous for improving restorative outcomes.

Pre-neuromusculoskeletal injury Risk factor Evaluation and Post-neuromusculoskeletal injury Assessment for Return-to-duty/activity Enhancement (PREPARE) in military service members: a prospective, observational study protocol.

BACKGROUND: Non-battle related musculoskeletal injuries (MSKI) are one of the primary medical issues diminishing Service member medical readiness. The MSKI problem is challenging because it is difficult to assess all of the factors that increase MSKI risk and influence post-MSKI outcomes. Currently, there are no high-throughput, clinically-feasible, and comprehensive assessments to generate patient-centric data for informing pre- and post-MSKI risk assessment and mitigation strategies. The objective of the "Pre-neuromusculoskeletal injury Risk factor Evaluation and Post-neuromusculoskeletal injury Assessment for Return-to-duty/activity Enhancement (PREPARE)" study is to develop a comprehensive suite of clinical assessments to identify the patient-specific factors contributing to MSKI risks and undesired post-MSKI outcomes. METHODS: This is a phased approach, multi-center prospective, observational study (ClinicalTrials.gov number: NCT05111925) to identify physical and psychosocial factors contributing to greater MSKI risk and undesired post-MSKI outcomes, and to identify and validate a minimal set of assessments to personalize risk mitigation and rehabilitation strategies. In Phase I, one cohort (n = 560) will identify the physical and psychosocial factors contributing to greater MSKI risks (single assessment), while a second cohort (n = 780) will identify the post-MSKI physical and psychosocial factors contributing to undesired post-MSKI outcomes (serial assessments at enrollment, 4 weeks post-enrollment, 12 weeks post-enrollment). All participants will complete comprehensive movement assessments captured via a semi-automated markerless motion capture system and instrumented walkway, joint range of motion assessments, psychosocial measures, and self-reported physical fitness performance and MSKI history. We will follow participants for 6 months. We will identify the minimum set of clinical assessments that provide requisite data to personalize MSKI risk mitigation and rehabilitation strategies, and in Phase II validate our optimized assessments in new cohorts. DISCUSSION: The results of this investigation will provide clinically relevant data to efficiently inform MSKI risk mitigation and rehabilitation programs, thereby helping to advance medical care and retain Service members on active duty status. TRIAL REGISTRATION: PREPARE was prospectively registered on ClinicalTrials.gov (NCT05111925) on 5 NOV 2021, prior to study commencement.

Repetitive Transcranial Magnetic Stimulation Promotes Rapid Psychiatric Stabilization in Acutely Suicidal Military Service Members.

OBJECTIVE: This study presents data for using accelerated transcranial magnetic stimulation (TMS) as an intervention for suicidal crisis (SC). METHODS: This prospective, single-site, randomized, double-blind trial enrolled active-duty military participants with SC to receive either active TMS (n = 59) or sham TMS (n = 61) 3 times per day for 3 consecutive days. Our primary outcome, the Beck Scale for Suicidal Ideation-current (SSI-C), was measured before each session of TMS. Secondary outcomes measured both the SSI-C and the Beck Scale for Suicidal Ideation-total daily for the 3 intervention days and at 1, 3, and 6 months of follow-up. RESULTS: In the modified intention to treat (mITT) analysis of SSI-C changes over treatment sessions, the TMS active group had accelerated decline in suicidal ideation as compared with sham: ß for interaction was 0.12 points greater SSI-C decline per session (standard error [SE], 0.06) in TMS versus sham (P = 0.04). In both the mITT and per-protocol active TMS groups, the mean final SSI-C scores were below 3. These scores remained below 3 for the entire 6-month follow-up period. CONCLUSIONS: In this military trial of suicidal patients, we found that both active and sham accelerated TMS rapidly reduces SC. Moreover, in the mITT analysis, there was a statistically significant antisuicidal benefit of active TMS versus sham TMS in the primary outcome. Both the mITT and per-protocol groups moved from higher to approximately 7 times lower suicide risk strata and remained there for the duration of the study. Further studies are warranted to understand accelerated TMS' full potential as a treatment for SC.

A Retrospective Test-Negative Case-Control Study to Evaluate Influenza Vaccine Effectiveness in Preventing Hospitalizations in Children.

BACKGROUND: Vaccination is the primary strategy to reduce influenza burden. Influenza vaccine effectiveness (VE) can vary annually depending on circulating strains. METHODS: We used a test-negative case-control study design to estimate influenza VE against laboratory-confirmed influenza-related hospitalizations among children (aged 6 months-17 years) across 5 influenza seasons in Atlanta, Georgia, from 2012-2013 to 2016-2017. Influenza-positive cases were randomly matched to test-negative controls based on age and influenza season in a 1:1 ratio. We used logistic regression models to compare odds ratios (ORs) of vaccination in cases to controls. We calculated VE as [100% × (1 - adjusted OR)] and computed 95% confidence intervals (CIs) around the estimates. RESULTS: We identified 14 596 hospitalizations of children who were tested for influenza using the multiplex respiratory molecular panel; influenza infection was detected in 1017 (7.0%). After exclusions, we included 512 influenza-positive cases and 512 influenza-negative controls. The median age was 5.9 years (interquartile range, 2.7-10.3), 497 (48.5%) were female, 567 (55.4%) were non-Hispanic Black, and 654 (63.9%) children were unvaccinated. Influenza A accounted for 370 (72.3%) of 512 cases and predominated during all 5 seasons. The adjusted VE against influenza-related hospitalizations during 2012-2013 to 2016-2017 was 51.3% (95% CI, 34.8% to 63.6%) and varied by season. Influenza VE was 54.7% (95% CI, 37.4% to 67.3%) for influenza A and 37.1% (95% CI, 2.3% to 59.5%) for influenza B. CONCLUSIONS: Influenza vaccination decreased the risk of influenza-related pediatric hospitalizations by >50% across 5 influenza seasons.

Variability in the Management of Adults With Pulmonary Nontuberculous Mycobacterial Disease.

BACKGROUND: The increasing global prevalence of pulmonary nontuberculous mycobacteria (NTM) disease has called attention to challenges in NTM diagnosis and management. This study was conducted to understand management and outcomes of patients with pulmonary NTM disease at diverse centers across the United States. METHODS: We conducted a 10-year (2005-2015) retrospective study at 7 Vaccine and Treatment Evaluation Units to evaluate pulmonary NTM treatment outcomes in human immunodeficiency virus-negative adults. Demographic and clinical information was abstracted through medical record review. Microbiologic and clinical cure were evaluated using previously defined criteria. RESULTS: Of 297 patients diagnosed with pulmonary NTM, the most frequent NTM species were Mycobacterium avium-intracellulare complex (83.2%), M. kansasii (7.7%), and M. abscessus (3.4%). Two hundred forty-five (82.5%) patients received treatment, while 45 (15.2%) were followed without treatment. Eighty-six patients had available drug susceptibility results; of these, >40% exhibited resistance to rifampin, ethambutol, or amikacin. Of the 138 patients with adequate outcome data, 78 (56.5%) experienced clinical and/or microbiologic cure. Adherence to the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) treatment guidelines was significantly more common in patients who were cured (odds ratio, 4.5, 95% confidence interval, 2.0-10.4; P < .001). Overall mortality was 15.7%. CONCLUSIONS: Despite ATS/IDSA Guidelines, management of pulmonary NTM disease was heterogeneous and cure rates were relatively low. Further work is required to understand which patients are suitable for monitoring without treatment and the impact of antimicrobial therapy on pulmonary NTM morbidity and mortality.

Clinical Epidemiology and Outcomes of Pediatric Musculoskeletal Infections.

OBJECTIVES: To understand the epidemiology of acute hematogenous osteomyelitis and septic arthritis, including clinical and demographic features, microbiology, treatment approaches, treatment-associated complications, and outcomes. STUDY DESIGN: Retrospective cohort study of 453 children with acute hematogenous osteomyelitis and/or septic arthritis from 2009 to 2015. RESULTS: Among the 453 patients, 218 (48%) had acute hematogenous osteomyelitis, 132 (29%) had septic arthritis, and 103 (23%) had concurrent acute hematogenous osteomyelitis/septic arthritis. Treatment failure/recurrent infection occurred in 41 patients (9%). Patients with concurrent acute hematogenous osteomyelitis/septic arthritis had longer hospital stays, longer duration of antibiotic therapy, and were more likely to have prolonged bacteremia and require intensive care. Staphylococcus aureus was identified in 228 (51%) patients, of which 114 (50%) were methicillin-resistant S aureus. Compared with septic arthritis, acute hematogenous osteomyelitis and concurrent acute hematogenous osteomyelitis/septic arthritis were associated with higher odds of treatment failure (OR, 8.19; 95% CI, 2.02-33.21 [P = .003]; and OR, 14.43; 95% CI, 3.39-61.37 [P < .001], respectively). The need for more than 1 surgical procedure was also associated with higher odds of treatment failure (OR, 2.98; 95% CI, 1.18-7.52; P = .021). Early change to oral antibiotic therapy was not associated with treatment failure (OR, 0.64; 95% CI, 0.24-1.74; P = .386). Most (73%) medically attended treatment complications occurred while on parenteral therapy. CONCLUSIONS: Musculoskeletal infections are challenging pediatric infections. S aureus remains the most common pathogen, with methicillin-resistant S aureus accounting for 25% of all cases. Concurrent acute hematogenous osteomyelitis/septic arthritis is associated with more severe disease and worse outcomes. Fewer treatment-related complications occurred while on oral therapy. Early transition to oral therapy was not associated with treatment failure.

Pain catastrophising in the oro-facial pain population.

BACKGROUND: Pain catastrophising is a maladaptive cognitive response characterised by an exaggerated negative interpretation of pain experiences. It has been associated with greater disability and poorer outcomes in chronic pain, to include several specific oro-facial pain conditions. The goal of this study was to examine pain catastrophising at a military oro-facial pain specialty clinic. METHODS: This retrospective chart review (RCR) examined information collected at initial examination from 699 new patients seen between September 2016 and August 2019 at the Orofacial Pain Center at the Naval Postgraduate Dental School (Bethesda, MD). Pain catastrophising, pain characteristics, psychosocial factors and sleep were assessed using standardised scales. Linear regression was used to evaluate associations of patient characteristics and pain intensity with pain catastrophising. Mediation analyses were done to characterise the extent to which the relationship between pain intensity and pain catastrophising may be explained by anxiety, depression and insomnia. RESULTS: Higher pain intensity, depression, anxiety, insomnia and younger age were each associated with higher pain catastrophising (all p < .05). A primary diagnosis of neuropathic pain was the strongest independent predictor of higher pain catastrophising. The relationship between pain intensity and pain catastrophising was partially mediated by anxiety, depression and insomnia. CONCLUSIONS: In this RCR of a population of oro-facial pain patients, those diagnosed with neuropathic pain were most likely to display high levels of pain catastrophising, a characteristic which is associated with poor long-term pain outcomes. This is the first study to show that, independent of other patient characteristics, those suffering from neuropathic pains displayed the highest levels of pain catastrophising. This highlights the importance of also addressing psychosocial factors in the treatment of neuropathic pain conditions, which are commonly treated using a predominantly biomedical approach. Additionally, anxiety, depression and insomnia each partially explains the relationship between pain intensity and pain catastrophising.

Group B Streptococcus (GBS) Colonization and Disease among Pregnant Women: A Historical Cohort Study.

Background: Maternal GBS colonization is associated with early-onset neonatal sepsis and extensive efforts are directed to preventing this complication. Less is known about maternal risks of GBS colonization. We seek to provide a modern estimate of the incidence and impact of maternal GBS colonization and invasive GBS disease. Methods: A single center historical cohort study of all births between 2003 and 2015 was performed. Data was collected via electronic health record abstraction using an institutional specific tool. Descriptive statistics were performed regarding GBS status. Inferential statistics were performed comparing risk of adverse pregnancy outcomes in cohorts with and without GBS colonization as well as cohorts with GBS colonization and invasive GBS disease. Results: A total of 60,029 deliveries were included for analysis. Overall, 21.6% of the population was GBS colonized and 0.1% had invasive GBS disease. GBS colonization was associated with younger maternal age, Black race, non-Hispanic ethnicity, chronic hypertension, preexisting diabetes, and tobacco use (p<0.01). In the adjusted analyses, there was an increased risk of gestational diabetes (aRR 1.21, 95% CI 1.11-1.32) in colonized pregnancies and a decreased incidence of short cervix (aRR 0.64, 95% CI 0.52-0.79), chorioamnionitis (aRR 0.76, 95% CI 0.66-0.87), wound infection (aRR 0.75, 95% CI 0.64-0.88), and operative delivery (aRR 0.85, 95% CI 0.83-0.88). Conclusions: This modern-day large cohort of all births over a 12-year period demonstrates a GBS colonization rate of 21.6%. This data reflects a need to assess maternal and perinatal outcomes in addition to neonatal GBS sepsis rates to inform decisions regarding the utility of maternal vaccination.

Data Management and Data Quality in PERCH, a Large International Case-Control Study of Severe Childhood Pneumonia.

The Pneumonia Etiology Research for Child Health (PERCH) study is the largest multicountry etiology study of pediatric pneumonia undertaken in the past 3 decades. The study enrolled 4232 hospitalized cases and 5325 controls over 2 years across 9 research sites in 7 countries in Africa and Asia. The volume and complexity of data collection in PERCH presented considerable logistical and technical challenges. The project chose an internet-based data entry system to allow real-time access to the data, enabling the project to monitor and clean incoming data and perform preliminary analyses throughout the study. To ensure high-quality data, the project developed comprehensive quality indicator, data query, and monitoring reports. Among the approximately 9000 cases and controls, analyzable laboratory results were available for ≥96% of core specimens collected. Selected approaches to data management in PERCH may be extended to the planning and organization of international studies of similar scope and complexity.

Microscopic Analysis and Quality Assessment of Induced Sputum From Children With Pneumonia in the PERCH Study.

BACKGROUND.: It is standard practice for laboratories to assess the cellular quality of expectorated sputum specimens to check that they originated from the lower respiratory tract. The presence of low numbers of squamous epithelial cells (SECs) and high numbers of polymorphonuclear (PMN) cells are regarded as indicative of a lower respiratory tract specimen. However, these quality ratings have never been evaluated for induced sputum specimens from children with suspected pneumonia. METHODS.: We evaluated induced sputum Gram stain smears and cultures from hospitalized children aged 1-59 months enrolled in a large study of community-acquired pneumonia. We hypothesized that a specimen representative of the lower respiratory tract will contain smaller quantities of oropharyngeal flora and be more likely to have a predominance of potential pathogens compared to a specimen containing mainly saliva. The prevalence of potential pathogens cultured from induced sputum specimens and quantity of oropharyngeal flora were compared for different quantities of SECs and PMNs. RESULTS.: Of 3772 induced sputum specimens, 2608 (69%) had <10 SECs per low-power field (LPF) and 2350 (62%) had >25 PMNs per LPF, measures traditionally associated with specimens from the lower respiratory tract in adults. Using isolation of low quantities of oropharyngeal flora and higher prevalence of potential pathogens as markers of higher quality, <10 SECs per LPF (but not >25 PMNs per LPF) was the microscopic variable most associated with high quality of induced sputum. CONCLUSIONS.: Quantity of SECs may be a useful quality measure of induced sputum from young children with pneumonia.

The Diagnostic Utility of Induced Sputum Microscopy and Culture in Childhood Pneumonia.

BACKGROUND.: Sputum microscopy and culture are commonly used for diagnosing the cause of pneumonia in adults but are rarely performed in children due to difficulties in obtaining specimens. Induced sputum is occasionally used to investigate lower respiratory infections in children but has not been widely used in pneumonia etiology studies. METHODS.: We evaluated the diagnostic utility of induced sputum microscopy and culture in patients enrolled in the Pneumonia Etiology Research for Child Health (PERCH) study, a large study of community-acquired pneumonia in children aged 1-59 months. Comparisons were made between induced sputum samples from hospitalized children with radiographically confirmed pneumonia and children categorized as nonpneumonia (due to the absence of prespecified clinical and laboratory signs and absence of infiltrate on chest radiograph). RESULTS.: One induced sputum sample was available for analysis from 3772 (89.1%) of 4232 suspected pneumonia cases enrolled in PERCH. Of these, sputum from 2608 (69.1%) met the quality criterion of <10 squamous epithelial cells per low-power field, and 1162 (44.6%) had radiographic pneumonia. Induced sputum microscopy and culture results were not associated with radiographic pneumonia, regardless of prior antibiotic use, stratification by specific bacteria, or interpretative criteria used. CONCLUSIONS.: The findings of this study do not support the culture of induced sputum specimens as a diagnostic tool for pneumonia in young children as part of routine clinical practice.

Density of Upper Respiratory Colonization With Streptococcus pneumoniae and Its Role in the Diagnosis of Pneumococcal Pneumonia Among Children Aged <5 Years in the PERCH Study.

BACKGROUND.: Previous studies suggested an association between upper airway pneumococcal colonization density and pneumococcal pneumonia, but data in children are limited. Using data from the Pneumonia Etiology Research for Child Health (PERCH) study, we assessed this potential association. METHODS.: PERCH is a case-control study in 7 countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. Cases were children aged 1-59 months hospitalized with World Health Organization-defined severe or very severe pneumonia. Controls were randomly selected from the community. Microbiologically confirmed pneumococcal pneumonia (MCPP) was confirmed by detection of pneumococcus in a relevant normally sterile body fluid. Colonization density was calculated with quantitative polymerase chain reaction analysis of nasopharyngeal/oropharyngeal specimens. RESULTS.: Median colonization density among 56 cases with MCPP (MCPP cases; 17.28 × 106 copies/mL) exceeded that of cases without MCPP (non-MCPP cases; 0.75 × 106) and controls (0.60 × 106) (each P < .001). The optimal density for discriminating MCPP cases from controls using the Youden index was >6.9 log10 copies/mL; overall, the sensitivity was 64% and the specificity 92%, with variable performance by site. The threshold was lower (≥4.4 log10 copies/mL) when MCPP cases were distinguished from controls who received antibiotics before specimen collection. Among the 4035 non-MCPP cases, 500 (12%) had pneumococcal colonization density >6.9 log10 copies/mL; above this cutoff was associated with alveolar consolidation at chest radiography, very severe pneumonia, oxygen saturation <92%, C-reactive protein ≥40 mg/L, and lack of antibiotic pretreatment (all P< .001). CONCLUSIONS.: Pneumococcal colonization density >6.9 log10 copies/mL was strongly associated with MCPP and could be used to improve estimates of pneumococcal pneumonia prevalence in childhood pneumonia studies. Our findings do not support its use for individual diagnosis in a clinical setting.

Colonization Density of the Upper Respiratory Tract as a Predictor of Pneumonia-Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pneumocystis jirovecii.

BACKGROUND.: There is limited information on the association between colonization density of upper respiratory tract colonizers and pathogen-specific pneumonia. We assessed this association for Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pneumocystis jirovecii. METHODS.: In 7 low- and middle-income countries, nasopharyngeal/oropharyngeal swabs from children with severe pneumonia and age-frequency matched community controls were tested using quantitative polymerase chain reaction (PCR). Differences in median colonization density were evaluated using the Wilcoxon rank-sum test. Density cutoffs were determined using receiver operating characteristic curves. Cases with a pathogen identified from lung aspirate culture or PCR, pleural fluid culture or PCR, blood culture, and immunofluorescence for P. jirovecii defined microbiologically confirmed cases for the given pathogens. RESULTS.: Higher densities of H. influenzae were observed in both microbiologically confirmed cases and chest radiograph (CXR)-positive cases compared to controls. Staphylococcus aureus and P. jirovecii had higher densities in CXR-positive cases vs controls. A 5.9 log10 copies/mL density cutoff for H. influenzae yielded 86% sensitivity and 77% specificity for detecting microbiologically confirmed cases; however, densities overlapped between cases and controls and positive predictive values were poor (<3%). Informative density cutoffs were not found for S. aureus and M. catarrhalis, and a lack of confirmed case data limited the cutoff identification for P. jirovecii. CONCLUSIONS.: There is evidence for an association between H. influenzae colonization density and H. influenzae-confirmed pneumonia in children; the association may be particularly informative in epidemiologic studies. Colonization densities of M. catarrhalis, S. aureus, and P. jirovecii are unlikely to be of diagnostic value in clinical settings.

Detection of Pneumococcal DNA in Blood by Polymerase Chain Reaction for Diagnosing Pneumococcal Pneumonia in Young Children From Low- and Middle-Income Countries.

BACKGROUND.: We investigated the performance of polymerase chain reaction (PCR) on blood in the diagnosis of pneumococcal pneumonia among children from 7 low- and middle-income countries. METHODS.: We tested blood by PCR for the pneumococcal autolysin gene in children aged 1-59 months in the Pneumonia Etiology Research for Child Health (PERCH) study. Children had World Health Organization-defined severe or very severe pneumonia or were age-frequency-matched community controls. Additionally, we tested blood from general pediatric admissions in Kilifi, Kenya, a PERCH site. The proportion PCR-positive was compared among cases with microbiologically confirmed pneumococcal pneumonia (MCPP), cases without a confirmed bacterial infection (nonconfirmed), cases confirmed for nonpneumococcal bacteria, and controls. RESULTS.: In PERCH, 7.3% (n = 291/3995) of cases and 5.5% (n = 273/4987) of controls were blood pneumococcal PCR-positive (P < .001), compared with 64.3% (n = 36/56) of MCPP cases and 6.3% (n = 243/3832) of nonconfirmed cases (P < .001). Blood pneumococcal PCR positivity was higher in children from the 5 African countries (5.5%-11.5% among cases and 5.3%-10.2% among controls) than from the 2 Asian countries (1.3% and 1.0% among cases and 0.8% and 0.8% among controls). Among Kilifi general pediatric admissions, 3.9% (n = 274/6968) were PCR-positive, including 61.7% (n = 37/60) of those with positive blood cultures for pneumococcus. DISCUSSION.: The utility of pneumococcal PCR on blood for diagnosing childhood pneumococcal pneumonia in the 7 low- and middle-income countries studied is limited by poor specificity and by poor sensitivity among MCPP cases.

Evaluation of Pneumococcal Load in Blood by Polymerase Chain Reaction for the Diagnosis of Pneumococcal Pneumonia in Young Children in the PERCH Study.

BACKGROUND.: Detection of pneumococcus by lytA polymerase chain reaction (PCR) in blood had poor diagnostic accuracy for diagnosing pneumococcal pneumonia in children in 9 African and Asian sites. We assessed the value of blood lytA quantification in diagnosing pneumococcal pneumonia. METHODS.: The Pneumonia Etiology Research for Child Health (PERCH) case-control study tested whole blood by PCR for pneumococcus in children aged 1-59 months hospitalized with signs of pneumonia and in age-frequency matched community controls. The distribution of load among PCR-positive participants was compared between microbiologically confirmed pneumococcal pneumonia (MCPP) cases, cases confirmed for nonpneumococcal pathogens, nonconfirmed cases, and controls. Receiver operating characteristic analyses determined the "optimal threshold" that distinguished MCPP cases from controls. RESULTS.: Load was available for 290 of 291 cases with pneumococcal PCR detected in blood and 273 of 273 controls. Load was higher in MCPP cases than controls (median, 4.0 × 103 vs 0.19 × 103 copies/mL), but overlapped substantially (range, 0.16-989.9 × 103 copies/mL and 0.01-551.9 × 103 copies/mL, respectively). The proportion with high load (≥2.2 log10 copies/mL) was 62.5% among MCPP cases, 4.3% among nonconfirmed cases, 9.3% among cases confirmed for a nonpneumococcal pathogen, and 3.1% among controls. Pneumococcal load in blood was not associated with respiratory tract illness in controls (P = .32). High blood pneumococcal load was associated with alveolar consolidation on chest radiograph in nonconfirmed cases, and with high (>6.9 log10 copies/mL) nasopharyngeal/oropharyngeal load and C-reactive protein ≥40 mg/L (both P < .01) in nonconfirmed cases but not controls. CONCLUSIONS.: Quantitative pneumococcal PCR in blood has limited diagnostic utility for identifying pneumococcal pneumonia in individual children, but may be informative in epidemiological studies.

PHQ-9 and GAD-7 Score Response After Parathyroidectomy for Primary Hyperparathyroidism: a Systematic Review and Meta-analysis.

OBJECTIVE: Currently, the relationship between parathyroidectomy and objective neuropsychiatric outcomes are not clearly defined. The purpose of this study is to perform the first ever Meta-analysis of preoperative and postoperative PHQ-9 and GAD-7 scores in patients with primary hyperparathyroidism undergoing parathyroidectomy with the goal of identifying a specific psychometric score that could be used as an indication for surgical intervention. DATA SOURCES: A comprehensive search of the literature was performed using PubMed, Embase, PsycINFO, Web of Science, and Ovid All EBM Reviews. REVIEW METHODS: Studies met inclusion criteria if they evaluated preoperative and postoperative PHQ-9 and/or GAD-7 scores in patients with primary hyperparathyroidism undergoing parathyroidectomy. Random effects Meta-analyses were used to analyze the compiled data. RESULTS: The literature search returned 1433 articles for initial review of which 6 (1105 participants) met criteria for inclusion and Meta-analysis. Meta-analysis revealed that primary hyperparathyroidism patients had significantly higher presurgical PHQ-9 scores when compared to control groups. Additionally, patients experienced a statistically significant and sustained decrease in PHQ-9 scores following parathyroidectomy. Notably, there was a dramatic decrease in the percentage of patients with PHQ-9 scores ≥10 (considered clinically significant for depression) following parathyroidectomy. CONCLUSION: Patients with primary hyperparathyroidism experience a statistically significant and sustained improvement in PHQ-9 scores following parathyroidectomy. Additionally, symptoms of anxiety and suicidal ideation appear to decrease after parathyroidectomy. We propose that a PHQ-9 score ≥10 could potentially be used as an indication for parathyroidectomy in patients with asymptomatic primary hyperparathyroidism.