Telehealth and Public Health Practice in the United States-Before, During, and After the COVID-19 Pandemic.

Telehealth is the use of electronic information and telecommunication technologies to provide care when the patient and the provider are not in the same room at the same time. Telehealth accounted for less than 1% of all Medicare Fee-for-Service outpatient visits in the United States in 2019 but grew to account for 46% of all visits in April 2020. Changes in reimbursement and licensure policies during the COVID-19 pandemic appeared to greatly facilitate this increased use. Telehealth will continue to account for a substantial portion of care provided in the United States and globally. A better understanding of telehealth approaches and their evidence base by public health practitioners may help improve their ability to collaborate with health care organizations to improve population health. The article summarizes the Centers for Disease Control and Prevention's (CDC's) approach to understanding the evidence base for telehealth in public health practice, possible applications for telehealth in public health practice, and CDC's use of telehealth to improve population health.

Telehealth Practice Among Health Centers During the COVID-19 Pandemic - United States, July 11-17, 2020.

Early in the coronavirus disease 2019 (COVID-19) pandemic, in-person ambulatory health care visits declined by 60% across the United States, while telehealth* visits increased, accounting for up to 30% of total care provided in some locations (1,2). In March 2020, the Centers for Medicare & Medicaid Services (CMS) released updated regulations and guidance changing telehealth provisions during the COVID-19 Public Health Emergency, including the elimination of geographic barriers and enhanced reimbursement for telehealth services† (3-6). The Health Resources and Services Administration (HRSA) administers a voluntary weekly Health Center COVID-19 Survey§ to track health centers' COVID-19 testing capacity and the impact of COVID-19 on operations, patients, and staff. CDC and HRSA analyzed data from the weekly COVID-19 survey completed by 1,009 HRSA-funded health centers (health centers¶) for the week of July 11-17, 2020, to describe telehealth service use in the United States by U.S. Census region,** urbanicity,†† staffing capacity, change in visit volume, and personal protective equipment (PPE) supply. Among the 1,009 health center respondents, 963 (95.4%) reported providing telehealth services. Health centers in urban areas were more likely to provide >30% of health care visits virtually (i.e., via telehealth) than were health centers in rural areas. Telehealth is a promising approach to promoting access to care and can facilitate public health mitigation strategies and help prevent transmission of SARS-CoV-2 and other respiratory illnesses, while supporting continuity of care. Although CMS's change of its telehealth provisions enabled health centers to expand telehealth by aligning guidance and leveraging federal resources, sustaining expanded use of telehealth services might require additional policies and resources.

Protracted Hypocalcemia following 3.5 Parathyroidectomy in a Kidney Pancreas Recipient with a History of Robotic-Assisted Roux-en-Y Gastric Bypass.

BACKGROUND: Hypocalcemia is a frequent complication of parathyroidectomy for secondary/tertiary hyperparathyroidism. In patients with a history of prior Roux-en-Y gastric bypass (RYGBP), changes in nutritional absorption make management of hypocalcemia after parathyroidectomy difficult. CASE REPORT: A 41-old-year morbidly obese female with c-peptide negative diabetes mellitus and renal failure had RYGBP. Following significant weight loss she underwent simultaneous pancreas-kidney transplantation. She had excellent transplant graft function but developed tertiary hyperparathyroidism with calciphylaxis. She underwent resection of 3.5 glands leaving a small, physiologic remnant remaining in situ at the left inferior position. She was discharged on postoperative day one in good condition, asymptomatic with serum calcium of 7.6 mg/dL and intact PTH of 12 pg/mL. The patient had to be readmitted on postoperative day #14 for severe hypocalcemia of 5.0 mg/dl and ionized calcium 2.4 mg/dl. She required intravenous calcium infusion to achieve calcium levels of >6.5 mg/dl. Long-term treatment includes 5 g of elemental oral calcium TID, vitamin D, and hydrochlorothiazide. She remains in the long term on high-dose medical therapy with normal serum calcium levels and PTH levels around 100 pg/mL. DISCUSSION: Our patient's protracted hypocalcemia originates from a combination of 3.5 gland parathyroidectomy, altered intestinal anatomy post-RYGBP, and potentially her pancreas transplant causing additional metabolic derangement. Alternative bariatric procedures such as sleeve gastrectomy may be more suitable for patients with renal failure or organ transplants in whom adequate absorption of vitamins, minerals, and drugs such as immunosuppressants is essential.

Esophagectomy: Comparison of Short-Term Outcomes between Single-versus Two-Team Approach.

Literature about combining expertise of two specialties in esophageal cancer surgery is limited. We present the experience at a single institute comparing single-team (ST) versus two-team (TT) approach combining thoracic and abdominal surgeons. This is a retrospective study from a single tertiary care center. Data were collected from electronic medical records. Patients undergoing esophagectomy for esophageal cancer from November 2006 until August 2014 were included. The primary outcome measured was 30-day postoperative morbidity, secondary outcomes measured were operative time, intraoperative blood loss, and 30-day mortality. Results are reported as mean with an interquartile range. Forty-nine patients underwent esophagectomy by an ST and 51 patients by TT. Patient demographics, tumor characteristics, stage, pathology, and use of neoadjuvant therapy were comparable between groups. Charlson comorbidity index was significantly higher in TT group [3 (2, 4) vs 2 (2, 3), P = 0.02]. The TT group had a significantly shorter operative time compared to the ST group [304 (252,376) minutes vs 438 (375, 494] minutes, P < 0.0001). Intraoperative blood loss was 300 (200, 550) mL for the TT group and 250 (200,400) mL for the ST group (P = 0.29). There was no difference in 30-day postoperative morbidity (68.6% for TT, 59.2% for ST, P = 0.32) and mortality (2% each, P = 1) between the two groups. In conclusion, the operative time by the TT approach was significantly shorter than the ST approach with comparable postoperative morbidity and mortality. Long-term follow-up is needed to study this approach's effect on long-term survival.

The Investigational Fungal Cyp51 Inhibitor VT-1129 Demonstrates Potent In Vitro Activity against Cryptococcus neoformans and Cryptococcus gattii.

Thein vitroactivities of the novel fungal Cyp51 inhibitor VT-1129 were evaluated against a large panel ofCryptococcus neoformansandCryptococcus gattiiisolates. VT-1129 demonstrated potent activities against bothCryptococcusspecies as demonstrated by low MIC50and MIC90values. ForC. gattii, thein vitropotency was maintained against all genotypes. In addition, significantly lower geometric mean MICs were observed for VT-1129 than for fluconazole againstC. neoformans, including isolates with reduced fluconazole susceptibility.

Multilaboratory testing of antifungal drug combinations against Candida species and Aspergillus fumigatus: utility of 100 percent inhibition as the endpoint.

Four laboratories tested three isolates of Candida species and two isolates of Aspergillus fumigatus using 96-well plates containing combinations of amphotericin B, anidulafungin, caspofungin, micafungin, fluconazole, itraconazole, posaconazole, and voriconazole. The majority of summation fractional inhibitory concentration indices (ΣFICI) based on the Lowe additivity formula suggested indifferent drug interactions (ΣFICI > 0.5 and ≤4.0) and no instance of drug antagonism (ΣFICI > 4.0). The intra- and interlaboratory agreement rates were superior when MIC100 readings were used as endpoints (at a 99% confidence interval [CI]).

Isolation of Cryptococcus gattii from Oregon soil and tree bark, 2010-2011.

BACKGROUND: In Oregon, human and animal infections by C. gattii were first identified in 2004. Cryptococcus gattii is considered to be an emerging non-zoonotic infection affecting animals and humans in Oregon. We report a longitudinal environmental isolation of C. gattii after an Oregon dog was diagnosed with the disease in 2009. RESULTS: Cryptococcus gattii was isolated twice from the same location with a span of one year between isolation dates. Cryptococcus gattii molecular types VGIIa and VGI were isolated in 2010 from soil and tree bark near the home of a 9-month-old dog which three months previously had an infection caused by C. gattii genotype VGIIa. The environment featured heavy growth of Douglas Fir trees. In 2011, a second set of soil and tree bark samples was collected in the same area and C. gattii VGIIa was again identified from the environment, along with genotypes VGIIb and VGIIc. CONCLUSIONS: The use of animal surveillance data to identify environmental niches of C. gattii should be considered to expand the understanding of this emerging pathogen. Understanding the ecology and how the environment and other factors might modify the existing niches is important for assessing risk and for designing measures to protect human and animal health.

Role of FKS Mutations in Candida glabrata: MIC values, echinocandin resistance, and multidrug resistance.

Candida glabrata is the second leading cause of candidemia in U.S. hospitals. Current guidelines suggest that an echinocandin be used as the primary therapy for the treatment of C. glabrata disease due to the high rate of resistance to fluconazole. Recent case reports indicate that C. glabrata resistance to echinocandins may be increasing. We performed susceptibility testing on 1,380 isolates of C. glabrata collected between 2008 and 2013 from four U.S. cities, Atlanta, Baltimore, Knoxville, and Portland. Our analysis showed that 3.1%, 3.3%, and 3.6% of the isolates were resistant to anidulafungin, caspofungin, and micafungin, respectively. We screened 1,032 of these isolates, including all 77 that had either a resistant or intermediate MIC value with respect to at least one echinocandin, for mutations in the hot spot regions of FKS1 and FKS2, the major mechanism of echinocandin resistance. Fifty-one isolates were identified with hot spot mutations, 16 in FKS1 and 35 in FKS2. All of the isolates with an FKS mutation except one were resistant to at least one echinocandin by susceptibility testing. Of the isolates resistant to at least one echinocandin, 36% were also resistant to fluconazole. Echinocandin resistance among U.S. C. glabrata isolates is a concern, especially in light of the fact that one-third of those isolates may be multidrug resistant. Further monitoring of U.S. C. glabrata isolates for echinocandin resistance is warranted.

Cryptococcus gattii in the United States: genotypic diversity of human and veterinary isolates.

BACKGROUND: Cryptococcusgattii infections are being reported in the United States (US) with increasing frequency. Initially, US reports were primarily associated with an ongoing C. gattii outbreak in the Pacific Northwest (PNW) states of Washington and Oregon, starting in 2004. However, reports of C. gattii infections in patients from other US states have been increasing since 2009. Whether this is due to increasing frequency of disease, greater recognition within the clinical community, or both is currently unknown. METHODOLOGY/PRINCIPAL FINDINGS: During 2005-2013, a total of 273 C. gattii isolates from human and veterinary sources in 16 US states were collected. Of these, 214 (78%) were from the Pacific Northwest (PNW) and comprised primarily the clonal C. gattii genotypes VGIIa (64%), VGIIc (21%) and VGIIb (9%). The 59 isolates from outside the PNW were predominantly molecular types VGIII (44%) and VGI (41%). Genotyping using multilocus sequence typing revealed small clusters, including a cluster of VGI isolates from the southeastern US, and an unrelated cluster of VGI isolates and a large cluster of VGIII isolates from California. Most of the isolates were mating type MATα, including all of the VGII isolates, but one VGI and three VGIII isolates were mating type MATa. CONCLUSIONS/SIGNIFICANCE: We provide the most comprehensive report to date of genotypic diversity of US C. gattii isolates both inside and outside of the PNW. C. gattii may have multiple endemic regions in the US, including a previously-unrecognized endemic region in the southeast. Regional clusters exist both in California and the Southeastern US. VGII strains associated with the PNW outbreak do not appear to have spread substantially beyond the PNW.

Preliminary laboratory report of fungal infections associated with contaminated methylprednisolone injections.

In September 2012, the Centers for Disease Control and Prevention (CDC) initiated an outbreak investigation of fungal infections linked to injection of contaminated methylprednisolone acetate (MPA). Between 2 October 2012 and 14 February 2013, the CDC laboratory received 799 fungal isolates or human specimens, including cerebrospinal fluid (CSF), synovial fluid, and abscess tissue, from 469 case patients in 19 states. A novel broad-range PCR assay and DNA sequencing were used to evaluate these specimens. Although Aspergillus fumigatus was recovered from the index case, Exserohilum rostratum was the primary pathogen in this outbreak and was also confirmed from unopened MPA vials. Exserohilum rostratum was detected or confirmed in 191 specimens or isolates from 150 case patients, primarily from Michigan (n=67 patients), Tennessee (n=26), Virginia (n=20), and Indiana (n=16). Positive specimens from Michigan were primarily abscess tissues, while positive specimens from Tennessee, Virginia, and Indiana were primarily CSF. E. rostratum antifungal susceptibility MIC50 and MIC90 values were determined for voriconazole (1 and 2 µg/ml, respectively), itraconazole (0.5 and 1 µg/ml), posaconazole (0.5 and 1 µg/ml), isavuconazole (4 and 4 µg/ml), and amphotericin B (0.25 and 0.5 µg/ml). Thirteen other mold species were identified among case patients, and four other fungal genera were isolated from the implicated MPA vials. The clinical significance of these other fungal species remains under investigation. The laboratory response provided significant support to case confirmation, enabled linkage between clinical isolates and injected vials of MPA, and described significant features of the fungal agents involved in this large multistate outbreak.

Detection of fungal DNA in human body fluids and tissues during a multistate outbreak of fungal meningitis and other infections.

Exserohilum rostratum was the major cause of an outbreak of fungal infections linked to injections of contaminated methylprednisolone acetate. Because almost 14,000 persons were exposed to product that was possibly contaminated with multiple fungal pathogens, there was unprecedented need for a rapid throughput diagnostic test that could detect both E. rostratum and other unusual agents of fungal infection. Here we report development of a novel PCR test that allowed for rapid and specific detection of fungal DNA in cerebrospinal fluid (CSF), other body fluids and tissues of infected individuals. The test relied on direct purification of free-circulating fungal DNA from fluids and subsequent PCR amplification and sequencing. Using this method, we detected Exserohilum rostratum DNA in 123 samples from 114 case-patients (28% of 413 case-patients for whom 627 samples were available), and Cladosporium DNA in one sample from one case-patient. PCR with novel Exserohilum-specific ITS-2 region primers detected 25 case-patients with samples that were negative using broad-range ITS primers. Compared to fungal culture, this molecular test was more sensitive: of 139 case-patients with an identical specimen tested by culture and PCR, E. rostratum was recovered in culture from 19 (14%), but detected by PCR in 41 (29%), showing a diagnostic sensitivity of 29% for PCR compared to 14% for culture in this patient group. The ability to rapidly confirm the etiologic role of E. rostratum in these infections provided an important contribution in the public health response to this outbreak.

Species identification and antifungal susceptibility testing of Candida bloodstream isolates from population-based surveillance studies in two U.S. cities from 2008 to 2011.

Between 2008 and 2011, population-based candidemia surveillance was conducted in Atlanta, GA, and Baltimore, MD. Surveillance had been previously performed in Atlanta in 1992 to 1993 and in Baltimore in 1998 to 2000, making this the first population-based candidemia surveillance conducted over multiple time points in the United States. From 2,675 identified cases of candidemia in the current surveillance, 2,329 Candida isolates were collected. Candida albicans no longer comprised the majority of isolates but remained the most frequently isolated species (38%), followed by Candida glabrata (29%), Candida parapsilosis (17%), and Candida tropicalis (10%). The species distribution has changed over time; in both Atlanta and Baltimore the proportion of C. albicans isolates decreased, and the proportion of C. glabrata isolates increased, while the proportion of C. parapsilosis isolates increased in Baltimore only. There were 98 multispecies episodes, with C. albicans and C. glabrata the most frequently encountered combination. The new species-specific CLSI Candida MIC breakpoints were applied to these data. With the exception of C. glabrata (11.9% resistant), resistance to fluconazole was very low (2.3% of isolates for C. albicans, 6.2% for C. tropicalis, and 4.1% for C. parapsilosis). There was no change in the proportion of fluconazole resistance between surveillance periods. Overall echinocandin resistance was low (1% of isolates) but was higher for C. glabrata isolates, ranging from 2.1% isolates resistant to caspofungin in Baltimore to 3.1% isolates resistant to anidulafungin in Atlanta. Given the increase at both sites and the higher echinocandin resistance, C. glabrata should be closely monitored in future surveillance.

Epidemiologic cutoff values for triazole drugs in Cryptococcus gattii: correlation of molecular type and in vitro susceptibility.

Cryptococcus gattii causes infection in tropical and subtropical regions worldwide but has garnered increased attention since its 1999 emergence in North America. C. gattii can be divided into 4 molecular types that may represent cryptic species. Recent evidence has shown that azole antifungal MIC values differ among these molecular types. We tested a large collection of C. gattii isolates for susceptibility to 4 azole drugs. We found that isolates of molecular type VGII have the highest geometric mean (GM) fluconazole MIC values (8.6 µg/mL), while isolates of molecular type VGI have the lowest (1.7 µg/mL). For fluconazole, itraconazole, and voriconazole GM MIC values, VGI < VGIII < VGIV < VGII. The GM MIC values for posaconazole were similarly represented across molecular types, with the exception that VGII < VGIII and VGIV. We used the MIC values to establish preliminary epidemiologic cutoff values for each azole and molecular type of C. gattii.

Bloodstream and non-invasive isolates of Candida glabrata have similar population structures and fluconazole susceptibilities.

We have compared multilocus sequence typing (MLST) and fluconazole susceptibility profiles of Candida glabrata bloodstream isolates obtained during active, population-based surveillance to those obtained from non-sterile sites of individuals with no evidence of fungal disease (i.e., non-invasive isolates) in the same US city during an overlapping time period. In each of the two populations, different proportions of the same six major sequence types (STs) encompassed 82% of the isolates. One ST was more prevalent in the candidemia population and two other STs were more prevalent in the non-invasive population, but the overall allelic frequencies within the groups suggested little, if any, genotypic diversity between them. Fluconazole susceptibility profiles of isolates from the patients in the two groups were not significantly different and were not associated with a particular sequence type. Our results support the hypothesis that C. glabrata strains causing bloodstream infections are genetically indistinguishable from those normally residing in/on the host, suggesting that relative pathogenicity may be closely tied to commensalism.

Validation of 24-hour flucytosine MIC determination by comparison with 48-hour determination by the Clinical and Laboratory Standards Institute M27-A3 broth microdilution reference method.

Flucytosine and itraconazole are the only antifungal agents for which the Clinical Laboratory and Standards Institute recommendations include MIC breakpoint readings at 48 h only. Here we show good essential and categorical agreement between the flucytosine MIC readings at 48 and 24 h for Candida species.

Comparison of in vitro susceptibility characteristics of Candida species from cases of invasive candidiasis in solid organ and stem cell transplant recipients: Transplant-Associated Infections Surveillance Network (TRANSNET), 2001 to 2006.

Invasive fungal infections (IFI) are a major cause of morbidity and mortality among both solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients. Candida is the most common cause of IFI in SOT recipients and the second most common cause of IFI in HSCT recipients. We determined susceptibilities to fluconazole, voriconazole, itraconazole, posaconazole, amphotericin B, and caspofungin for 383 invasive Candida sp. isolates from SOT and HSCT recipients enrolled in the Transplant-Associated Infection Surveillance Network and correlated these results to clinical data. Fluconazole resistance in C. albicans, C. tropicalis, and C. parapsilosis isolates was low (1%), but the high percentage of C. glabrata and C. krusei isolates within this group of patients increased the overall percentage of fluconazole resistance to 16%. Voriconazole resistance was 3% overall but was 8% among C. glabrata isolates. On multivariable analysis, among HSCT recipients fluconazole nonsusceptibility was independently associated with C. glabrata, non-Hodgkin's lymphoma, cytomegalovirus (CMV) antigenemia, diabetes active at the time of the IFI, and any prior amphotericin B use; among SOT recipients, fluconazole nonsusceptibility was independently associated with any fluconazole use in the 3 months prior to the IFI, C. glabrata, ganciclovir use in the 3 months prior to the IFI, diabetes acquired since the transplant, and gender.

FKS mutations and elevated echinocandin MIC values among Candida glabrata isolates from U.S. population-based surveillance.

Candida glabrata is the second leading cause of candidemia in the United States. Its high-level resistance to triazole antifungal drugs has led to the increased use of the echinocandin class of antifungal agents for primary therapy of these infections. We monitored C. glabrata bloodstream isolates from a population-based surveillance study for elevated echinocandin MIC values (MICs of ≥0.25 µg/ml). From the 490 C. glabrata isolates that were screened, we identified 16 isolates with an elevated MIC value (2.9% of isolates from Atlanta and 2.0% of isolates from Baltimore) for one or more of the echinocandin drugs caspofungin, anidulafungin, and micafungin. All of the isolates with elevated MIC values had a mutation in the previously identified hot spot 1 of either the glucan synthase FKS1 (n = 2) or FKS2 (n = 14) gene. No mutations were detected in hot spot 2 of either FKS1 or FKS2. The predominant mutation was mutation of FKS2-encoded serine 663 to proline (S663P), found in 10 of the isolates with elevated echinocandin MICs. Two of the mutations, R631G for FKS1 and R665G for FKS2, have not been reported previously for C. glabrata. Multilocus sequence typing indicated that the predominance of the S663P mutation was not due to the clonal spread of a single sequence type. With a rising number of echinocandin therapy failures reported, it is important to continue to monitor rates of elevated echinocandin MIC values and the associated mutations.

Correlation of genotype and in vitro susceptibilities of Cryptococcus gattii strains from the Pacific Northwest of the United States.

Cryptococcus gattii emerged in North America in 1999 as a human and veterinary pathogen on Vancouver Island, British Columbia. The emergent subtype, VGIIa, and the closely related subtype VGIIb can now be found in the United States in Washington, Oregon, and California. We performed multilocus sequence typing and antifungal susceptibility testing on 43 isolates of C. gattii from human patients in Oregon, Washington, California, and Idaho. In contrast to Vancouver Island, VGIIa was the most frequent but not the predominant subtype in the northwest United States. Antifungal susceptibility testing showed statistically significant differences in MICs between the subtypes. This is the first study to apply antifungal susceptibility testing to C. gattii isolates from the Pacific Northwest and the first to make direct comparisons between subtypes.

Determination of in vitro susceptibility of ocular Fusarium spp. isolates from keratitis cases and comparison of Clinical and Laboratory Standards Institute M38-A2 and E test methods.

We evaluated the susceptibility of 85 Fusarium spp. isolates from cases of fungal keratitis with 8 antifungal drugs using the standard Clinical and Laboratory Standards Institute broth microdilution and E test methods. Members of the Fusarium solani species complex showed consistently higher MICs to the triazole drugs itraconazole, voriconazole, and posaconazole than did members of other species complexes (Fusarium oxysporum and other minor species). High MICs to amphotericin B, natamycin, and echinocandins were consistently obtained with no discrimination based on species or method. Further work is required to determine any potential correlation between MIC and clinical outcome in keratitis.

Molecular epidemiology of Candida parapsilosis sepsis from outbreak investigations in neonatal intensive care units.

The DNA probe, Cp3-13, was used in a Southern blot assay for genotyping Candida parapsilosis (CP) from 3 fungemia outbreaks in neonatal intensive care units (NICUs) in the southeastern U.S. Genotyping, in 2 outbreaks, supplied evidence of horizontal transmission of CP. In the third outbreak, bloodstream isolates (BSIs) of 2 genotypes circulated in the NICU, one was shared by a BSI and a healthcare worker's hand culture. A fourth cluster of recurrent episodes of fungemia occurred in outpatients of a children's hospital receiving total parenteral nutrition (TPN) at home. Each child was infected with a different CP genotype which persisted during recurrences. These genotypes were included in a dendrogram from a CDC population-based surveillance for candidemia consisting of 73 clone-corrected Cp3-13 genotypes (overall SAB = 0.36). Analysis revealed a cluster of 11 genotypes (mean SAB = 0.66) including 3 pairs with identical hybridization profiles. A second cluster of 8 genotypes contained clones from 3 outbreaks (mean SAB = 0.76) but no clustering of genotypes specific for neonates was identified. No decreased susceptibility to azole and polyene antifungal agents was detected in this collection of CP. The frequent occurrence of transmission of CP in this vulnerable population underlines the relevance of Cp3-13 subtyping to investigate suspected transmission and persistence of CP strains in the NICU.