Making the EHR Work for You-Modifications of an Electronic Health Record System to Improve Tracking and Management of Patients Receiving Outpatient Parenteral Antibiotic Therapy.

Background: Managing the complex needs of outpatient parenteral antibiotic therapy (OPAT) patients is challenging and time-consuming. We describe development of multimodal interventions to facilitate patient management within an Epic® (Epic Systems Corporation)-based electronic health record (EHR) platform. Methods: During 2016-2018, a multidisciplinary team created several modifications in our local EHR to improve gaps in OPAT care, including shared note templates, shared patient lists, automatically triggered notifications, and comprehensive order sets. A SmartForm was created, allowing collection of discrete, self-contained extractable data about each OPAT episode. We reviewed OPAT episodes from January 2019 through December 2022. Results: The multimodal EHR interventions culminated in the creation of a patient report, the "OPAT Monitoring View" collating OPAT-relevant data from multiple sections of the chart onto 1 screen display. This view is accessible both within the patient chart and from multiple list-based, in-basket, and snapshot-anchored preview functions in the EHR. Implementation of the EHR bundle facilitated management of 3402 OPAT episodes from 2019 to 2022 (850 episodes/year), about 50% higher than anticipated based on 540 OPAT courses in 2016. The OPAT EHR bundle allowed efficient (<3 hours) multidisciplinary rounds for management of 130-145 patients each week, streamlining of care transitions, and increasing staff satisfaction. Conclusions: Bundled multimodal modifications to the local EHR increased patient care efficiency and staff satisfaction and facilitated data collection to support a large OPAT program. These modifications apply commonly available EHR functionalities to OPAT care and could be adapted to other settings with different EHR platforms.

Mycobacterium szulgai cavitary lung disease progression over a three year period - A case report.

Mycobacterium szulgai is a slow growing non-tuberculous mycobacterium associated with rare but severe infections. It most commonly presents as pulmonary disease in people with underlying structural lung disease. We report a case of progressive cavitary lung disease over a three year period due to Mycobacterium szulgai and the subsequent outcome.

Safety and immunogenicity of an AS03-adjuvanted SARS-CoV-2 recombinant protein vaccine (CoV2 preS dTM) in healthy adults: interim findings from a phase 2, randomised, dose-finding, multicentre study.

BACKGROUND: We evaluated our SARS-CoV-2 prefusion spike recombinant protein vaccine (CoV2 preS dTM) with different adjuvants, unadjuvanted, and in a one-injection and two-injection dosing schedule in a previous phase 1-2 study. Based on interim results from that study, we selected a two-injection schedule and the AS03 adjuvant for further clinical development. However, lower than expected antibody responses, particularly in older adults, and higher than expected reactogenicity after the second vaccination were observed. In the current study, we evaluated the safety and immunogenicity of an optimised formulation of CoV2 preS dTM adjuvanted with AS03 to inform progression to phase 3 clinical trial. METHODS: This phase 2, randomised, parallel-group, dose-ranging study was done in adults (≥18 years old), including those with pre-existing medical conditions, those who were immunocompromised (except those with recent organ transplant or chemotherapy) and those with a potentially increased risk for severe COVID-19, at 20 clinical research centres in the USA and Honduras. Women who were pregnant or lactating or, for those of childbearing potential, not using an effective method of contraception or abstinence, and those who had received a COVID-19 vaccine, were excluded. Participants were randomly assigned (1:1:1) using an interactive response technology system, with stratification by age (18-59 years and ≥60 years), rapid serodiagnostic test result (positive or negative), and high-risk medical conditions (yes or no), to receive two injections (day 1 and day 22) of 5 7mu;g (low dose), 10 7mu;g (medium dose), or 15 7mu;g (high dose) CoV2 preS dTM antigen with fixed AS03 content. All participants and outcome assessors were masked to group assignment; unmasked study staff involved in vaccine preparation were not involved in safety outcome assessments. All laboratory staff performing the assays were masked to treatment. The primary safety objective was to describe the safety profile in all participants, for each candidate vaccine formulation. Safety endpoints were evaluated for all randomised participants who received at least one dose of the study vaccine (safety analysis set), and are presented here for the interim study period (up to day 43). The primary immunogenicity objective was to describe the neutralising antibody titres to the D614G variant 14 days after the second vaccination (day 36) in participants who were SARS-CoV-2 naive who received both injections, provided samples at day 1 and day 36, did not have protocol deviations, and did not receive an authorised COVID-19 vaccine before day 36. Neutralising antibodies were measured using a pseudovirus neutralisation assay and are presented here up to 14 days after the second dose. As a secondary immunogenicity objective, we assessed neutralising antibodies in non-naive participants. This trial is registered with ClinicalTrials.gov (NCT04762680) and is closed to new participants for the cohort reported here. FINDINGS: Of 722 participants enrolled and randomly assigned between Feb 24, 2021, and March 8, 2021, 721 received at least one injection (low dose=240, medium dose=239, and high dose=242). The proportion of participants reporting at least one solicited adverse reaction (injection site or systemic) in the first 7 days after any vaccination was similar between treatment groups (217 [91%] of 238 in the low-dose group, 213 [90%] of 237 in the medium-dose group, and 218 [91%] of 239 in the high-dose group); these adverse reactions were transient, were mostly mild to moderate in intensity, and occurred at a higher frequency and intensity after the second vaccination. Four participants reported immediate unsolicited adverse events; two (one each in the low-dose group and medium-dose group) were considered by the investigators to be vaccine related and two (one each in the low-dose and high-dose groups) were considered unrelated. Five participants reported seven vaccine-related medically attended adverse events (two in the low-dose group, one in the medium-dose group, and four in the high-dose group). No vaccine-related serious adverse events and no adverse events of special interest were reported. Among participants naive to SARS-CoV-2 at day 36, 158 (98%) of 162 in the low-dose group, 166 (99%) of 168 in the medium-dose group, and 163 (98%) of 166 in the high-dose group had at least a two-fold increase in neutralising antibody titres to the D614G variant from baseline. Neutralising antibody geometric mean titres (GMTs) at day 36 for participants who were naive were 2189 (95% CI 1744-2746) for the low-dose group, 2269 (1792-2873) for the medium-dose group, and 2895 (2294-3654) for the high-dose group. GMT ratios (day 36: day 1) were 107 (95% CI 85-135) in the low-dose group, 110 (87-140) in the medium-dose group, and 141 (111-179) in the high-dose group. Neutralising antibody titres in non-naive adults 21 days after one injection tended to be higher than titres after two injections in adults who were naive, with GMTs 21 days after one injection for participants who were non-naive being 3143 (95% CI 836-11 815) in the low-dose group, 2338 (593-9226) in the medium-dose group, and 7069 (1361-36 725) in the high-dose group. INTERPRETATION: Two injections of CoV2 preS dTM-AS03 showed acceptable safety and reactogenicity, and robust immunogenicity in adults who were SARS-CoV-2 naive and non-naive. These results supported progression to phase 3 evaluation of the 10 7mu;g antigen dose for primary vaccination and a 5 7mu;g antigen dose for booster vaccination. FUNDING: Sanofi Pasteur and Biomedical Advanced Research and Development Authority.

Rate of broad-spectrum antibiotic overuse in patients receiving outpatient parenteral antibiotic therapy (OPAT).

Broad-spectrum antibiotics with once-daily dosing are often chosen for outpatient parenteral antibiotic therapy (OPAT) due to convenience even when narrower-spectrum antibiotics are appropriate. At our institution, up to 50% of select broad-spectrum OPAT regimens had potential to be narrowed, highlighting the need to re-evaluate regimens for de-escalation prior to discharge.

Chronic tenosynovitis of the hand caused by Mycobacterium heraklionense.

Non-tuberculous mycobacteria are increasingly recognized as a cause of infection in both immunocompromised and immunocompetent hosts. Mycobacterium heraklionense is a recently described member of the Mycobacterium terrae complex. Herein we report a case of M. heraklionense chronic flexor tenosynovitis in the hand, managed with surgery and antibiotics.

Mycobacterium tuberculosis cluster with developing drug resistance, New York, New York, USA, 2003-2009.

In 2004, identification of patients infected with the same Mycobacterium tuberculosis strain in New York, New York, USA, resulted in an outbreak investigation. The investigation involved data collection and analysis, establishing links between patients, and forming transmission hypotheses. Fifty-four geographically clustered cases were identified during 2003-2009. Initially, the M. tuberculosis strain was drug susceptible. However, in 2006, isoniazid resistance emerged, resulting in isoniazid-resistant M. tuberculosis among 17 (31%) patients. Compared with patients with drug-susceptible M. tuberculosis, a greater proportion of patients with isoniazid-resistant M. tuberculosis were US born and had a history of illegal drug use. No patients named one another as contacts. We used patient photographs to identify links between patients. Three links were associated with drug use among patients infected with isoniazid-resistant M. tuberculosis. The photographic method would have been more successful if used earlier in the investigation. Name-based contact investigation might not identify all contacts, particularly when illegal drug use is involved.

The impact of monitoring tuberculosis reporting delays in New York City.

Public health departments rely on the timely receipt of tuberculosis (TB) reports to promptly initiate patient management and contact investigations. In 2003, 43% of persons in New York City with confirmed or suspected TB were reported 4 or more days late. An intervention to increase the timeliness of TB reporting was initiated in 2004. A list of patients who were reported late and had a smear positive for acid-fast bacilli, a pathology finding consistent with TB, or who initiated 2 or more anti-TB medications was generated quarterly. Health care providers and laboratories were contacted to determine the reasons for reporting late and were educated on TB reporting requirements. To assess the effectiveness of the intervention, we evaluated the trend in delayed reports between 2003 and 2006, using the Jonckheere-Terpstra test for trend. The proportion of patients who were reported late decreased from 43% (942/2183) in 2003 to 20% (386/1930) in 2006 (Ptrend < .0001). There were improvements in reporting timeliness for all 3 reporting criteria included in the evaluation and all provider types (all Ptrend < .0001); however, private providers consistently had a higher proportion of delayed reporting (22% reported late in 2006). This relatively simple intervention was very effective in improving the timeliness of TB reporting and could be utilized for other reportable diseases where prompt reporting is critical.

Changing sociodemographic and clinical characteristics of tuberculosis among HIV-infected patients, New York City, 1992-2005.

BACKGROUND: Although highly active antiretroviral therapy (HAART) has decreased human immunodeficiency virus (HIV)-related morbidity, tuberculosis remains an important disease among HIV-infected individuals. METHODS: By use of surveillance data, sociodemographic and clinical changes among HIV-infected and HIV-uninfected tuberculosis patients in New York City were evaluated using the Cochran-Armitage trend test and multivariate logistic regression across 3 periods: 1992-1995 (pre-HAART), 1996-2000 (early HAART), and 2001-2005 (late HAART). RESULTS: Among tuberculosis patients with known HIV status, 4345 (60%) of 7224 were HIV-infected in pre-HAART, 1943 (33%) of 5933 in early HAART, and 851 (22%) of 3815 in late HAART (P < .001 for trend). During the study period, the age of HIV-infected tuberculosis patients increased, and greater proportions were female, non-Hispanic black, Asian, and foreign born; the proportion that was non-Hispanic white decreased. The proportion that was culture-negative for Mycobacterium tuberculosis increased (from 7% pre-HAART to 21% late HAART; P < .001 for trend; early HAART vs pre-HAART adjusted odds ratio [aOR], 1.68; 95% confidence interval [CI], 1.38-2.04), and the proportion with extrapulmonary disease also increased (from 32% to 46%; P < .001 for trend). The proportion with multidrug-resistant tuberculosis decreased (from 16% to 4%; P < .001 for trend), especially from pre-HAART to early HAART (aOR, 0.31; 95% CI, 0.25-0.40). The proportion who died before tuberculosis treatment decreased (from 12% to 7%), and the proportion who died during tuberculosis treatment also decreased (from 29% to 11%) (both, P < .001 for trend). Over time, HIV-infected tuberculosis patients had AIDS longer before the diagnosis of tuberculosis (P < .001 for trend). Similar trends for culture, site of disease, and drug resistance were seen for HIV-uninfected tuberculosis patients. CONCLUSIONS: The sociodemographic and clinical characteristics changed substantially among HIV-infected tuberculosis patients in New York City. Awareness of these changes may speed diagnosis of tuberculosis. Future studies should evaluate HAART's effect on tuberculosis presentation among HIV-infected patients.

Linezolid use for treatment of multidrug-resistant and extensively drug-resistant tuberculosis, New York City, 2000-06.

UNLABELLED: Rationale Linezolid may be effective for the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB); however, serious adverse events are common and there is little information on the management of these toxicities. METHODS: We retrospectively reviewed public health and medical records of 16 MDR TB patients, including 10 patients with XDR TB, who were treated with linezolid in New York City between January 2000 and December 2006, to determine treatment outcomes and describe the incidence, management and predictors of adverse events. RESULTS: Linezolid was added to MDR TB regimens for a median duration of 16 months (range: 1-29). Eleven patients (69%) completed treatment, four (25%) died and one (6%) discontinued treatment without relapse. Myelosuppression occurred in 13 (81%) patients a median of 5 weeks (range: 1-11) after starting linezolid, gastrointestinal adverse events occurred in 13 (81%) patients after a median of 8 weeks (range: 1-57) and neurotoxicity occurred in seven (44%) patients after a median of 16 weeks (range: 10-111). Adverse events were managed by combinations of temporary suspension of linezolid, linezolid dose reduction and symptom management. Five (31%) patients required eventual discontinuation of linezolid. Myelosuppression was more responsive to clinical management strategies than was neurotoxicity. Leucopenia and neuropathy occurred more often in males and older age was associated with thrombocytopenia (P < 0.05). CONCLUSIONS: The majority of MDR TB patients on linezolid had favourable treatment outcomes, although treatment was complicated by adverse events that required extensive clinical management.

Adherence to treatment of latent tuberculosis infection in a clinical population in New York City.

BACKGROUND: Low adherence to treatment of latent tuberculosis infection (TLTBI) diminishes TB prevention efforts. This study examined the treatment completion rate among those who started TLTBI and factors associated with adherence to TLTBI. METHODS: Patients who started TLTBI in New York City (NYC) Health Department chest clinics during January 2002-August 2004 were studied. TLTBI completion rate were described and compared according to patient demographic and clinical characteristics by regimen using univariate analysis and log-binomial regression. RESULTS: A total of 15 035 patients started and 6788 (45.2%) completed TLTBI. Treatment completers were more likely than non-completers to be >or=35 years old (52.5%, adjusted relative risk (aRR)=1.2, 95% confidence interval (CI)=1.1, 1.2), contacts to pulmonary TB patients (57.4%, aRR=1.5, 95% CI=1.4, 1.7), treated by directly observed preventive therapy (DOPT) (71.4%, aRR=1.3, 95% CI=1.2, 1.3), and to have received the rifamycin-based regimen (60.0%, aRR=1.2, 95% CI=1.1, 1.3). The completion rate with an isoniazid regimen did not differ between HIV-infected and HIV-uninfected persons. Among those who failed to complete, 3748 (47.8%) failed to return for isoniazid and 59 (14.7%) for rifamycin after the first month of medication dispensing. CONCLUSIONS: Shorter regimen and DOPT increased completion rates for LTBI. Though efforts to improve TLTBI completion need to address all groups, greater focus is needed for persons who are contacts and HIV-infected, as they have higher risk of developing TB.

Prevalence of tuberculin skin test positivity in clinical population in New York City.

The prevalence of latent tuberculosis infection (LTBI) in the various populations of New York City (NYC), a city with a high density of non-US-born persons, is unknown. We examined the prevalence of TST positivity in patients who received a tuberculin skin test (TST) between 1/2002 and 8/2004 at any of 10 NYC health department chest centers. A positive TST was defined as an induration reaction to tuberculin of ≥10 mm. In the study population of 41,022 individuals, prevalence of TST positivity was 24.4% (95%CI = 24.0, 24.8); four times higher among non-US-born persons than US-born (39.5% vs. 8.8%, Prevalence ratio (PR) = 4.5; 95%CI = 4.4, 4.6). Prevalence of TST positivity increased with age in both US and non-US-born persons. Persons from countries with a TB case rate >100/100,000 population had higher prevalence of TST positivity (47% vs. ≤39%), even after controlling for BCG (PR = 1.3, 95%CI = 1.2, 1.4). These findings provide insight into current prevalence of TST positivity in many immigrant populations and will help both clinicians and health departments to target patients for LTBI treatment.

Performance of nucleic acid amplification tests for diagnosis of tuberculosis in a large urban setting.

BACKGROUND: A diagnosis of tuberculosis (TB) relies on acid-fast bacilli (AFB) smear and culture results. Two rapid tests that use nucleic acid amplification (NAA) have been approved by the US Food and Drug Administration for the diagnosis of TB based on detection of Mycobacterium tuberculosis from specimens obtained from the respiratory tract. We evaluated the performance of NAA testing under field conditions in a large urban setting with moderate TB prevalence. METHODS: The medical records of patients with suspected TB during 2000-2004 were reviewed. Analysis was restricted to the performance of NAA on specimens collected within 7 days after the initiation of treatment for TB. The assay's sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) were evaluated. RESULTS: The proportion of patients with confirmed or suspected TB whose respiratory tract specimens were tested by use of NAA increased from 429 (12.9%) of 3334 patients in 2000 to 527 (15.6%) of 3386 patients in 2004; NAA testing among patients whose respiratory tract specimens tested positive for AFB increased from 415 (43.6%) of 952 patients in 2000 to 487 (55.5%) of 877 patients in 2004 (P < .001 for both trends). Of the 16,511 patients being evaluated for pulmonary TB, 4642 (28.1%) had specimens that tested positive for AFB on smear. Of those 4642 patients, 2241 (48.3%) had NAA performed on their specimens. Of those 2241 patients, 1279 (57.1%) had positive test results. Of those 1279 patients, 1262 (98.7%) were confirmed to have TB. For 1861 (40.1%) of the 4642 patients whose specimens tested positive for AFB on smear, the NAA test had a sensitivity of 96.0%, a specificity of 95.3%, a PPV of 98.0%, and an NPV of 90.9%. For 158 patients whose specimens tested negative for AFB on smear, the NAA test had a sensitivity of 79.3%, a specificity of 80.3%, a PPV of 83.1%, and an NPV of 76.0%, respectively. For the 215 specimens that tested positive for AFB by smear, we found a sensitivity, specificity, PPV, and NPV of 97.5%, 93.6%, 95.1%, and 96.8%, respectively. A high-grade smear was associated with a better test performance. CONCLUSION: NAA testing was helpful for determining whether patients whose specimens tested positive for AFB on smear had TB or not. This conclusion supports the use of this test for early diagnosis of pulmonary and extrapulmonary TB.

Human immunodeficiency virus counseling, testing, and referral of close contacts to patients with pulmonary tuberculosis: feasibility and costs.

BACKGROUND: We aimed to increase human immunodeficiency virus (HIV) counseling, testing, referral (CTR), and knowledge of HIV serostatus of close contacts of tuberculosis patients and improve tuberculosis screening and treatment of HIV-infected contacts. METHODS: Of close contacts to infectious tuberculosis patients reported from December 2002 to November 2003, investigators (1) offered HIV CTR, (2) identified factors associated with HIV testing, and (3) assessed study costs. RESULTS: Of 614 contacts, 569 (93%) were provided HIV information and offered HIV CTR. Of the 569, 58 (10%) were previously HIV tested; 165 (29%) were newly HIV tested; and 346 (61%) were not tested. None of the 165 newly HIV tested contacts were HIV infected. Contacts more likely to be newly HIV tested (vs not tested) included those aged 18-24, Hispanic, or non-Hispanic Black. Of 24 HIV-infected contacts, 71 percent received chest-radiograph screening for tuberculosis disease; 56 percent of 18 eligible for latent-tuberculosis-infection treatment started and half completed. It cost $1 per patient to provide HIV information and $5-$8 to offer HIV CTR. CONCLUSION: The project increased HIV CTR of close contacts of infectious tuberculosis patients. The important factor for success in knowing contacts' HIV serostatus was simply for TB program staff to ask about it and offer the test to those who did not know their status.

Rifapentine for the treatment of pulmonary tuberculosis.

Rifapentine is a recently approved antituberculosis drug that has not yet been widely used in clinical settings. Clinical data support intermittent use of rifapentine with isoniazid during the continuation phase of tuberculosis treatment. Patients with culture-positive, noncavitary, pulmonary tuberculosis whose sputum smear is negative for acid-fast bacilli at the end of the 2-month intensive treatment phase are eligible for rifapentine therapy. Rifapentine should not be used in human immunodeficiency virus-infected patients, given their increased risk of developing rifampin resistance with currently recommended dosages. Rifapentine is not currently recommended for children aged <12 years, pregnant or lactating women, or individuals with culture-negative or extrapulmonary tuberculosis. Rifapentine (600 mg) is administered once weekly with isoniazid (900 mg) during the continuation phase of treatment. This combination should only be given under direct observation. As with rifampin, drug-drug interactions are common, and regular patient monitoring is required. Ease of administration makes this regimen attractive both for tuberculosis-control programs and for patients.

Strain-specific differences in two large Mycobacterium tuberculosis genotype clusters in isolates collected from homeless patients in New York City from 2001 to 2004.

We studied two large Mycobacterium tuberculosis genotype clusters associated with recent outbreaks in homeless persons to determine factors associated with these tuberculosis (TB) strains. Isolates from all culture-positive TB cases diagnosed from 1 January 2001 to 31 December 2004 were genotyped. Patients whose isolates had identical restriction fragment length polymorphism patterns and spoligotypes were considered clustered. Health department records were reviewed and reinterviews attempted for clustered cases. Patients with the Cs30 and BEs75 strains were compared to other genotypically clustered cases and to each other. The two largest genotype clusters among homeless persons were the Cs30 strain (n = 105) and the BEs75 strain (n = 47). Fifty-one (49%) patients with the Cs30 strain and 28 (60%) with the BEs75 strain were homeless. Compared to patients with the BEs75 strain, patients with the Cs30 strain were less likely to be respiratory acid-fast bacillus smear positive (51% versus 72%). Furthermore, patients with the BEs75 strain were more likely to be HIV infected (74% versus 42%), which suggests that most patients with this strain advanced to disease after recent infection. Cases in clusters of strains that have been circulating in the community over a long time period, such as the Cs30 strain, require additional investigation to determine whether clustering is a result of recent transmission or reactivation of remote infection.