Medical data collection on UK Military Exercise Saif Sareea 3: the EpiNATO-2 surveillance system.

INTRODUCTION: Epidemiological data from military exercises are important to identify trends in medical presentations and treatment requirements to aid planning for future operations. UK Military exercises use the EpiNATO-2 surveillance system for this purpose, however it has some limitations in the spectrum of data it can collect. An enhanced reporting system titled EpiNATO-2 PLUS was developed and introduced in all LAND (Army) Role 1 Medical Treatment Facilities (MTFs) as part of Exercise Saif Sareea 3 (SS3). It was assessed as part of a Quality Improvement Project for its utility in terms of spectrum and validity of data capture. METHOD: Epidemiological data were collected over a 2-month period from medical consultations in Camp Shafa during SS3 by EpiNATO-2 or EpiNATO-2 PLUS. This involved categorisation of symptoms into a coding system which represents a spectrum of clinical presentations, as well as collecting data on the effect of medical issues on personnel productivity. Halfway through the collection period, an EpiNATO-2 PLUS education session and Summary Guide were introduced. Data were audited for the period before and after these introductions. RESULTS: Of the 1163 consultations conducted in the 2-month period, the use of EpiNATO-2 PLUS captured an additional 169 patient contacts not collected by EpiNATO-2. The provision of a summary guide and teaching session decreased coding errors in the second audit period from 12.9% to 6.8% for EpiNATO-2 and from 19.4% to 6.6% for EpiNATO-2 PLUS, respectively. CONCLUSIONS: The use of EpiNATO-2 PLUS collected a broader spectrum of medical activity in the Role 1 MTF, by capturing an additional 10% of the clinical workload compared with EpiNATO-2. The increase in coding accuracy correlates with the introduction of the education session and EpiNATO-2 PLUS Summary Guide. It is recommended that EpiNATO-2 PLUS is used in future deployments.

Letermovir prophylaxis through day 100 post transplant is safe and effective compared with alternative CMV prophylaxis strategies following adult cord blood and haploidentical cord blood transplantation.

We compared CMV outcomes of three prophylactic approaches used for CBT and haploidentical cord transplants from December 2009 through 2018: letermovir (n = 32) through day 100 post transplant, "valacyclovir day 100" (valacyclovir 2 g orally three times daily through day 100) (n = 60), and "valacyclovir hospital discharge" (valacyclovir 2 g orally three times daily through hospital discharge then acyclovir 800 mg twice daily) (n = 41). Through day 100, none in the letermovir group, six (10%) in the "valacyclovir day 100," and nine (22%) in the "valacyclovir hospital discharge" group required CMV directed treatment (p = 0.005 and 0.06 comparing letermovir to "valacyclovir hospital discharge" and "valacyclovir day 100"). Fewer patients in the letermovir group (n = 7, 22%) had any CMV reactivation versus the "valacyclovir day 100" group (n = 20, 33%) versus the "valacyclovir hospital discharge" group (n = 23, 57%) (p = 0.003 and 0.21 comparing letermovir to "valacyclovir hospital discharge" and "valacyclovir day 100"). Among patients not reactivating CMV before 100 days, reactivation rates between day 100 and 180 were higher in the letermovir and "valacyclovir day 100" groups than the "valacyclovir hospital discharge" group. Letermovir is safe and effective compared with alternative prophylaxis approaches following CBT through day 100. Reactivation and monitoring after day 100 remain potential concerns.

Real-world experience of venetoclax with azacitidine for untreated patients with acute myeloid leukemia.

Venetoclax is approved for older untreated acute myeloid leukemia (AML) patients. Venetoclax was available prior to approval off-label. We assessed our single-institution off-label experience with venetoclax/azacitidine, comparing outcomes with a clinical trial cohort that administered this regimen at the same institution. Thirty-three untreated AML patients unfit or unwilling to receive induction chemotherapy and prescribed venetoclax/azacitidine off-trial were retrospectively analyzed and compared with 33 patients who received the same therapy on trial. Outcomes were compared, and comparisons were made to a theoretical scenario in which off-trial patients received induction. Digital droplet polymerase chain reaction evaluated measurable residual disease (MRD). Off-trial venetoclax was attainable in nearly all patients for whom this was desired. The complete remission (CR)/CR with incomplete blood count recovery rate was 63.3% for off-trial patients who received treatment and 84.9% for trial patients (P = .081). The median overall survival for off-trial patients who received treatment was 381 days (95% confidence interval [CI], 174, not reached) vs 880 days (95% CI, 384, not reached) for trial patients (P = .041). Prior exposure to hypomethylating agents was associated with worse outcomes. Response rates with venetoclax/azacitidine were not inferior to a theoretical scenario in which patients received induction, and early death rates were less than expected with induction. MRD negativity was achievable. Newly diagnosed AML patients treated in a "real-world" scenario with off-trial venetoclax/azacitidine had inferior outcomes compared with patients treated in the setting of a clinical trial. Additionally, this therapy may be as effective, and less toxic, when compared with induction chemotherapy.

Oral Vancomycin Prophylaxis as Secondary Prevention Against Clostridioides difficile Infection in the Hematopoietic Stem Cell Transplantation and Hematologic Malignancy Population.

Clostridioides difficile infection (CDI) is a common complication in the hematopoietic stem cell transplantation (HSCT) and hematologic malignancy (HM) population. CDI is associated with increased hospital length of stay, health care and societal costs, morbidity, and mortality. Identifying strategies for secondary prevention of CDI is of extreme importance in the HSCT/HM population. In this study, our primary objective was to evaluate the effectiveness and safety of an oral vancomycin prophylaxis (OVP) protocol for secondary prevention of CDI in a retrospective cohort of adult autologous/allogeneic HSCT recipients and patients with HM who did not undergo HSCT with a first CDI episode treated with concomitant broad-spectrum antibiotics (BSA). Patients were diagnosed and treated for CDI as inpatients and/or outpatients and were divided into 2 groups based on a preprotocol versus postprotocol analysis: the OVP group, comprising patients who received planned monotherapy with oral vancomycin 125 mg every 6 hours for 14 days for a first episode of CDI and subsequently received OVP posttreatment and a no OVP (NOVP) group, comprising patients who received planned monotherapy with oral vancomycin 125 mg every 6 hours for 14 days for a first episode of CDI and subsequently did not receive OVP posttreatment. OVP was defined as vancomycin 125 mg every 12 hours for up to 7 days after BSA discontinuation. The primary endpoint was recurrent CDI (rCDI), defined as symptoms of loose stools/diarrhea with high clinical suspicion for CDI prompting empiric therapy within 60 days of completion of treatment/prophylaxis for the first CDI episode. The incidence of vancomycin-resistant enterococcal (VRE) infection and 60-day mortality were also compared between the 2 groups. Multivariate logistic regression was created from associated variables to identify independent associations with rCDI. A total of 50 patients were included, 21 in the OVP group (42%) and 29 in the NOVP group (58%). The mean patient age was 58 years, and the cohort was 60% male and 86% Caucasian. HSCT was performed in 60% of the patients, and 76% of CDI cases were diagnosed during hospitalization. The rate of rCDI was significantly lower in the OVP group compared with the NOVP group (5% [1 of 21] versus 35% [10 of 29]; P= .016), with no subsequent increase in VRE infection rate (14% [3 of 21] versus 10% [3 of 29]; P = .686). By multivariable logistic regression, rCDI was inversely associated with OVP (odds ratio [OR], .14; 95% confidence interval [CI], .007 to .994; P = .049) and directly associated with outpatient CDI diagnosis (OR, 8.72; 95% CI, 1.816 to 49.158; P = .007). No between-group differences were found in 60-day mortality (10% [2 of 21] for OVP versus 7% [2 of 29] for NOVP; P > 0.999). OVP appears to be safe and effective for secondary prevention of CDI in the HSCT/HM population. Prospective trials are needed to validate the effectiveness of OVP in this vulnerable population to prevent rCDI.

Central nervous system-specific knockout of steroidogenic factor 1 results in increased anxiety-like behavior.

Steroidogenic factor 1 (SF-1) plays key roles in adrenal and gonadal development, expression of pituitary gonadotropins, and development of the ventromedial hypothalamic nucleus (VMH). If kept alive by adrenal transplants, global knockout (KO) mice lacking SF-1 exhibit delayed-onset obesity and decreased locomotor activity. To define specific roles of SF-1 in the VMH, we used the Cre-loxP system to inactivate SF-1 in a central nervous system (CNS)-specific manner. These mice largely recapitulated the VMH structural defect seen in mice lacking SF-1 in all tissues. In multiple behavioral tests, mice with CNS-specific KO of SF-1 had significantly more anxiety-like behavior than wild-type littermates. The CNS-specific SF-1 KO mice had diminished expression or altered distribution in the mediobasal hypothalamus of several genes whose expression has been linked to stress and anxiety-like behavior, including brain-derived neurotrophic factor, the type 2 receptor for CRH (Crhr2), and Ucn 3. Moreover, transfection and EMSAs support a direct role of SF-1 in Crhr2 regulation. These findings reveal important roles of SF-1 in the hypothalamic expression of key regulators of anxiety-like behavior, providing a plausible molecular basis for the behavioral effect of CNS-specific KO of this nuclear receptor.

Trends in the BVDV serological response in the Upper Midwest.

Bovine viral diarrhoea continues to be an important disease affecting both beef and dairy animals of all ages. One of the quickest means of measuring bovine viral diarrhoea virus (BVDV) exposure and infection in the herd is a serum neutralization (SN) assay. Type 1 and type 2 BVDV SN results from the Animal Disease Research and Diagnostic Laboratory at South Dakota State University were collected over a seven-year period (1995-2001) to determine any trends. These results indicated that in 1996, 31% of the animals had titres > or =512 while in 2001, 74% of the titres were > or = 512. There has been a progressive increase over the seven-year period in the number of cases with titres > or = 512 with the exception of 1999 when there was a slight decrease. When analyzing the titres greater than 512, a further increase was seen. In 1995, 80% of the titres were < or = 1024 and 20% were 2048 and no titres were >2048. In 2001, 47% of the antibody levels were < or = 1024 while 53% were < or =2048 and 30% were >4096. The most dramatic increase in titres occurred in 1997 and the percentage of animals with titres from 512-8192 has remained fairly constant for the last five years (1997-2001). This increase is in part due to more extensive use of vaccination but probably also reflects a rise in field infections. In the future, standardizing existing BVDV SN serology along with developing new BVDV serology methods is necessary to provide continuity for any full-scale eradication programme.