Active Surveillance Program Research Articles

Pandemic preparedness—political perspectives

Abstract Pandemic preparedness is explored for the antibiotic resistance crisis and the threat of a next viral pandemic. Bacterial pathogens escaping from control by antibiotics are well defined, and resistance develops over decades while a next viral pandemic occurs suddenly with a novel virus. The death toll for resistant bacterial infections is reviewed, and the scientific and economic hurdles to the development of new antibiotics are discussed. Regulatory adaptations and financial push and pull programs to restimulate new antibiotic development are explored. The COVID-19 pandemic caused not only millions of deaths, but also economic losses in excess of 10 trillion US dollars. Coronaviruses and influenza viruses remain usual suspects for new viral pandemics, followed by paramyxoviruses. Viral infections at the animal–human interface in wet markets and in disturbed environments need active virus surveillance programs. Learning lessons from the COVID-19 for non-pharmaceutical interventions is difficult to draw since measures were frequently applied in combination against different variant viruses and against changing population immunity levels. The Randomised Evaluation of COVID-19 Therapy (RECOVERY) clinical trials demonstrated that even under emergency situations clinical trials can rapidly provide solid treatment data. Various novel vaccine approaches were the most efficient control measures for the COVID-19 pandemic. Pandemic preparedness also requires a fact-based discussion both in the public and in parliaments to settle the conflict between individual freedom and necessary restrictions during a pandemic. Mature and educated citizens are needed not only for coping with pandemics but also for creating stress-resistant democratic societies. Learned scientific societies should contribute to this discussion.

Evidence of tick-borne encephalitis virus neutralizing antibodies in Serbian individuals exposed to tick bites.

Tick-borne encephalitis (TBE) is an emerging vector-borne and food-borne disease caused by the tick-borne encephalitis virus (TBEV; Orthoflavivirus encephalitidis), with a distribution spanning the Eurasian continent. Despite its significant public health impact in various European regions, TBE remains largely underdiagnosed in Serbia due to limited awareness and diagnostic challenges. In response to this, our study aimed to comprehensively assess TBEV exposure in individuals infested with ticks and to identify potential TBEV foci within Serbia. From 2019 to 2021, we conducted an observational study involving 450 patients who reported tick infestations. Our demographic analysis revealed a median age of 38 years, with a slight male predominance among the participants. We documented tick infestations in 38 municipalities across 14 districts of Serbia, with a notable concentration in proximity to Fruška Gora Mountain. The ticks most frequently removed were Ixodes ricinus, with nymphs and adult females being the predominant stages. On average, nymphs were removed after about 27.1 hours of feeding, while adult females remained attached for approximately 44.4 hours. Notably, we found age as a significant predictor of infestation time for both nymphs and adult females. Furthermore, we detected TBEV-neutralizing antibodies in 0.66% of the serum samples, shedding light on potential TBEV foci, particularly in Fruška Gora Mountain and other regions of Serbia. Our study emphasizes the urgent need for active TBE surveillance programs, especially in areas suspected of hosting TBEV foci, in order to assess the true TBE burden, identify at-risk populations, and implement effective preventive measures.

A brief mind-body intervention to reduce pain and anxiety during prostate needle biopsy: a clinically integrated randomized controlled trial with 2-staged consent

ObjectivesMany patients experience pain, anxiety, and discomfort with prostate biopsy, which may discourage enrollment in active surveillance programs or follow-up biopsy. Guided meditation can significantly reduce pain and anxiety during percutaneous biopsy. We sought to evaluate the effectiveness of a brief mind-body intervention on patient-reported outcomes after prostate biopsy. Methods and materialsWe performed a clinically-integrated randomized controlled trial of a brief mind-body intervention during biopsy compared to usual care at a single tertiary care center from 2018 to 2022. All patients offered transrectal ultrasound-guided prostate biopsy in the clinic with local anesthesia were eligible for enrollment. This clinically integrated trial was conducted simultaneously with a randomized controlled trial of 1-stage and 2-stage consent. The primary outcome was patient-reported pain, anxiety, discomfort, and tolerability on a visual-analog scale (0–10). A 15% improvement was prespecified as clinically relevant. We compared the proportion of men in each arm reporting a severe score (7–10) on any of the 4 scales using Fisher's exact test and then compared means for each scale separately using ANCOVA with randomization stratum (first vs. prior biopsy) as a covariate. ResultsOf 263 eligible patients, 238 enrolled (119 per arm). One hundred seventy-two (72%) enrolled with 2-stage consent. A total of 37/94 (39%) and 38/102 (37%) patients randomized to usual care and intervention, respectively, reported severe scores in any of the 4 domains, a difference of 2.1% (95% confidence interval [CI] -13, 17%, P = 0.8). There was no evidence of a difference in mean postbiopsy anxiety (P = 0.3), discomfort (P = 0.09), pain (P = 0.4) or tolerability scores (P = 0.2). ConclusionsA clinically meaningful benefit for this brief mind-body intervention during prostate biopsy is unlikely. Robust patient enrollment is feasible using 2-stage consent.

Impact of beta blockers on perioperative complications in patients undergoing major noncardiac surgery

Abstract Introduction Beta blockers (BB) are broadly used in patients with cardiovascular disease because they are known to decrease myocardial oxygen consumption by decreasing heart rate and myocardial contractility. Pilot studies have shown conflicting results. Therefore, we aimed to evaluate the impact of preoperative BB therapy on (1) the incidence of cardiac perioperative myocardial injury/infarction (PMI) within 48 hours after surgery and (2) long-term MACE within 365 days in patients after major noncardiac surgery. Methods We prospectively included consecutive high-risk patients undergoing inpatient major noncardiac surgery at a university hospital and a hospital, both in Switzerland, who were eligible for the institutional active PMI surveillance and response program. The primary endpoint was PMI due to cardiac causes (type 1 myocardial infarction (MI), tachyarrhythmia, acute heart failure, or type 2 MI) within 3 days after surgery, centrally adjudicated by two independent experts. The secondary endpoint was the occurrence of MACE, defined as a composite of acute myocardial infarction, acute heart failure, life-threatening arrhythmia, and cardiovascular death, within 365 days. We used inverse probability of treatment weighting to account for differences between BB and non-BB users and then performed a univariable logistic regression with cardiac PMI and a univariable Cox proportional hazard model with MACE as a dependent variable. Results Between October 2014 and February 2018, we included 7751 high-risk patients undergoing major inpatient noncardiac surgery. The median age was 74 years and 45% were female. 2856 of 7751 patients (36.8%) received preoperative BB therapy. Patients receiving BB therapy had more cardiovascular comorbidities like known coronary artery disease, atrial fibrillation, or hypertension. After IPTW, we achieved a good balance between patients receiving BB therapy and those who did not. 812 patients (10.5%) had a cardiac PMI within 3 days after surgery. When comparing the patients receiving BB to those that did not, we did not see any difference in the occurrence of cardiac PMI, resulting in a weighted odds ratio of 0.99 (95% Confidence interval [CI] 0.89-1.10). The composite secondary endpoint MACE within 365 days occurred in 9% of all patients. In multivariable analysis, there was no difference between patients receiving BB and those that did not, with a weighted hazard ratio of 1.07 (95% CI 0.86-1.33). Conclusion In our patient cohort, we could not see any difference in cardiac PMI between patients receiving BB therapy and those who did not, suggesting that continuing BB perioperatively is safe but not associated with any benefit. Also after 1 year, we saw no difference in MACE between patients receiving BB therapy versus those who did not.MACE within 365 days

Specific Polo-Like Kinase 1 Expression in Nodular Lymphocyte-Predominant Hodgkin Lymphoma Suggests an Intact Immune Surveillance Program

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare and relatively indolent B-cell lymphoma. Characteristically, the [lymphocyte-predominant (LP)] tumor cells are embedded in a microenvironment enriched in lymphocytes. More aggressive variants of mature B-cell and peripheral T-cell lymphomas exhibit nuclear expression of the polo-like kinase 1 (PLK1) protein, stabilizing MYC (alias c-myc) and associated with worse clinical outcomes. This study demonstrated expression of PLK1 in the LP cells in 100% of NLPHL cases (n=76). In contrast, <5% of classic Hodgkin lymphoma cases (n=70) showed PLK1 expression within the tumor cells. Loss-of-function approaches demonstrated that the expression of PLK1 promoted cell proliferation and increased MYC stability in NLPHL cell lines. Correlation with clinical parameters revealed that the increased expression of PLK1 was associated with advanced-stage disease in patients with NLPHL. A multiplex immunofluorescence panel coupled with artificial intelligence algorithms was used to correlate the composition of the tumor microenvironment with the proliferative stage of LP cells. The results showed that LP cells with PLK1 (high) expression were associated with increased numbers of cytotoxic and T-regulatory T cells. Overall, the findings demonstrate that PLK1 signaling increases NLPHL proliferation and constitutes a potential vulnerability that can be targeted with PLK1 inhibitors. An active immune surveillance program in NLPHL may be a critical mechanism limiting PLK1-dependent tumor growth.

Adverse events following immunization (AEFIs) with anti-meningococcus type B vaccine (4CMenB): Data of post-marketing active surveillance program. Apulia Region (Italy), 2019–2023

The four-component recombinant-DNA anti-meningococcus B vaccine (4CMenB) has been approved by the European Medicines Agency in 2013. In Italy, 4CMenB is recommended since 2017 for use in infants under one year of age. Due to the strong evidence of increased risk of fever after administration, surveillance of adverse events following immunization (AEFIs) is a priority for 4CMenB.This cross-sectional prospective study aims at investigating 4CMenB’s safety profile. The study population is represented by infants under twelve months of age vaccinated with 4CMenB in selected ambulatories in Apulia, a region in South-Eastern Italy, from October 1st, 2020, to March 31st, 2023. Parents were provided with a post-vaccination diary covering up to seven days after immunization and were contacted one week after the vaccination day. Information about AEFIs was collected, and reactions were classified following World Health Organization guidelines. For serious AEFIs, causality assessment was carried out. AEFI risk determinants were investigated via logistic regression.A total of 4,773 diaries were completed, with 78.13 % of them (3,729/4,773) containing one or more AEFI reports. Systemic reactions such as malaise, drowsiness/insomnia and fatigue were the most common ones, followed by fever and local pain, tenderness, redness and swelling.Twenty-three cases of serious AEFIs were reported. Following causality assessment, 78.26 % of serious adverse events (18/23) were deemed to have a consistent causal association with the administration of 4CMenB (reporting rate: 0.38 %). Three infants were hospitalized following vaccination, but no cases of death or permanent/severe impairment were reported. Prophylactic paracetamol administration showed a significant protective effect against the risk of manifesting fever within the first 24 h after administration (OR: 0.75; p < 0.005).Our data confirms existing evidence regarding the safety of 4CMenB vaccination in babies under 2 years of age, but also highlight a significant risk of fever after vaccination. Prophylactic paracetamol administration could represent a protective factor against fever, especially during the first 24 h after vaccination.

An effective internet-based system for surveillance and elimination of triatomine insects: AlertaChirimacha.

Vector-borne diseases remain a significant public health threat in many regions of the world. Traditional vector surveillance and control methods have relied on active and passive surveillance programs, which are often costly and time-consuming. New internet-based vector surveillance systems have shown promise in removing some of the cost and labor burden from health authorities. We developed and evaluated the effectiveness of a new internet-based surveillance system, "AlertaChirimacha", for detecting Triatoma infestans (known locally by its Quechua name, Chirimacha), the Chagas disease vector, in the city of Arequipa, Peru. In the first 26 months post-implementation, AlertaChirimacha received 206 reports of residents suspecting or fearing triatomines in their homes or neighborhoods, of which we confirmed, through pictures or inspections, 11 (5.3%) to be Triatoma infestans. After microscopic examination, none of the specimens collected were infected with Trypanosoma cruzi. AlertaChirimacha received 57% more confirmed reports than the traditional surveillance system and detected 10% more infested houses than active and passive surveillance approaches combined. Through in-depth interviews we evaluate the reach, bilateral engagement, and response promptness and efficiency of AlertaChirimacha. Our study highlights the potential of internet-based vector surveillance systems, such as AlertaChirimacha, to improve vector surveillance and control efforts in resource-limited settings. This approach could decrease the cost and time horizon for the elimination of vector-mediated Chagas disease in the region.

Role of targeted biopsy, perilesional biopsy, random biopsy, and their combination in the detection of clinically significant prostate cancer by mpMRI/transrectal ultrasonography fusion biopsy in confirmatory biopsy during active surveillance program.

Based on the findings of different trials in biopsy naïve patients, target biopsy (TB) plus random biopsy (RB) during mpMRI-guided transrectal ultrasound fusion biopsy (FB) are often also adopted for the biopsy performed during active surveillance (AS) programs. At the moment, a clear consensus on the extent and modalities of the procedure is lacking. To evaluate the increase in diagnostic accuracy achieved by perilesional biopsy (PL) and different RB schemes during FB performed in AS protocol. We collected prospectively the data of 112 consecutive patients with low- or very-low-risk prostate cancer; positive mpMRI underwent biopsy at a single academic institution in the context of an AS protocol. mpMRI/transrectal US FB with Hitachi RVS system with 3 TB and concurrent transrectal 24-core RB. The diagnostic yield of the different possible biopsy schemes (TB only; TB + 4 perilesional (PL) cores; TB + 12-core RB; TB + 24-core RB) was compared by the McNemar test. Univariable and multivariable regression analyses were adopted to identify predictors of any cancer, Gleason grade group (GGG) ≥2 cancers, and the presence of GGG≥2 cancers in the larger schemes only. The detection rate of GGG ≥2 cancers increased to 30%, 39%, and 49% by adding 4 PL cores, 14, and 24 RB cores, respectively, to TB cores (all p values <0.01). On the whole, TB alone, 14-core RB, and 24-core-RB identified 38%, 47%, and 56% of all the GGG ≥2 cancers. Such figures increased to 62% by adding to TB 4 PL cores, and to 80% by adding 14 RB cores. Most of the differences were observed in PI-RADS 4 lesions. We found that PL biopsy increased the detection rate of GGG ≥2 cancers as compared with TB alone. However, the combination of those cores missed a large percentage of the CS cancers identified with larger RB cores, including a 20% of CS cancers diagnosed only by the combination of TB plus 24-core RB.

SAT147 A Pharmacist Driven Active Surveillance Program To Reduce Hypoglycemic Recurrences In The Inpatient Setting

Abstract Disclosure: S. Kim: None. H. Tran: None. R.Y. Gianchandani: None. Background: Hyper and hypoglycemia increase morbidity and mortality in hospitalized patients. Glucose excursions are time sensitive and require timely response to prevent future episodes of dysglycemia. As part of a quality improvement initiative, we implemented an Active Glycemic Surveillance (AGS) program in July 2022 targeting patients with hypoglycemia (BG &amp;lt;70 mg/dL) based on a preliminary evaluation that revealed recurrent hypoglycemia was an opportunity for improvement. Pharmacist involvement in glycemic management has been shown to improve clinical outcomes in the acute care setting. Our AGS program is unique in that pharmacist trained in inpatient glycemic management is empowered to directly intervene on antihyperglycemic medication orders under scope of practice by a protocol approved through the pharmacy and therapeutics committee. Intervention: The AGS team consists of an endocrinologist and a diabetes stewardship pharmacist. A policy was developed and approved by P and T that outlines the types of interventions and orders that the diabetes stewardship pharmacist is able to make under scope of practice. These interventions include the ability to order certain labs (POCT BG, HgbA1C), and to adjust or discontinue certain anti-hyperglycemic agents Hospitalized patients who have a BG &amp;lt;70 mg/dL in the last 24 hours are reviewed by the AGS team. Chart review is performed on each patient to identify contributing factors and complicated cases are discussed with the endocrinologist prior to contacting the providers or making changes to orders. Providers are given rationale for changes as well as any other recommendations related to glycemic management. Results: During a 3 month period between August and October 2022, 848 cases of hypoglycemia were evaluated. Of these, 450 (53%) were found to be caused by an antihyperglycemic agent and 401 interventions were made by either the AGS team or other providers. The AGS team made 167 (41.6%) interventions and had a 24 h recurrence rate of 8.3% compared to 16.3% for all other providers. The most common types of interventions made by the AGS team were adjusting the insulin correction scale (78), basal insulin (57), bolus/meal insulin (16), oral medications (10), and TPN insulin (3). Conclusion: Our preliminary data show that a pharmacist-driven active surveillance program can reduce hypoglycemic recurrences. In the short time our AGS program has been implemented we have seen in increased utilization of appropriate correction scales, a decreased reliance on basal insulin or correction scale as the sole means of glycemic management, and an increase in endocrinology consultation for glycemic guidance. Future data will show the impact of this program on our overall hypoglycemia and hyperglycemia rates in future. Presentation: Saturday, June 17, 2023

Surveillance of SARS-CoV-2 Genetic Variants in the Polish Armed Forces Using Whole Genome Sequencing Analysis.

Military operations involve the global movement of personnel and equipment, increasing the risk of spreading infectious pathogens such as SARS-CoV-2. Given the continuous engagement of the Polish Armed Forces in overseas operations, an active surveillance program targeting Variants of Concern (VOC) of SARS-CoV-2 was implemented among military personnel. Screening using RT-qPCR tests was conducted on 1699 soldiers between November 2021 and May 2022. Of these, 84 SARS-CoV-2 positive samples met the criteria for whole genome sequencing analysis and variant identification. Whole genome sequencing was performed using two advanced next-generation sequencing (NGS) technologies: sequencing by synthesis and nanopore sequencing. Our analysis revealed eleven SARS-CoV-2 lineages belonging to 21K, 21L, and 21J. The predominant lineage was BA.1.1 (57% of the samples), followed by BA.1 (23%) and BA.2 (6%). Notably, all identified lineages detected in post-deployment screening tests were classified as VOC and were already present in Poland, showing the effectiveness of the Military Sanitary Inspection measures in mitigating the COVID-19 spread. Pre-departure and post-mission screening and isolation successfully prevented SARS-CoV-2 VOC exportation and importation. Proactive measures are vital in minimizing the impact of COVID-19 in military settings, emphasizing the need for continued vigilance and response strategies.

Development of a Novel Korean H9-Specific rRT-PCR Assay and Its Application for Avian Influenza Virus Surveillance in Korea.

Since the 2000s, the Y439 lineage of H9N2 avian influenza virus (AIV) has been the predominant strain circulating in poultry in Korea; however, in 2020, the Y280 lineage emerged and spread rapidly nationwide, causing large economic losses. To prevent further spread and circulation of such viruses, rapid detection and diagnosis through active surveillance programs are crucial. Here, we developed a novel H9 rRT-PCR assay that can detect a broad range of H9Nx viruses in situations in which multiple lineages of H9 AIVs are co-circulating. We then evaluated its efficacy using a large number of clinical samples. The assay, named the Uni Kor-H9 assay, showed high sensitivity for Y280 lineage viruses, as well as for the Y439 lineage originating in Korean poultry and wild birds. In addition, the assay showed no cross-reactivity with other subtypes of AIV or other avian pathogens. Furthermore, the Uni Kor-H9 assay was more sensitive, and had higher detection rates, than reference H9 rRT-PCR methods when tested against a panel of domestically isolated H9 AIVs. In conclusion, the novel Uni Kor-H9 assay enables more rapid and efficient diagnosis than the "traditional" method of virus isolation followed by subtyping RT-PCR. Application of the new H9 rRT-PCR assay to AI active surveillance programs will help to control and manage Korean H9 AIVs more efficiently.

Guideline adherence to statin therapy and association with short-term and long-term cardiac complications following noncardiac surgery: A cohort study.

Peri-operative complications are common and associated with high morbidity and mortality. Optimising the use of statins might be of important benefit in peri-operative care and reduce morbidity and mortality. To evaluate adherence to current guideline recommendations regarding statin therapy and its association with peri-operative and long-term cardiac complications. Prospective cohort study. Multicentre study with enrolment from October 2014 to February 2018. Eight thousand one hundred and sixteen high-risk inpatients undergoing major noncardiac surgery who were eligible for the institutional peri-operative myocardial injury/infarction (PMI) active surveillance and response program. Class I indications for statin therapy were derived from the current ESC Clinical Practice Guidelines during the time of enrolment. PMI was prospectively defined as an absolute increase in cTn concentration of the 99th percentile in healthy individuals above the preoperative concentration within the first three postoperative days. Long-term cardiac complications included cardiovascular death and spontaneous myocardial infarction (MI) within 120 days. The mean age was 73.7 years; 45.2% were women. Four thousand two hundred and twenty-seven of 8116 patients (52.1%) had a class I indication for statin therapy. Of these, 2440 of 4227 patients (57.7%) were on statins preoperatively. Adherence to statins was lower in women than in men (46.9 versus 63.9%, P < 0.001). PMI due to type 1 myocardial infarction/injury (T1MI; n = 42), or likely type 2 MI (lT2MI; n = 466) occurred in 508 of 4170 (12.2%) patients. The weighted odds ratio in patients on statin therapy was 1.15 [95% confidence interval (CI) 1.01 to 1.31, P = 0.036]. During the 120-day follow-up, 192 patients (4.6%) suffered cardiovascular death and spontaneous MI. After multivariable adjustment, preoperative use of statins was associated with reduced risk; weighted hazard ratio 0.59 (95% CI 0.41 to 0.86, P = 0.006). Adherence to guideline-recommended statin therapy was suboptimal, particularly in women. Statin use was associated with an increased risk of PMI due to T1MI and lT2MI but reduced risk of cardiovascular death and spontaneous MI within 120 days. Clinicaltrials.gov identifier NCT02573532.

Study of coagulase-negative staphylococci in hospital-acquired neonatal sepsis

Background Coagulase-negative staphylococci (CoNS) has become increasingly prevalent as the leading cause of late-onset bacteremia in neonatal ICUs. Diagnosing CoNS septicemia poses challenges because this bacterium commonly resides on the skin, leading to potential contamination of blood culture samples. Therefore, this study aimed to identify the bacterial causes of sepsis in neonates who exhibit clinical signs of the condition, also to assess the methicillin susceptibility of CoNS through both phenotypic and molecular methodologies. Materials and methods This study was carried out at Mansoura University Children Hospital. Blood samples were obtained and directly cultured using the BACT/ALERT system. All isolates were identified using BD Phoenix system. CoNS isolates were subjected to a disk diffusion susceptibility test with cefoxitin 30 µg, serving as an initial screening test to identify methicillin resistance. Automated antibiotic susceptibility was done using BD Phoenix system followed by PCR testing to detect the presence of the mecA gene in resistant CoNS isolates. Results Among all the isolated micro-organisms, Klebsiella pneumoniae and CoNS were found to be significantly higher in early-onset sepsis and late-onset sepsis, respectively. Staphylococcus epidermidis constituted 30% of the isolates, with Staphylococcus haemolyticus and Staphylococcus hominis each accounting for 20%, while other Staphylococcus species made up the remaining 20%. Among the identified CoNS, 47.4% tested positive for the mecA gene. The presence of the mecA gene was significantly associated with a higher incidence of late-onset sepsis (P=0.033). Conclusion CoNS are the predominant culprits behind late-onset sepsis in hospitalized newborns. Notably, the presence of the mecA gene was significantly linked to a higher occurrence of late-onset sepsis. Our study has uncovered a concerning surge in antibiotic resistance genes within our community. This underscores the urgency of implementing an active antibiotic surveillance program and exploring alternative therapeutic strategies to effectively combat neonatal sepsis.

Hypospadias prevalence by severity and associated risk factors: A population-based active surveillance analysis

Hypospadias is one of the most common congenital anomalies. Trends of hypospadias prevalence by severity are not well reported. Most prevalence studies consist of pooled data from different countries or states suffer from low data quality due to inconsistent methodologies, limited variables, and lack of categorization of hypospadias severity. The objective of this study is to examine the prevalence of hypospadias by degrees of severity and associated risk factors using combined data sources from a stable and well-defined population. The study population includes infants born with hypospadias to mothers residing in Arkansas from 1997 to 2016. Cases were identified from an active population-based surveillance program of birth defects. Identified hypospadias cases from surveillance data were linked to birth certificate and to a clinical database. These two data sources provide more details on the location of the defect and maternal and infant characteristics. The prevalence and 95% confidence intervals were calculated using total male live births as denominator. Chi-square test was used to assess the association of nominal variables. Logistic regression was used to calculate adjusted odds ratio. A total 3230 hypospadias cases were identified from 1997 to 2016. The overall prevalence is 83.0 per 10,000 male births. A majority of cases (56.7%) were classified as first degree with the others having second degree (22.8%), third degree (4.7%) or not otherwise specified (15.6%). The highest prevalence of hypospadias was observed among Non-Hispanic whites. Higher prevalence also was observed among mothers in the older age group with no prenatal care in the first trimester and with gestational hypertension or diabetes. Premature or small for gestational age infants tend to have higher prevalence across all levels of severity. The number of hypospadias cases increased over time. After maternal age, race and education were adjusted, higher risk persisted for infants of restricted fetal growth, mothers with gestational hypertension or diabetes and the cohort of 2013-2016. There is an increase of hypospadias cases in Arkansas. Several maternal and infant characteristics associated with higher prevalence for all levels of severity are worth further investigation.

Neonatal Bloodstream Infection with Ceftazidime-Avibactam-Resistant blaKPC-2-Producing Klebsiella pneumoniae Carrying blaVEB-25.

Although ceftazidime/avibactam (CAZ/AVI) has become an important option for treating adults and children, no data or recommendations exist for neonates. We report a neonatal sepsis case due to CAZ/AVI-resistant blaKPC-2-harboring Klebsiella pneumoniae carrying blaVEB-25 and the use of a customized active surveillance program in conjunction with enhanced infection control measures. The index case was an extremely premature neonate hospitalized for 110 days that had been previously treated with multiple antibiotics. Customized molecular surveillance was implemented at hospital level and enhanced infection control measures were taken for early recognition and prevention of outbreak. Detection and identification of blaVEB-25 was performed using next-generation sequencing. This was the first case of a bloodstream infection caused by KPC-producing K. pneumoniae that was resistant to CAZ/AVI without the presence of a metalo-β-lactamase in the multiplex PCR platform in a neonate. All 36 additional patients tested (12 in the same NICU and 24 from other hospital departments) carried wild-type blaVEB-1 but they did not harbor blaVEB-25. The emergence of blaVEB-25 is signal for the horizontal transfer of plasmids at hospital facilities and it is of greatest concern for maintaining a sharp vigilance for the surveillance of novel resistance mechanisms. Molecular diagnostics can guide appropriate antimicrobial therapy and the early implementation of infection control measures against antimicrobial resistance.

History of Thyroid Ultrasound.

From low-resolution images in the 1960s to current high-resolution technology, ultrasound has proven to be the initial imaging modality of choice for thyroid application. Point-of-care ultrasound has brought the technology to the thyroid specialist. Combined with physical examination, it provides real-time information regarding goiter, thyroid nodules, and thyroid cancer. Ultrasound-guided fine-needle aspiration biopsy has become the accepted norm, with biopsies rarely performed using palpation alone. Advantages of ultrasound-guided biopsy include precise placement of the needle within the nodule, selective sampling of areas with suspicious features, and accurate direction of the biopsy needle to actively growing viable cells in the periphery of the nodule. Education of endocrinologists in thyroid ultrasound began in the late 1990s and by 2016 more than 6000 clinicians had completed an ultrasound course. Concurrent with this rapid expansion of use of thyroid ultrasound was a rise in the diagnosis of small papillary carcinomas, which might have otherwise remained indolent and undetected. The 2009 American Thyroid Association Guidelines for the Management of Thyroid Nodules and Thyroid Cancer recommended biopsy for all solid hypoechoic nodules measuring larger than 1 cm. Attempting to decrease the frequency of biopsies of low-risk nodules, subsequent guidelines have focused on identifying and selectively biopsying those thyroid nodules at higher risk of clinically significant carcinoma based on ultrasound appearance. A major role for thyroid ultrasound has been in both preoperative staging and mapping to help determine the extent of surgery, as well as postoperative monitoring for locoregional soft tissue or lymph node metastases. With the recognition that the increase in papillary carcinoma was predominantly a result of early diagnosis of small often indolent cancers, active surveillance has become a promising management strategy for papillary thyroid microcarcinomas. Thyroid ultrasound is essential to active surveillance of thyroid cancer. Easy access to high-quality ultrasound studies is a requirement for a successful active surveillance program. Thyroid ultrasound has been used to facilitate interventional procedures, including treatment of thyroid nodules, treatment of recurrent thyroid cancer, and therapy of papillary thyroid microcarcinoma.

Active surveillance and clinical analysis of anaphylaxis based on the China Hospital Pharmacovigilance System.

Objective: This study aimed to develop active surveillance programs (ASPs) for anaphylaxis using the China Hospital Pharmacovigilance System (CHPS) and analyze the characteristics, allergens, and management strategies for anaphylaxis within a tertiary hospital setting in China. Methods: We retrospectively analyzed the anaphylaxis cases reported to the National Adverse Drug Reaction Monitoring System in our hospital from 2014 to 2021. Characteristic medical orders, progress notes, and diagnoses in these cases were recorded to identify initial anaphylaxis trigger entries. Based on these initial entries, the questionnaire was developed, and the Delphi method was used to establish consensus entries for anaphylaxis triggers. The CHPS was used to program these trigger entries and construct ASPs, which were then tested on the 238,194 discharged patients to evaluate their performance and analyze the related clinical data. Results: Ten anaphylaxis triggers and three ASPs were ultimately identified. The ASPs captured 309 cases, out of which 94 cases were confirmed as anaphylaxis following manual screening. After removing duplicates, we noted 76 patients who experienced anaphylaxis 79 times. The positive rate of triggers and the positive predictive value of the programs were 0.13% and 30.42%, respectively. The incidence of anaphylaxis in our study was 0.03%, and the number of anaphylaxis cases detected by the ASPs was 5.64 times higher than those detected by the spontaneous reporting system. Anaphylaxis was more common among female patients. Antibacterial drugs, antineoplastic drugs, and contrast media were the most prevalent allergens in clinical practice. Anaphylaxis to antineoplastic drugs had the highest incidence (0.6%) when compared with patients admitted during the same period. Our study revealed a significant underuse of epinephrine and overuse of second-line therapy (glucocorticoids and antihistamines) in the management of anaphylaxis. Furthermore, we found the use and dosage of epinephrine to be inappropriate. Conclusion: The CHPS can effectively utilize both structured and unstructured data to construct anaphylaxis ASPs, and this could counteract the under-reporting by the spontaneous reporting system, the primary adverse reaction monitoring method in China. The treatment and management of anaphylaxis are currently inadequate and require improvement to reduce mortality risk.

Value of Prostate-Specific Antigen Kinetics in Patients with Low-Risk Prostate Cancer under Active Surveillance

Introduction: This study analyzes the value of PSA kinetics, PSA speed (vPSA), and PSA doubling time (PSAdt), in patients with low-risk prostate cancer who are in an active surveillance (AS) program. Methods: An observational, retrospective, and longitudinal study of a sample of 86 patients included in AS program between January 2014 and October 2021 was conducted. A review of their medical records was performed, and PSA kinetics were calculated, analyzing the causes of discontinuation of the AS program and its relationship with PSA kinetics. Results: The mean age was 63.39 years, and the median follow-up was 62.55 months. The mean PSA at diagnosis was 8.27 ng/mL. A median of PSAdt of 62.55 months and 1.3 ng/mL/year for vPSA was obtained. 35 patients left the program, with a higher percentage of patients leaving with a PSAdt less than 36 months (73.7 vs. 31.1%) and a vPSA greater than 2 ng/mL/year (68.2 vs. 31.3%). The probability of permanence and the time of permanence in AS were statistically significantly higher for those patients with favorable kinetic parameters. Conclusion: PSA kinetics is a parameter to take into account when making decisions to keep patients in an AS program.

A brief mind-body intervention to reduce pain and anxiety during prostate needle biopsy: A randomized, controlled trial with two-staged consent.

e17092 Background: Prostate biopsy is among the most common oncologic procedures performed annually. A substantial proportion of patients experience significant morbidity related to biopsy, including pain, anxiety, and discomfort which may discourage follow-up biopsy crucial for identifying progression or discourage enrollment in active surveillance programs that require serial biopsy. Guided meditation significantly reduces pain and anxiety during breast biopsy. We developed a brief mind-body intervention that could easily integrate into general practice for patients during prostate biopsy and compared patient-reported outcomes after biopsy with and without this intervention. Methods: We conducted a clinically-integrated randomized controlled trial (MSK IRB 18-089) of a brief mind-body intervention during prostate biopsy compared to usual care. All adult patients offered biopsy were eligible. Patients randomized to the intervention were offered both a pre-biopsy mind-body exercise and guided mindfulness meditation during biopsy via headphones. The primary outcome of interest was any severe patient-reported pain, anxiety, discomfort, or tolerability on a visual-analog scale (0-10). We compared the proportion of men in each arm reporting a severe score (7-10) on any of the four scales using Fisher’s exact test. The pre-specified clinically relevant improvement justifying integration into clinical practice was 15%. We compared means separately using ANCOVA with randomization stratum (first vs. prior biopsy) as a covariate. Results: 238 patients (119 per arm) enrolled. 102 in the intervention arm and 94 in the usual care arm proceeded to biopsy and completed the questionnaire. A total of 37/94 (39%) and 38/102 (37%) patients in the usual care and the intervention arms, respectively, reported severe scores in any of the four domains, a difference of 2.1% (95% confidence interval -13, 17%, p = 0.8). The upper bound of the confidence interval includes the pre-specified clinically relevant difference. There was no evidence of a difference in mean post-biopsy anxiety (p = 0.3), discomfort (p = 0.09), pain (p = 0.4) or tolerability scores (p = 0.2), Table. Conclusions: There was no difference in patient reported outcomes between a mind-body intervention and usual care for prostate biopsy. Though the upper bound of the 95% confidence interval included the clinically relevant difference in severe scores, the difference in means for each outcome suggests a clinically meaningful benefit for this brief mindfulness intervention is unlikely. [Table: see text]

Antimicrobial-Resistant Enterobacterales Recovered from the Environment of Two Zoological Institutions Include Enterobacter cloacae Complex ST171 Producing KPC-4 Carbapenemase.

Environmental surfaces can serve as reservoirs for pathogens and antimicrobial-resistant (AMR) bacteria in healthcare settings. Although active surveillance programs are used in veterinary and human healthcare, unconventional settings like zoological facilities are often overlooked, even though antimicrobials are used to maintain the health of their animal collections. Here, we used electrostatic cloths to conduct active environmental surveillance over a 2-year period at two zoological institutions to determine contamination prevalence of human-only and mixed animal-human touch environments with AMR bacteria. We recovered Enterobacterales isolates that expressed quinolone resistance, an AmpC-like phenotype, and an extended-spectrum β-lactamase phenotype from 144 (39%), 141 (38.2%), and 72 (19.5%) of the environmental samples, respectively. The zoological institutions, areas and exhibits within the zoological facility, and sampling surface type affected the odds of recovering AMR bacteria from the environment. Three carbapenemase-producing Enterobacter cloacae complex ST171 isolates recovered from one zoological facility harbored an IncH12 plasmid with a Tn4401b-KPC-4 transposon conferring multidrug resistance. One isolate maintained three tandem repeats of a Tn4401b-KPC-4 element on an IncHI2 plasmid, although this isolate was susceptible to the four carbapenem drugs tested. These three isolates and their IncH12 plasmids shared significant genomic similarity with two E. cloacae complex isolates recovered from canine patients at a regional veterinary hospital during year 2 of this study. Our results indicated that surface environments at zoological institutions can serve as reservoirs for AMR bacteria and their genes and have implications for animal and public health. IMPORTANCE Environmental surfaces can be a source of antimicrobial-resistant (AMR) bacteria that pose a risk to human and animal health. Zoological institutions are unique environments where exotic animals, staff, and visitors intermingle and antimicrobials are used to maintain animal health. However, zoological environments are often overlooked as reservoirs of AMR bacteria. Here, we show that zoological environments can serve as reservoirs of fluoroquinolone-resistant and extended-spectrum cephalosporin-resistant bacteria. In addition, we isolated three carbapenemase-producing Enterobacter cloacae complex strains carrying blaKPC-4, including one with a unique, tandem triplicate of the Tn4401b-KPC-4 element. Comparative whole genomics of these isolates with two E. cloacae complex isolates from patients at a regional veterinary hospital highlighted the possibility of local KPC-4 spread between animal environments. Our results suggest that environments at zoological institutions serve as reservoirs for AMR bacteria and pose a hypothetical One Health risk to the public, staff, and the wild animal populations in captivity.