Best practice recommendations for the management of anxiety during the pegvaliase journey.

BACKGROUND: Pegvaliase, an enzyme substitution therapy, is a treatment option for phenylketonuria (PKU). Due to the neuropathophysiology and disease burden of PKU, individuals can experience baseline anxiety unrelated to pegvaliase therapy. In addition, there are aspects of pegvaliase therapy that may be anxiety-inducing for those considering or receiving treatment. The aim of this manuscript is to present best practice recommendations for the identification and management of anxiety symptoms that can occur along the pegvaliase journey. METHODS: A modified Delphi approach was used to seek consensus among a multidisciplinary panel of experts. To this end, an in-person meeting was held that was preceded by a medical specialist- and patient-specific survey to develop preliminary recommendations on ways to address anxiety along the pegvaliase journey. After the meeting, an additional survey was conducted to rank the proposed solutions and mitigation strategies from which a set of recommendations was developed. All recommendations were voted on with the aim of consensus generation, defined as achieving ≥75% agreement among experts. RESULTS: The panel reached consensus on a total of 28 best practice recommendations for the management of anxiety during the pre-treatment, induction and titration, early maintenance (pre-efficacy), and late maintenance (post-efficacy) stages. The recommendations offer strategies to identify and address the most common causes of pegvaliase-related anxiety, including self-injection, side effects, the titration schedule, prescribed dietary changes, and variable time to efficacy. Overall, managing anxiety in those considering or receiving pegvaliase involves patient-centered communication, shared decision-making, and personalized treatment plans. CONCLUSIONS: The best practice recommendations described herein can guide healthcare providers in proactively addressing anxiety during the different stages of pegvaliase treatment, and support providers with initiating and managing pegvaliase in individuals who may experience baseline and treatment-related anxiety.

Evaluating the Influence of Social Determinants of Health on Blood Phenylalanine Levels in Phenylketonuria Patients.

Phenylketonuria (PKU) is a genetic metabolic disorder that causes the accumulation of phenylalanine (Phe) in tissues, leading to intellectual disability, seizures, and socioemotional challenges. The role of social determinants of health (SDOH) in PKU management has not been formally studied, and this investigation evaluates the association between in-home and in-office factors on blood Phe levels in PKU patients. We conducted a retrospective chart review on over 200 patients attending the well-resourced PKU Clinic at Lurie Children's Hospital of Chicago. Data included patients' average Phe level, various demographic information, and CDC/ATSDR social vulnerability index (SVI) score. The analysis revealed no significant association between social vulnerability status and average Phe level. However, a significant correlation was found between sapropterin dihydrochloride use and average Phe level. Age interacted separately with sex assigned at birth, pegvaliase use, total Phe samples submitted, and the presence of genetic testing to significantly influence the average Phe level. This study highlights the multifactorial influences on PKU management and underscores the importance of social resources, such as clinic social workers and state-provided formula, in modulating the effects of SDOH on PKU control. Further research in different healthcare settings is needed to understand the social determinants affecting PKU patients comprehensively, which will strengthen advocacy efforts for this population.

Hematopoietic Stem Cell Transplantation to Treat Leukodystrophies: Clinical Practice Guidelines from the Hunter's Hope Leukodystrophy Care Network.

The leukodystrophies are a heterogeneous group of inherited diseases characterized by progressive demyelination of the central nervous system leading to devastating neurologic symptoms and premature death. Hematopoietic stem cell transplantation (HSCT) has been successfully used to treat certain leukodystrophies, including adrenoleukodystrophy, globoid leukodystrophy (Krabbe disease), and metachromatic leukodystrophy, over the past 30 years. To date, these complex patients have primarily been transplanted at a limited number of pediatric centers. As the number of cases identified through pregnancy and newborn screening is increasing, additional centers will be required to treat these children. Hunter's Hope created the Leukodystrophy Care Network in part to create and standardize high-quality clinical practice guidelines to guide the care of affected patients. In this report the clinical guidelines for the care of pediatric patients with leukodystrophies undergoing treatment with HSCT are presented. The initial transplant evaluation, determination of patient eligibility, donor selection, conditioning, supportive care, and post-transplant follow-up are discussed. Throughout these guidelines the need for early detection and treatment and the role of the partnership between families and multidisciplinary providers are emphasized.

Nutrient production from dairy cattle manure and loading on arable land.

OBJECTIVE: Along with increasing livestock products via intensive rearing, the accumulation of livestock manure has become a serious issue due to the fact that there is finite land for livestock manure recycling via composting. The nutrients from livestock manure accumulate on agricultural land and the excess disembogues into streams causing eutrophication. In order to systematically manage nutrient loading on agricultural land, quantifying the amount of nutrients according to their respective sources is very important. However, there is a lack of research concerning nutrient loss from livestock manure during composting or storage on farms. Therefore, in the present study we quantified the nutrients from dairy cattle manure that were imparted onto agricultural land. METHODS: Through investigation of 41 dairy farms, weight reduction and volatile solids (VS), total nitrogen (TN), and total phosphorus (TP) changes of dairy cattle manure during the storage and composting periods were analyzed. In order to support the direct investigation and survey on site, the three cases of weight reduction during the storing and composting periods were developed according to i) experiment, ii) reference, and iii) theoretical changes in phosphorus content (ΔP = 0). RESULTS: The data revealed the nutrient loading coefficients (NLCs) of VS, TN, and TP on agricultural land were 1.48, 0.60, and 0.66, respectively. These values indicated that the loss of nitrogen and phosphorus was 40% and 34%, respectively, and that there was an increase of VS since bedding materials were mixed with excretion in the barn. CONCLUSION: As result of nutrient-footprint analyses, the amounts of TN and TP particularly entered on arable land have been overestimated if applying the nutrient amount in fresh manure. The NLCs obtained in this study may assist in the development of a database to assess the accurate level of manure nutrient loading on soil and facilitate systematic nutrient management.

Management of a urea cycle disorder in the setting of socioeconomic and language barriers.

Argininosuccinic aciduria (ASA) is a disorder that results from a deficiency in the urea cycle enzyme argininosuccinate lyase. Variable manifestations of this hereditary disorder are associated with hyperammonemia and can include lethargy, somnolence, and respiratory alkalosis in neonates, and vomiting, headaches, and neurocognitive deficiencies later in life. Management of ASA includes rapid measures to address hyperammonemia and long-term steps to maintain metabolic stability. Management paradigms should also consider social determinants of health, which are non-medical factors that influence health outcomes. Here, we describe the case of a male pediatric patient with ASA whose treatment has included considerations for his family's refugee status, language barriers, cultural adjustments, limited income, and transportation challenges.

The effect of 6% hydroxyethyl starch 130/0.4 preloading on the blood glucose levels in diabetic patients undergoing orthopedic surgery with spinal anesthesia: a randomized pilot study.

BACKGROUND: Perioperative hyperglycemia can occur in surgical patients and may increase postoperative morbidity and mortality, especially in patients with diabetes. Therefore, we conducted the present study to evaluate whether the administration of 6% hydroxyethyl starch (HES)-130/0.4 increases blood glucose levels in patients with diabetes. METHODS: Forty patients undergoing lower limb surgery under spinal anesthesia were randomly allocated into two groups according to the fluids administered 20 min before spinal anesthesia (Group L, lactated Ringer's solution; Group H, 6% HES-130/0.4). Patient characteristics, intraoperative variables, blood glucose levels, mean blood pressure (MBP), and heart rate (HR) were recorded at five time-points (0, 20, 60, 120, and 240 min). RESULTS: A total of 39 patients were analyzed (Group L, n = 20; Group H, n = 19). The amount of intraoperative fluid was significantly higher in Group L than in Group H (718.2 ml vs. 530.0 ml, P = 0.010). There were no significant differences in the changes in blood glucose levels, HR, or MBP between the two groups (P = 0.737, P = 0.896, and P = 0.141, respectively). Serial changes in mean blood glucose levels from baseline also showed no significant differences between the groups (P = 0.764). CONCLUSIONS: There were no significant changes in blood glucose levels when lactated Ringer's solution or 6% HES-130 was used. When compared to the lactated Ringer's solution, no evidence that 6% HES-130/0.4 produces hyperglycemia in diabetic patients could be found. Further evaluation of larger populations is needed.

Getting by with a Little Help from Friends: A Qualitative Case Study of Students' Strategies for Coping with Failure in an Undergraduate Biology Laboratory Course.

Recent emphasis on research competencies in undergraduate biology education means that more students are doing course-based research. Professional research scientists learn from failed research, but undergraduate students who encounter failure in their biology lab research may not always respond in ways that advance their learning. There is a need to examine individual students' responses to failed research as they conduct investigations in an undergraduate lab course. Here, we report a qualitative research case study based on data from interviews and course work to examine five undergraduate students' emotional responses, coping strategies, and perceptions of learning as they confronted failure in a semester-long intro lab course investigation. All five students displayed negative emotions when they encountered a research obstacle, but their coping strategies varied. However, by the end of their research process, all had responded with competent actions, relationship actions, and autonomous actions as adaptive coping strategies. Support seeking played a critical role to promote autonomy as a foundation for research self-efficacy. After completing their research, the students reported valuable learning from the experience. Implications for instruction are based on examples of coping strategies for managing negative emotions from failed research.

Perceptions and Treatment of Precocious Puberty: A Questionnaire Survey among Caregivers in South Korea.

This study aims to provide the basis for developing complementary and alternative treatment approaches for precocious puberty (PP) by examining caregivers' awareness, along with their preferences and expectations from various treatments. It included data collected between July 2019 and March 2020, from 175 caregivers of children who were undergoing or had undergone treatment for PP. The questionnaire comprised 53 questions on the awareness, acquisition of information, perceptions of treatments, and concerns about PP, as well as awareness of habit management (HM) and children's actual habits. The collected data were analysed using the Chi-square test, t-tests, and one-way analysis of variance. The caregivers responded that PP could be recognized on the basis of breast development (79.8%) in girls and hair and body odor (73.1%) in boys. However, 86.9% of respondents were getting inaccurate information from the Internet. With respect to PP treatment approaches, 16% of respondents hoped to manage PP through conventional treatment (CT), 21.1% preferred traditional Korean medicine (TKM), and 62.3% preferred HM. Expectations of the effectiveness were highest in HM, followed by CT and TKM. Only the TKM group had statistically significant higher expectations than the nontreatment experience group (F = 4.566, p=0.004). The caregivers were concerned about the side effects and high costs of CT. Around 43% of respondents had difficulties with the management of their children's diet, 64.6% with exercise, and 57.1% with smart device usage. Clinicians should be aware of caregivers' information acquisition patterns, preferences and expectations of various treatments, and their concerns. Considering these results, clinicians should try to establish more appropriate treatment plans for children with PP.

Effectiveness and Safety of Combination Therapy with Herbal Medicine and Growth Hormone Compared to Growth Hormone Monotherapy for Short Stature Children: A Systematic Review and Meta-Analysis.

Introduction: Herbal medicines (HM) and growth hormones (GH) are widely used to treat short stature (SS) in children. This systematic review aimed to evaluate the effectiveness and safety of combination therapy with HM and GH (CHG) compared to those of GH monotherapy (GHM) in children with SS. Methods: We searched 17 electronic databases from inception to 1 April 2021. Only randomized controlled trials (RCTs) were included. Two authors independently performed the selection and quality assessment of the included studies using Cochrane Handbook criteria. Relative risk (RR) was used to measure dichotomous outcomes with a 95% confidence interval (CI). Mean difference (MD) or standard MD (SMD) was used to measure continuous outcomes with a 95% CI. Results: Seven RCTs involving 455 participants with SS were included. Standard deviations in height (MD = 0.31, 95% CI: 0.24-0.38, p < 0.00001), and insulin-like growth factor binding protein-3 (MD = 1.39, 95% CI: 0.93-1.85, p < 0.00001) were significantly higher in the CHG group than in the GHM group. Growth velocity (MD = 1.82, 95% CI: 1.34-2.31, p < 0.00001) and insulin-like growth factor-1 (MD = 61.85, 95% CI: 55.80-67.90, p < 0.00001) were significantly higher in the CHG group. Adverse events were significantly lower in the CHG group (risk ratio: 0.10, 95% CI: 0.02-0.54, p = 0.007). However, the level of evidence was low. Conclusions: CHG demonstrated significantly better efficacy than GHM for treating SS, with a low incidence of adverse events. However, since the level of evidence is low, methodologically standardized RCTs are required to verify these results.

C3435T polymorphism of the MDR1 gene is not associated with P-glycoprotein function of leukemic blasts and clinical outcome in patients with acute myeloid leukemia.

We investigated the association between the MDR1 C3435T polymorphism and P-glycoprotein function of leukemic blasts as well as clinical outcomes in 200 patients with AML, excluding the M3 subtype. The CC, CT and TT genotype frequencies of the C3435T polymorphism among patients were 71, 93 and 36, respectively. The C3435T polymorphism genotypes did not have influence on the P-glycoprotein function of leukemic blasts. Complete remission rates and overall, relapse-free and event-free survival rates were not significantly different among the C3435T polymorphism genotypes. In conclusion, the MDR1 C3435T polymorphism does not appear to have significant clinical implications in AML.

Cytokine response in Balb/c mice infected with Francisella tularensis LVS and the Pohang isolate.

We investigated the immune response induced by the Francisella (F.) tularensis live vaccine strain (LVS) and the Pohang isolate. After the Balb/c mice were infected intradermally (i.d) with 2 x 10(4) cfu of F. tularensis LVS and Pohang, respectively, their blood and organs were collected at different times; 0, 3, 6, 24, 72, 96, 120 and 168 h after infection. Using these samples, RT-PCR and ELISA analysis were carried out for the comparative study of the cytokines, including TNF-alpha, INF-gamma, IL-2, IL-4, IL-10 and IL-12. In the Pohang-infected mice at 120 h, the liver showed a 53 times higher level of TNF-alpha and a 42 times higher level of IFN-gamma than the respective levels at the early time points after infection. The levels of TNF-alpha and IFN-gamma induced by LVS were 5 times lower than those induced by the Pohang isolate. Also, the organs from the Pohang-infected mice showed higher levels of TNF-alpha, IFN-gamma, IL-10 and IL-12 than the levels in the LVS-infected mice. The blood from the Pohang-infected mice at 120 h revealed about a 40 times increased level of IFN-gamma, and IL-10 was also increased by 4 times at 96 h compared to an early infection time point, while IL-4 was not induced during the whole infection period. These results suggest that F. tularensis may induce a Th1-mediated immune response to in vivo infection and the Pohang isolate has a higher capacity than the LVS to induce an acute immune response in Blab/c mice.

Clinical usefulness of eschar polymerase chain reaction for the diagnosis of scrub typhus: a prospective study.

BACKGROUND: The aim of this study was to determine the diagnostic utility of performing eschar polymerase chain reaction (PCR) for the diagnosis of scrub typhus through a prospective comparison of eschar PCR results with indirect immunofluorescent antibody assay (IFA) results. METHODS: We conducted a multicenter prospective study involving patients with possible scrub typhus. Whole-blood samples and eschars were obtained for serological evaluation and PCR. A new crust was formed several days later at the site of the removed eschar. The newly formed crust was taken for performance of the second eschar PCR. Additional blood samples and eschars were collected, if possible, at 1-week intervals for 1 month after antibiotic treatment. RESULTS: We prospectively studied 135 patients with possible scrub typhus. Of these patients, 118 had scrub typhus confirmed on the basis of either a single indirect immunofluorescent specific immunoglobulin M titer against Orientia tsutsugamushi of > or = 1:10 or a > or = 4-fold increase in the follow-up titer. The results of nested PCR assay of the eschars demonstrated a sensitivity of 0.86 (95% confidence interval, 0.78-0.92) and a specificity of 1 (95% confidence interval, 0.05-1). Among the 50 patients who showed positive results of eschar PCR at admission, 46 (92%) also showed positive results for the follow-up PCR test of the newly formed eschar after the treatment with antibiotics. CONCLUSIONS: The eschar PCR assay was useful as a rapid and reliable test to confirm the diagnosis of scrub typhus, even though the patients received treatment with appropriate antibiotics, such as macrolides, quinolones, and tetracycline, which are all active against Orientia and Rickettsia species.

Scrub typhus during pregnancy and its treatment: a case series and review of the literature.

Although scrub typhus is uncommon in pregnant women, when present, it can have serious repercussions for the mother and developing fetus. Since it is uncommon, the clinical impact of scrub typhus on pregnancy has not been elucidated and an effective and safe therapeutic regimen has not been validated. The medical records of pregnant women whose scrub typhus were treated at Chungnam National University Hospital were reviewed and their clinical outcomes were evaluated. A review of the literature was also performed on pregnant women with scrub typhus and their clinical outcomes. Eight pregnant women with scrub typhus were treated successfully with a single 500-mg dose of azithromycin, and no relapses were reported. They all delivered healthy babies at term, without congenital or neonatal complications. In the reviews, azithromycin was effective against scrub typhus and had favorable pregnancy outcomes. Ciprofloxacin and cefuroxime failed to treat scrub typhus and fetal loss resulted. A single 500-mg dose of azithromycin may be a reasonable treatment regimen for pregnant women with scrub typhus. Ciprofloxacin might not be advisable for the treatment of scrub typhus during pregnancy. Scrub typhus itself seems to have serious adverse effects on pregnancy if not appropriately controlled.

Usefulness of nested PCR for the diagnosis of scrub typhus in clinical practice: A prospective study.

The aims of this study were to determine the diagnostic accuracy and clinical usefulness of using nested polymerase chain reaction (PCR) for the diagnosis of scrub typhus through a prospective comparison of nested PCR and indirect immunofluorescent antibody assay (IFA). We conducted a multi-center prospective study of patients who were suffering with possible scrub typhus infection. Whole blood samples were collected for PCR testing, and sera were obtained for serology evaluation using the indirect IFA and the passive hemagglutination assay (PHA). We prospectively studied 135 patients with possible scrub typhus. One hundred eighteen patients were confirmed as having scrub typhus, 7 patients were undetermined, and 10 patients were confirmed as having other diseases. The results of nested PCR assay showed a sensitivity of 82.2% and a specificity of 100%. Ninety-six of the 118 patients were positive for IgM on their admission day. Of the 22 patients who were negative for IgM antibody at admission, 19 had positive results for nested PCR of the buffy coat. The nested PCR assay of the buffy coat is useful as a rapid and reliable test for confirming the diagnosis of scrub typhus.

Effect of hydroxyethyl starch on blood glucose levels.

BACKGROUND: Hydroxyethyl starch (HES), a commonly used resuscitation fluid, has the property to induce hyperglycemia as it contains large ethyl starch, which can be metabolized to produce glucose. We evaluated the effect of 6% HES-130 on the blood glucose levels in non-diabetic patients undergoing surgery under spinal anesthesia. METHODS: Patients scheduled to undergo elective lower limb surgery were enrolled. Fifty-eight patients were divided into two groups according to the type of the main intravascular fluid used before spinal anesthesia (Group LR: lactated Ringer's solution, n = 30 vs. Group HES: 6% hydroxyethyl starch 130/0.4, n = 28). Blood glucose levels were measured at the following time points: 0 (baseline), 20 min (T1), 1 h (T2), 2 h (T3), 4 h (T4), and 6 h (T6). RESULTS: Mean blood glucose levels at T5 in the LR group and T4, T5 in the HES group, increased significantly compared to baseline. There were no significant changes in the serial differences of mean blood glucose levels from baseline between the two groups. CONCLUSIONS: Administration of 6% HES-130 increased blood glucose levels within the physiologic limits, but the degree of glucose increase was not greater than that caused by administration of lactated Ringer's solution. In conclusion, we did not find evidence that 6% HES-130 induces hyperglycemia in non-diabetic patients.

Clinical evaluation of a newly designed fluid warming kit on fluid warming and hypothermia during spinal surgery.

BACKGROUND: The Mega Acer Kit® (MAK) is a newly designed heated and humidified breathing circuit that warms fluid passing through the circuit lumen. In this study, we investigated the system's efficacy for the perioperative prevention of hypothermia and fluid warming. METHODS: Ninety patients undergoing spinal surgery were enrolled in this study and randomly assigned to 3 groups based on the fluid warming device used: no fluid warming system (Group C, n = 30), via a Standard Ranger (Group R, n = 30), or via the MAK (Group M, n = 30). Distal esophageal temperatures (Teso) and infusion fluid temperature (TF) were recorded at 15 min intervals for duration of 180 min during surgery. If Teso was < 35.0℃, a forced-air convective warming device was used. RESULTS: Final Teso values were 34.8 ± 0.3℃, 35.1 ± 0.1℃, and 35.8 ± 0.3℃ in groups C, R, and M, respectively (P < 0.01). Teso was significantly higher in group M when compared with that in groups C and R throughout the study period (P < 0.05). The number of patients requiring a forced-air convective warming device was significantly lower in group M (n = 0) when compared with that in groups R (n = 17) and C (n = 30) (P < 0.05). The final infusion fluid temperature was higher in group M when compared with that in groups C and R throughout the study period (35.4 ± 1.0 vs. 23.0 ± 0.3 and 32.8 ± 0.6℃; P < 0.01). CONCLUSIONS: The MAK is more effective for preventing hypothermia and for warming fluid than the Standard Ranger.

A comparative trial of a single dose of azithromycin versus doxycycline for the treatment of mild scrub typhus.

BACKGROUND: Scrub typhus is one of the most important endemic infections in the Asia-Pacific region. Although tetracyclines or chloramphenicol are the recommended drugs of choice for the treatment of scrub typhus, reports of doxycycline-resistant strains have prompted a search for alternative treatments. METHODS: We conducted a prospective, open-label, randomized trial from September 2002 through November 2003 to compare azithromycin with doxycycline for the treatment of mild scrub typhus. The time to defervescence was assessed to compare the efficacy of the 2 treatment regimens. RESULTS: A total of 93 patients were randomly assigned to receive either a single 500-mg dose of azithromycin or a 1-week course of daily oral 200-mg dose of doxycycline. Cure was achieved in 47 (100%) of 47 patients in the azithromycin-treated group and in 43 (93.5%) of 46 patients in the doxycycline-treated group (P=.117). The median time to defervescence was 21 h for the azithromycin-treated group and 29 h for the doxycycline-treated group (P=.097). There were no serious adverse events during the study. No relapses occurred in either group during a 1-month follow-up period. CONCLUSION: The single 500-mg dose of azithromycin was as effective as the 1-week course of daily 200-mg doses of doxycycline for the treatment of mild scrub typhus acquired in South Korea.

Detection of Orientia tsutsugamushi, the causative agent of scrub typhus, in a novel mite species, Eushoengastia koreaensis, in Korea.

To identify potential vector species of scrub typhus in the Republic of Korea (ROK), chigger mites were harvested from wild rodents captured at nine localities in October 2005. The bodies of the chigger mites were individually punctured with a fine pin, squeezed out internal contents, and examined for Orientia tsutsugamushi DNA by nested polymerase chain reaction. The exoskeleton of associated chiggers was mounted on glass slides with polyvinylalcohol (PVA) medium for identification. Among 830 individuals belonging to 4 genera and 14 species, O. tsutsugamushi was detected from 22 chiggers of six species, with an overall infection rate of 2.7%. The infection rate was highest for Leptotrombidium palpale (5.3%), followed by Neotrombicula japonica (4.3%), Leptotrombidium scutellare (3.7%), Leptotrombidium orientale (3.6%), Eushoengastia koreaensis (1.9%), and Leptotrombidium pallidum (1.5%). This study first reported O. tsutsugamushi infection from N. japonica and E. koreaensis larvae in the ROK. The population densities of L. pallidum (33.4 chiggers/rodent), historically confirmed as a primary vector of scrub typhus in the ROK, were high, whereas its infection rate was relatively low (1.5%). However, E. koreaensis was only collected from 154 individuals at seven collection sites and its infection rate was demonstrated relatively high (mean 1.9%). Additional studies are needed to determine the role of vector species in the epidemiology of scrub typhus.