Patient-reported outcomes and daily activity assessed with a digital wearable device in patients with paroxysmal nocturnal hemoglobinuria treated with ravulizumab: REVEAL, a prospective, observational study.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, chronic blood disorder. Symptoms such as fatigue can have a substantial impact on patients' physical activity levels, sleep, quality of life, and work productivity. Ravulizumab treatment can reduce thrombosis risk, improve survival and quality of life, and reduce fatigue in PNH, but information is limited on how it impacts sleep and physical activity. Here, data on resting heart rate, daily physical activity, and sleep in ravulizumab-treated patients with PNH were passively collected via a digital wearable activity-tracking device and patient-reported outcome (PRO) data were collected via weekly surveys in the same cohort. METHODS: REVEAL was a 32-week prospective observational cohort study in individuals with PNH receiving ravulizumab in the USA. A wrist-worn Fitbit™ collected data on resting heart rate, daily step count, and sleep duration from eligible patients. Patients also completed the following electronic weekly surveys: Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue, Patient-Reported Outcomes Measurement Information System (PROMIS) Global Physical Health, PROMIS Global Mental Health, PROMIS Sleep-Related Impairment and Sleep Disturbance, and Work Productivity and Activity Impairment Questionnaire - Specific Health Problem (WPAI-SHP). Data collected from the activity trackers and surveys were compared against US general population values reported in the literature. RESULTS: Twenty-eight ravulizumab-treated patients were included (median age: 34 years; 54% female). PRO scores were within US general population normative values, including FACIT-Fatigue (40.0), PROMIS Global Physical Health (51.0), Global Mental Health (51.0), Sleep-Related Impairment (50.0), and Sleep Disturbance (49.0). Similarly, mean resting heart rate (67 bpm), daily step count (7476), and sleep duration (7.7 h) were within the range of US general population values. Daily step count was positively correlated with PROMIS Global Physical and Mental Health scores. CONCLUSIONS: This was the first study to use digital monitoring technology to collect data on physical activity and sleep in patients with PNH. The findings indicate that ravulizumab treatment enables patients with PNH to achieve activity levels (heart rate, sleep duration, step count) and quality of life that are comparable to those of the US general population. A weak positive correlation was identified between patient-reported physical and mental health and daily physical activity levels.

Progressive Pain Response in Idiopathic Clubfoot Children Undergoing Ponseti Casting: A Prospective Evaluation in 34 Feet.

BACKGROUND: Investigations of pain and physiologic responses response during Ponseti casting are in the preliminary stage. This short-term study aims to quantify pain responses and to note the variations, if any, during subsequent casting sessions. METHODS: In this prospective study, the pain parameters were evaluated in 34 clubfeet. Video recording of each casting session was performed 1 minute before casting, during casting, and after 1 minute of casting. The videos were scored objectively using Neonatal Infant Pain Score (NIPS). Heart rate (HR) and oxygen saturation were recorded by using a pulse oximeter. RESULTS: There was progressive increase in pain response until, at the last casting session, it was recorded as NIPS 4 (interquartile range, 1) (P = .02479). Before, during, and after casting, HR rose significantly in succeeding sessions. The mean HR during the first cast session was 175.5 ± 27.2/min, which increased to a mean of 197.3 ± 18.9/min (P = .000282). For the third parameter (oxygen saturation), no differences were observed between the first and last casting sessions. CONCLUSIONS: There was moderate pain response during Ponseti casting sessions as demonstrated by the NIPS. It rose significantly toward the last cast. The clubfoot child showed an exaggerated heart rate in succeeding casting sessions. No variations were noticed for oxygen saturation.

Framework for implementing collaborative TB-silicosis activities in India: insights from an expert panel.

Tuberculosis (TB) treatment is more challenging for patients with silicosis, as it complicates the diagnosis of both diseases and increases mortality risk. Silicosis, an incurable occupational disease, confounds the diagnosis of TB and vice versa, making it more difficult to accurately identify and treat either condition. Moreover, TB appears to accelerate the progression of silicosis. Exposure to silica dust, a common cause of silicosis, can also trigger latent TB to become active TB. This correspondence outlines a proposed framework for implementing collaborative TB-silicosis activities in India, aimed at improving early diagnosis and management for both diseases. An expert panel of medical professionals developed this framework through online consultations in October and November 2022. The panel's goal was to establish a consensus on integrating TB-silicosis activities, with a focus on early detection and proper management. The framework suggests testing all patients with silicosis for active TB and screening workers exposed to silica dust for latent TB infection. It also recommends that patients with TB who have a history of occupational exposure to silica dust should be tested for silicosis. Reliable diagnostic tools, such as chest X-rays, are emphasized, providing guidance on their use for both diseases. The proposed collaborative TB-silicosis framework offers a structured approach to identifying and managing these two diseases, contributing to the global goal of eliminating silicosis by 2030 and aligning with the World Health Organization's targets for reducing TB incidence and mortality. It recommends specific strategies for implementation, including testing, referral systems, and workplace-based interventions. The framework also underscores the need for coordinated efforts among stakeholders, including the ministries of health, labor, industry, and environment. This correspondence provides valuable insights into how India can successfully implement collaborative TB-silicosis activities, serving as a model for other regions with similar challenges.

Impact of Lactate Dehydrogenase and Hemoglobin Levels on Clinical Outcomes in Patients With Paroxysmal Nocturnal Hemoglobinuria: Results From the National Korean PNH Registry.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder caused by uncontrolled terminal complement activation, which leads to intravascular hemolysis (IVH), thromboembolism (TE), renal failure, and premature mortality. METHODS: We performed a secondary analysis of data collected from patients enrolled in the Korean National PNH Registry to assess the relative importance of risk factors, specifically lactate dehydrogenase (LDH) and hemoglobin (Hb), in predicting the incidence of TE, impaired renal function, and death in complement inhibitor-naïve patients with PNH. RESULTS: Multivariate regression modeling indicated that LDH ≥ 1.5 × upper limit of normal (ULN), male sex, and pain were associated with increased risk of TE (P = 0.016, 0.045, and 0.033, respectively), hemoglobinuria and pain were associated with an increased risk of impaired renal function (P = 0.034 and 0.022, respectively), and TE was associated with an increased incidence of death (P < 0.001). Hb < 8 g/dL was not a predictor of TE, impaired renal function, or death in multivariate regression analyses. Standardized mortality ratio analysis indicated that LDH ≥ 1.5 × ULN (P < 0.001), Hb < 8 g/dL (P < 0.001), and Hb ≥ 8 g/dL (P = 0.004) were all risk factors for death; in contrast, patients with LDH < 1.5 × ULN had similar mortality to the general population. CONCLUSION: In complement inhibitor-naïve patients with PNH, LDH ≥ 1.5 × ULN was a significant predictor of TE, and TE was a significant predictor of death. Hb was not a significant predictor of TE, impaired renal function, or death. Therefore, controlling IVH will improve clinical outcomes for patients with PNH.

Exploring private sector perspectives on barriers and facilitators in availing tuberculosis care cascade services: a qualitative study from the Indian state.

INTRODUCTION: The private sector plays an important role in tuberculosis (TB) elimination by providing access to quality TB care services like diagnosis and treatment, advocacy for preventive measures, innovation to address challenges in TB elimination, vaccines etc. The study aims to understand the perspectives of private practitioners on patients' TB care cascade to reinforce existing interventions by assuring the quality of care to TB patients. METHODS: The study utilized a qualitative design through in-depth interviews of private practitioners and was conducted in Ranchi and Purbi Singhbhum District of Jharkhand State from March-August 2021. The pilot-tested, semi-structured, open-ended interview guide questionnaire collected information from private practitioners on various aspects of the TB care cascade. The data from the provider interviews were transcribed into multiple codes and themes on the TB program. An inductive analysis was carried out with a focus on content credibility to eliminate bias. Ethical approval was received from the Institutional Ethics Committee of the Indian Institute of Public Health Gandhinagar (IIPHG), India. Written consent was taken from the private practitioners involved in the study. RESULT: In-depth interviews of 17 private practitioners reveal various factors contributing to delays in TB care cascades, especially delay in access to TB diagnosis and TB Care, delay in providing treatment once after diagnosis and poor adherence to the TB treatment. According to the perception of private practitioners, there was an array of client, provider and system side factors affecting the TB care cascade gaps positively and negatively. Positive aspects mainly emerged from interviews: strong governance, consistent supply chain management, innovative PPP models and financial schemes reducing out-of-pocket expenditure (OOPE). Various factors affecting the TB care cascade negatively include awareness among the patient, socio-economic status, approach and decision-making power of providers, adverse effects of drugs, staff capacity building, etc. CONCLUSIONS: Engaging private practitioner in TB elimination efforts is critical to achieving global targets and reducing the burden of TB. The study helps to determine geography-specific barriers and facilitators of the TB care cascade to achieve the aim of providing universal access to TB healthcare with the inclusion of private practitioners.

Retrospective multi-center study of robotic-assisted cholecystectomy: after-hours surgery and business-hours surgery outcomes.

The effect of robotic-assisted cholecystectomy (RAC), when performed after hours, on perioperative outcomes has not been evaluated against outcomes achieved during normal business hours. Subjects 18-80 years old who underwent da Vinci robotic-assisted cholecystectomy from August 2018 to February 2021 were included. Baseline and 30-day perioperative outcomes were retrospectively and consecutively collected and analyzed. Inverse probability treatment weighting (IPTW) was performed to balance patient characteristics between groups. A weighted comparative analysis was followed. Outcomes from 505 patients (after hours, n = 169; business hours, n = 336) undergoing RAC across 5 U.S. medical institutions were analyzed. The higher rates of acute cholecystitis and gallbladder inflammation, gangrene, and intraoperative abnormalities in the after-hours group were associated with higher rates of urgent cases and longer operative times-but not increased complication rates-compared to the business-hours group. There were no significant differences in rates of intraoperative or postoperative complications, readmissions, or reoperations. Integrated da Vinci Firefly fluorescence imaging system was used extensively, and the critical view of safety was achieved in > 96% of cases in both groups. No conversions occurred in the after-hours group compared to four conversions in the business-hours group (p = 0.0266). After-hours patients had shorter outpatient lengths of stay. No mortalities were reported for either group (p = 0.0139). After-hours RAC with integrated da Vinci Firefly imaging performed by surgeons experienced in RAC is associated with similar or improved outcomes than the same procedures during business hours in terms of complications, conversions, readmissions, reoperations, and length of stay. ClinicalTrials.gov identifier: NCT04551820; August 5, 2020.

Predictors for improvement in patient-reported outcomes: post hoc analysis of a phase 3 randomized, open-label study of eculizumab and ravulizumab in complement inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by uncontrolled terminal complement activation leading to intravascular hemolysis (IVH), thrombosis, and impairments in quality of life (QoL). The aim of this study was to identify the clinical drivers of improvement in patient-reported outcomes (PROs) in patients with PNH receiving the complement component 5 (C5) inhibitors eculizumab and ravulizumab.This post hoc analysis assessed clinical outcomes and PROs from 246 complement inhibitor-naive patients with PNH enrolled in a phase 3 randomized non-inferiority study that compared the C5 inhibitors ravulizumab and eculizumab (study 301; NCT02946463). The variables of interest were lactate dehydrogenase (LDH) levels, a surrogate measure of IVH, and hemoglobin (Hb) levels. PROs were collected using Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) to assess fatigue and QoL, respectively.Improvements in absolute mean LDH levels were significantly associated with improvements in mean FACIT-F score (p = 0.0024) and EORTC QLQ-C30 global health (GH) score (p < 0.0001) from baseline to day 183. Improvements in scores were achieved despite a non-significant increase in Hb levels. To understand the interaction between LDH and Hb, a regression analysis was performed: LDH response with Hb improvements was a significant predictor of improvement in fatigue. The independent effect of improved Hb did not significantly affect FACIT-F or EORTC QLQ-C30 GH scores.These findings suggest that LDH levels are an important determinant of fatigue and QoL outcomes in patients with PNH. CTR: NCT02946463, October 27, 2016.

Deaths among tuberculosis patients of the western state of India: A secondary record based analytical study on its determinants.

INTRODUCTION: India has a significant TB burden, and ongoing attempts are being made to eradicate the disease. Globally, the number of TB deaths is declining, but not quickly enough to meet the End TB Goals. The National Strategic Plan (NSP) 2017-2025 in India set in motion an ambitious effort to expand the scope and efficacy of the National Tuberculosis Elimination Program (NTEP). METHODS: A descriptive retrospective study based on secondary data was conducted on information obtained from the electronic TB notification register for 2019, abstracted from Ni-kshay. Further, descriptive analysis was undertaken to identify the factors associated with deaths and successful treatment outcomes. The binomial logistic regression model estimates the crude relative risk and a 95% confidence interval to describe the association between predictor variables and TB treatment outcomes. RESULTS: After applying the eligibility criteria for the study population, a total of 1,44,643 (88%) TB patients were included in the study. 1,35,934 (94%) TB patients had completed the treatment and survived, while 8709 (6%) TB patients died. A significant association of treatment outcomes was observed in age, gender, key population, site of diseases, type of case, type of health facilities, HIV and Diabetes. When a logistic regression was applied, the model showed the association of the independent variables with the risk of death in TB patients. CONCLUSION: The epidemiological factors associated with treatment outcomes among TB patients should be audited systematically. A structure of TB death surveillance and response system should be established with a mortality audit, including a community-based death review (CBDR) and a facility-based medical audit (FBMA) in case the patient is hospitalized or discharged from a hospital.

Limb length deceleration or coronal plane deformity correction using tension band plates: does plate configurations determine the intraarticular deformity of proximal tibia?

We studied whether the two-plate tension band configuration is more prone for intraarticular deformations than the single plate application used for coronal plane deformities (CPD). The study was based on radiological chart review (retrospective cross-sectional) of records of children [15 patients (30 plates) with limb length discrepancies (LLD) and 20 patients (36 plates) with CPD]. Interscrew angle, slope angle, and roof angle were compared in the initial postoperative and final radiographs to determine changes of tibial morphology. The mean patient age and follow up for the LLD and CPD groups respectively were 6.5 years, 39.8 months and 8.1 years, 15.5 months respectively. The interscrew angles widened between initial and final radiographs in the CPD group and for both sides in the LLD group. The initial and final slope angles were not significantly different in both LLD and CPD groups. Similar trend was observed for roof angle in either group. In the intergroup comparisons between LLD and CPD group, the slope angle of medial/lateral operated side in LLD group versus that of the operated side in CPD group matched statistically in the final radiographs. Similarly, the final roof angle in LLD and CPD groups was statistically similar. No significant intraarticular morphological change was demonstrated following tension band plating epiphysiodesis of the proximal tibia for our series involving young children. It was observed neither with the two-plate configuration used for limb length decelerations nor with the single plate application for coronal plane corrections.

Capacity Building, Knowledge Enhancement, and Consultative Processes for Development of a Digital Tool (Ni-kshay SETU) to Support the Management of Patients with Tuberculosis: Exploratory Qualitative Study.

BACKGROUND: Achieving the target for eliminating tuberculosis (TB) in India by 2025, 5 years ahead of the global target, critically depends on strengthening the capacity of human resources as one of the key components of the health system. Due to the rapid updates of standards and protocols, the human resources for TB health care suffer from a lack of understanding of recent updates and acquiring necessary knowledge. OBJECTIVE: Despite an increasing focus on the digital revolution in health care, there is no such platform available to deliver the key updates in national TB control programs with easy access. Thus, the aim of this study was to explore the development and evolution of a mobile health tool for capacity building of the Indian health system's workforce to better manage patients with TB. METHODS: This study involved two phases. The first phase was based on a qualitative investigation, including personal interviews to understand the basic requirements of staff working in the management of patients with TB, followed by participatory consultative meetings with stakeholders to validate and develop the content for the mobile health app. Qualitative information was collected from the Purbi Singhbhum and Ranchi districts of Jharkhand and Gandhinagar, and from the Surat districts of Gujarat State. In the second phase, a participatory design process was undertaken as part of the content creation and validation exercises. RESULTS: The first phase collected information from 126 health care staff, with a mean age of 38.4 (SD 8.9) years and average work experience of 8.9 years. The assessment revealed that more than two-thirds of participants needed further training and lacked knowledge of the most current updates to TB program guidelines. The consultative process determined the need for a digital solution in easily accessible formats and ready reckoner content to deliver practical solutions to address operational issues for implementation of the program. Ultimately, the digital platform named Ni-kshay SETU (Support to End Tuberculosis) was developed to support the knowledge enhancement of health care workers. CONCLUSIONS: The development of staff capacity is vital to the success or failure of any program or intervention. Having up-to-date information provides confidence to health care staff when interacting with patients in the community and aids in making quick judgments when handling case scenarios. Ni-kshay SETU represents a novel digital capacity-building platform for enhancing human resource skills in achieving the goal of TB elimination.

Pain behavior of children with bilateral idiopathic clubfoot undergoing Ponseti casting and the effect of non-pharmaceutical pain-relieving agents.

INTRODUCTION: This study prospectively investigated the pain response and physiological parameters [heart rate (HR) and oxygen saturation (SpO2)] during sequential casting in bilateral clubfoot. Additionally, it explored the role of non-nutritive sucking and human care contact on the observed responses during casting. METHODS: Subjects were allotted to control group (Group A with no intervention) and two intervention groups (Group B: non-nutritive sucking intervention, Group C: human care contact intervention). Neonatal Infant Pain Score (NIPS), heart rate (HR), and oxygen saturation (SpO2) were used to assess the response. RESULTS: The three groups matched in age and gender characteristics of the participants. Pain response was noted across all groups. The left foot demonstrated a statistically significant preexisting tachycardia which rose further during casting (p < 0.01). Intergroup comparisons revealed that the alteration for NIPS during casting was in following sequence (Group A > C > B, p < 0.00001). The effect of interventions offered in Group B and C lasted in the post-cast period as well (B > C). CONCLUSION: The clubfoot child exhibited moderate pain response during casting of both feet. A tachycardia was noted prior to initiation of second cast which further exaggerated with subsequent cast. Pacifier (non-nutritive sucking) intervention produced better control of pain response than human care contact during casting for both feet.

Evaluation of safety, pharmacokinetics, and pharmacodynamics of apixaban in pediatric subjects at risk of venous or arterial thrombotic disorder.

Apixaban is an oral small-molecule, direct factor Xa (FXa) inhibitor approved in adults for treatment of deep vein thrombosis and pulmonary embolism, and for reducing risk of venous thromboembolism recurrence after initial anticoagulant therapy. This phase I study (NCT01707394) evaluated the pharmacokinetics (PKs), pharmacodynamics (PDs), and safety of apixaban in pediatric subjects (<18 years), enrolled by age group, at risk of venous or arterial thrombotic disorder. A single apixaban dose, targeting adult steady-state exposure with apixaban 2.5 mg, was administered using two pediatric formulations: 0.1 mg sprinkle capsule (age <28 days); 0.4 mg/ml solution (age 28 days to <18 years; dose range, 1.08-2.19 mg/m2 ). End points included safety, PKs, and anti-FXa activity. For PKs/PDs, four to six blood samples were collected ≤26 h postdosing. A population PK model was developed with data from adults and pediatric subjects. Apparent oral clearance (CL/F) included fixed maturation function based on published data. From January 2013 to June 2019, 49 pediatric subjects received apixaban. Most adverse events were mild/moderate, and the most common was pyrexia (n = 4/15). Apixaban CL/F and apparent central volume of distribution increased less than proportionally with body weight. Apixaban CL/F increased with age, reaching adult values in subjects aged 12 to <18 years. Maturation affected CL/F most notably in subjects aged <9 months. Plasma anti-FXa activity values were linearly related to apixaban concentrations, with no apparent age-related differences. Pediatric subjects tolerated single apixaban doses well. Study data and population PK model supported phase II/III pediatric trial dose selection.

Why and where?-Delay in Tuberculosis care cascade: A cross-sectional assessment in two Indian states, Jharkhand, Gujarat.

Tuberculosis (TB) is the second leading cause of death due to infectious diseases globally, and delay in the TB care cascade is reported as one of the major challenges in achieving the goals of the TB control programs. The main aim of this study was to investigate the delay and responsible factors for the delay in the various phases of care cascade among TB patients in two Indian states, Jharkhand and Gujarat. This cross-sectional study was conducted among 990 TB patients from the selected tuberculosis units (TUs) of two states. This study adopted a mixed-method approach for the data collection. The study targeted a diverse profile of TB patients, such as drug-sensitive TB (DSTB), drug resistance TB (DRTB), pediatric TB, and extra-pulmonary TB. It included both public and private sector patients. The study findings suggested that about 41% of pulmonary and 51% of extra-pulmonary patients reported total delay. Delay in initial formal consultation is most common, followed by a delay in diagnosis and treatment initiation in pulmonary patients. While in extra-pulmonary patients, delay in treatment initiation is most common, followed by the diagnosis and first formal consultation. DR-TB patients are more prone to total delay and delay in the treatment initiation among pulmonary patients. Addiction, co-morbidity and awareness regarding monetary benefits available for TB patients contribute significantly to the total delay among pulmonary TB patients. There were system-side factors like inadequacy in active case findings, poor infrastructure, improper adverse drug reaction management and follow-up, resulting in delays in the TB care cascade in different phases. Thus, the multi-disciplinary strategies covering the gambit of both system and demand side attributes are recommended to minimize the delays in the TB care cascade.

Accelerated biodecolorization and detoxification of synthetic textile dye Acid Maroon V by bacterial consortium under redox mediator system.

The treatment of textile industrial wastewater is an important concern owing to its negative impact on the biosphere. The present study highlighted dye decolorization potential of bacterial consortium EDPA containing Enterobacter dissolvens AGYP1 and Pseudomonas aeruginosa AGYP2 in the presence of redox mediators. Rapid decolorization of Acid Maroon V (100 mg l-1) was achieved in the presence of lawsone compared to other redox mediators. The dye decolorization was best fitted with first order kinetics with higher reaction kinetics (k1 = 0.328 h-1) and regression coefficient (R2 = 0.979). The removal of dye by the consortium was 1.47 times faster in 8 h with 0.01 mM lawsone. The consortium EDPA was able to decolorize 1200 mg l-1 concentration of dye with apparent R max , K m and R max /K m values 1000 mg l-1 h-1, 5000 mg l-1 and 0.2 h-1, respectively. The lawsone-mediated system could decolorize the dye 80.44% in 10 h at the end of 11 dye spiking cycle. The superior biodecolorization of 14 different textile dyes was obtained in the presence of lawsone-mediated system. The intracellular enzyme activities of azoreductase, NADH-DCIP reductase, laccase, manganese peroxidase and lignin peroxidase increased significantly. The sequential microaerophilic-aerobic incubation resulted into 89.31% reduction of total aromatic amines. The microbial toxicity, phytotoxicity and genotoxicity measurements revealed biotransformation of toxic nature of dye Acid Maroon V into non-toxic metabolites by the action of consortium EDPA, and thus its suitability for biotreatment of dye containing industrial effluents. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03466-6.

Efficacy of 2 Nonpharmaceutical (Non-nutritive Sucking and Human Care Contact) Pain Relief Measures for Idiopathic Clubfoot Casted Using Ponseti Technique.

PURPOSE: This study aimed at exploring the pain and physiological responses exhibited during Ponseti manipulation and casting in clubfoot infants. In addition, we compared the efficacy of 2 nonpharmaceutical techniques (non-nutritive sucking and human care contact) for tackling these responses. METHODS: The study included children with unilateral and bilateral idiopathic clubfeet between 15 days to 6 months of age. For comparisons, children were divided into control group without any intervention (group A), non-nutritive sucking group (group B), and human care contact group (group C). Pain score (Neonatal Infant Pain Score), heart rate (HR), and oxygen saturation (SpO2) was assessed before, during and 1 minute after casting. These measurements were compared using statistical methods. RESULTS: There were 16 children (11 bilateral) in group A, 17 (10 bilateral) in group B, and 18 (8 bilateral) in group C. Before casting, the baseline parameters (Neonatal Infant Pain Score, HR, and SpO2) of the 3 groups were comparable. Groups B and C had a significant reduction in pain score at casting and in postcasting period when compared with group A (P<0.05). Group B (at casting-mean: 174.1/min, postcasting-mean: 168.2/min) had the lowest HR both during and after cast application. Group B had the highest SpO2 among all the 3 groups, both during casting (mean: 95.7%) and after casting (mean: 97.4%) (P<0.05). CONCLUSIONS: Infants exhibit moderate pain response and altered physiological responses during and after Ponseti casting. Non-nutritive sucking emerged as a better method to lessen these parameters when compared with the conventional technique and human care contact. LEVEL OF EVIDENCE: Level II.

What exactly is "foot abduction" during management of idiopathic clubfoot in clinical practice?

PURPOSE: There is however gross ambiguity regarding the use of term "foot abduction" in clubfoot treatment. We measured below defined angles at different stages of clubfoot treatment to decipher their precise interpretation. METHODS: In a prospective evaluation of 25 unilateral clubfeet in infants' age less than six months treated with Ponseti technique, clinical leg foot and thigh foot angle were measured at talar head reduction (LHT0), pre-tenotomy, and post-tenotomy stage. A "normal" reference was available in the form of measurements of contralateral limb. RESULTS: Talar head (LHT0) was reduced at mean leg foot angle of 26 degrees. The corresponding pre- and post-tenotomy angles were 42.6 and 50.0 degrees, respectively. The reference leg foot angles for contralateral limb were 49.8 degrees. The thigh foot angle for LHT0, pre-tenotomy, post-tenotomy, and contralateral side were, respectively, 39.2, 56, 68, and 65.6 degrees. There was an additional tibial external rotation component of mean 13.4 degrees (SD 4.5) in the thigh foot angle when compared to the leg foot angle at tenotomy. This increased to 18 degrees (SD 3.4) post-tenotomy. CONCLUSIONS: The study suggested that the foot abduction described in the "Ponseti Manual" probably intends thigh foot rather than leg foot angles. There was a significant difference in the angles when talar head reduced and tenotomy was decided. The foot abduction is an ambiguous term which should be replaced by the more specific leg or thigh foot abduction angle.

Ceftolozane/Tazobactam Probability of Target Attainment in Patients With Hospital-Acquired or Ventilator-Associated Bacterial Pneumonia.

Probability of target attainment (PTA) analyses were conducted to support the recommended ceftolozane/tazobactam dosing regimens, adjusted for renal function, in patients with hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP). Previously published population pharmacokinetic models describing the disposition of ceftolozane and tazobactam in plasma and epithelial lining fluid (ELF) in patients with HABP/VABP were used to simulate ceftolozane and tazobactam concentration-time profiles in plasma and ELF over the course of 14 days. The simulations were conducted for patients with normal renal function and for patients receiving adjusted doses for mild, moderate, and severe renal impairment. PTA was calculated using established pharmacokinetic/pharmacodynamic targets for ceftolozane and tazobactam. Across renal function groups, plasma PTA was 100% for ceftolozane and >99% for tazobactam; ELF PTA was >99% for ceftolozane and >87% for tazobactam. These results provided support for the currently recommended ceftolozane/tazobactam dosing regimens for HABP/VABP, which were efficacious and well tolerated in the Ceftolozane-Tazobactam Versus Meropenem for Treatment of Nosocomial Pneumonia (ASPECT-NP) trial.

Probability of Target Attainment Analyses to Inform Ceftolozane/Tazobactam Dosing Regimens for Patients With Hospital-Acquired or Ventilator-Associated Bacterial Pneumonia and End-Stage Renal Disease Receiving Intermittent Hemodialysis.

ASPECT-NP, a phase 3 trial of ceftolozane/tazobactam in hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP), excluded patients with end-stage renal disease (ESRD). A modeling/simulation approach was undertaken to inform optimal dosing in this population, using previously developed ceftolozane and tazobactam population pharmacokinetic models informed by data from 16 clinical studies. Stochastic simulations were performed using NONMEM to support dose justification. Probability of target attainment (PTA) simulations in plasma and epithelial lining fluid were conducted using a 14-day treatment, with hemodialysis every other weekday for a high-dose (4X), middle-dose (3X), or low-dose (2X) regimen, where X was the recommended dose in patients with complicated intra-abdominal infection/complicated urinary tract infection and ESRD (500 mg/250 mg ceftolozane/tazobactam loading dose and 100 mg/50 mg ceftolozane/tazobactam maintenance dose administered by 1-hour infusion every 8 hours). PTA was determined using established pharmacokinetic/pharmacodynamic targets: ceftolozane, 30% of the interdose interval (8 hours) in which free ceftolozane concentration exceeded the minimum inhibitory concentration value of 4 µg/mL; tazobactam, 20% of the interdose interval in which free tazobactam concentration exceeded 1 µg/mL. Plasma PTA was >90% for both agents for all 3 regimens. Plasma ceftolozane exposures at the high-dose regimen exceeded those from phase 3 study experience. Epithelial lining fluid PTA was >90% for high- and middle-dose regimens but was <80% for tazobactam on dialysis days at the low-dose regimen. For patients with HABP/VABP and ESRD requiring intermittent hemodialysis, the middle-dose regimen of 1.5 g/0.75 g ceftolozane/tazobactam loading + 300 mg/150 mg maintenance every 8 hours by 1-hour infusion is recommended.

Predisposing factors for migration of epiphyseal screws into physis in tension band plating.

The migration of epiphyseal screws into growing physis in tension band plating is a known complication. We investigated the screw migration into physis in 10 patients (18 plates) to study the various technical details, which may have contributed to this complication. The methodology involved retrospective review of radiological records. Among these 10 affected patients, in four patients, there were eight additional tension band plates, which had remained uncomplicated ('controls') at the time when implant failure was detected. We statistically compared the length of epiphyseal screw, proximity of screw start point to the physis, screw trajectory angle, interscrew angle and correction rate between the migrated and other uncomplicated plates. Majority patients were postrachitic ( n = 7). The mean time from primary procedure to detection of radiological complication was 15.1 months. The mean epiphyseal screw length proportion in migrated and uncomplicated plates matched. The starting point of epiphyseal screw was relatively closer to physis in migrated plates. The trajectory of epiphyseal screw with respect to physis was more divergent in the migrated plates ( P = 0.02). All implants were inserted in a divergent manner with mean interscrew angle being 22.3° for migrated and 13.8° for the uncomplicated plates ( P = 0.02). The correction rate of the implant reduced as it failed. Osteopenic bone and pathological physis predispose to migrated plates. Technically, a wider trajectory of epiphyseal screw and too divergent screws should be avoided. A migrated implant becomes less effective in its function.