The First Differentiated TB Care Model From India: Delays and Predictors of Losses in the Care Cascade.

To reduce TB deaths in resource-limited settings, a differentiated care strategy can be used to triage patients with high risk of severe illness (i.e., those with very severe undernutrition, respiratory insufficiency, or inability to stand without support) at diagnosis and refer them for comprehensive assessment and inpatient care. Globally, there are few examples of implementing this type of strategy in routine program settings. Beginning in April 2022, the Indian state of Tamil Nadu implemented a differentiated care strategy called Tamil Nadu-Kasanoi Erappila Thittam (TN-KET) for all adults aged 15 years and older with drug-susceptible TB notified by public facilities. Before evaluating the impact on TB deaths, we sought to understand the retention and delays in the care cascade as well as predictors of losses. During April-June 2022, 14,961 TB patients were notified and 11,599 (78%) were triaged. Of those triaged, 1,509 (13%) were at high risk of severe illness; of these, 1,128 (75%) were comprehensively assessed at a nodal inpatient care facility. Of 993 confirmed as severely ill, 909 (92%) were admitted, with 8% unfavorable admission outcomes (4% deaths). Median admission duration was 4 days. From diagnosis, the median delay in triaging and admission of severely ill patients was 1 day each. Likelihood of triaging decreased for people with extrapulmonary TB, those diagnosed in high-notification districts or teaching hospitals, and those transferred out of district. Predictors of not being comprehensively assessed included: aged 25-34 years, able to stand without support, and diagnosis at a primary or secondary-level facility. Inability to stand without support was a predictor of unfavorable admission outcomes. To conclude, the first quarter of implementation suggests that TN-KET was feasible to implement but could be improved by addressing predictors of losses in the care cascade and increasing admission duration.

--Eleven tips for operational researchers working with health programmes: our experience based on implementing differentiated tuberculosis care in south India.

Due to the workload and lack of a critical mass of trained operational researchers within their ranks, health systems and programmes may not be able to dedicate sufficient time to conducting operational research (OR). Hence, they may need the technical support of operational researchers from research/academic organisations. Additionally, there is a knowledge gap regarding implementing differentiated tuberculosis (TB) care in programme settings. In this 'how we did it' paper, we share our experience of implementing a differentiated TB care model along with an inbuilt OR component in Tamil Nadu, a southern state in India. This was a health system initiative through a collaboration of the State TB cell with the Indian Council of Medical Research institutes and the World Health Organisation country office in India. The learnings are in the form of eleven tips: four broad principles (OR on priority areas and make it a health system initiative, implement simple and holistic ideas, embed OR within routine programme settings, aim for long-term engagement), four related to strategic planning (big team of investigators, joint leadership, decentralised decision-making, working in advance) and three about implementation planning (conducting pilots, smart use of e-tools and operational research publications at frequent intervals). These may act as a guide for other Indian states, high TB burden countries that want to implement differentiated care, and for operational researchers in providing technical assistance for strengthening implementation and conducting OR in health systems and programmes (TB or other health programmes). Following these tips may increase the chances of i) an enriching engagement, ii) policy/practice change, and iii) sustainable implementation.

Upshot of Concentration of Zirconium (IV) Oxynitrate Hexa Hydrate on Preparation and Analyses of Zirconium Oxide (ZrO2) Nanoparticles by Modified Co-Precipitation Method.

In the present work, pure nanocrystalline monoclinic Zirconia (ZrO2) has been successfully synthesized and optimized by the modified co-precipitation method. The concentration of raw material has been optimized with the fixed amount of precipitation agent (Potassium hydroxide KOH). The thermal history of the precursor has been examined through TG/DTA analysis. All the samples are subjected to study the structure, fingerprints of the molecular vibrations, and morphology analyses. The representative sample has been analyzed through Transmission Electron Microscope (TEM) and X-ray Photo Electron Spectroscopy (XPS) analyses. The as-prepared sample exhibits the better crystallinity and surface morphology with lesser particle size (190 nm) when the raw material concentration is 0.2 M. The as-prepared ZrO2 filler (0, 3, 6, 9, and 12 wt.%) is spread through the enhanced polymer electrolyte P(S-MMA) (27 Wt.%)-LiClO4 (8 wt.%)-EC + PC (1;1 of 65 wt.%) complex system via solution casting method. The as-synthesized electrolyte films are examined via complex impedance analysis. P(S-MMA) (27 wt.%)-LiCIO4 (8 wt.%)-EC + PC (1 ;1 of 65 wt.%)-6 wt.% of ZrO2 shows the high ionic conductivity 2.35 × 10-3 Scm-1. Temperature-dependent ionic conductivity studies obey the non-linear behavior. The enhanced ZrO2 has been expected to enhance the other electrochemical properties of the lithium secondary battery.

Appropriateness of metformin prescription for type 2 diabetes mellitus patients with chronic kidney disease (Stages 3-5).

INTRODUCTION: Metformin is the first-line pharmacological therapy for type 2 diabetes mellitus (T2DM). Guidelines recommend metformin to be given at reduced dosages for those with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 and omitted in those with eGFR<30 mL/min/1.73m2. Lactic acidosis is a known complication of those on metformin. This study aimed to determine the appropriateness of metformin prescription in T2DM patients with chronic kidney disease (CKD) stages 3-5 in a tertiary centre in Malaysia. MATERIALS AND METHODS: A cross-sectional design using retrospective secondary data of T2DM patients on metformin attending nephrology and diabetic clinics in the year 2017. eGFR calculated using the CKD-EPI formula identified those in CKD stage 3-5 defined using the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative criteria. Metformin prescription was considered appropriate when the metformin maximum daily dosage does not exceed 1500 mg in CKD stage 3a and 1000 mg in CKD stage 3b and metformin stopped in CKD stages 4 and 5. RESULTS: A total of 143 patients were included. Majority were in the elderly age group (62.9%), male (60.8%) and had concurrent hypertension (85.3%). Median HbA1c was 8.3% (67 mmol/mol) with most patients (88.8%) having HbA1c above 6.5% (48 mmol/ mol). Majority (92.3%) were categorised as stage 3 CKD. Eleven (7.7%) subjects had inappropriate metformin prescription. Seven of nine (78%) subjects in CKD stage 4 were on metformin with a maximum daily dose of 500 mg to1000 mg. Three patients had serum lactate measured. CONCLUSION: The majority of CKD patients had appropriate metformin prescription. However, a considerable number of CKD stage 4 patients continued to be on metformin. The many benefits of metformin may be a reason why it is still continued against recommendations. Only three patients had lactate measured which, although may suggest that lactic acidosis is not a common occurrence, the potential for metformin-associated lactic acidosis especially in those at risk should be considered.

Two-year clinical results of a novel load redistribution device for the treatment of medial knee OA.

PURPOSE: A potential method to relieve the pain from medial osteoarthritis of the knee is to offload the medial compartment. The Latella™ Knee Implant is a novel device designed to offload the medial compartment. The objective of the Cotera-1 study was to evaluate the preliminary safety and feasibility of the Latella implant to treat patients with medial OA of the knee, by a 2-year follow-up of a prospective multicenter feasibility study (Cotera-1) performed in the Netherlands and UK METHODS: In this first-in-man study, 11 participants received the Latella implant and were followed for 2 years, documenting physician assessment, Patient-Reported Outcome (PRO) scoring (KOOS, IKDC, Kujala, SF-36); Patient Global Assessment (PGA), radiographic analysis and MRI analysis, complications, reoperation rate and hip-knee-ankle axis. RESULTS: The Latella Knee Implant system proved to be well tolerated and demonstrated a low-risk safety profile up to 24 months post-treatment. A responder analysis was performed of the subjects who still had the Latella implanted at 24-month time point (n = 9). Based on a MCID of eight for KOOS pain sub-scale, 78% of the subjects at the 24 month time point would be considered as responders. Similarly, based on improvement in the medial knee pain compared to baseline using the NRS scale of 1-10, 89% of the subjects at the 24-month time point would be considered as responders. Two patients were revised during follow-up: one for arthrofibrosis and one converted to TKA for progression of OA. CONCLUSIONS: The early clinical experience with the Latella Knee Implant in this pilot feasibility study has been encouraging. It appears to be a safe implant with possible effect on medial OA. Additional studies need to be performed to assess the safety and efficacy of the procedure in a larger patient population. LEVEL OF EVIDENCE: II.

Facile Synthesis and Characterization of ZrO2 Nanoparticles via Modified Co-Precipitation Method.

The crystalline Zirconium oxide (ZrO2) nano particles were synthesized using optimized content of Zirconium nitrate (Zr(NO3)2·3H2O) with varying KOH concentration (0.5, 1 and 1.5 M) by co-precipitation method. The thermal history of the precursor was carefully analyzed through Thermogravimetric (TG/DTA) measurement. The as prepared samples were characterized to ensure structural, functional, morphological, compositional, chemical composition and band gap by X-ray diffractometer (XRD), Fourier transform infrared spectroscopy (FTIR), Laser Raman, scanning electron microscopy (SEM), High resolution Transverse Electron Microscopy (HR-TEM), X-ray photo electron spectroscopy (XPS), EDX, Photo luminescence spectroscopy (PL). The monoclinic structure with space group P21/c has been confirmed from XRD (JCPDS 89-9066). The Zr-O stretching vibration and Zr-O2-Zr bending vibrations were confirmed through FTIR analysis. The well dispersed particles with spherical morphology were confirmed through SEM and TEM analysis. The oxidation states of Zr, O and C were confirmed through XPS analysis. The oxygen vacancies and band gap of the particles were investigated through PL analysis.

Circulating tumour DNA analysis demonstrates spatial mutational heterogeneity that coincides with disease relapse in myeloma.

Mutational characterisation in multiple myeloma (MM) currently relies on bone marrow (BM) biopsy, which fails to capture the putative spatial and genetic heterogeneity of this multifocal disease. Analysis of plasma (PL)-derived circulating free tumour DNA (ctDNA) as an adjunct to BM biopsy, for mutational characterisation and tracking disease progression, was evaluated. Paired BM MM cell DNA and ctDNA from 33 relapsed/refractory (RR) and 15 newly diagnosed (ND) patients were analysed for KRAS, NRAS, BRAF and TP53 mutations using the OnTarget Mutation Detection (OMD) platform. OMD detected 128 mutations (PL=31, BM=59, both=38) indicating the presence of PL mutations (54%). A higher frequency of PL-only mutations was detected in RR patients than ND (27.2% vs 6.6%, respectively), authenticating the existence of spatial and genetic heterogeneity in advanced disease. Activating RAS mutations were more highly prevalent than previously described with 69% harboring at least one RAS mutation. Sequential ctDNA quantitation with droplet digital PCR through longitudinal PL tracking of specific clones in seven patients demonstrated changes in fractional abundance of certain clones reflective of the disease status. We conclude that ctDNA analysis as an adjunct to BM biopsy represents a noninvasive and holistic strategy for improved mutational characterisation and therapeutic monitoring of MM.

C-type natriuretic peptide signalling drives homeostatic effects in human chondrocytes.

Signals induced by mechanical loading and C-type natriuretic peptide (CNP) represent chondroprotective routes that may potentially prevent osteoarthritis (OA). We examined whether CNP will reduce hyaluronan production and export via members of the multidrug resistance protein (MRP) and diminish pro-inflammatory effects in human chondrocytes. The presence of interleukin-1ß (IL-1ß) increased HA production and export via MRP5 that was reduced with CNP and/or loading. Treatment with IL-1ß conditioned medium increased production of catabolic mediators and the response was reduced with the hyaluronan inhibitor, Pep-1. The induction of pro-inflammatory cytokines by the conditioned medium was reduced by CNP and/or Pep-1, αCD44 or αTLR4 in a cytokine-dependent manner, suggesting that the CNP pathway is protective and should be exploited further.

Farming practices and genetic characterization of Nicobari pig, an indigenous pig germplasm of Nicobar group of islands, India.

The Nicobari pig, locally known as Ha-un, is an indigenous pig germplasm located only in the Nicobar group of islands, India. The present study documents the Nicobari pig-rearing practices of the tribal farmers and genetically characterizes them using 23 FAO-recommended microsatellite markers. The study was conducted over a period of 3 years (2010-2012) in Car Nicobar, India. A total of 225 farmers were surveyed (15 farmers per village of 15 villages). Information on herd statistics, husbandry practices, and constraints faced by the farmers in pig production were collected. The pigs were reared in a free-range system. Mean pig herd size per house hold was 8.9, and main feed for pigs was coconut and some indigenous feed materials such as pandanus, bread fruit, and Nicobari alu. The main constraints faced by the farmers were lack of feed after the tsunami, different disease conditions, piglet mortality, and predator attack. The Nicobari pigs were genotyped by 23 FAO-recommended microsatellite markers. The mean observed number of alleles for all 23 loci in Nicobari pigs was 6.96 ± 0.31. The mean observed and expected heterozygosities were 0.66 ± 0.02 and 0.75 ± 0.01, respectively. It was found that the genetic diversity of this pig breed was very high compared to Large White Yorkshire and other European pig breeds. This genetic characterization of the pig breed will be helpful in their conservation effort.

Reverse Ponseti-type treatment for children with congenital vertical talus: comparison between idiopathic and teratological patients.

Children with congenital vertical talus (CVT) have been treated with extensive soft-tissue releases, with a high rate of complications. Recently, reverse Ponseti-type casting followed by percutaneous reduction and fixation has been described, with excellent results in separate cohorts of children with CVT, of either idiopathic or teratological aetiology. There are currently no studies that compare the outcome in these two types. We present a prospective cohort of 13 children (21 feet) with CVT of both idiopathic and teratological aetiology, in which this technique has been used. Clinical, radiological and parent-reported outcomes were obtained at a mean follow-up of 36 months (8 to 57). Six children (nine feet) had associated neuromuscular conditions or syndromes; the condition was idiopathic in seven children (12 feet). Initial correction was achieved in all children, with significant improvement in all radiological parameters. Recurrence was seen in ten feet. Modification of the technique to include limited capsulotomy at the initial operation may reduce the risk of recurrence. The reverse Ponseti-type technique is effective in the initial correction of CVT of both idiopathic and teratological aetiology. Recurrence is a problem in both these groups, with higher rates than first reported in the original paper. However, these rates are less than those reported after open surgical release.

Management of developmental dysplasia of the hip in young adults: current concepts.

The term developmental dysplasia of the hip (DDH) describes a spectrum of disorders that results in abnormal development of the hip joint. If not treated successfully in childhood, these patients may go on to develop hip symptoms and/or secondary osteoarthritis in adulthood. In this review we describe the altered anatomy encountered in adults with DDH along with the management options, and the challenges associated with hip arthroscopy, osteotomies and arthroplasty for the treatment of DDH in young adults.

Surgical treatment of femoroacetabular impingement in patients with slipped capital femoral epiphysis: A review of current surgical techniques.

Slipped capital femoral epiphysis (SCFE) is relatively common in adolescents and results in a complex deformity of the hip that can lead to femoroacetabular impingement (FAI). FAI may be symptomatic and lead to the premature development of osteoarthritis (OA) of the hip. Current techniques for managing the deformity include arthroscopic femoral neck osteochondroplasty, an arthroscopically assisted limited anterior approach to the hip, surgical dislocation, and proximal femoral osteotomy. Although not a routine procedure to treat FAI secondary to SCFE deformity, peri-acetabular osteotomy has been successfully used to treat FAI caused by acetabular over-coverage. These procedures should be considered for patients with symptoms due to a deformity of the hip secondary to SCFE.

Dexamethasone, light anaesthesia, and tight glucose control (DeLiT) randomized controlled trial.

BACKGROUND: The inflammatory response to surgical tissue injury is associated with perioperative morbidity and mortality. We tested the primary hypotheses that major perioperative morbidity is reduced by three potential anti-inflammatory interventions: (i) low-dose dexamethasone, (ii) intensive intraoperative glucose control, and (iii) lighter anaesthesia. METHODS: We enrolled patients having major non-cardiac surgery who were ≥40 yr old and had an ASA physical status ≤IV. In a three-way factorial design, patients were randomized to perioperative i.v. dexamethasone (a total of 14 mg tapered over 3 days) vs placebo, intensive vs conventional glucose control 80-110 vs 180-200 mg dl(-1), and lighter vs deeper anaesthesia (bispectral index target of 55 vs 35). The primary outcome was a collapsed composite of 15 major complications and 30 day mortality. Plasma high-sensitivity (hs) C-reactive protein (CRP) concentration was measured before operation and on the first and second postoperative days. RESULTS: The overall incidence of the primary outcome was about 20%. The trial was stopped after the second interim analysis with 381 patients, at which all three interventions crossed the futility boundary for the primary outcome. No three-way (P=0.70) or two-way (all P>0.52) interactions among the interventions were found. There was a significantly smaller increase in hsCRP in patients given dexamethasone than placebo [maximum 108 (64) vs 155 (69) mg litre(-1), P<0.001], but none of the other two interventions differentially influenced the hsCRP response to surgery. CONCLUSIONS: Among our three interventions, dexamethasone alone reduced inflammation. However, no intervention reduced the risk of major morbidity or 1 yr mortality. TRIAL REGISTRATION IDENTIFIER: NCT00433251 at www.clinicaltrials.gov.

Haematogenous acute and subacute paediatric osteomyelitis: a systematic review of the literature.

A delay in the diagnosis of paediatric acute and subacute haematogenous osteomyelitis can lead to potentially devastating morbidity. There are no definitive guidelines for diagnosis, and recommendations in the literature are generally based on expert opinions, case series and cohort studies. All articles in the English literature on paediatric osteomyelitis were searched using MEDLINE, CINAHL, EMBASE, Google Scholar, the Cochrane Library and reference lists. A total of 1854 papers were identified, 132 of which were examined in detail. All aspects of osteomyelitis were investigated in order to formulate recommendations. On admission 40% of children are afebrile. The tibia and femur are the most commonly affected long bones. Clinical examination, blood and radiological tests are only reliable for diagnosis in combination. Staphylococcus aureus is the most common organism detected, but isolation of Kingella kingae is increasing. Antibiotic treatment is usually sufficient to eradicate the infection, with a short course intravenously and early conversion to oral treatment. Surgery is indicated only in specific situations. Most studies were retrospective and there is a need for large, multicentre, randomised, controlled trials to define protocols for diagnosis and treatment. Meanwhile, evidence-based algorithms are suggested for accurate and early diagnosis and effective treatment.

The World Health Organization '5 moments of hand hygiene': the scientific foundation.

The World Health Organization (WHO) launched the first Global Patient Safety Challenge in 2005 and introduced the '5 moments of hand hygiene' in 2009 in an attempt to reduce the burden of health care associated infections. Many NHS trusts in England adopted this model of hand hygiene, which prompts health care workers to clean their hands at five distinct stages of caring for the patient. Our review analyses the scientific foundation for the five moments of hand hygiene and explores the evidence, as referenced by WHO, to support these recommendations. We found no strong scientific support for this regime of hand hygiene as a means of reducing health care associated infections. Consensus-based guidelines based on weak scientific foundations should be assessed carefully to prevent shifting the clinical focus from more important issues and to direct limited resources more effectively. We recommend caution in the universal adoption of the WHO '5 moments of hand hygiene' by orthopaedic surgeons and other health care workers and emphasise the need for evidence-based principles when adopting hospital guidelines aimed at promoting excellence in clinical practice.

Arthroscopy of the hip for paediatric and adolescent disorders: current concepts.

Hip arthroscopy is particularly attractive in children as it confers advantages over arthrotomy or open surgery, such as shorter recovery time and earlier return to activity. Developments in surgical technique and arthroscopic instrumentation have enabled extension of arthroscopy of the hip to this age group. Potential challenges in paediatric and adolescent hip arthroscopy include variability in size, normal developmental change from childhood to adolescence, and conditions specific to children and adolescents and their various consequences. Treatable disorders include the sequelae of traumatic and sports-related hip joint injuries, Legg-Calve-Perthes' disease and slipped capital femoral epiphysis, and the arthritic and septic hip. Intra-articular abnormalities are rarely isolated and are often associated with underlying morphological changes. This review presents the current concepts of hip arthroscopy in the paediatric and adolescent patient, covering clinical assessment and investigation, indications and results of the experience to date, as well as technical challenges and future directions.

Management of congenital talipes equinovarus using the Ponseti method: a systematic review.

We present a systematic review of the results of the Ponseti method of management for congenital talipes equinovarus (CTEV). Our aims were to assess the method, the effects of modifications to the original method, and compare it with other similar methods of treatment. We found 308 relevant citations in the English literature up to 31 May 2010, of which 74 full-text articles met our inclusion criteria. Our results showed that the Ponseti method provides excellent results with an initial correction rate of around 90% in idiopathic feet. Non-compliance with bracing is the most common cause of relapse. The current best practice for the treatment of CTEV is the original Ponseti method, with minimal adjustments being hyperabduction of the foot in the final cast and the need for longer-term bracing up to four years. Larger comparative studies will be required if other methods are to be recommended.

Elastic intramedullary nailing of paediatric fractures of the forearm: a decade of experience in a teaching hospital in the United Kingdom.

We present the results of 90 consecutive children with displaced fractures of the forearm treated by elastic stable intramedullary nailing with a mean follow-up of 6.6 months (2.0 to 17.6). Eight (9%) had open fractures and 77 (86%) had sustained a fracture of both bones. The operations were performed by orthopaedic trainees in 78 patients (86%). All fractures healed at a mean of 2.9 months (1.1 to 8.7). There was one case of delayed union of an ulnar fracture. An excellent or good functional outcome was achieved in 76 patients (84%). There was no statistical difference detected when the grade of operating surgeon, age of the patient and the diaphyseal level of the fracture were correlated with the outcome. A limited open reduction was required in 40 fractures (44%). Complications included seven cases of problematic wounds, two transient palsies of the superficial radial nerve and one case each of malunion and a post-operative compartment syndrome. At final follow-up, all children were pain-free and without limitation of sport and play activities. Our findings indicate that the functional outcome following paediatric fractures of the forearm treated by elastic stable intramedullary nailing is good, without the need for anatomical restoration of the radial bow.