A practical evidence-based approach to management of type 2 diabetes in children and young people (CYP): UK consensus.

BACKGROUND: Type 2 diabetes in young people is an aggressive disease with a greater risk of complications leading to increased morbidity and mortality during the most productive years of life. Prevalence in the UK and globally is rising yet experience in managing this condition is limited. There are no consensus guidelines in the UK for the assessment and management of paediatric type 2 diabetes. METHODS: Multidisciplinary professionals from The Association of Children's Diabetes Clinicians (ACDC) and the National Type 2 Diabetes Working Group reviewed the evidence base and made recommendations using the Grading Of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. RESULTS AND DISCUSSION: Young people with type 2 diabetes should be managed within a paediatric diabetes team with close working with adult diabetes specialists, primary care and other paediatric specialties. Diagnosis of diabetes type can be challenging with many overlapping features. Diabetes antibodies may be needed to aid diagnosis. Co-morbidities and complications are frequently present at diagnosis and should be managed holistically. Lifestyle change and metformin are the mainstay of early treatment, with some needing additional basal insulin. GLP1 agonists should be used as second-line agents once early ketosis and symptoms are controlled. Glycaemic control improves microvascular but not cardiovascular risk. Reduction in excess adiposity, smoking prevention, increased physical activity and reduction of hypertension and dyslipidaemia are essential to reduce major adverse cardiovascular events. CONCLUSIONS: This evidence-based guideline aims to provide a practical approach in managing this condition in the UK.

Do baseline patient reported outcome measures predict changes in self-reported function, following a chronic pain rehabilitation programme?

Background: Interdisciplinary pain management programmes, based on cognitive-behavioural principles, aim to improve physical and psychological functioning and enhance self-management in people living with chronic pain. Currently there is insufficient evidence about whether psychological, biological or social factors are predictive of positive outcomes following pain rehabilitation. This study aims to evaluate predictors of change in Brief Pain Inventory - pain interference score (BPI) in a clinical data set to determine whether age, sex and baseline outcome measures are predictive of improvement in pain interference following pain rehabilitation. Methods: A retrospective, pragmatic observational analysis of routinely collected clinical data in two pain rehabilitation programmes, Balanced Life Programme (BLP) and Get Back Active (GBA) was conducted. Standard regression and hierarchical regression analyses were used to identify predictors of change to assess temporal changes in BPI. Responder analysis was also conducted. Results: Standard regression analyses of 208 (BLP) and 310 (GBA) patients showed that higher baseline BPI and better physical performance measures predicted better improvement in BPI across both programmes. Hierarchical regression showed that age and sex accounted for 2.7% (BLP) and 0.002% (GBA) of the variance in change in BPI. After controlling for age and sex, the other measures explained an additional 23% (BLP) and 19% (GBA) of the variance, p = < .001 where BPI and physical performance measures were consistently statistically significant predictors, p < .05. Responder analysis also showed that pain interference and physical performance were significantly associated with improvement (p = < .0005). Conclusions: The combination of high self-reported pain interference and better physical performance measures may be a useful indicator of who would benefit from interdisciplinary rehabilitation. Further validation of the results is required.

Sex-specific differences and how to handle them in early psoriatic arthritis.

OBJECTIVES: The prevalence of psoriatic arthritis (PsA) is the same in men and women; however, the latter experience a higher burden of disease and are affected more frequently by polyarthritis. Here, we performed an early PsA cohort analysis to assess sex-related differences in demographics, disease characteristics, and evolution over 1 year including applied treatment strategies. METHODS: Our study is embedded in the Dutch south-west Early Psoriatic Arthritis cohoRt. We described patient characteristics and treatment decisions. For the comparison across sexes and baseline and 1 year follow-up, appropriate tests depending on the distribution were used. RESULTS: Two hundred seventy-three men and 294 women with no significant differences in age and ethnicity were included. Women reported significantly longer duration of symptoms before diagnosis and significantly higher tender joint count, a higher disease activity, higher levels of pain, and lower functional capacity. Although minimal disease activity (MDA) rates increased over time for both sexes, MDA remained significantly more prevalent among men at 1 year (58.1% vs 35.7%, p < 0.00). Initially, treatment strategies were similar in both sexes with methotrexate being the most frequently used drug during the first year. Women received methotrexate for a shorter period [196 (93-364) vs 306 (157-365), p < 0.00] and therefore received a lower cumulative dose compared to men. Retention time was shorter for all DMARDs, and women had a delayed start on b-DMARDs. CONCLUSION: After 1 year of standard-of-care treatment, women did not surpass their baseline disadvantages. Despite the overall improvement, they still presented higher disease activity, higher levels of pain, and lower functional capacity score than men. The nature of these findings may advocate a need for sex specific adjustment of treatment strategies and evaluation in early PsA patients.

A practical approach to continuous glucose monitoring (rtCGM) and FreeStyle Libre systems (isCGM) in children and young people with Type 1 diabetes.

Real-time continuous glucose monitoring (rtCGM) and FreeStyle Libre glucose monitoring systems (isCGM) are new evolving technologies used in the management of Type 1 diabetes. They offer potential to improve diabetes control and reduce hypoglycaemia. rtCGM can be linked to insulin pump providing hybrid closed loop therapy. Families of children and young people are keen to have the benefit from these technologies. These are relatively expensive so it is important that health care professionals, families of children and young people (CYP) with diabetes are adequately trained in the use of these devices. Health care professionals need to be able to make patient selection based on individual needs and preferences to achieve maximum benefit. Association of Children's Diabetes Clinicians (ACDC) developed a comprehensive guideline in 2017 to help identify which patients may be most likely to benefit and how these technologies may be practically implemented. Since then new technologies have been introduced and the use of GCM has expanded in routine clinical practice. This article, aims to provide a practical approach and help identify which patients may be most likely to benefit and how the technology may be implemented in order to maximise the clinical benefits.

Diagnosis of osteoarticular tuberculosis by immuno-PCR assay based on mycobacterial antigen 85 complex detection.

Diagnosis of osteoarticular tuberculosis (OATB) exhibits serious challenges owing to paucibacillary nature of specimens and localization of disease at sites that are difficult to access. We recently developed indirect immuno-PCR (I-PCR) and real-time I-PCR (RT-I-PCR) assays for the detection of mycobacterial antigen 85 complex (Ag85) in OATB patients. Detection limits for the purified Ag85 protein were found to be 1 and 41 fg ml-1 by I-PCR and RT-I-PCR, respectively, which were at least 105 -fold lower than respective ELISA. While spiking synovial fluids of non-TB control subjects with the purified Ag85 protein, LODs of 100 and 120 fg ml-1 were obtained by I-PCR and RT-I-PCR, respectively, thus demonstrating the sample matrix effect. Sensitivities of 87·5 and 70·5% were observed in bodily fluids of confirmed (n = 8) and clinically suspected (n = 51) OATB cases, respectively, by I-PCR, with a specificity of 93·9% (n = 33). Markedly, the sensitivities obtained by I-PCR/RT-I-PCR were significantly higher (P < 0·05-0·01) than ELISA and GeneXpert assay (n = 30). However, no substantial difference in sensitivity was observed between the I-PCR and RT-I-PCR assays. After further improving the accuracy of I-PCR, this test may lead to development of an attractive diagnostic kit.

Comparison of Bone-Patellar Tendon-Bone Graft, Semitendinosus-Gracilis Graft and Semitendinosus-Gracilis with Preserved Tibial Insertion Graft in Anterior Cruciate Ligament Reconstruction in Sports Persons.

INTRODUCTION: Bone-patellar tendon-bone (BPTB) and semitendinosus-gracilis (STG) are the commonest grafts used for ACL reconstruction. However even after having been debated for years, there is no consensus about the ideal graft. Moreover, the literature is deficient about STG graft with preserved tibial insertion (STGPI) which preserves the proprioception. Our aim is to compare the outcome of BPTB, free STG and STGPI grafts after ACL reconstruction in professional sports persons. We compared the outcome in terms of mechanical stability, functional outcome, return to sports activity and degenerative changes. MATERIAL AND METHODS: Professional sports persons aged between 16-50 years operated for ACL tear using BPTB, free STG and STGPI grafts with minimum follow-up of two years were identified from hospital records. Patients with associated knee injuries were excluded. Patients, divided in three groups according to graft used, were compared in terms of mechanical stability (arthrometric examination KT-1000 score), functional outcome (Lysholm Score), return to sports activity (Tegner score and difference in thigh circumference) and degenerative changes (KL grading). RESULTS: BPTB graft group was found to be better than free STG and STGPI graft groups in terms of KT-1000 score. There was no statistically significant difference among the groups in terms of Lysholm score, Tegner score, difference in thigh circumference and KL grading. CONCLUSION: BPTB graft is better than free STG and STGPI grafts in terms of knee stability. When compared for patient reported outcome, return to sports activity, osteoarthritic changes and graft failure there is no significant difference among the three types of grafts.

Integrated hydrochemical and ERT approach for seawater intrusion study in a coastal aquifer: a case study from Jafrabad Town, Gujarat State, India.

Hydrochemical and geophysical approach has been adopted to evaluate the seawater intrusion (SWI) in coastal aquifers of Jafrabad Town, Gujarat State, India. Electrical Resistivity Tomography (no. 9) was carried out with spread length of 160-400 m which provided penetration depth of about 23 to 76 m. Very low resistivity zone (0-3 Ω-m range) has been observed in the ERT profiles conducted in the study area. Parameters, namely, TDS, Na, and Cl, have been considered to examine the signature of SWI. The results obtained from ionic ratios, Piper plot, and Chaddha's diagram also confirm the influence of saline water within aquifer. The very low resistivity signature is correlated with the high TDS values in the nearby wells. SWI has been observed up to 9 km from the coast, and it is observed at a depth of 20-22 m in the existing limestone mines near the coast.

Comparison of Bone-Patellar Tendon-Bone Graft, Semitendinosus–Gracilis Graft and Semitendinosus–Gracilis with Preserved Tibial Insertion Graft in Anterior Cruciate Ligament Reconstruction in Sports Persons

@#Introduction: Bone-patellar tendon-bone (BPTB) and semitendinosus–gracilis (STG) are the commonest grafts used for ACL reconstruction. However even after having been debated for years, there is no consensus about the ideal graft. Moreover, the literature is deficient about STG graft with preserved tibial insertion (STGPI) which preserves the proprioception. Our aim is to compare the outcome of BPTB, free STG and STGPI grafts after ACL reconstruction in professional sports persons. We compared the outcome in terms of mechanical stability, functional outcome, return to sports activity and degenerative changes. Materials and Methods: Professional sports persons aged between 16-50 years operated for ACL tear using BPTB, free STG and STGPI grafts with minimum follow-up of two years were identified from hospital records. Patients with associated knee injuries were excluded. Patients, divided in three groups according to graft used, were compared in terms of mechanical stability (arthrometric examination KT-1000 score), functional outcome (Lysholm Score), return to sports activity (Tegner score and difference in thigh circumference) and degenerative changes (KL grading). Results: BPTB graft group was found to be better than free STG and STGPI graft groups in terms of KT-1000 score. There was no statistically significant difference among the groups in terms of Lysholm score, Tegner score, difference in thigh circumference and KL grading. Conclusion: BPTB graft is better than free STG and STGPI grafts in terms of knee stability. When compared for patient reported outcome, return to sports activity, osteoarthritic changes and graft failure there is no significant difference among the three types of grafts.

Jamun fruit (Syzgium cumini) skin extract based indicator for monitoring chicken patties quality during storage.

Natural plant pigment, anthocyanins have the capability to change its color with the change of its structure influenced by changing pH. This feature of anthocyanin has been harnessed to design a meat products quality indicator. In the present experiment anthocyanin rich Jamun fruit (Syzgium cumini) skin extract was used to develop quality indicator by immobilizing on filter paper strips with the purpose of application in chicken patties packets stored at refrigeration temperature (4 ± 1 °C). The indicator changed its color from violet to yellow due to changed pH in it when it was attached inside packet of chicken patties during storage, due to reaction with volatile basic compounds generated from meat. During storage for 21 days, various changes in quality attributes of chicken patties viz., pH, Total volatile basic nitrogen (TVBN), ammonia level, color value, sensory attributes and microbial evaluation were estimated. The pH decreased (P < 0.5) from 6.22 to 6.04. TVBN and ammonia and level increased significantly (P < 0.5) throughout storage. Redness, yellowness, hue and chroma value gradually changed during storage. Sensory scores also decreased significantly (P < 0.5). Microbial count also increased (P < 0.5) during this time. The experiment showed that, during storage, the color changing pattern of quality indicator was well correlated with the changes in quality attributes of chicken meat patties. Therefore, it is expected that the developed quality indicator can provide a convenient, non destructive, visual mean to monitor the meat products quality during refrigerated storage.

Pulmonary protective efficacy of S-2[2-aminoethylamino] ethyl phenyl sulphide (DRDE-07) and its analogues against sulfur mustard induced toxicity in mice.

Our previous study showed that percutaneous sulfur mustard (SM) exposure induced pulmonary toxicity, which was attenuated by DRDE-07 (S-2[2-aminoethylamino] ethyl phenyl sulphide) pretreatment. The present study aimed to evaluate the protective efficacy of DRDE-07 and its analogues viz., DRDE-30 (S-2(2-aminoethyl amino)ethyl propyl sulphide) and DRDE-35 (S-2(2-aminoethyl amino)ethyl butyl sulphide) against SM. Thirty minutes before percutaneous SM (0.8 LD50) exposure, female Swiss mice were orally gavaged with DRDE-07 and its analogues(0.2 LD50). Animals were sacrificed on day 3 and 7, BAL fluid (BALF) and lung tissue were collected for biochemical, histopathological studies. As results, DRDE-07 and its analogues were beneficial in reducing the number of BALF inflammatory cells, protein level, lactate dehydrogenase (LDH) activity, myeloperoxidase (MPO) and ß-glucuronidase activity, while content of BALF and lung reduced glutathione level (GSH) were significantly protected. The pretreatment of DRDE-07 and its analogues inhibited the recruitment of inflammatory cells into the lung. The beneficial effects of DRDE-07 and its analogues were attributed to their antioxidant and anti-inflammatory activity. Among the analogues, DRDE-30 exhibited significant beneficial effects as compared to the other two compounds. These analogues may be considered as prototype candidate molecules as there is no effective antidote for SM toxicity.

Predictors for Anterior Cruciate Ligament (ACL) Re-injury after Successful Primary ACL Reconstruction (ACLR).

INTRODUCTION: Few authors have addressed risk factors related to an ipsilateral graft rupture and contralateral anterior cruciate ligament (ACL) injury after return to sports (RTS) following primary ACL reconstruction. MATERIAL AND METHODS: Patients with ACL re-injury to either knee after successful primary ACLR were included in Group I and those with no further re-injury were included in Group II. Variables including age, gender, side, body mass index (BMI), thigh atrophy, anterior knee laxity difference between both knees measured by KT-1000 arthrometer, mean time of return to sports (RTS), graft type, type of game, mode of injury, Tegner Activity Score, hormone levels, femoral tunnel length (FTL), posterior tibial slope (PTS) and notch width index (NWI) were studied. Binary logistic regression was used to measure the relative association. RESULTS: A total of 128 athletes were included with 64 in each group. Mean age in Group I and II were 24.90 and 26.47 years respectively. Mean follow-up of Group I and Group II were 24.5 and 20.11 months respectively. Significant correlation was present between ACL re-injury and following risk factors; PTS of >10º, KT difference of >3.0mm, thigh atrophy of >2.50cm and time to RTS <9.50 months P value <0.05). No correlation was found with age, sex, BMI, type of game, Tegner Activity Score, mode of injury, NWI, size of graft, FTL and hormone levels. CONCLUSION: Possible risk factors include PTS of ≥ 10º, KT difference of ≥ 3.0mm at 1 year follow-up, thigh atrophy of ≥ 2.50cm at 1 year follow-up and RTS <9.5 months after primary ACLR.

Outcome of uncorrected CSF leak and consequent recurrent meningitis in a patient: a case presentation and literature review.

Purpose: Post-traumatic CSF leaks are a complication in 2% of all head injuries. Majority of these patients will recover spontaneously. Whilst recent literature has predominantly centred on CSF leaks and their general investigations and management thereof, there is a paucity of information when it comes to those patients who have persistent post-traumatic CSF leaks, as well as the complication of recurrent meningitis. We present a patient with a persistent post-traumatic CSF leak who presented with recurrent bacterial meningitis thirteen times- the highest documented amount in an adult. We reviewed the literature with regards to the above as well.Material and Methods: We reviewed a vast array of journal articles on the topic of CSF leaks from the PubMed resource, and focused this review specifically on those that documented patients who had uncorrected CSF leaks and their outcomes.Results: Complications include meningitis and rhinorrhoea with brain abscesses and pneumocephalus occurring less frequently. Mortality has been documented to be 9% after 1 year. The rates of persistent CSF leaks were within the same range with an average calculated rate of 21%. Whilst meningitis was recorded and is common, it was not stipulated whether the incidences were recurrent.Conclusion: Post-traumatic persistent CSF leaks remain a therapeutic challenge and continued follow-up with early surgical intervention is highly recommended to prevent complications. One of the more serious complications of a persistent leak is meningitis. The long-term outcomes of recurrent meningitis could include cumulative focal neurological deficitis and cognitive impairment.

Excitation Density Dependent Photoluminescence Studies on Homo-Epitaxial GaN Nanowall Networks Grown by Laser Assisted Molecular Beam Epitaxy.

The optical properties of laser-assisted molecular beam epitaxy grown homo-epitaxialGaN nanowall networks (NWNs) were investigated using power dependent photoluminescence (PL) spectroscopy and compared with homo-epitaxial GaN thin film. The pore size and tip width of GaN NWN sample is ˜120-180 nm and 10-15 nm, respectively. The ultraviolet-visible spectroscopy study shows that the GaN NWNs have low optical light reflection and minimum Fabry-Perot cavity effect than GaN film. The room temperature PL spectroscopy reveals that the GaN NWNs possesses enhanced band gap of 3.51 eV with blue shift of 90 meV than the GaN film (3.42 eV). The excitation density dependent PL spectroscopy measurements reveal that the GaN NWNs nanowall and near band emission (NBE) peak position and its linewidth invariant. The intensity of NBE peak for GaN film and nanowalls varies linearly whereas NBE to defect related yellow luminescence peak intensity ratio shows a non-linear variation on the excitation density. The excitation density in PL measurements plays a key role when the sample quality compared on the basis of PL data.

Predictors for Anterior Cruciate Ligament (ACL) Re-injury after Successful Primary ACL Reconstruction (ACLR)

@#Introduction: Few authors have addressed risk factors related to an ipsilateral graft rupture and contralateral anterior cruciate ligament (ACL) injury after return to sports (RTS) following primary ACL reconstruction. Material and Methods: Patients with ACL re-injury to either knee after successful primary ACLR were included in Group I and those with no further re-injury were included in Group II. Variables including age, gender, side, body mass index (BMI), thigh atrophy, anterior knee laxity difference between both knees measured by KT-1000 arthrometer, mean time of return to sports (RTS), graft type, type of game, mode of injury, Tegner Activity Score, hormone levels, femoral tunnel length (FTL), posterior tibial slope (PTS) and notch width index (NWI) were studied. Binary logistic regression was used to measure the relative association. Results: A total of 128 athletes were included with 64 in each group. Mean age in Group I and II were 24.90 and 26.47 years respectively. Mean follow-up of Group I and Group II were 24.5 and 20.11 months respectively. Significant correlation was present between ACL re-injury and following risk factors; PTS of >10º, KT difference of >3.0mm, thigh atrophy of >2.50cm and time to RTS <9.50 months P value <0.05). No correlation was found with age, sex, BMI, type of game, Tegner Activity Score, mode of injury, NWI, size of graft, FTL and hormone levels. Conclusion: Possible risk factors include PTS of ≥ 10º, KT difference of ≥ 3.0mm at 1 year follow-up, thigh atrophy of ≥ 2.50cm at 1 year follow-up and RTS <9.5 months after primary ACLR.

Neutrophil mediated inflammatory lung damage following single Sub lethal inhalation exposure to plant protein toxin abrin in mice.

Abrin, a highly toxic plant protein found in the seeds of Abrus precatorius plant. To date, there is no antidote against abrin intoxication. Abrin is toxic by all routes of exposure, but inhalation exposure is the most toxic of all routes. Present study was conducted to evaluate the acute inhalation toxicity of aerosolized abrin in BALB/c mice. Animals were exposed to 0.2 and 0.8LC50 doses of aerosolized abrin and evaluated at 1 and 3 day post toxin exposure. Bronchoalveolar fluid from lungs was used for evaluation of markers for lung injury. Abrin inhalation exposure caused rise in LDH activity, protein content, increase in ß-glucuronidase and myeloperoxidase activity. Increase in CRP activity, MMP-9 expression and recruitment of CD11b + inflammatory cells in lungs was also observed which was associated with severe inflammation and lung damage. Histopathological findings support the lung damage after abrin exposure. Our results indicate lung injury after single aerosol inhalation exposure, associated with excessive inflammation, oxidative stress, pulmonary edema followed by lung damage. These results could supplement treatment strategies and planning for therapeutic approaches against aerosolized abrin inhalation exposure.

In Situ Fixation of Symptomatic Fibrous Non-union Hoffa Fracture: A Case Report.

Femoral condyle fracture in coronal plane, also known as Hoffa fracture, is a rare fracture. Non-union of Hoffa fracture is even rarer. We present a case of fibrous nonunion of a Hoffa fracture in which the fractured fragment, though not freely movable, led to painful walking. Since the fragment was un-displaced and non-movable we fixed the fractured fragment in situ. Patient regained full range of motion of the knee and was asymptomatic on follow-up.

Major pathologic response on biopsy (MPRbx) in patients with advanced melanoma treated with anti-PD-1: evidence for an early, on-therapy biomarker of response.

BACKGROUND: With increasing anti-PD-1 therapy use in patients with melanoma and other tumor types, there is interest in developing early on-treatment biomarkers that correlate with long-term patient outcome. An understanding of the pathologic features of immune-mediated tumor regression is key in this endeavor. MATERIALS AND METHODS: Histologic features of immune-related pathologic response (irPR) following anti-PD-1 therapy were identified on hematoxylin and eosin (H&E)-stained slides in a discovery cohort of pre- and on-treatment specimens from n = 16 patients with advanced melanoma. These features were used to generate an irPR score [from 0 = no irPR features to 3 = major pathologic response on biopsy (MPRbx, ≤10% residual viable tumor)]. This scoring system was then tested for an association with objective response by RECIST1.1 and overall survival in a prospectively collected validation cohort of pre- and on-treatment biopsies (n = 51 on-treatment at 4-week timepoint) from melanoma patients enrolled on the nivolumab monotherapy arm of CA209-038 (NCT01621490). RESULTS: Specimens from responders in the discovery cohort had features of immune-activation (moderate-high TIL densities, plasma cells) and wound-healing/tissue repair (neovascularization, proliferative fibrosis) compared to nonresponders, (P ≤ 0.021, for each feature). In the validation cohort, increasing irPR score associated with objective response (P = 0.009) and MPRbx associated with increased overall survival (n = 51; HR 0.13; 95%CI, 0.054-0.31, P = 0.015). Neither tumoral necrosis nor pretreatment histologic features were associated with response. Eight of 16 (50%) of patients with stable disease showed irPR features, two of which were MPRbx, indicating a disconnect between pathologic and radiographic features at the 4-week on-therapy timepoint for some patients. CONCLUSIONS: Features of immune-mediated tumor regression on routine H&E-stained biopsy slides from patients with advanced melanoma correlate with objective response to anti-PD-1 and overall survival. An on-therapy biopsy may be particularly clinically useful for informing treatment decisions in patients with radiographic stable disease. This approach is inexpensive, straightforward, and widely available.

In Situ Fixation of Symptomatic Fibrous Non-union Hoffa Fracture: A Case Report

@#Femoral condyle fracture in coronal plane, also known as Hoffa fracture, is a rare fracture. Non-union of Hoffa fracture is even rarer. We present a case of fibrous nonunion of a Hoffa fracture in which the fractured fragment, though not freely movable, led to painful walking. Since the fragment was un-displaced and non-movable we fixed the fractured fragment in situ. Patient regained full range of motion of the knee and was asymptomatic on follow-up.