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.

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.

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.

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.

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.

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.

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.

Impact of pain and functional impairment in US adults with haemophilia: Patient-reported outcomes and musculoskeletal evaluation in the pain, functional impairment and quality of life (P-FiQ) study.

INTRODUCTION: Standardized and disease-specific patient-reported outcome (PRO) instruments assessing pain, functional impairment and health-related quality of life (HRQoL) in people with haemophilia (PWH) have been used in studies, but infrequently in comprehensive care settings for individual assessment or treatment planning. AIM: To assess the impact of pain and functional impairment on HRQoL in PWH. METHODS: P-FiQ enrolled 381 adult PWH with a history of joint pain/bleeding and included 5 PROs and a clinical joint evaluation (Hemophilia Joint Health Score v2.1 [HJHS]). RESULTS: Median age was 34 years; 49.9% reported a history of joint procedure or surgery. On EQ-5D-5L, most reported problems with mobility (61.4%), usual activities (53.2%) and pain/discomfort (76.1%). On Brief Pain Inventory v2 Short Form, median worst pain (range 0-10) was 6, least pain 1, average pain 3 and current pain 2. Ankles were most frequently reported as the most painful joints (37.4%), followed by knees (23.7%) and elbows (18.9%). On International Physical Activity Questionnaire, 51% reported no activity in the prior week. On SF-36v2 health survey, median subscores were worse for 4 physical health domains vs 4 mental health domains. Among Hemophilia Activities List domains (range 0 [worst]-100 [best]), functions of the legs (median, 66.7) and lying/sitting/kneeling/standing (median, 67.5) were most impacted and self-care least impacted (median, 100.0). On HJHS, ankle scores (median, 6.0; range, 0-40) were worse than elbow/knee scores (median, 4.0/4.0). Results were consistent across PROs/HJHS. CONCLUSION: Data demonstrate challenges of predominantly ankle/knee pain and lower extremity functional impairment in US adult PWH, affecting HRQoL across PROs/HJHS.

Comparative evaluation of antidotal efficacy of 2-PAM and HNK-102 oximes during inhalation of sarin vapor in Swiss albino mice.

Efficacy of two oximes treatments evaluated during inhalation of sarin vapor (LCt50, 755.9 mg/min/m3) in simulated real scenario in vivo. Majority of mice either became moribund or died within 1-2 min during exposure to multifold-lethal concentrations of sarin vapor. Protection indices were determined by exposing to sarin vapor in two sessions, 1 min exposure followed by treatments with or without HNK-102 (56.56 mg/kg, im) or 2-PAM (30 mg/kg, im) and atropine (10 mg/kg, ip), and again exposed for remaining 14 min. Protection offered by HNK-102 was found to be four folds higher compared to 2-PAM in the same toxic environment. Secondly, sub-lethal concentration of sarin vapor (0.8 × LCt50 or 605 mg/min/m3), 24 h post investigations revealed that the oximes could not reactivate brain and serum acetylcholinesterase (AChE) activity. The treatments prevented increase in protein concentration (p < .05) and macrophages infiltration compared to sarin alone group in broncho-alveolar lavage fluid. Lung histopathology showed intense peribronchial infiltration and edema with desquamating epithelial lining and mild to moderate alveolar septal infiltration in sarin and atropine groups, respectively. Noticeable peeling-off observed in epithelial lining and sporadic mild infiltration of epithelial cells at bronchiolar region in 2-PAM and HNK-102 groups, respectively. The oximes failed to reactivate AChE activity; however, the mice survived up to 6.0 × LCt50, proved involvement of non-AChE targets in sarin toxicity. Atropine alone treatment was found to be either ineffective or increased the toxicity. HNK-102, exhibited better survivability with lung protection, can be considered as a better replacement for 2-PAM to treat sarin inhalation induced poisoning.

Radionuclide synovectomy/synoviorthesis (RS) in patients with bleeding disorders: A review of patient and procedure demographics and functional outcomes in the ATHNdataset.

INTRODUCTION: Radionuclide synovectomy/synoviorthesis (RS) to manage proliferative synovitis in persons with bleeding disorders has been utilized for decades; however, aggregate US results are limited. AIM: To determine the prevalence of RS utilization, patient and procedure related demographics and functional outcomes in United States haemophilia treatment centres (HTCs). The ATHNdataset includes US patients with bleeding disorders who have authorized the sharing of their demographic and clinical information for research. METHODS: We performed a multi-institutional, observational cohort study utilizing this dataset through 2010. Cases treated with RS procedure were compared to controls within the dataset. Standard template for data collection included patient and procedure related demographics as well as functional outcomes including range of motion (ROM) of the affected joint. Normative age- and sex-matched control ROM was obtained from published data. RESULTS: In the ATHNdataset there were 19 539 control-patients and 196 case-patients treated with RS. Patients with severe haemophilia were more likely to have had RS compared to those with mild/moderate haemophilia, although the proportion of RS performed was similar between severe HA and HB. Inhibitory antibodies, HIV and hepatitis C infection were significantly more common in cases. There were 362 RS procedures captured with 94 cases having >1 RS procedures. CONCLUSIONS: Right-sided joint procedures were more prevalent than left-sided procedures. Overall, case-patients had worse joint ROM compared to control-patients and published normative values. Geographically, there was regional variation in RS utilization, as the Southeast region had the largest percent of case-patients.

Study of thermoluminescence (TL) and optically stimulated luminescence (OSL) from α-keratin protein found in human hairs and nails: potential use in radiation dosimetry.

The thermoluminescence (TL) and optically stimulated luminescence (OSL) properties of human nails and hairs containing α-keratin proteins have been investigated. For the present studies, black hairs and finger nails were selectively collected from individuals with ages between 25 and 35 years. The collected hairs/nails were cut to a size of < 1 mm and cleaned with distilled water to remove dirt and other potential physical sources of contamination. All samples were optically beached with 470 nm of LED light at 60 mW/cm(2) intensity and irradiated by a (60)Co γ source. The hair and nail samples showed overlapping multiple TL glow peaks in the temperature range from 70 to 210 ° C. Continuous wave (CW)-OSL measurements of hair samples at a wavelength of 470 nm showed the presence of two distinct OSL components with photoionization cross section (PIC) values of about 1.65 × 10(-18) cm(2) and about 3.48 × 10(-19) cm(2), while measurements of nail samples showed PIC values of about 6.98 × 10(-18) cm(2) and about 8.7 × 10(-19) cm(2), respectively. This difference in PIC values for hair and nail samples from the same individual is attributed to different arrangement of α-keratin protein concentrations in the samples. The OSL sensitivity was found to vary ± 5 times among nail and hair samples from different individuals, with significant fading (60% in 11 h) at room temperature. The remaining signal (after fading) can be useful for dose estimation when a highly sensitive OSL reader is used. In the absorbed dose range of 100 mGy-100 Gy, both the TL and OSL signals of hair and nail samples showed linear dose dependence. The results obtained in the present study suggest that OSL using hair and nail samples may provide a supplementary method of dose estimation in radiological and nuclear emergencies.

Standard Model Prediction for Direct CP Violation in K→ππ Decay.

We report the first lattice QCD calculation of the complex kaon decay amplitude A_{0} with physical kinematics, using a 32³×64 lattice volume and a single lattice spacing a, with 1/a=1.3784(68) GeV. We find Re(A_{0})=4.66(1.00)(1.26)×10(-7) GeV and Im(A_{0})=-1.90(1.23)(1.08)×10(-11) GeV, where the first error is statistical and the second systematic. The first value is in approximate agreement with the experimental result: Re(A_{0})=3.3201(18)×10(-7) GeV, while the second can be used to compute the direct CP-violating ratio Re(ϵ^{'}/ϵ)=1.38(5.15)(4.59)×10^{-4}, which is 2.1σ below the experimental value 16.6(2.3)×10(-4). The real part of A_{0} is CP conserving and serves as a test of our method while the result for Re(ϵ^{'}/ϵ) provides a new test of the standard model theory of CP violation, one which can be made more accurate with increasing computer capability.

Presentation and management of acute coronary syndromes among adult persons with haemophilia: results of an international, retrospective, 10-year survey.

Sparse data are available on presentation and management of acute coronary syndromes (ACS), including unstable angina and non-ST- and ST-elevation myocardial infarction, among persons with haemophilia (PWH). The aim of this study was to determine demographics, bleeding disorder characteristics, cardiovascular risk factors (CRFs), interventions, haemostatic protocol, revascularization outcomes and complications among PWH with ACS. Members of an international consortium comprising >2000 adult PWH retrospectively completed case report forms for episodes of ACS in a >10-year follow-up period (2003-2013). Twenty ACS episodes occurred among 19 patients [rate, 0.8% (95% CI 0.4, 1.2)]. Seven patients (37%) were aged <50 years; 10 (53%) had ≥3 CRFs. In 5/20 episodes (25%), the initial ACS management protocol was altered because of the bleeding disorder. None of the eight patients with severe haemophilia underwent coronary artery bypass grafting (CABG), compared with 54.5% of patients with non-severe disease (P = 0.02). Revascularization with percutaneous coronary intervention (PCI) or CABG was rated successful in 13/13 cases, with no excessive bleeding during initial management. During chronic exposure to antiplatelet agents, secondary haemophilia prophylaxis was more prevalent in patients with severe haemophilia compared with non-severe haemophilia (85.7% vs. 30%, P = 0.05). No ACS-related deaths occurred during initial management, but one patient with severe haemophilia A died of undetermined cause 36 months after the ACS event while on aspirin therapy. ACS occurs even among relatively younger PWH, typically in association with multiple CRFs. Revascularization with PCI/CABG is feasible, and antiplatelet agents plus secondary prophylaxis appears to be well tolerated in selected PWH with ACS.

Medical students and interns' knowledge about and attitude towards homosexuality.

BACKGROUND AND RATIONALE: Medical professionals' attitude towards homosexuals affects health care offered to such patients with a different sexual orientation. There is absence of literature that explores the attitudes of Indian medical students or physicians towards homosexuality. AIM: This study aimed to evaluate Indian medical students and interns' knowledge about homosexuality and attitude towards homosexuals. MATERIALS AND METHODS: After IEC approval and written informed consent, a cross-sectional study was conducted on a purposive sample of undergraduate medical students and interns studying in one Indian medical college. The response rate was 80.5%. Only completely and validly filled responses (N = 244) were analyzed. The participants filled the Sex Education and Knowledge about Homosexuality Questionnaire (SEKHQ) and the Attitudes towards Homosexuals Questionnaire (AHQ). SEKHQ consisted of 32 statements with response chosen from 'true', 'false', or 'don't know'. AHQ consisted of 20 statements scorable on a 5-point Likert scale. Multiple linear regression was used to find the predictors of knowledge and attitude. RESULTS: Medical students and interns had inadequate knowledge about homosexuality, although they endorsed a neutral stance insofar as their attitude towards homosexuals is concerned. Females had more positive attitudes towards homosexuals. Knowledge emerged as the most significant predictor of attitude; those having higher knowledge had more positive attitudes. CONCLUSION: Enhancing knowledge of medical students by incorporation of homosexuality related health issues in the curriculum could help reduce prejudice towards the sexual minority and thus impact their future clinical practice.

K(L) - K(S) mass difference from lattice QCD.

We report on the first complete calculation of the K_{L}-K_{S} mass difference, ΔM_{K}, using lattice QCD. The calculation is performed on a 2+1 flavor, domain wall fermion ensemble with a 330 MeV pion mass and a 575 MeV kaon mass. We use a quenched charm quark with a 949 MeV mass to implement Glashow-Iliopoulos-Maiani cancellation. For these heavier-than-physical particle masses, we obtain ΔM_{K}=3.19(41)(96)×10^{-12} MeV, quite similar to the experimental value. Here the first error is statistical, and the second is an estimate of the systematic discretization error. An interesting aspect of this calculation is the importance of the disconnected diagrams, a dramatic failure of the Okubo-Zweig-Iizuka rule.

Neuropathic features of joint pain: a community-based study.

OBJECTIVE: Quantitative sensory testing (QST) and questionnaire-based assessments have been used to demonstrate features of neuropathic pain in subjects with musculoskeletal pain. However, their direct relationship has not been investigated in the community. The purpose of this study was to conduct an observational study to describe the characteristics of joint pain and to examine the relationship between QST measures and the PainDETECT Questionnaire (PD-Q). METHODS: Warm detection, heat pain, and mechanical pain thresholds as well as mechanical pain sensitivity over the sternum were determined and the PD-Q scores were calculated in a cross-sectional study of 462 participants in the Chingford Study. Comparisons were made between subjects with and those without joint pain. Logistic regression modeling was used to describe the association between neuropathic pain features, as determined by the PD-Q score, and each of the QST measures individually, adjusting for age, body mass index, and use of pain-modifying medications. RESULTS: A total of 66.2% of the subjects reported recent joint pain, with a median average pain severity of 5 of 10. There was increased sensitivity to painful stimuli in the group with pain as compared to the pain-free group, and this persisted after stratification by pain-modifying medication use. While only 6.7% of subjects had possible neuropathic pain features and 1.9% likely neuropathic pain features according to the standard PD-Q thresholds, features of neuropathic pain were common and were present in >50% of those reporting pain of at least moderate severity. Heat pain thresholds and mechanical pain sensitivity were significantly associated with features of neuropathic pain identified using the PD-Q, with an odds ratio (OR) of 0.88 (95% confidence interval [95% CI] 0.79-0.97; P = 0.011) and an OR of 1.24 (95% CI 1.04-1.48; P = 0.018), respectively. CONCLUSION: QST measures and the PD-Q identified features of neuropathic pain in subjects in this community-based study, with significant overlap between the findings of the two techniques.

Emerging understanding of the ΔI=1/2 rule from lattice QCD.

There has been much speculation as to the origin of the ΔI=1/2 rule (ReA0/ReA2≃22.5). We find that the two dominant contributions to the ΔI=3/2, K→ππ correlation functions have opposite signs, leading to a significant cancelation. This partial cancelation occurs in our computation of ReA2 with physical quark masses and kinematics (where we reproduce the experimental value of A2) and also for heavier pions at threshold. For ReA0, although we do not have results at physical kinematics, we do have results for pions at zero momentum with mπ≃420 MeV [ReA0/ReA2=9.1(2.1)] and mπ≃330 MeV [ReA0/ReA2=12.0(1.7)]. The contributions which partially cancel in ReA2 are also the largest ones in ReA0, but now they have the same sign and so enhance this amplitude. The emerging explanation of the ΔI=1/2 rule is a combination of the perturbative running to scales of O(2 GeV), a relative suppression of ReA2 through the cancelation of the two dominant contributions, and the corresponding enhancement of ReA0. QCD and electroweak penguin operators make only very small contributions at such scales.

Prevalence of reported knee pain over twelve years in a community-based cohort.

OBJECTIVE: To describe the temporal patterns of knee pain in a community-based cohort over 12 years. METHODS: Data on self-reported knee pain at 4 time points over 12 years were analyzed in participants from the Chingford Women's Study of osteoarthritis (OA) and osteoporosis. Pain status was defined as any pain in the preceding month and pain on most days in the preceding month. This status was used to classify participants according to pain patterns of asymptomatic, persistent, incident, or intermittent pain. Multinomial logistic regression was used to identify baseline predictors for each pain pattern. RESULTS: Among the 489 women with complete followup data, the median age at baseline was 52 years (interquartile range [IQR] 48-58 years), the median body mass index (BMI) was 24.39 kg/m(2) (IQR 22.46-27.20), and 11.7% of the women had a Kellgren/Lawrence radiographic OA severity grade of ≥2 in at least one knee. Among subjects reporting any pain in the preceding month versus those reporting pain on most days in the preceding month, 9% versus 2% had persistent pain, 24% versus 16% had incident pain, and 29% versus 18% had intermittent pain. A higher BMI was predictive of persistent pain (odds ratio [OR] 1.14, 95% confidence interval [95% CI] 1.04-1.25) and incident pain (OR 1.10, 95% CI 1.02-1.18). The presence of radiographic knee OA was predictive of persistent pain (OR 3.70, 95% CI 1.34-10.28; P = 0.012), and reported knee injury was predictive of both persistent pain (OR 4.13, 95% CI 1.34-12.66; P = 0.013) and intermittent pain (OR 4.25, 95% CI 1.81-9.98; P = 0.001). CONCLUSION: Significant variability in the temporal fluctuation of self-reported knee pain was seen in this community-based prospective study over a period of 12 years, with few women consistently reporting knee pain at each time point. Distinct baseline predictors for each pain pattern were identified and may explain the observed heterogeneity of self-reported knee pain when pain status is measured at only one time point.

The natural history of radiographic knee osteoarthritis: a fourteen-year population-based cohort study.

OBJECTIVE: To establish the natural history of radiographic knee osteoarthritis (OA) over 14 years in a community-based cohort. METHODS: We examined women from the Chingford Women's Study, a community-based cohort followed up for more than 14 years. We selected women for whom bilateral radiographs of the knees (with the legs in full extension) were obtained at approximately 5-year intervals. Radiographs were scored for OA in a blinded manner, using Kellgren/Lawrence (K/L) grades. Descriptive statistics and odds ratios (ORs) were used to compare the incidence, worsening, and progression of radiographic knee OA. RESULTS: A complete radiography series was available for 561 of the original 1,003 subjects enrolled in the study. The median age of these subjects at baseline was 53 years (interquartile range 48-58 years). At baseline, 13.7% of the subjects had radiographic knee OA (K/L grade≥2) in at least one knee, and the prevalence increased to 47.8% by year 15. The annual cumulative incidence of radiographic knee OA was 2.3% between baseline and year 15. The annual rates of disease progression and worsening between baseline and year 15 were 2.8% and 3.0%, respectively. Subjects with a K/L grade of 1 at baseline were more likely to experience worsening by year 15 compared with subjects with a baseline grade of 0 (OR 4.5, 95% confidence interval 2.7-7.4). CONCLUSION: This is the longest natural history study of radiographic knee OA to date. The results showed relatively low rates for the incidence and progression of radiographic knee OA; more than half of all subjects had no radiographic evidence of knee OA over a 15-year period of time. Subjects with a baseline K/L grade of 1 were more likely than subjects with other baseline K/L grades to experience worsening of knee OA.