Near-Infrared Spectroscopy to Monitor Nutritional Status of Neonates: A Review.

The World Health Organization reported that half or more of all under five deaths were caused by undernutrition in developing countries, with the majority of these deaths occurring in the first week of life. Even if the undernourished neonates manage to survive, they are exposed to long-term health impacts, including obesity, cardiovascular disease, and hypertension. Along with those health-impacts they can be exposed to risks related to detrimental early development, such as physical impairment, stunting, brain dysfunction, and reduced cognitive development. Body fat percentage has been recognized to be closely associated with undernutrition in neonates. In this article, the potential of near infrared spectroscopy (NIRS), along with previous methods to measure body fat in neonates, is reviewed and discussed.

Subthalamic Nucleus Neurons Differentially Encode Early and Late Aspects of Speech Production.

Basal ganglia-thalamocortical loops mediate all motor behavior, yet little detail is known about the role of basal ganglia nuclei in speech production. Using intracranial recording during deep brain stimulation surgery in humans with Parkinson's disease, we tested the hypothesis that the firing rate of subthalamic nucleus neurons is modulated in sync with motor execution aspects of speech. Nearly half of 79 unit recordings exhibited firing-rate modulation during a syllable reading task across 12 subjects (male and female). Trial-to-trial timing of changes in subthalamic neuronal activity, relative to cue onset versus production onset, revealed that locking to cue presentation was associated more with units that decreased firing rate, whereas locking to speech onset was associated more with units that increased firing rate. These unique data indicate that subthalamic activity is dynamic during the production of speech, reflecting temporally-dependent inhibition and excitation of separate populations of subthalamic neurons.SIGNIFICANCE STATEMENT The basal ganglia are widely assumed to participate in speech production, yet no prior studies have reported detailed examination of speech-related activity in basal ganglia nuclei. Using microelectrode recordings from the subthalamic nucleus during a single-syllable reading task, in awake humans undergoing deep brain stimulation implantation surgery, we show that the firing rate of subthalamic nucleus neurons is modulated in response to motor execution aspects of speech. These results are the first to establish a role for subthalamic nucleus neurons in encoding of aspects of speech production, and they lay the groundwork for launching a modern subfield to explore basal ganglia function in human speech.

Genetic mapping of quantitative trait loci for tuber-cadmium and zinc concentration in potato reveals associations with maturity and both overlapping and independent components of genetic control.

KEY MESSAGE: Cd is a toxic metal, whilst Zn is an essential for plant and human health. Both can accumulate in potato tubers. We examine the genetic control of this process. The aim of this study was to map quantitative trait loci (QTLs) influencing tuber concentrations of cadmium (Cd) and zinc (Zn). We developed a segregating population comprising 188 F1 progeny derived from crossing two tetraploid cultivars exhibiting divergent tuber-Cd-accumulation phenotypes. These progeny were genotyped using the SolCap 8303 SNP array, and evaluated for Cd, Zn, and maturity-related traits. Linkage and QTL mapping were performed using TetraploidSNPMap software, which incorporates all allele dosage information. The final genetic map comprised 3755 SNP markers with average marker density of 2.94 per cM. Tuber-Cd and Zn concentrations were measured in the segregating population over 2 years. QTL mapping identified four loci for tuber-Cd concentration on chromosomes 3, 5, 6, and 7, which explained genetic variance ranging from 5 to 33%, and five loci for tuber-Zn concentration on chromosome 1, 3, 5, and, 6 explaining from 5 to 38% of genetic variance. Among the QTL identified for tuber-Cd concentration, three loci coincided with tuber-Zn concentration. The largest effect QTL for both tuber-Cd and Zn concentration coincided with the maturity locus on chromosome 5 where earliness was associated with increased tuber concentration of both metals. Coincident minor-effect QTL for Cd and Zn sharing the same direction of effect was also found on chromosomes 3 and 6, and these were unrelated to maturity The results indicate partially overlapping genetic control of tuber-Cd and Zn concentration in the cross, involving both maturity-related and non-maturity-related mechanisms.

Association of Medication Intensity and Stages of Airflow Limitation With the Risk of Hospitalization or Death in Patients With Heart Failure and Chronic Obstructive Pulmonary Disease.

Importance: In heart failure (HF), chronic obstructive pulmonary disease (COPD) increases the risk of poor outcomes, but the effect of COPD severity is unknown. This information is important for early intervention tailored to the highest-risk groups. Objectives: To determine the associations between COPD medication intensity or stage of airflow limitation and the risk of hospitalization or death in patients with HF. Design, Setting, and Participants: This UK population-based, nested case-control study with risk-set sampling used the Clinical Practice Research Datalink linked to Hospital Episode Statistics between January 1, 2002, to January 1, 2014. Participants included patients aged 40 years and older with a new diagnosis of HF in their family practice clinical record. Data analysis was conducted from 2017 to 2018. Exposures: In patients with HF, those with COPD were compared with those without it. International COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD]) guidelines were used to stratify patients with COPD by 7 medication intensity levels and 4 airflow limitation severity stages using automatically recorded prescriptions and routinely requested forced expiratory volume in 1 second (FEV1) data. Main Outcomes and Measures: First all-cause admission or all-cause death. Results: There were 50 114 patients with new HF (median age, 79 years [interquartile range, 71-85 years]; 46% women) during the study period. In patients with HF, COPD (18 478 [13.8%]) was significantly associated with increased mortality (adjusted odds ratio [AOR], 1.31; 95% CI, 1.26-1.36) and hospitalization (AOR, 1.33; 95% CI, 1.26-1.39). The 3 most severe medication intensity levels showed significantly increasing mortality associations from full inhaler therapy (AOR, 1.17; 95% CI, 1.06-1.29) to oral corticosteroids (AOR, 1.69; 95% CI, 1.57-1.81) to oxygen therapy (AOR, 2.82; 95% CI, 2.42-3.28). The respective estimates for hospitalization were AORs of 1.17 (95% CI, 1.03-1.33), 1.75 (95% CI, 1.59-1.92), and 2.84 (95% CI, 1.22-3.63). Availability of spirometry data was limited but showed that increasing airflow limitation was associated with increased risk of mortality, with the following AORs: FEV1 80% or more, 1.63 (95% CI, 1.42-1.87); FEV1 50% to 79%, 1.69 (95% CI, 1.56-1.83); FEV1 30% to 49%, 2.21 (95% CI, 2.01-2.42); FEV1 less than 30%, 2.93 (95% CI, 2.49-3.43). The strength of associations between FEV1 and hospitalization risk were similar among stages ranging from FEV1 80% or more (AOR, 1.48; 95% CI, 1.31-1.68) to FEV1 less than 30% (AOR, 1.73; 95% CI, 1.40-2.12). Conclusions and Relevance: In the UK HF community setting, increasing COPD severity was associated with increasing risk of mortality and hospitalization. Prescribed COPD medication intensity and airflow limitation provide the basis for targeting high-risk groups.

Association Between Type 2 Diabetes and All-Cause Hospitalization and Mortality in the UK General Heart Failure Population: Stratification by Diabetic Glycemic Control and Medication Intensification.

OBJECTIVES: This study sought to investigate in the general heart failure (HF) population, whether the associations between type 2 diabetes (T2D) and risk of hospitalization and death, are modified by changing glycemic or drug treatment intensity. BACKGROUND: In the general HF population, T2D confers a higher risk of poor outcomes, but whether this risk is modified by the diabetes status is unknown. METHODS: A nested case-control study in an incident HF database cohort (2002 to 2014) compared patients with T2D with those without for risk of all-cause first hospitalization and death. T2D was stratified by categories of glycosylated hemoglobin (HbA1c) or drug treatments measured 6 months before hospitalization and 1 year before death and compared with the HF group without T2D. RESULTS: In HF, T2D was associated with risk of first hospitalization (adjusted odds ratio [aOR]: 1.29; 95% confidence interval [CI]: 1.24 to 1.34) and mortality (aOR: 1.24; 95% CI: 1.29 to 1.40). Stratification of T2D by HbA1c levels, compared with the reference HF group without T2D, showed U-shaped associations with both outcomes. Highest risk categories were HbA1c >9.5% (hospitalization, aOR: 1.75; 95% CI: 1.52 to 2.02; mortality, aOR: 1.30; 95% CI: 1.24 to 1.47) and <5.5% (hospitalization, aOR: 1.42; 95% CI: 1.12 to 1.80; mortality, aOR: 1.29; 95% CI: 1.10 to 1.51, respectively). T2D group with change in HbA1c of >1% decrease was associated with hospitalization (aOR: 1.33; 95% CI: 1.18 to 1.49) and mortality (aOR: 1.36; 95% CI: 1.24 to 1.48). T2D drug group associations with hospitalization were no medication (aOR: 1.12; 95% CI: 1.04 to 1.19), oral antihyperglycemic only (aOR: 1.34; 95% CI: 1.27 to 1.41), oral antihyperglycemic+insulin (aOR: 1.36; 95% CI: 1.21 to 1.52), and insulin only (aOR: 1.61; 95% CI: 1.43 to 1.81); and with mortality for the same drug groups were 1.31 (95% CI: 1.23 to 1.39), 1.16 (95% CI: 1.11 to 1.22), 1.19 (95% CI: 1.06 to 1.34), and 1.43 (95% CI: 1.31 to 1.57), respectively. The T2D group with reduced drug treatments were associated with hospitalization (aOR: 2.13; 95% CI: 1.68 to 2.69) and mortality (aOR: 2.09; 95% CI: 1.81 to 2.41). CONCLUSIONS: In the general HF population, T2D stratified by glycemic control and drug treatments showed differential risk associations. Routine measures of dynamic diabetes status provide important prognostic indication of poor outcomes in HF.

Cadmium uptake and partitioning in potato (Solanum tuberosum L.) cultivars with different tuber-Cd concentration.

Potatoes grown in soil with high Cd concentrations can accumulate high levels of Cd in the tubers. Although there is significant environmental variation involved in the trait of crop uptake of Cd, there are also distinctive cultivar differences. In order to understand this differential Cd accumulation mechanism, two potato cultivars were chosen that accumulate high and low levels of Cd in tubers. The patterns of Cd concentration, Cd content and dry weight accumulation of the two cultivars were examined at different stages of plant growth. The data suggest that differences in total Cd uptake and in Cd partitioning among organs are the mechanisms governing differential Cd-tuber accumulation in the two cultivars. The low tuber-Cd accumulator exhibited lower root-to-shoot and shoot-to-tuber translocation driven by higher root and shoot biomass that retained more Cd in roots and shoots, respectively, reducing its movement to the tubers. Higher remobilization and more efficient tuber loading was observed in the high tuber-Cd accumulator, indicating that remobilization of Cd from leaves to tubers was a major factor, not only in tuber-Cd loading, but also in the establishment of differential tuber-Cd levels. Regardless of cultivar differences, the concentration of Cd in the tuber was very low compared to that in other organs suggesting that, despite its high phloem mobility, Cd tends to be sequestered in the shoots.

A preliminary study to estimate contact rates between free-roaming domestic dogs using novel miniature cameras.

Information on contacts between individuals within a population is crucial to inform disease control strategies, via parameterisation of disease spread models. In this study we investigated the use of dog-borne video cameras-in conjunction with global positioning systems (GPS) loggers-to both characterise dog-to-dog contacts and to estimate contact rates. We customized miniaturised video cameras, enclosed within 3D-printed plastic cases, and attached these to nylon dog collars. Using two 3400 mAh NCR lithium Li-ion batteries, cameras could record a maximum of 22 hr of continuous video footage. Together with a GPS logger, collars were attached to six free roaming domestic dogs (FRDDs) in two remote Indigenous communities in northern Australia. We recorded a total of 97 hr of video footage, ranging from 4.5 to 22 hr (mean 19.1) per dog, and observed a wide range of social behaviours. The majority (69%) of all observed interactions between community dogs involved direct physical contact. Direct contact behaviours included sniffing, licking, mouthing and play fighting. No contacts appeared to be aggressive, however multiple teeth baring incidents were observed during play fights. We identified a total of 153 contacts-equating to 8 to 147 contacts per dog per 24 hr-from the videos of the five dogs with camera data that could be analysed. These contacts were attributed to 42 unique dogs (range 1 to 19 per video) which could be identified (based on colour patterns and markings). Most dog activity was observed in urban (houses and roads) environments, but contacts were more common in bushland and beach environments. A variety of foraging behaviours were observed, included scavenging through rubbish and rolling on dead animal carcasses. Identified food consumed included chicken, raw bones, animal carcasses, rubbish, grass and cheese. For characterising contacts between FRDD, several benefits of analysing videos compared to GPS fixes alone were identified in this study, including visualisation of the nature of the contact between two dogs; and inclusion of a greater number of dogs in the study (which do not need to be wearing video or GPS collars). Some limitations identified included visualisation of contacts only during daylight hours; the camera lens being obscured on occasion by the dog's mandible or the dog resting on the camera; an insufficiently wide viewing angle (36°); battery life and robustness of the deployments; high costs of the deployment; and analysis of large volumes of often unsteady video footage. This study demonstrates that dog-borne video cameras, are a feasible technology for estimating and characterising contacts between FRDDs. Modifying camera specifications and developing new analytical methods will improve applicability of this technology for monitoring FRDD populations, providing insights into dog-to-dog contacts and therefore how disease might spread within these populations.

Statin, testosterone and phosphodiesterase 5-inhibitor treatments and age related mortality in diabetes.

AIM: To determine how statins, testosterone (T) replacement therapy (TRT) and phosphodiesterase 5-inhibitors (PDE5I) influence age related mortality in diabetic men. METHODS: We studied 857 diabetic men screened for the BLAST study, stratifying them (mean follow-up = 3.8 years) into: (1) Normal T levels/untreated (total T > 12 nmol/L and free T > 0.25 nmol/L), Low T/untreated and Low T/treated; (2) PDE5I/untreated and PDE5I/treated; and (3) statin/untreated and statin/treated groups. The relationship between age and mortality, alone and with T/TRT, statin and PDE5I treatment was studied using logistic regression. Mortality probability and 95%CI were calculated from the above models for each individual. RESULTS: Age was associated with mortality (logistic regression, OR = 1.10, 95%CI: 1.08-1.13, P < 0.001). With all factors included, age (OR = 1.08, 95%CI: 1.06-1.11, P < 0.001), Low T/treated (OR = 0.38, 95%CI: 0.15-0.92, P = 0.033), PDE5I/treated (OR = 0.17, 95%CI: 0.053-0.56, P = 0.004) and statin/treated (OR = 0.59, 95%CI: 0.36-0.97, P = 0.038) were associated with lower mortality. Age related mortality was as described by Gompertz, r2 = 0.881 when Ln (mortality) was plotted against age. The probability of mortality and 95%CI (from logistic regression) of individuals, treated/untreated with the drugs, alone and in combination was plotted against age. Overlap of 95%CI lines was evident with statins and TRT. No overlap was evident with PDE5I alone and with statins and TRT, this suggesting a change in the relationship between age and mortality. CONCLUSION: We show that statins, PDE5I and TRT reduce mortality in diabetes. PDE5I, alone and with the other treatments significantly alter age related mortality in diabetic men.

Near infrared spectroscopy for body fat sensing in neonates: quantitative analysis by GAMOS simulations.

BACKGROUND: Under-nutrition in neonates is closely linked to low body fat percentage. Undernourished neonates are exposed to immediate mortality as well as unwanted health impacts in their later life including obesity and hypertension. One potential low cost approach for obtaining direct measurements of body fat is near-infrared (NIR) interactance. The aims of this study were to model the effect of varying volume fractions of melanin and water in skin over NIR spectra, and to define sensitivity of NIR reflection on changes of thickness of subcutaneous fat. GAMOS simulations were used to develop two single fat layer models and four complete skin models over a range of skin colour (only for four skin models) and hydration within a spectrum of 800-1100 nm. The thickness of the subcutaneous fat was set from 1 to 15 mm in 1 mm intervals in each model. RESULTS: Varying volume fractions of water in skin resulted minimal changes of NIR intensity at ranges of wavelengths from 890 to 940 nm and from 1010 to 1100 nm. Variation of the melanin volume in skin meanwhile was found to strongly influence the NIR intensity and sensitivity. The NIR sensitivities and NIR intensity over thickness of fat decreased from the Caucasian skin to African skin throughout the range of wavelengths. For the relationship between the NIR reflection and the thickness of subcutaneous fat, logarithmic relationship was obtained. CONCLUSIONS: The minimal changes of NIR intensity values at wavelengths within the ranges from 890 to 940 nm and from 1010 to 1100 nm to variation of volume fractions of water suggests that wavelengths within those two ranges are considered for use in measurement of body fat to solve the variation of hydration in neonates. The stronger influence of skin colour on NIR shows that the melanin effect needs to be corrected by an independent measurement or by a modeling approach. The logarithmic response obtained with higher sensitivity at the lower range of thickness of fat suggests that implementation of NIRS may be suited for detecting under-nutrition and monitoring nutritional interventions for malnutrition in neonates in resource-constrained communities.

Length-free near infrared measurement of newborn malnutrition.

Under-nutrition in neonates can cause immediate mortality, impaired cognitive development and early onset adult disease. Body fat percentage measured using air-displacement-plethysmography has been found to better indicate under-nutrition than conventional birth weight percentiles. However, air-displacement-plethysmography equipment is expensive and non-portable, so is not suited for use in developing communities where the burden is often the greatest. We proposed a new body fat measurement technique using a length-free model with near-infrared spectroscopy measurements on a single site of the body - the thigh. To remove the need for length measurement, we developed a model with five discrete wavelengths and a sex parameter. The model was developed using air-displacement-plethysmography measurements in 52 neonates within 48 hours of birth. We identified instrumentation required in a low-cost LED-based screening device and incorporated a receptor device that can increase the amount of light collected. This near-infrared method may be suitable as a low cost screening tool for detecting body fat levels and monitoring nutritional interventions for malnutrition in neonates and young children in resource-constrained communities.

Mortality in patients with Cushing's disease more than 10 years after remission: a multicentre, multinational, retrospective cohort study.

BACKGROUND: No agreement has been reached on the long-term survival prospects for patients with Cushing's disease. We studied life expectancy in patients who had received curative treatment and whose hypercortisolism remained in remission for more than 10 years, and identified factors determining their survival. METHODS: We did a multicentre, multinational, retrospective cohort study using individual case records from specialist referral centres in the UK, Denmark, the Netherlands, and New Zealand. Inclusion criteria for participants, who had all been in studies reported previously in peer-reviewed publications, were diagnosis and treatment of Cushing's disease, being cured of hypercortisolism for a minimum of 10 years at study entry, and continuing to be cured with no relapses until the database was frozen or death. We identified the number and type of treatments used to achieve cure, and used mortality as our primary endpoint. We compared mortality rates between patients with Cushing's disease and the general population, and expressed them as standardised mortality ratios (SMRs). We analysed survival data with multivariate analysis (Cox regression) with no corrections for multiple testing. FINDINGS: The census dates on which the data were frozen ranged from Dec 31, 2009, to Dec 1, 2014. We obtained data for 320 patients with 3790 person-years of follow-up from 10 years after cure (female:male ratio of 3:1). The median patient follow-up was 11·8 years (IQR 17-26) from study entry and did not differ between countries. There were no significant differences in demographic characteristics, duration of follow-up, comorbidities, treatment number, or type of treatment between women and men, so we pooled data from both sexes for survival analysis. 51 (16%) of the cohort died during follow-up from study entry (10 years after cure). Median survival from study entry was similar for women (31 years; IQR 19-38) and men (28 years; 24-42), and about 40 years (IQR 30-48) from remission. The overall SMR for all-cause mortality was 1·61 (95% CI 1·23-2·12; p=0·0001). The SMR for circulatory disease was increased at 2·72 (1·88-3·95; p<0·0001), but deaths from cancer were not higher than expected (0·79, 0·41-1·51). Presence of diabetes, but not hypertension, was an independent risk factor for mortality (hazard ratio 2·82, 95% CI 1·29-6·17; p=0·0095). We noted a step-wise reduction in survival with increasing number of treatments. Patients cured by pituitary surgery alone had long-term survival similar to that of the general population (SMR 0·95, 95% CI 0·58-1·55) compared with those who were not (2·53, 1·82-3·53; p<0·0001). INTERPRETATION: Patients with Cushing's disease who have been in remission for more than 10 years are at increased risk of overall mortality compared with the general population, particularly from circulatory disease. However, median survival from cure is excellent at about 40 years of remission. Treatment complexity and an increased number of treatments, reflecting disease that is more difficult to control, appears to negatively affect survival. Pituitary surgery alone is the preferred treatment to secure an optimum outcome, and should be done in a centre of surgical excellence. FUNDING: None.

Neuroendocrine Carcinoma of the Cervix: Review of a Series of Cases and Correlation With Outcome.

Introduction Neuroendocrine carcinoma (NEC) of the cervix is associated with a poor prognosis despite multimodal treatment. The correct diagnosis of this tumor type is imperative to provide clinicians and patients with prognostic information and ensure that appropriate treatment is provided. Methods A clinicopathological study was undertaken on all cervical tumors registered as NEC with the West Midlands Cancer Intelligence Unit between January 1, 1998 and December 31, 2009. Of the 45 cases diagnosed during the study period, the tumor samples of 41 cases were traced, anonymized, and then independently reviewed by 2 gynecological pathologists. Results The review confirmed 31/41 (78%) cases to be NEC, which overall, represented 1.3% of all the cervical cancers registered in the West Midlands over the period of the study. In the correct histological context, synaptophysin was the most sensitive and specific positive immunohistochemical marker of NEC differentiation. The cases that on review were confirmed as NEC had a significantly worse outcome than the non-NEC cases: median survival for NEC cases was 33.3 months versus 315.0 months for the non-NEC cases, P = .013. Conclusions Histological review of a series of NECs has shown significantly reduced survival in those patients with confirmed NEC in comparison with those patients where a diagnosis of NEC was not confirmed. We propose morphological and immunohistochemical criteria for the diagnosis of cervical NEC; and discourage unqualified use of the term "small cell carcinoma" as this does not accurately convey the diagnosis of SCNEC. We urge pathologists to use the 2014 World Health Organization classification when reporting these tumors.

Synthesis of novel 24-amino-25,26,27-trinorlanost-8-enes: cytotoxic and apoptotic potential in U937 cells.

In the present study, the synthesis of a range of novel 24-amino-25,26,27-trinorlanost-8-ene derivatives including 24-piperadino-trinorlanost-8-enes, 24-piperazino-trinorlanost-8-enes, 24-morpholino-trinorlanost-8-enes, and 24-diethylamino-trinorlanost-8-enes is reported and their cytotoxic and apoptotic potential evaluated in U937 cell lines. Excellent IC50 results for piperidine and 1-(2-hydroxyethyl)piperazine derivatives have been observed (IC50 values of 1.9 µM and 2.7 µM in U937 cells, respectively).

Extended elution of phospholipid from silicone hydrogel contact lenses.

Characterization of phospholipid release from an experimental reusable wear silicone hydrogel contact lens was performed to assess the possible use of these lenses for phospholipid delivery to increase eye comfort to patients who prefer reusable wear lenses. Contact lenses were loaded with 200 µg of radio-labeled 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) from a solution of n-propanol. To simulate 30 days of diurnal use with overnight cleaning, these lenses were eluted for 16 h at 35 °C into artificial tear fluid (ATF), and then eluted at room temperature (~22 °C) for 8 h in one of three commercial contact lens cleaning systems. This was repeated for 30 days. The elution of DMPC into ATF was greater on the first day, followed by a fairly constant amount of elution each day thereafter. The type of cleaning system had a statistically significant effect on the elution rate during daily exposure to ATF. The rate of elution into cleaning solutions did not show any enhanced elution on the first day; there was a fairly constant elution rate. Again, the type of cleaning system significantly influenced the elution rate into the nightly cleaner.

Pain medication management of musculoskeletal conditions at first presentation in primary care: analysis of routinely collected medical record data.

BACKGROUND: Primary care pharmacological management of new musculoskeletal conditions is not consistent, despite guidelines which recommend prescribing basic analgesics before higher potency medications such as opioids or non-steroidal inflammatory drugs (NSAIDs).The objective was to describe pharmacological management of new musculoskeletal conditions and determine patient characteristics associated with type of medication prescribed. METHODS: The study was set within a UK general practice database, the Consultations in Primary Care Archive (CiPCA). Patients aged 15 plus who had consulted for a musculoskeletal condition in 2006 but without a musculoskeletal consultation or analgesic prescription in the previous 12 months were identified from 12 general practices. Analgesic prescriptions within two weeks of first consultation were identified. The association of socio-demographic and clinical factors with receiving any analgesic prescription, and with strength of analgesic, were evaluated. RESULTS: 3236 patients consulted for a new musculoskeletal problem. 42% received a prescribed pain medication at that time. Of these, 47% were prescribed an NSAID, 24% basic analgesics, 18% moderate strength analgesics, and 11% strong analgesics. Increasing age was associated with an analgesic prescription but reduced likelihood of a prescription of NSAIDs or strong analgesics. Those in less deprived areas were less likely than those in the most deprived areas to be prescribed analgesics (odds ratio 0.69; 95% CI 0.55, 0.86). Those without comorbidity were more likely to be prescribed NSAIDs (relative risk ratios (RRR) compared to basic analgesics 1.89; 95% CI 0.96, 3.73). Prescribing of stronger analgesics was related to prior history of analgesic medication (for example, moderate analgesics RRR 1.88; 95% CI 1.11, 3.10). CONCLUSION: Over half of patients were not prescribed analgesia for a new episode of a musculoskeletal condition, but those that were often received NSAIDs. Analgesic choice appears multifactorial, but associations with age, comorbidity, and prior medication history suggest partial use of guidelines.

Reduced testing frequency for glycated hemoglobin, HbA1c, is associated with deteriorating diabetes control.

OBJECTIVE: We previously showed that in patients with diabetes mellitus, glycated hemoglobin (HbA1c) monitoring outside international guidance on testing frequency is widespread. Here we examined the relationship between testing frequency and diabetes control to test the hypothesis that retest interval is linked to change in HbA1c level. RESEARCH DESIGN AND METHODS: We examined repeat HbA1c tests (400,497 tests in 79,409 patients, 2008-2011) processed by three U.K. clinical laboratories. We examined the relationship between retest interval and 1) percentage change in HbA1c and 2) proportion of cases showing a significant HbA1c rise. The effect of demographics factors on these findings was also explored. RESULTS: Our data showed that the optimal testing frequency required to maximize the downward trajectory in HbA1c was four times per year, particularly in those with an initial HbA1c of ≥7% (≥53 mmol/mol), supporting international guidance. Testing 3-monthly was associated with a 3.8% reduction in HbA1c compared with a 1.5% increase observed with annual testing; testing more frequently provided no additional benefit. Compared with annual monitoring, 3-monthly testing was associated with a halving of the proportion showing a significant rise in HbA1c (7-10 vs. 15-20%). CONCLUSIONS: These findings provide, in a large, multicenter data set, objective evidence that testing outside guidance on HbA1c monitoring frequency is associated with a significant detrimental effect on diabetes control. To achieve the optimum downward trajectory in HbA1c, monitoring frequency should be quarterly, particularly in cases with suboptimal HbA1c. While this impact appears small, optimizing monitoring frequency across the diabetes population may have major implications for diabetes control and comorbidity risk.

Distinct trajectories of multimorbidity in primary care were identified using latent class growth analysis.

OBJECTIVES: To investigate the use of latent class growth analysis (LCGA) in understanding onset and changes in multimorbidity over time in older adults. STUDY DESIGN AND SETTING: This study used primary care consultations for 42 consensus-defined chronic morbidities over 3 years (2003-2005) by 24,615 people aged >50 years at 10 UK general practices, which contribute to the Consultations in Primary Care Archive database. Distinct groups of people who had similar progression of multimorbidity over time were identified using LCGA. These derived trajectories were tested in another primary care consultation data set with linked self-reported health status. RESULTS: Five clusters of people representing different trajectories were identified: those who had no recorded chronic problems (40%), those who developed a first chronic morbidity over 3 years (10%), a developing multimorbidity group (37%), a group with increasing number of chronic morbidities (12%), and a multi-chronic group with many chronic morbidities (1%). These trajectories were also identified using another consultation database and associated with self-reported physical and mental health. CONCLUSION: There are distinct trajectories in the development of multimorbidity in primary care populations, which are associated with poor health. Future research needs to incorporate such trajectories when assessing progression of disease and deterioration of health.

Why routine clinical follow-up for patients with early stage endometrial cancer is not always necessary: a study on women in South Wales.

OBJECTIVE: This study aimed to examine the existing methods of follow-up in women who have undergone treatment of early endometrial carcinoma in South Wales and to assess if they are appropriate. DESIGN: This study used a retrospective analysis of follow-up data. SETTING: This study was performed in the Virtual Gynaecological Oncology Centre, South Wales, United Kingdom. SAMPLE: This study sample is composed of 552 women. METHODS: Data regarding follow-up were collected retrospectively from patient case notes and computerized data systems. Data were analyzed using the Pearson χ test, Cox proportional hazard regression analysis, and Kaplan-Meier curves. MAIN OUTCOME MEASURES: This study aimed to determine whether routine follow-up was beneficial in detecting disease recurrence and whether outcome was influenced by routine follow-up. RESULTS: Between January 1, 2000, and December 31, 2010, 552 women were treated for early stage endometrial carcinoma. The 5-year survival was 81%, and the 5-year progression-free survival was 77%. Of these 552 women, 81 (15%) developed a disease recurrence; the majority (61/81 [75%]) recurred within 3 years. The median survival was 35 months compared with 47 months in patients who did not develop a recurrence. Of the 81 patients, 73 (90%) were symptomatic and only 5 patients were truly asymptomatic at follow-up. The most important and significant prognostic factor was "recurrent disease" with overall survival (hazard ratio, 2.20; P < 0.001; 95% confidence interval, 1.75-2.65) and progression-free survival (hazard ratio, 2.52; P < 0.001; 95% confidence interval, 2.09-2.95). "Asymptomatic recurrence" was not an independent predictor of outcome. CONCLUSIONS: Routine follow-up for early endometrial cancer is not beneficial for patients because most were symptomatic at the time of detection. It does not significantly improve the outcome. We propose altering the follow-up time regimen and adopting alternative follow-up strategies for women in South Wales.

Associations between onset age and disability in multiple sclerosis patients studied using MSSS and a progression model.

BACKGROUND: While many factors have been examined, male gender and older age at multiple sclerosis onset are among few variables consistently associated with increased disability. Interestingly, the association between onset age and disability may not be linear with some data suggesting a faster rate of accumulation of disability in patients aged more than 30 years at onset. OBJECTIVE: Explore the relationship between onset age and disability. METHODS: We studied 500 MS patients grouped by cut-offs in onset age. Disability was assessed using Multiple Sclerosis Severity Scale (MSSS) and, a model based on time to reach an Extended Disability Severity Score (EDSS) (progression model). Data were analyzed using linear and logistic regression. RESULTS: The association between disability (assessed by both MSSS and the progression model) and onset age was different in patients whose MS onset occurred after an age band of 30-35 years. Before this age range, changing age was not associated with changes in disability while during and after this age range, disability was increased. CONCLUSION: We found a significant change in the relationship between disability and onset age after about 31 years supporting the idea that while onset age does not define a sharp cut-off, it can help define subgroups of patients with differing rates of accumulation of disability.

Mosaic segmentation, COPD and CHF multimorbidity and hospital admission costs: a clinical linkage study.

BACKGROUND: How multimorbidity and socio-economic factors influence healthcare costs is unknown. Geo-demographic profiling system, Mosaic, which adds to socio-economic factors, provides the potential for an investigation of the relationship with multimorbidity, and their influence on healthcare costs. METHODS: Using chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) registers from 53 general practices for a population aged 40 years and over in Stoke-on-Trent, England (N = 10,113), were linked to hospital admissions data and Healthcare Resource Groups as a measure of hospital cost (2007-09). Eleven Mosaic groups were linked on the basis of individual patients' post codes. RESULTS: The COPD and CHF multimorbid group (n = 763) had the highest proportion with at least one hospital admission in the 3-year time period (n = 550, 72%), compared with the index COPD (56%) and CHF (66%) groups. Multimorbid patients had significantly higher mean costs for hospital admission (£4896) compared with the index COPD (£2769) or CHF (£3876). The associations between multimorbid groups and hospital admission costs compared with index groups varied by different Mosaic groups. CONCLUSIONS: CHF and COPD multimorbidity is associated with high costs, and average hospital admission costs vary by Mosaic segmentation. Multimorbidity and Mosaic provide an innovative basis for developing and targeting healthcare interventions in high-hospital-cost patients.