Management of osteoporosis in rheumatoid arthritis patients

Introduction: In rheumatoid arthritis (RA) patients, the risk of both vertebral and non-vertebral fractures is roughly doubled, which is for an important part caused by inflammation-mediated amplification of bone loss and by immobilization. New treatments have become available in the last two decades to treat both RA and osteoporosis.

Areas covered: Epidemiology and assessment of osteoporosis and fracture risk (including the influence of RA disease activity and bone-influencing medications such as glucocorticoids), the importance of vertebral fracture assessment in addition to bone density measurement in patients with RA, the use of disease-modifying antirheumatic drugs and their effects on generalized bone loss, and current and possible future anti-osteoporotic pharmacotherapeutic options are discussed with special focus on RA.

Expert opinion: Assessment of osteoporosis in RA patients should include evaluation of the effects of disease activity and bone-influencing medications such as (the dose of) glucocorticoids, above standard risk factors for fractures or osteoporosis as defined by the FRAX instrument. Disease-modifying antirheumatic drugs are now well able to control disease activity using treat to target strategies. This lowering of disease activity by antirheumatic medications such as anti-TNF-α results in hampering of generalized bone loss; however, no fracture data are currently available. When treating osteoporosis in RA patients, additional focus should be on calcium supplementation, particularly in glucocorticoid users, and also on sufficient vitamin D use. Several anti-osteoporotic medications are now on the market; oral bisphosphonates are most commonly used, but in recent years, more agents have entered the market such as the parenteral antiresorptives denosumab (twice yearly) and zoledronic acid (once yearly), and the anabolic agent parathyroid hormone analogues. New agents, such as odanacatib and monoclonal antibodies against sclerostin, are now being tested and will most likely enlarge the possibilities of osteoporosis treatment in RA patients.     

D-Serine and D-Cycloserine Reduce Compulsive Alcohol Intake in Rats

There is considerable interest in NMDAR modulators to enhance memory and treat neuropsychiatric disorders such as addiction, depression, and schizophrenia. D-serine and D-cycloserine, the NMDAR activators at the glycine site, are of particular interest because they have been used in humans without serious adverse effects. Interestingly, D-serine also inhibits some NMDARs active at hyperpolarized potentials (HA-NMDARs), and we previously found that HA-NMDARs within the nucleus accumbens core (NAcore) are critical for promoting compulsion-like alcohol drinking, where rats consume alcohol despite pairing with an aversive stimulus such as quinine, a paradigm considered to model compulsive aspects of human alcohol use disorders (AUDs). Here, we examined the impact of D-serine and D-cycloserine on this aversion-resistant alcohol intake (that persists despite adulteration with quinine) and consumption of quinine-free alcohol. Systemic D-serine reduced aversion-resistant alcohol drinking, without altering consumption of quinine-free alcohol or saccharin with or without quinine. Importantly, D-serine within the NAcore but not the dorsolateral striatum also selectively reduced aversion-resistant alcohol drinking. In addition, D-serine inhibited EPSCs evoked at −70 mV in vitro by optogenetic stimulation of mPFC–NAcore terminals in alcohol-drinking rats, similar to reported effects of the NMDAR blocker AP5. Further, D-serine preexposure occluded AP5 inhibition of mPFC-evoked EPSCs, suggesting that D-serine reduced EPSCs by inhibiting HA-NMDARs. Systemic D-cycloserine also selectively reduced intake of quinine-adulterated alcohol, and D-cycloserine inhibited NAcore HA-NMDARs in vitro. Our results indicate that HA-NMDAR modulators can reduce aversion-resistant alcohol drinking, and support testing of D-serine and D-cycloserine as immediately accessible, FDA-approved drugs to treat AUDs.     

Radiographic evidence of nonoccupational asbestos exposure from processing Libby vermiculite in Minneapolis, Minnesota

Background: Community exposure to asbestos from contaminated vermiculite ore from Libby, Montana, occurred in many processing sites in the United States, including a densely populated urban residential neighborhood of Minneapolis, Minnesota.Objective: We examined exposed community residents who never worked at the plant or never lived with a plant worker for radiographic evidence of lung changes consistent with asbestos exposure.Methods: We obtained posteroanterior chest radiographs to identify the prevalence of pleural abnormalities consistent with pneumoconiosis, as determined by consensus of two National Institute for Occupational Safety and Health–certified B-reader radiologists. We estimated cumulative asbestos exposure (fibers per cubic centimeters × months) with air dispersion model data and activity-based modeled exposure estimates for vermiculite processing waste contact. We modeled associations between pleural abnormalities and asbestos exposure using multiple logistic regression to adjust for year of birth, sex, and potential occupational asbestos exposure.Results: Radiographs were obtained for 461 participants. The prevalence of pleural abnormalities by B-reader consensus was 10.8%. A history of direct contact with the waste and ever playing in the waste piles was associated with pleural abnormalities {odds ratio [OR] 2.78 [95% confidence interval (CI): 1.26, 6.10] and 2.17 (95% CI: 0.99, 4.78), respectively, when adjusted for background exposure}. The regression coefficients for log-transformed measures (fibers per cubic centimeters × months) of background exposure and activity-based exposure were 0.322 (95% CI: 0.078, 0.567) and 0.063 (95% CI: –0.013, 0.139), respectively, when adjusted for each other, and 0.283 (95% CI: 0.104, 0.463) for cumulative exposure from all sources.Conclusion: These results support the hypothesis that community exposure to asbestos-contaminated vermiculite originating from Libby, Montana, is associated with measurable effects based on radiographic evidence.     

Nitrates in drinking water and methemoglobin levels in pregnancy: a longitudinal study

Background  

Private water systems are more likely to have nitrate levels above the maximum contaminant level (MCL). Pregnant women are considered vulnerable to the effects of exposure to high levels of nitrates in drinking water due to their altered physiological states. The level of methemoglobin in the blood is the biomarker often used in research for assessing exposure to nitrates. The objective of this study was to assess methemoglobin levels and examine how various factors affected methemoglobin levels during pregnancy. We also examined whether differences in water use practices existed among pregnant women based on household drinking water source of private vs. public supply.     

A 3-month double-blind randomised study comparing an olive oil- with a soyabean oil-based intravenous lipid emulsion in home parenteral nutrition patients

Intravenous lipid emulsions (ILE) have demonstrated advantages including prevention of essential fatty acid (EFA) deficiency; however, too much EFA can down regulate fatty acid elongation leading to an imbalance of nutritional compounds in plasma and cell membranes. An olive oil-based ILE containing long-chain triacylglycerols (LCT) with a low content (20 %) of PUFA was administered for home parenteral nutrition (HPN) and compared with a conventional soyabean oil-based ILE (PUFA content, 60 %). Thirteen patients (26-92 years) with stable intestinal failure were randomised after a 1-month run-in period with a medium-chain triacylglycerols-LCT-based ILE, to receive 3 months of HPN with either olive oil- (n 6) or soyabean oil-based (n 7) ILE. The nutritional impact and safety of HPN, oral intakes and absorption rates, phospholipid fatty acids in plasma and lymphocyte cell membrane were assessed. The only clinical event reported was one case of pneumonia (soya group). In both groups, 20 : 3n-9:20 : 4n-6 ratios remained within normal ranges (0.03-0.07). There was a significant increase of gamma-linolenic acid (gamma-LA) in plasma and lymphocyte cell membrane (P=0.02) and of oleic acid in plasma (P<0.01) in the olive compared with the soya group. A significant correlation was found between gamma-LA (day 90 - day 0) in plasma and PUFA parenteral intakes (P=0.02), but neither with fat intakes nor with fat absorption rates. In conclusion, plasma and lymphocyte EFA pattern remained in normal ranges without EFA deficiency with both lipid emulsions, despite a lower content of n-3 and n-6 series with the olive oil-based ILE.     

Effect of lifestyle intervention for people with diabetes or prediabetes in real-world primary care: propensity score analysis

Background

It is important to keep the level of antibiotic prescribing low to contain the development of resistant bacteria. This study was conducted to reveal new knowledge about how GPs think in relation to the prescribing of antibiotics - knowledge that could be used in efforts toward rational treatment of infectious diseases in primary care. The aim was to explore and describe the variations in GPs' perceptions of infectious disease management, with special reference to antibiotic prescribing.

Methods

Twenty GPs working at primary care centres in a county in south-west Sweden were purposively selected based on the strategy of including GPs with different kinds of experience. The GPs were interviewed and perceptions among GPs were analysed by a phenomenographic approach.

Results

Five qualitatively different perceptions of infectious disease management were identified. They were: (A) the GP must help the patient to achieve health and well-being; (B) the management must meet the GP's perceived personal, professional and organisational demands; (C) restrictive antibiotic prescribing is time-consuming; (D) restrictive antibiotic prescribing can protect the effectiveness of antibiotics; and (E) patients benefit personally from restrictive antibiotic prescribing.

Conclusions

Restrictive antibiotic prescribing was considered important in two perceptions, was not an issue as such in two others, and was considered in one perception although the actual prescribing was greatly influenced by the interaction between patient and GP. Accordingly, to encourage restrictive antibiotic prescribing several aspects must be addressed. Furthermore, different GPs need various kinds of support. Infectious disease management in primary care is complex and time-consuming, which must be acknowledged in healthcare organisation and planning.     

The burden of bladder cancer in men and women: analysis of the years of life lost

Study Type – Harms (individual cohort) Level of Evidence 2a What’s known on the subject? and What does the study add? Previously, it was appreciated that men lost about 12 years of expected remaining life if they died of bladder cancer. However, nothing was known about how exposure history, gender, age and stage at diagnosis, and other factors affected life expectancy of bladder cancer patients. The impact of these factors was now taken into consideration when determining years of potential life lost from bladder cancer death and the loss in median life expectancy at bladder cancer diagnosis. Compared with men, women lose more years of life and a greater fraction of their life expectancy to bladder cancer.

OBJECTIVE

? To estimate the average loss in life expectancy (LE) due to bladder cancer (BC) in men and women in the USA.

PATIENTS AND METHODS

? Cancer records for 51 528 patients diagnosed with BC during 1988–1997 were obtained from the Surveillance, Epidemiology, and End Results database. ? Potential follow‐up ranged from 10 to 20 years (median 14 years). Loss in median LE at BC diagnosis was computed as the difference between expected median survival and observed median survival. ? Expected survival was calculated using two methods: method 1 used age, sex, and race‐specific LE in the general population, method 2 used the hazard of death from non‐BC causes in patients with BC (to account for past exposures and treatment‐related toxicities not present in the general population).

RESULTS

? During the study period, BC death occurred in 17% of men and 23% of women and non‐BC death occurred in 53% of men and 47% of women. ? Using LE in the general population as the reference (method 1), loss in median LE at BC diagnosis was 3.9 years for men (33% of their potential remaining years of life) and 6.5 years for women (47% of their potential remaining years of life). ? Using non‐BC‐specific hazard as the reference (method 2), loss in median LE was 2.7 years for men (26% of their potential remaining years of life) and 4.1 years for women (36% of their potential remaining years of life).

CONCLUSION

? Compared with men, women loose more years of life and a greater fraction of their life expectancy to BC.     

Comparison of Acute Toxicities in Two Primary Chemoradiation Regimens in the Treatment of Advanced Head and Neck Squamous Cell Carcinoma

Purpose

The optimal dosage and frequency of platinum-based chemoradiotherapy (CRT) regimen for treating advanced head and neck squamous cell carcinoma remains unresolved. This study aims to compare the toxicity and efficacy of weekly versus more dose-intensive cisplatin-based CRTs.

Methods

We reviewed 155 stage III/IV head and neck squamous cell carcinoma patients with no evidence of distant metastasis treated with one of two CRT regimens from 2000 to 2010 at Greater Baltimore Medical Center. Twice-daily radiation was provided as a split course over a 45-day period. Regimen A consisted of concomitant cisplatin (30?mg/m²/1?h) weekly for 6 cycles; regimen B consisted of concomitant cisplatin (12?mg/m²/1?h) and 5-fluorouracil (600?mg/m²/20?h) on days 1 through 5 and days 29 through 33. Main outcome measures included acute toxicities (myelosuppression, neurotoxicity, nephrotoxicity, gastrointestinal dysfunction), unplanned hospitalizations, and disease control at 12?months.

Results

Patients on regimen A were much less likely to experience ototoxicity due to their treatment (0% vs. 9.8%, P?=?0.04). They were more likely to experience thrombocytopenia acutely (46% vs. 26%, P?=?0.02), but the toxicity was not limiting (grade 1?C2). No significant differences exist in the incidence of other toxicities or unplanned hospitalizations. At 1?year, 97% of patients on A vs. 86% of patients on regimen B were free of disease (P?=?0.11).

Conclusions

With concurrent radiotherapy, low-dose, single-agent, weekly cisplatin is less likely than higher-dose daily cisplatin plus 5-fluorouracil provided at the beginning and end of treatment to be associated with ototoxicity. The preliminary data suggest at least equivalent efficacy, but longer follow-up is required.     

Glucocorticoid safety for treating rheumatoid arthritis

Introduction: Glucocorticoids (GCs) are often used in the treatment of rheumatoid arthritis and many other inflammatory diseases. Besides strong favorable effects on disease activity, GCs can cause (serious) side effects as well.

Areas covered: Side effects of GCs that are ranked as most important by rheumatologists as well as by patients are bone loss and fractures, cardiovascular events, hypertension, and diabetes mellitus. In evaluating these side effects, confounding by indication is a disturbing factor: not only the use of GCs can increase the risk of several side effects, but so can the activity of the underlying disease, which in turn is related to the amount of GCs that is prescribed to the patient.

Expert opinion: Generally, side effects predominantly occur in patients with a high disease activity and when used in high doses and for a long period of time. For these patients, caution and monitoring are most warranted. However, monitoring is not only recommended in patients with a high disease activity, and high-dose or long-term use of GCs, but in all GC users, since side effects may also occur in patients treated with low-dose GCs. When detecting possible negative effects in time, they might be managed and serious damage due to side effects might hopefully be prevented.