Depression and Time to Knee Arthroplasty Among Adults Who Have Knee Osteoarthritis.

BACKGROUND: Depression is common in osteoarthritis (OA) and is associated with poor outcomes following total knee arthroplasty (TKA). Depression can increase pain sensitivity and may be related to an increased likelihood of TKA. METHODS: Nationally distributed electronic health record data from 2010 to 2018 were used to identify eligible patients (n = 9,466) who had knee OA and were 45 to 80 years of age. Cox proportional hazard models were computed to estimate the association between depression and incident TKA for all patients and by age group (45 to 54, 55 to 64, and 65 to 80 years of age). Confounding was controlled using entropy balancing. Sensitivity analyses determined if the association between depression and TKA differed when depression occurred in the 12 months occurring 90, 60, 30, and 0 days lag time before TKA. RESULTS: The mean age of the sample was 63 (range, 45 to 80), 64.0% were women, 83.3% were White race, and approximately 50% resided in the Midwest. There was no association between depression and incident TKA (hazard ratio = 0.97; confidence interval = 0.81 to 1.16]). Results did not differ in age-stratified analyses. Sensitivity analyses revealed a higher percentage of TKA among depressed versus nondepressed patients (24.2 versus 21.6%; P = .028) when the patient's depression diagnosis was established in the 12 months with no lag time before TKA. CONCLUSIONS: Patients who have knee OA and comorbid depression, compared to those who have only knee OA, do not have an increased likelihood of TKA. The multifactorial, complex decision to obtain TKA does not appear to be influenced by depression, but depression is a common comorbidity.

Marsh sediments chronically exposed to nitrogen enrichment contain degraded organic matter that is less vulnerable to decomposition via nitrate reduction.

Blue carbon habitats, including salt marshes, can sequester carbon at rates that are an order of magnitude greater than terrestrial forests. This ecosystem service may be under threat from nitrate (NO3-) enrichment, which can shift the microbial community and stimulate decomposition of organic matter. Despite efforts to mitigate nitrogen loading, salt marshes continue to experience chronic NO3- enrichment, however, the long-term consequence of this enrichment on carbon storage remains unclear. To investigate the effect of chronic NO3- exposure on salt marsh organic matter decomposition, we collected sediments from three sites across a range of prior NO3- exposure: a relatively pristine marsh, a marsh enriched to ~70 µmol L-1 NO3- in the flooding seawater for 13 years, and a marsh enriched between 100 and 1000 µmol L-1 for 40 years from wastewater treatment effluent. We collected sediments from 20 to 25 cm depth and determined that sediments from the most chronically enriched site had less bioavailable organic matter and a distinct assemblage of active microbial taxa compared to the other two sites. We also performed a controlled anaerobic decomposition experiment to test whether the legacy of NO3- exposure influenced the functional response to additional NO3-. We found significant changes to microbial community composition resulting from experimental NO3- addition. Experimental NO3- addition also increased microbial respiration in sediments collected from all sites. However, sediments from the most chronically enriched site exhibited the smallest increase, the lowest rates of total NO3- reduction by dissimilatory nitrate reduction to ammonium (DNRA), and the highest DNF:DNRA ratios. Our results suggest that chronic exposure to elevated NO3- may lead to residual pools of organic matter that are less biologically available for decomposition. Thus, it is important to consider the legacy of nutrient exposure when examining the carbon cycle of salt marsh sediments.

Differences Between General Internal Medicine and Family Medicine Physicians' Initiation of Pre-Exposure Prophylaxis.

OBJECTIVE: Preexposure Prophylaxis (PrEP) is under-utilized in primary care. Given differences in treatment approaches for other conditions between family medicine (FM) and general internal medicine (GIM), this study compared PrEP-prescribing between FM and GIM physicians. METHODS: De-identified electronic health record data from a multi-state health care system was used in this retrospective observational study. The time period from 1/1/13 to 9/30/21 was used to identify PrEP eligible patients using measures of current sexually transmitted disease and condomless sex at the time of eligibility. Receipt of PrEP was measured in the 12 months after PrEP eligibility. The odds of receiving PrEP in GIM as compared to FM was computed before and after adjusting for demographics and physical and psychiatric comorbidities. RESULTS: The majority of eligible patients were 18 to 39 years of age, 60.9% were female and 71.6% were White race. Among PrEP eligible patients, 1.1% received PrEP in the first year after index date. Receiving PrEP was significantly more likely among patients treated in GIM versus FM (OR = 2.30; 95% CI:1.63-3.25). After adjusting for covariates, this association remained statistically significant (OR = 2.02; 95% CI:1.41-2.89). CONCLUSIONS: PrEP is grossly under-utilized in primary care. The majority of Americans enter the health care system through primary care and not through HIV providers or other specialties. Therefore, educational interventions are needed to increase confidence and knowledge and to encourage PrEP prescribing by FM and GIM physicians.

Erectile dysfunction associated with undiagnosed prediabetes and type 2 diabetes in young adult males: A retrospective cohort study.

Erectile dysfunction (ED) is a common comorbidity in type 2 diabetes (T2D). ED has been studied as an outcome in diabetes, but it is not known if ED is a risk factor for T2D. We determined if patients with ED have an increased risk for prediabetes and/or T2D and measured the duration between ED and prediabetes/T2D diagnosis. Retrospective cohort study using de-identified medical record data from a large mid-western health care system to measure ED, T2D and potential confounding factors. Patients were 18 to 40 years of age because we were interested in early onset pre-diabetes/T2D. Eligible patients had ED and were free of prediabetes, hyperglycemia and T2D at index. Entropy balancing controlled for confounding. Modified Poisson regression models with robust error variances calculated relative risk (RR) and 95% confidence intervals for the association of ED and pre-diabetes/T2D. Patients' mean age was 28.3 (±7.0) years, 81.7% were White and 14.0% were Black. After controlling for confounding, ED was associated with increased risk for prediabetes/T2D (RR = 1.34; 95%CI:1.16-1.55). This association was similar to that between ED and T2D alone (RR = 1.38; 95% CI: 1.10-1.74). About 30% had ED and prediabetes/T2D diagnosed on the same day and nearly 75% were diagnosed within a year of ED. ED is a marker for undiagnosed prediabetes/T2D and a risk factor for near term onset of prediabetes/T2D. ED may offer the opportunity for earlier detection and diagnoses of T2D, particularly in younger men. Younger patients presenting with ED should be screened for hyperglycemia.

Provider specialty and odds of a new codeine, hydrocodone, oxycodone and tramadol prescription before and after the CDC opioid prescribing guideline publication.

The CDC Guideline for Prescribing Opioids for Chronic Pain cautioned against high dose prescribing but did not provide guidance on type of opioid for new pain episodes. We determined if new prescriptions for Schedule II opioids vs. tramadol decreased in the 18 months after vs. before the CDC guideline and if this decrease was associated with physician specialty. New opioid prescriptions, provider type and covariates were measured using a nationally distributed, Optum® de-identified Electronic Health Record (EHR) data base. Eligible patients were free of cancer and HIV and started a new prescription for Schedule II opioids (i.e. codeine, hydrocodone, oxycodone) or Schedule IV (tramadol) in the 18 months before (n = 141,219) or 18 months after (n = 138,216) guideline publication. Fully adjusted multilevel multinomial models estimated the association between provider type (anesthesiology/pain medicine, surgical specialty, emergency, hospital, primary care, other specialty and unknown) before and after adjusting for covariates. New oxycodone prescriptions were most common among surgical and anesthesia/pain management, and new tramadol prescriptions were most common in primary care. The greatest decreases in odds of a Schedule II opioid vs. tramadol were observed in emergency care (oxycodone vs. tramadol OR = 0.82; 95%CI:0.76-0.88) and primary care (hydrocodone vs. tramadol OR = 0.85; 95%CI:0.81-0.89). Surgical specialists were least likely to start opioid therapy with tramadol. In the 18 months after vs. before the CDC guideline, emergency care and primary care providers increased tramadol prescribing. Guidelines tailored to specialists that frequently begin opioid therapy with oxycodone may enhance safe opioid prescribing.

Comparison of Opioids Prescribed for Patients at Risk for Opioid Misuse Before and After Publication of the Centers for Disease Control and Prevention's Opioid Prescribing Guidelines.

Importance: It is not known whether decreases in Schedule II (high abuse potential) vs Schedule IV (lower abuse potential) opioid prescriptions overall and among high-risk patients followed publication of the Centers for Disease Control and Prevention (CDC) opioid prescribing guideline on March 15, 2016. Objectives: To compare the odds of new Schedule II opioid (codeine, hydrocodone, oxycodone) prescriptions vs Schedule IV opioid (tramadol) prescriptions in the 18-month periods before and after the CDC guideline release to determine whether new prescriptions for Schedule II opioids decreased relative to new prescriptions for tramadol and to assess whether patients with benzodiazepine prescriptions or those with depression, anxiety, or substance use disorders had a greater decrease in receipt of Schedule II vs Schedule IV opioids. Design, Setting, and Participants: Cross-sectional study of Optum's deidentified Integrated Claims-Clinical data set for 5 million US adults 18 months before and 18 months after March 15, 2016. Eligible patients were 18 years or older, free of HIV and cancer diagnoses, and had a noncancer painful condition. Patients received new prescriptions for codeine, hydrocodone, oxycodone, or tramadol. Data were analyzed from September 5, 2014, to September 14, 2017. Exposure: The CDC opioid prescribing guideline published on March 15, 2016. Main Outcomes and Measures: The odds of prescriptions for each Schedule II opioid vs tramadol after guideline publication. Results: Data from 279 435 patients were included in the study. The mean (SD) age of patients was 52.9 (16.5) years; 61% were female and 79.4% were White. The prevalence of new prescriptions for each drug before and after guideline publication was as follows: codeine, 7.1% vs 7.0%; hydrocodone, 47.4% vs 45.6%; oxycodone, 22.4% vs 24.0%; and tramadol, 23.0% vs 23.4%. Overall, the odds of being prescribed hydrocodone or oxycodone vs tramadol significantly decreased after guideline publication (odds ratios, 0.95; 95% CI, 0.91-0.98 and 0.86; 95% CI, 0.82-0.90, respectively). Odds of being prescribed a Schedule II opioid vs tramadol after vs before guideline publication were similar in patients with and without benzodiazepine comedication or psychiatric disorders. Conclusions and Relevance: In the 18 months after compared with the 18 months before publication of the CDC prescribing guideline, a 14% decrease in oxycodone prescriptions was observed relative to tramadol. Little change in prescriptions of other Schedule II opioids was observed. Schedule II opioids continue to be prescribed to high-risk patients 18 months after publication of the CDC guideline.

"I'll try the veggie burger": Increasing purchases of sustainable foods with information about sustainability and taste.

Food production--especially raising animals for meat--has a massive negative impact on the environment and contributes to global warming. To address this, we investigated whether information about food sustainability would increase purchases of sustainable foods by patrons of university cafés. In Study 1, patrons were randomly assigned either to see a menu that had sustainability labels indicating the degree of environmental impact of each item, or to see a menu without labels. Women who saw the labels were significantly more likely to purchase sustainable foods, whereas men were not influenced by the labels. In Study 2 we targeted one sustainable menu item (a veggie burger) and, in a 2 (sustainability) x 2 (taste) design, varied whether patrons learned that the veggie burger was especially sustainable or especially tasty. Women were significantly more likely to purchase the veggie burger if they learned it was sustainable or tasty, but again, the manipulations had no effect on men. We discuss why women are more likely to change their food choices to eat more sustainably than are men.

Happiness, Meaning, and Psychological Richness.

What kind of life do people want? In psychology, a good life has typically been conceptualized in terms of either hedonic or eudaimonic well-being. We propose that psychological richness is another neglected aspect of what people consider a good life. In study 1 (9-nation cross-cultural study), we asked participants whether they ideally wanted a happy, a meaningful, or a psychologically rich life. Roughly 7 to 17% of participants chose the psychologically rich life. In study 2, we asked 1611 Americans and 680 Koreans what they regret most in their lives; then, if they could undo or reverse the regretful event, whether their lives would have been happier, more meaningful, or psychologically richer as a result. Roughly 28% of Americans and 35% of Koreans reported their lives would have been psychologically richer. Together, this work provides a foundation for the study of psychological richness as another dimension of a good life.

Wastewater input reductions reverse historic hypereutrophication of Boston Harbor, USA.

This paper documents the changes that followed large nutrient (N and P) and organic matter input reductions to a major metropolitan marine bay, Boston Harbor (USA). Before input reduction, its N and P inputs fell in the upper range of the < 1-> 300 gN m-2 year-1 and < 0.1-> 40 gP m-2 year-1 for coastal systems. Elevated nutrient and organic matter inputs are recognized causes of coastal eutrophication. Treatment upgrades and then diversion of its wastewater discharges offshore, lowered its N, P, and organic C inputs by 80-90%. The input decreases lowered its trophic status from hypereutrophic to eutrophic-mesotrophic. With the reversal of hypereutrophication, pelagic production and phytoplankton biomass decreased, and the nitrogen limitation relative to phosphorus limitation increased. Benthic metabolism and dissolved inorganic N fluxes decreased, and benthic-pelagic coupling was altered. Bottom-water dissolved oxygen, already at healthy levels, increased, and seagrass expanded. Coastal management requires that the changes, following the nutrient and organic matter input reductions implemented to address eutrophication, be understood. Boston Harbor's recovery, because its water column was vertically well mixed and marine, was more pronounced than in many other systems.

Nitrate addition stimulates microbial decomposition of organic matter in salt marsh sediments.

Salt marshes sequester carbon at rates more than an order of magnitude greater than their terrestrial counterparts, helping to mitigate climate change. As nitrogen loading to coastal waters continues, primarily in the form of nitrate, it is unclear what effect it will have on carbon storage capacity of these highly productive systems. This uncertainty is largely driven by the dual role nitrate can play in biological processes, where it can serve as a nutrient-stimulating primary production or a thermodynamically favorable electron acceptor fueling heterotrophic metabolism. Here, we used a controlled flow-through reactor experiment to test the role of nitrate as an electron acceptor, and its effect on organic matter decomposition and the associated microbial community in salt marsh sediments. Organic matter decomposition significantly increased in response to nitrate, even at sediment depths typically considered resistant to decomposition. The use of isotope tracers suggests that this pattern was largely driven by stimulated denitrification. Nitrate addition also significantly altered the microbial community and decreased alpha diversity, selecting for taxa belonging to groups known to reduce nitrate and oxidize more complex forms of organic matter. Fourier Transform-Infrared Spectroscopy further supported these results, suggesting that nitrate facilitated decomposition of complex organic matter compounds into more bioavailable forms. Taken together, these results suggest the existence of organic matter pools that only become accessible with nitrate and would otherwise remain stabilized in the sediment. The existence of such pools could have important implications for carbon storage, since greater decomposition rates as N loading increases may result in less overall burial of organic-rich sediment. Given the extent of nitrogen loading along our coastlines, it is imperative that we better understand the resilience of salt marsh systems to nutrient enrichment, especially if we hope to rely on salt marshes, and other blue carbon systems, for long-term carbon storage.

Primary Care of Breast Cancer Survivors.

With declining mortality rates, the number of breast cancer survivors is increasing. Ongoing care after breast cancer treatment is often provided by primary care physicians. This care includes surveillance for cancer recurrence with a history and physical examination every three to six months for the first three years after treatment, every six to 12 months for two more years, and annually thereafter. Mammography is performed annually. Magnetic resonance imaging of the breast is not indicated unless patients are at high risk of recurrence, such as having a hereditary cancer syndrome. Many breast cancer survivors experience long-term sequelae from the disease or treatment. Premature menopause with hot flashes can occur and is managed with pharmacologic and nonpharmacologic treatments. Vaginal dryness is treated with vaginal lubricants and gels. Because cardiotoxicity from chemotherapy is possible, clinicians should be alert for this complication and perform echocardiography if appropriate. Impaired cognition after chemotherapy is also common; treatment includes cognitive rehabilitation therapy. Patients with treatment-induced menopause develop decreased bone density and should receive dual energy x-ray absorptiometry and pharmacologic and nonpharmacologic therapies. Others experience lymphedema, often best managed with weight loss and complex decongestive therapy. Some women develop chronic pain, which is treated by addressing psychological factors and with appropriate pharmacologic therapy.

Race in Older but Not Younger Patients Associated With Greater Glycemic Burden in Primary Care Patients.

PURPOSE: The purpose of this study is to determine if race disparities in glycemic control differ in young vs older white and African American patients with diabetes. METHODS: Electronic medical record data were gathered from 1431 primary care patients ≥18 years old, diagnosed with type 2 diabetes, who had ≥2 A1C measurements between July 1, 2008, and June 30, 2015. A1C values were used to compute the average monthly glycemic burden (AMGB). AMGB is the average monthly cumulative amount of A1C >7.5. Age-stratified (18-50 vs >50 years old) linear regression models were computed to measure the association between race and AMGB before and after adjusting for covariates. RESULTS: Younger compared to older patients had significantly greater AMGB. In younger patients, AMGB was not significantly different in African American vs white patients. In older patients, African Americans had significantly greater AMGB compared to whites, and this association remained significant after adjusting for all covariates in a linear regression model. CONCLUSIONS: Results narrow the known race disparity in glycemic control to older African American patients. Substantial AMGB in white and African American younger patients warrants aggressive clinical and public health interventions that could help patients manage their diabetes and reduce their risk for diabetes-related health conditions.

External and local controls on land-sea coupling assessed by stable isotopic signatures of mangrove producers in estuaries of Pacific Panama.

Foliar stable isotopic signatures of nitrogen, carbon, and sulfur in mangrove vegetation from the Pacific coast of Panama were insensitive to inputs from watersheds with different area of forest land cover, and to seasonal, inter-annual, and global-scale-driven contrasts in rainfall and upwelling. N, C, and S content of mangrove vegetation were not affected by inputs from watersheds with different degrees of deforestation, but showed some influence of down-estuary transformations. While there was substantial variation that remained un-explained, isotopic signatures and nutrient contents were largely determined by species-specific features, and showed substantial small-scale variation reflecting local differences, within-estuary plant-sediment links. The ability of mangrove estuaries to erase effects of deforestation points out that conservation of these wetland ecosystems is important, because, at least in the sites we studied, transformations within mangrove estuaries were strong enough to protect water quality in receiving coastal waters.

Cardiomyopathy: An Overview.

The definition and classification of cardiomyopathy have evolved considerably in recent years. Cardiomyopathy can be separated into primary (genetic, mixed, or acquired) and secondary categories, which result in varied phenotypes including dilated, hypertrophic, and restrictive patterns. Hypertrophic cardiomyopathy is the most common primary cardiomyopathy and can cause exertional dyspnea, presyncope, atypical chest pain, heart failure, and sudden cardiac death. Dilated cardiomyopathy can be genetic or acquired and typically presents with classic symptoms of heart failure with reduced ejection fraction. Restrictive cardiomyopathy is much less common and often associated with systemic disease. Family physicians should be alert for acquired variants of cardiomyopathy, including peripartum and stress-induced cardiomyopathy, as well as rare variants, such as arrhythmogenic right ventricular dysplasia and left ventricular noncompaction. In addition to history and physical examination, diagnosis of cardiomyopathy includes electrocardiography and echocardiography testing. Treatment may include appropriately staged therapy for heart failure, appropriate activity restriction, evaluation for implantable cardioverter-defibrillator placement, and consideration of heart transplantation in refractory cases. Genetic testing of families is an emerging modality with some potential to augment traditional screening performed by family physicians.

Functionally distinct communities of ammonia-oxidizing bacteria along an estuarine salinity gradient.

The relationship between ammonia-oxidizing bacteria (AOB) and potential nitrification rates was examined along a salinity gradient in a New England estuary in spring and late summer over 3 years. Ammonia-oxidizing bacteria abundance was estimated by measuring gene copies of the ammonia monooxygenase catalytic subunit (amoA) using real-time polymerase chain reaction. Ammonia-oxidizing bacteria abundance ranged from below detection to 6.0 x 10(7)amoA copies (gdw sediment)(-1). Mean potential nitrification rates ranged from 0.5 to 186.5 nmol N (gdw sediment)(-1) day(-1). Both AOB abundance and potential rates were significantly higher in spring than late summer. Correlations between rates and abundance varied significantly among sites, but showed site-specific ammonia oxidation kinetics related to AOB community structure. The effect of salinity on potential nitrification rates was evaluated by incubating sediment from each site under four salinity conditions (0, 5, 10 and 30 psu). At all sites, rates were generally highest in the intermediate salinity treatments, but rates at the upstream site were inhibited at high salinity, while rates at the two downstream sites were inhibited at the lowest salinity. Although salinity appears to be an important factor in determining AOB distribution, it may not be the primary factor as AOB exhibited a broad range of salinity tolerance in our experiments. Our results indicate that there are significant differences in abundance and community composition of AOB along the salinity gradient, and the differences are reflected in community function.

Is acamprosate use in alcohol dependence treatment reflected in improved subjective health status outcomes beyond cognitive behavioural therapy alone?.

OBJECTIVE: To examine whether the addition of acamprosate to Cognitive Behavioural Therapy (CBT) outpatient alcohol dependence treatment impacted on subjective health status. METHOD: Among 268 patients consecutively treated for alcohol dependence, 149 chose CBT alone. A matched design was used. From a possible pool of 119 Acamprosate + CBT and 149 CBT-only patients, 86 Acamprosate + CBT subjects were individually matched with 86 CBT-only patients on parameters of gender, age, prior detoxification and alcohol dependence severity. Health Status (SF-36) and Psychological Well-Being (GHQ-28) was assessed pre- and post-treatment. RESULTS: Pre-treatment, both self-reported health status and psychological well-being was markedly below normative (community) ranges. Program completers significantly improved across both measures over 12 weeks of treatment and some health domains approximated community levels. No treatment group differences were observed. CONCLUSIONS: Participants who completed the CBT-based treatment showed significant improvement in self-reported health status. The use of acamprosate did not register additional improvement on either SF-36 or GHQ-28, beyond CBT alone.

Combined acamprosate and naltrexone, with cognitive behavioural therapy is superior to either medication alone for alcohol abstinence: a single centres' experience with pharmacotherapy.

AIMS: To compare treatment outcomes amongst patients offered pharmacotherapy with either naltrexone or acamprosate used singly or in combination, in a 12-week outpatient cognitive behavioural therapy (CBT) programme for alcohol dependence. METHODS: We matched 236 patients across gender, age group, prior alcohol detoxification, and dependence severity and conducted a cohort comparison study of three medication groups (CBT + acamprosate, CBT + naltrexone, CBT + combined medication) which included 59 patients per group. Outcome measures included programme attendance, programme abstinence and for those who relapsed, cumulative abstinence duration (CAD) and days to first breach (DFB). Secondary analyses compared the remaining matched 59 subjects who declined medication with the pharmacotherapy groups. RESULTS: Across medication groups, CBT + combined medication produced the greatest improvement across all outcome measures. Although a trend favoured the CBT + combined group, differences did not reach statistical significance. Programme attendance: CBT + Acamprosate group (66.1%), CBT + Naltrexone group (79.7%), and in the CBT + Combined group (83.1%). Abstinence rates were 50.8, 66.1, and 67.8%, respectively. For those that did not complete the programme abstinent, the average number of days abstinent (CAD) were 45.07, 49.95, and 53.58 days, respectively. The average numbers of days to first breach (DFB) was 26.79, 26.7, and 37.32 days. When the focal group (CBT + combined) was compared with patients who declined medication (CBT-alone), significant differences were observed across all outcome indices. Withdrawal due to adverse medication effects was minimal. CONCLUSIONS: The addition of both medications (naltrexone and acamprosate) resulted in measurable benefit and was well tolerated. In this patient population naltrexone with CBT is as effective as combined medication with CBT, but the trend favours combination medication.

Alcohol dependence: the impact of cognitive behaviour therapy with or without naltrexone on subjective health status.

OBJECTIVES: To examine the health-related quality of life of alcohol-dependent patients across a 12-week cognitive behaviour treatment (CBT) program and identify whether the patient selection of the anticraving medication naltrexone further enhanced these outcomes. METHOD: One hundred and thirty-six consecutive alcohol-dependent subjects voluntarily participated and were offered naltrexone, of which 73 (54%) participants declined medication. A matched design was used. Of the 136 subjects, 86 (43 naltrexone and CBT; 43 CBT only) could be individually matched (blind to outcome measures) for gender, age, prior alcohol detoxification and dependence severity. Measures of health status and mental health wellbeing included the Rand Corporation Medical Outcomes Short Form 36 Health Survey (SF-36) and the General Health Questionnaire (GHQ-28). RESULTS: Pre-treatment, all had SF-36 and GHQ-28 scores markedly below national norms. Post-treatment, significant improvement in seven of the eight SF-36 subscales and all of the GHQ-28 subscales occurred, approximating national normative levels. Patients in the CBT + naltrexone group were significantly more likely to have increased days abstinent (p=0.002) and to complete the program abstinent (p=0.051). The adjunctive use of naltrexone did not provide additional benefit as reflected in SF-36 and GHQ-28 scores, beyond CBT alone. CONCLUSIONS: Patients who completed the CBT-based treatment program reported significant improvements in self-reported health status (SF-36) and wellbeing (GHQ-28). The adjunctive use of naltrexone demonstrated no additional improvement in these measures.

The long-term survival of baboon-to-monkey kidney and liver xenografts.

The present study was undertaken to develop an optimum immunosuppressive regimen in baboon-to-monkey life-supporting kidney xenografts. Baseline therapy for all groups include cyclosporine (CsA) and steroids. We compared adding (1) cyclophosphamide (CyP) at dose of 20 mg/kg/day given on post-operative day (POD) 0, 2, 5 and 7; (2) mycophenolic mofetil (MMF) at a dose of 40 mg/kg/day by daily gavage; or (3) CyP + rapamycin (Rap). The latter group was divided into high and low dose subgroups. Untreated xenografts were rejected on POD 6, CsA alone treated xenografts survived for 35 days and CsA + CyP treated xenografts survived for 45 days. Adding MMF significantly prolonged mean survival to 111 +/- 53 days, but the xenografts eventually developed rejection. Combination therapy including CsA, CyP and Rap reliably prevented xenogenic rejection and achieved a mean survival of 290 +/- 30 days. However, high dose CyP + Rap led to high incidence of post-transplant lymphoproliferation disorders (PTLD), while the incidence of PTLD was significantly less in the low dose subgroup (P < 0.01). Four animals in this subgroup survived for more than 300 days with normal renal function and histology. In addition, two liver recipients treated with CsA + CyP survived for 91 and 1,076 days. We conclude that long-term survival of kidney or liver xenografts can be achieved in a non-human concordant xenograft model using currently available immunosuppressive agents.

Cognitive behavioural therapy combined with the relapse-prevention medication acamprosate: are short-term treatment outcomes for alcohol dependence improved?

OBJECTIVE: The relapse prevention medication acamprosate has been recently introduced to the Australian Pharmaceutical Benefits Scheme (PBS) for the treatment of alcohol dependence. Overseas clinical trials have demonstrated the efficacy of using acamprosate as an adjunct to existing psychotherapeutic approaches. Research has not examined treatment outcomes using a standardized clinical approach. The objective of this study is to investigate the impact of adding acamprosate to an established abstinence-based outpatient alcohol rehabilitation programme in an Australian population. METHODS: Fifty patients participated in an established 12-week, outpatient, "contract" based Cognitive Behavioural Therapy (CBT) alcohol abstinence programme and received acamprosate (CBT + acamprosate). Patients weighing > or = 60 kg were prescribed acamprosate calcium 333 mg tablets, two tablets three times daily (1998 mg/day) and those weighing < 60 kg received four tablets (1332 mg/day) daily. Outcomes were compared with 50 historical, matched controls, all of whom participated in the same program without a relapse prevention medication (CBT alone). All patients met DSM-IV criteria for alcohol dependence and the majority were socially disadvantaged. RESULTS: Programme attendance across the eight treatment sessions was similar in both the CBT + acamprosate and the CBT alone conditions (P = 0.268). Relapse to alcohol use occurred sooner and more frequently in the CBT alone group (P = < 0.0005). Rehabilitation programme completion at 12 weeks was 42% (CBT + acamprosate) compared with 32% for (CBT alone) (P = < 0.204). Alcohol abstinence at 12 weeks was 38% (CBT + acamprosate) compared with 14% (CBT alone) (P = < 0.006). CONCLUSION: Even within an alcohol dependent population characterized by poor prognostic indices, the addition of acamprosate to an established CBT outpatient programme significantly improved abstinence rates over a 12-week period. The use of acamprosate as an adjunctive treatment for alcohol dependence should be encouraged in Australia.