Australian women's understanding of menopause and its consequences: a qualitative study.

BACKGROUND: This study was undertaken to determine women's knowledge of menopause and its consequences, and their menopause-related health-care experiences. METHODS: Participants were recruited to this cross-sectional qualitative study from a nationally, representative sample of Australian women. Recruitment was stratified by age to achieve groups of premenopausal (PRE), perimenopausal (PERI), early postmenopausal (E-POST), and late postmenopausal (L-POST) women. RESULTS: The 32 participants were aged 46-69 years: 10 PRE, three PERI, 11 E-POST and eight L-POST women. All understood that menopause meant the end of reproductive function and were aware of menopause-associated symptoms. Most PRE and E-POST women referred to lifestyle changes to optimize health, and self-help and complementary therapies to manage symptoms. E-POST and L-POST women were more likely to nominate seeing a doctor for overall health and symptom management. Menopausal hormone therapy (MHT) was viewed negatively, with shared perceptions of cancer risk and over-prescription. A strong theme was lack of knowledge of long-term menopause sequelae, with only four women nominating osteoporosis. CONCLUSIONS: Our in-depth qualitative study would suggest that, while Australian midlife women have a good understanding of the immediate effects of menopause, their lack of knowledge of the long-term consequences is concerning. Despite the effectiveness and safety of MHT, the overall attitude to MHT remains negative.

Dosing vitamin C in critically ill patients with special attention to renal replacement therapy: a narrative review.

RATIONALE/METHODS: The primary aim of the present contribution is to find a literature-based agreement on dose adjustments of vitamin C in critically ill patients undergoing renal replacement therapy (RRT). AVAILABLE DATA/STUDY RESULTS: Critical illness is frequently accompanied by severe vitamin C deficiency. High-dose supplementation beneficially affects clinical outcome in small cohorts of patients with sepsis, burn injury, and trauma. There are no specific data on clinical outcomes in patients receiving renal replacement therapy (RRT). Vitamin C plasma concentrations in patients on RRT are comparable to critically ill patients not receiving RRT. Vitamin C is cleared from the circulation during RRT at a rate dependent on the plasma concentration, dose and duration of RRT. Sieving coefficient is about 1. While the dose of RRT is lower than normal renal function, tubular reabsorption is absent. Sparse evidence suggests that vitamin C dosing during continuous RRT should not exceed the dose administered to critically ill patients not receiving continuous RRT. Low plasma concentrations are expected during prolonged RRT because of persistent extracorporeal removal, absent renal reabsorption and enhanced metabolic loss due to circuit-induced oxidative stress. A dosage of twice 1 g vitamin C daily may be necessary to achieve normal plasma concentrations during RRT, but more studies are needed. There is no available evidence that high doses of vitamin C administered over a short period can induce oxalate stones or has pro-oxidant effects. CONCLUSIONS: Supplementing vitamin C 1 g twice daily to critically ill patients has a solid pathophysiological rationale and a good safety profile. Patients on RRT probably need similar doses as critically ill patients not receiving RRT. Intravenous vitamin C in a dose of 2 g/day may be necessary to achieve normal plasma concentrations during RRT. However, data on dose adjustment of vitamin C during intermittent or chronic RRT are sparse and require more thorough pharmacokinetic and dose-response studies.

Minding the brain: the role of pharmacotherapy in substance-use disorder treatment.

With its medicalization as a brain-based disease, addiction has come to be regarded as amenable to biomedical treatment approaches, most commonly pharmacotherapy. Various vulnerabilities are recognized to contribute to maladaptive substance use, and have been linked to diverse neurobiological alterations that may be targeted with pharmacotherapy: withdrawal, craving and cue reactivity, and aberrant reward processing are the most significant. Here, we summarize current thinking regarding pharmacotherapy for substance-use disorders, grouping medications by the type of vulnerability they propose to address and providing insight into their neurobiological mechanisms. We also examine the limitations of the brain-based disease model in addiction treatment, especially as these shortcomings pertain to the place of pharmacotherapy in recovery. We conclude by sketching a framework whereby medications might be integrated fruitfully with other interventions, such as behavioral, existential, or peer-based treatments, targeting aspects of addiction beyond neurobiological deficits.

La medicalización de la adicción como una enfermedad de base cerebral, ha llegado a ser considerada como una condición sensible a un abordaje terapéutico biomédico, en especial con farmacoterapia. Se han reconocido diversas vulnerabilidades que contribuyen a la mala adaptación al uso de sustancias, las cuales se han vinculado con diversas alteraciones neurobiológicas y con blancos farmacológicos; las más importantes son la abstinencia, el craving y la reactividad a señales, junto con el procesamiento aberrante de la recompensa. En este artículo se resume el pensamiento actual relacionado con la farmacoterapia para los trastornos por uso de sustancias, se agrupan los medicamentos de acuerdo con el tipo de vulnerabilidad a la que ellos están dirigidos y se proporciona una visión acerca de sus mecanismos neurobiológicos. También se examinan las limitaciones del modelo de enfermedad cerebral en el tratamiento de las adicciones, especialmente porque estas alteraciones se relacionan con el papel que tiene la farmacoterapia en la recuperación. Para concluir se propone un esquema en que los medicamentos se pueden integrar de manera fructífera con otras intervenciones como los tratamientos conductuales, existenciales o basados en pares, focalizando aspectos de la adicción más allá de las alteraciones neurobiológicas.

Médicalisée comme une maladie cérébrale, l'addiction est maintenant considérée comme étant susceptible de répondre à des traitements biomédicaux, le plus souvent de la pharmacothérapie. Des vulnérabilités diverses, responsables de l'utilisation inadaptée de substances, sont liées à différentes altérations neurobiologiques et représentent des cibles pharmacologiques dont les plus significatives sont le sevrage, l'état de manque, la réactivité aux indices environnementaux et un fonctionnement anormal du circuit de la récompense. Nous résumons ici les concepts actuels sur la pharmacothérapie des troubles liés à l'utilisation de substances en regroupant les médicaments par type de vulnérabilité traitée et en donnant un aperçu de leurs mécanismes neurobiologiques. Nous analysons aussi les limites du modèle de maladie cérébrale dans le traitement des addictions, surtout lorsque ces failles concernent la place de la pharmacothérapie dans la guérison. Nous concluons en esquissant un cadre selon lequel les médicaments pourraient trouver leur place avec succès aux côtés d'autres traitements comme les traitements comportementaux, existentiels ou collégiaux et qui ciblent des aspects de l'addiction au-delà des déficits neurobiologiques.

Older, Less Regulated Medical Marijuana Programs Have Much Greater Enrollment Rates Than Newer 'Medicalized' Programs.

Twenty-three states and the District of Columbia have passed laws implementing medical marijuana programs. The nineteen programs that were in operation as of October 2014 collectively had over one million participants. All states (including D.C.) with medical marijuana laws require physicians directly or indirectly to authorize the use of marijuana at their discretion, yet little is known about how medical marijuana programs vary regarding adherence to basic principles of medical practice and associated rates of enrollment. To explore this, we analyzed marijuana programs according to seven components of traditional medical care and pharmaceutical regulation. We then examined enrollment rates, while controlling for potentially confounding state characteristics. We found that fourteen of the twenty-four programs were nonmedical and collectively enrolled 99.4 percent of participants nationwide, with enrollment rates twenty times greater than programs deemed to be "medicalized." Policy makers implementing or amending medical marijuana programs should consider the powerful relationship between less regulation and greater enrollment. Researchers should consider variations across programs when assessing programs' population-level effects.

Nutritional and metabolic alterations during continuous renal replacement therapy.

Adequate feeding of critically ill patients under continuous renal replacement therapy (CRRT) remains a challenging issue. We performed a systematic search of the literature published between 1992 and 2012 using the quorum guidelines regarding nutrition in intensive care unit patients treated with CRRT. Daily recommended energy requirements during CRRT are between 25 and 35 kcal/kg with carbohydrates and lipids accounting for 60-70% and 30-40% of calorie intake, respectively. Daily protein needs range from 1.5 to 1.8 g/kg. Indirect calorimetry corrected for CRRT-induced CO2 diversion should be used to more correctly match calorie intake to the real needs. This type of tool is not yet available but hopefully soon. Electrolyte deficit as well as overload have been described during CRRT but, in general, can be easily controlled. Although not strongly evidenced, consensus exists to supplement important micronutrients such as amino acids (glutamine), water-soluble vitamins and trace elements.

Hemodialysis in chronic kidney disease--balancing fluid and salt on the inflammation tightrope.

Haemodialysis (HD) is a well-established, longstanding, and life-saving treatment for patients with chronic kidney disease (CKD) or acute kidney injury (AKI). However, side-effects of HD in CKD patients are numerous and remain problematic. Amongst others, CKD patients are susceptible to short-term effects caused by abnormalities in water and electrolyte balance and long-term effects related to sustained inflammation short-term side-effects of HD such as errors in sodium content of dialysate could readily be overcome by correct baseline labelling of dialysates and the ongoing rigorous implementation of safety procedures by staff nurses and physicians. The proper implementation of biofeedback systems, with tight safety alarm limits and conductivity based detection systems including the analysis of ionic mass balance could have prevented the shortfalls described. Long-term untoward effects of HD are mainly due to sustained inflammation and are correlated with higher morbidity and mortality. Unfortunately, the pathophysiologic mechanisms that underpin the inflammatory processes induced by HD remain poorly understood or incompletely unravelled. Within the wide array of inflammatory (inter)actions, cytokines are undoubtedly key players but interesting biomarkers (e.g. follistatin) and pathways (e.g. erythropoietin hyporesponsiveness) have come into play. Therapeutic interventions in differing fields such as vascular access, avoidance of intra-dialytic hypotension and pharmacologic interventions with statins, angiotensin II receptor antagonists or vitamine D supplementation may be of significance. However, confirmatory trials investigating of all these promising therapies are, as yet, lacking. The impact of the dialysis technique itself should not be underestimated.

Behavioral naltrexone therapy: an integrated treatment for opiate dependence.

Treatment of opiate dependence with naltrexone has been limited by poor compliance. Behavioral Naltrexone Therapy (BNT) was developed to promote adherence to naltrexone and lifestyle changes supportive of abstinence, by incorporating components from empirically validated treatments, including Network Therapy with a significant other to monitor medication compliance, the Community Reinforcement Approach, and voucher incentives. An overview is presented of the BNT treatment manual. In an uncontrolled Stage I trial (N = 47), 19% completed the 6-month course of treatment. Retention was especially poor in the subsample of patients who were using methadone at baseline (N = 18; 39% completed 1 month, none completed 6 months), and more encouraging among heroin-dependent patients (N = 29; 65% completed 1 month, 31% completed 6 months). Thus, attrition continues to be a serious problem for naltrexone maintenance, although further efforts to develop interventions such as BNT are warranted.

Acupuncture for the treatment of cocaine addiction: a randomized controlled trial.

CONTEXT: Auricular acupuncture is widely used to treat cocaine addiction in the United States and Europe. However, evidence from controlled studies regarding this treatment's effectiveness has been inconsistent. OBJECTIVE: To investigate the effectiveness of auricular acupuncture as a treatment for cocaine addiction. DESIGN: Randomized, controlled, single-blind clinical trial conducted from November 1996 to April 1999. SETTING: Six community-based clinics in the United States: 3 hospital-affiliated clinics and 3 methadone maintenance programs. PATIENTS: Six hundred twenty cocaine-dependent adult patients (mean age, 38.8 years; 69.2% men); 412 used cocaine only and 208 used both opiates and cocaine and were receiving methadone maintenance. INTERVENTION: Patients were randomly assigned to receive auricular acupuncture (n = 222), a needle-insertion control condition (n = 203), or a relaxation control condition (n = 195). Treatments were offered 5 times weekly for 8 weeks. Concurrent drug counseling was also offered to patients in all conditions. MAIN OUTCOME MEASURES: Cocaine use during treatment and at the 3- and 6-month postrandomization follow-up based on urine toxicology screens; retention in treatment. RESULTS: Intent-to-treat analysis of urine samples showed a significant overall reduction in cocaine use (odds ratio, 1.40; 95% confidence interval, 1.11-1.74; P =.002) but no differences by treatment condition (P =.90 for acupuncture vs both control conditions). There were also no differences between the conditions in treatment retention (44%-46% for the full 8 weeks). Counseling sessions in all 3 conditions were poorly attended. CONCLUSIONS: Within the clinical context of this study, acupuncture was not more effective than a needle insertion or relaxation control in reducing cocaine use. Our study does not support the use of acupuncture as a stand-alone treatment for cocaine addiction or in contexts in which patients receive only minimal concurrent psychosocial treatment. Research will be needed to examine acupuncture's contribution to addiction treatment when provided in an ancillary role.

YY1 and Sp1 transcription factors bind the human transferrin gene in an age-related manner.

The iron-binding protein transferrin has major roles in transporting, delivering, and sequestering ferric ions acquired by body tissues. Yet, during aging, serum transferrin levels decrease in humans. Likewise, in transgenic mice carrying chimeric human transferrin transgenes, liver expression of transferrin transgenes decreases with age. The aging regulation is due to decreased gene transcription. Electrophoretic mobility shift assays and antibody-recognition have revealed the binding of 5' regulatory elements of the human transferrin gene by three YY1 proteins, called YY1, YY1-a, and YY1-b, and an Sp1-a transcription factor. An age-related increase in YY1-a and YY1-b binding activities and a decrease in Sp1-like binding activity were shown. Since Sp1 is a positive transcription factor and YY1 can be a negative transcription factor, the alterations in their binding with age could cause the decreased transcription of the human transferrin transgene, and also the age-related decreased serum transferrin levels in humans.

In vitro experiments with Centella asiatica: investigation to elucidate the effect of an indigenously prepared powder of this plant on the acid-fastness and viability of M. tuberculosis.

The herb Centella asiatica (Linn.), found throughout India, is acclaimed to have medicinal properties and has been used in leprosy patients from very early times. It is considered that the active compound of this herb, called asiaticoside, probably acts on the waxy covering of M. leprae. The in vitro effect of an indigenously produced dry powder of Centella asiatica (CA) on the acid-fastness and viability of M. tuberculosis was investigated in the present study. The results indicate that CA may not have any direct action on the acid-fastness or viability of M.tuberculosis H37Rv in vitro. Further studies using purified asiaticoside of the plant or in vivo studies are required.

The effect of long-term diethylstilbestrol treatment or hyperprolactinemia on the response of the tuberoinfundibular dopamine neurons to elevated prolactin.

Adult male rats were rendered hyperprolactinemic by two different methods. Some animals received subcutaneous implants of diethylstilbestrol (DES) or empty capsules. After 2 months the capsules were removed. Other rats received 3 anterior pituitary homografts under the kidney capsule or had sham surgery. The DES-treated rats were killed 8 months after capsule removal, while pituitary-grafted rats were killed 4 or 12 months after surgery. The DES-treated rats had hyperplastic anterior pituitaries, and both the DES-treated rats and the rats with anterior pituitary homografts were hyperprolactinemic. The activity of the TIDA neurons, as evidenced by dopamine (DA) synthesis in the median eminence (ME), was markedly and comparably elevated in both of these experimental groups of rats when compared to their respective controls. These data: show that the maintenance of hyperplastic pituitaries 8 months after DES withdrawal is not due to impaired function of the TIDA neurons; and provide no evidence for a neurotoxic effect of prolonged hyperprolactinemia on the response of the TIDA neurons to elevated PRL.

Effects of estrogen-induced hyperprolactinemia on endocrine and sexual functions in adult male rats.

Chronic estrogen treatment can lead to development of prolactin (PRL) secreting pituitary tumors. We have tested the ability of diethylstilbestrol (DES) to produce persistent hyperprolactinemia (hyperPRL) in adult male rats and examined the effects of this treatment on hypothalamic-pituitary-testicular function, adenohypophyseal structure, copulatory behavior and fertility. Silastic capsules containing approximately 5 mg DES were subcutaneously implanted into adult male CDF (F-344)/CrlBR rats and removed 15 or 20 weeks later. Extreme hyperPRL, as well as suppression of plasma LH and FSH levels, persisted after DES capsules were removed. In contrast, plasma testosterone levels increased rapidly after removal of DES capsules and reached normal levels within 4-6 weeks. Copulatory behavior was assessed on two occasions between 7 and 14 weeks after removal of the DES capsules and was found to be suppressed in DES-treated rats, as evidenced by significant increases in latencies to mount, to intromit and to ejaculate. Moreover, when the animals were placed with normal females, the interval until conception was significantly greater in DES-treated than in control males. In spite of these differences in copulatory behavior, 10 of 11 DES-treated males were fertile. At autopsy, 44 weeks after capsule implantation (i.e. 24 or 29 weeks after capsule removal), DES-treated rats had marked enlargement of the anterior pituitary, increased weights of the lateral prostate and the adrenals, increased levels of testicular hCG-binding sites, reduced concentration of dopamine and norepinephrine in the median eminence and increased concentration of LHRH in the preoptic area.(ABSTRACT TRUNCATED AT 250 WORDS)