Future treatment strategies of aggressive pituitary tumors

While surgery remains the first-line treatment of most aggressive pituitary adenomas, medical therapy is important as second-line or adjunctive therapy in a large proportion of patients. Dopamine agonists (DAs) are the best treatment for prolactinomas, but when DAs are not tolerated, new somatostatin receptor subtype 5 (SSTR5) inhibitors may offer an alternative in the future. Unfortunately, these are unlikely to be effective in DA-resistant prolactinomas. In acromegaly, the existing somatostatin analogs, octreotide and lanreotide, will remain the medical treatment of choice for the foreseeable future. There is an urgent need for medical therapies in Cushing’s disease, and the SSTR5 analogs could offer an effective treatment in a proportion of patients within the next few years. Finally, the medical management options for non-functioning pituitary adenomas are also very limited, and a new chimeric agent with activity towards dopamine receptors, SSTR5 and SSTR2 may help reduce adenoma recurrence in the future

Addition of insulin glargine or NPH insulin to metformin monotherapy in poorly controlled type 2 diabetic patients decreases IGF-I bioactivity similarly

Aims/hypothesis The aim of this study was to compare IGFI bioactivity 36 weeks after the addition of insulin glargine (A21Gly,B31Arg,B32Arg human insulin) or NPH insulin to metformin therapy in type 2 diabetic patients who had poor glucose control under metformin monotherapy. Methods In the Lantus plus Metformin (LANMET) study, 110 poorly controlled insulin-naive type 2 diabetic patients were randomised to receive metformin with either insulin glargine (G+MET) or NPH insulin (NPH+MET). In the present study, IGF-I bioactivity was measured, retrospectively, in 104 out of the 110 initially included LANMET participants before and after 36 weeks of insulin therapy. IGF-I bioactivity was measured using an IGF-I kinase receptor activation assay. Results After 36 weeks of insulin therapy, insulin doses were comparable between the G+MET (68±5.7 U/day) and NPH+MET (71±6.2 U/day) groups (p=0.68). Before insulin therapy, circulating IGF-I bioactivity was similar between the G+MET (134±9 pmol/l) and NPH+MET (135 ±10 pmol/l) groups (p=0.83). After 36 weeks, IGF-I bioactivity had decreased significantly (p=0.001) and did not differ between the G+MET (116±9 pmol/l) and NPH+MET (117± 10 pmol/l) groups (p=0.91). At baseline and after insulin therapy, total IGF-I concentrations were comparable in both groups (baseline: G+MET 13.3±1.0 vs NPH+MET 13.3± 1.0 nmol/l, p=0.97; and 36 weeks: 13.4±1.0 vs 13.1± 0.9 nmol/l, p=0.71). Total IGF-I concentration did not change during insulin therapy (13.3±0.7 vs 13.3±0.7 nmol/l, baseline vs 36 weeks, p=0.86). Conclusions/interpretation Addition of insulin glargine or NPH insulin to metformin monotherapy in poorly controlled type 2 diabetic patients decreases serum IGF-I bioactivity in a similar manner

Episodic Abdominal Pain Characteristics Are Not Associated with Clinically Relevant Improvement of Health Status After Cholecystectomy

Background:  Cholecystectomy is the therapy of first choice in patients with uncomplicated symptomatic cholecystolithiasis, but it remains unclear which patients truly benefit in terms of health status improvement. Patients generally present with episodic abdominal pain of varying frequency, duration, and intensity. We assessed whether characteristics of abdominal pain episodes are determinants of clinically relevant improvement of health status after cholecystectomy. Methods:  In a post hoc analysis of a prospective multicenter cohort study, patients of ≥18 years of age with uncomplicated symptomatic cholecystolithiasis subjected to cholecystectomy were included. Preoperatively, patients received a structured interview and a questionnaire consisting of the visual analogue scale (VAS; range 0-100) and gastrointestinal quality of life index (GIQLI). At 12 weeks after cholecystectomy, the GIQLI was again administered. Logistic regression analyses were performed to determine significant associations. Results:  Questionnaires were sent to 261 and returned by 166 (63.6 %) patients (128 females, mean age at surgery 49.5 ± 13.8). A total of 131 (78.9 %) patients reported a clinically relevant improvement of health status. The median (interquartile range) frequency, duration, and intensity of abdominal pain episodes were 0.38 (0.18-0.75) a week, 4.00 (2.00-8.00) hours, and 92 (77-99), respectively. None of the characteristics was associated with a clinically relevant improvement of health status at 12 weeks after cholecystectomy. Conclusions:  Characteristics of abdominal pain episodes cannot be used to inform patients with symptomatic cholecystolithiasis who are skeptic about the timing of cholecystectomy for optimal benefit. Timing of cholecystectomy should therefore be based on other characteristics and preferences

Role of the general practitioner during the active breast cancer treatment phase: an analysis of health care use

PURPOSE: Little is known about the actual involvement of the general practitioner (GP) during the active breast cancer treatment phase. Therefore, this study explored (disease-specific) primary health care use among women undergoing active treatment for breast cancer compared with women without breast cancer. METHODS: A total of 185 women with a first diagnosis of early-stage breast cancer between 1998 and 2007 were identified in the primary care database of the Registration Network Groningen and matched with a reference population of 548 women without breast cancer on birth year and GP. RESULTS: Since diagnosis, patients with breast cancer had twice as many face-to-face contacts compared with women from the reference population (median 6.0 vs 3.0/year, Mann-Whitney (M-W) test p < 0.001). The median number of drug prescriptions and referrals was also significantly higher among patients than among the reference population (11.0 vs 7.0/year, M-W test p < 0.001 and 1.0 vs 0.0/year, M-W test p < 0.001). More patients than women from the reference population had face-to-face contacts or were prescribed drugs for reasons related to breast cancer and its treatment, including gastrointestinal problems, psychological reasons and endocrine therapy. CONCLUSIONS: During the active breast cancer treatment phase, GPs are involved in the management of treatment-related side effects and psychological symptoms, as well as in the administration of endocrine therapy. Based on the findings of this study, interventions across the primary/secondary interface can be planned to improve quality of life and other outcomes in patients undergoing breast cancer treatment

Transcriptome-Wide Assessment of Human Brain and Lymphocyte Senescence

Identifying biological pathways that vary across the age spectrum can provide insight into fundamental mechanisms that impact disease and frailty in the elderly. Few methodological approaches offer the means to explore this question on as broad a scale as gene expression profiling. Here, we have evaluated mRNA expression profiles as a function of age in two populations; one consisting of 191 individuals with ages-at-death ranging from 65-100 years and with post-mortem brain mRNA measurements of 13,216 genes and a second with 1240 individuals ages 15-94 and lymphocyte mRNA estimates for 18,519 genes.Among negatively correlated transcripts, an enrichment of mitochondrial genes was evident in both populations, providing a replication of previous studies indicating this as a common signature of aging. Sample differences were prominent, the most significant being a decrease in expression of genes involved in translation in lymphocytes and an increase in genes involved in transcription in brain, suggesting that apart from energy metabolism other basic cell processes are affected by age but in a tissue-specific manner. In assessing genomic architecture, intron/exon sequence length ratios were larger among negatively regulated genes in both samples, suggesting that a decrease in the expression of non-compact genes may also be a general effect of aging. Variance in gene expression itself has been theorized to change with age due to accumulation of somatic mutations and/or increasingly heterogeneous environmental exposures, but we found no evidence for such a trend here.Results affirm that deteriorating mitochondrial gene expression is a common theme in senescence, but also highlight novel pathways and features of gene architecture that may be important for understanding the molecular consequences of aging

Medical treatment of prolactinomas.

Prolactinomas, the most prevalent type of neuroendocrine disease, account for approximately 40% of all pituitary adenomas. The most important clinical problems associated with prolactinomas are hypogonadism, infertility and hyposexuality. In patients with macroprolactinomas, mass effects, including visual field defects, headaches and neurological disturbances, can also occur. The objectives of therapy are normalization of prolactin levels, to restore eugonadism, and reduction of tumor mass, both of which can be achieved in the majority of patients by treatment with dopamine agonists. Given their association with minimal morbidity, these drugs currently represent the mainstay of treatment for prolactinomas. Novel data indicate that these agents can be successfully withdrawn in a subset of patients after normalization of prolactin levels and tumor disappearance, which suggests the possibility that medical therapy may not be required throughout life. Nevertheless, multimodal therapy that involves surgery, radiotherapy or both may be necessary in some cases, such as patients who are resistant to the effects of dopamine agonists or for those with atypical prolactinomas. This Review reports on efficacy and safety of pharmacotherapy in patients with prolactinomas

Functional outcome in older adults with joint pain and comorbidity: design of a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Joint pain is a highly prevalent condition in the older population. Only a minority of the older adults consult the general practitioner for joint pain, and during consultation joint pain is often poorly recognized and treated, especially when other co-existing chronic conditions are involved. Therefore, older adults with joint pain and comorbidity may have a higher risk of poor functional outcome and decreased quality of life (QoL), and possibly need more attention in primary care. The main purpose of the study is to explore functioning in older adults with joint pain and comorbidity, in terms of mobility, functional independence and participation and to identify possible predictors of poor functional outcome. The study will also identify predictors of decreased QoL. The results will be used to develop prediction models for the early identification of subgroups at high risk of poor functional outcome and decreased QoL. This may contribute to better targeting of treatment and to more effective health care in this population.</p> <p>Methods/Design</p> <p>The study has been designed as a prospective cohort study, with measurements at baseline and after 6, 12 and 18 months. For the recruitment of 450 patients, 25 general practices will be approached. Patients are eligible for participation if they are 65 years or older, have at least two chronic conditions and report joint pain on most days. Data will be collected using various methods (i.e. questionnaires, physical tests, patient interviews and focus groups). We will measure different aspects of functioning (e.g. mobility, functional independence and participation) and QoL. Other measurements concern possible predictors of functioning and QoL (e.g. pain, co-existing chronic conditions, markers for frailty, physical performance, psychological factors, environmental factors and individual factors). Furthermore, health care utilization, health care needs and the meaning and impact of joint pain will be investigated from an older person's perspective.</p> <p>Discussion</p> <p>In this paper, we describe the protocol of a prospective cohort study in Dutch older adults with joint pain and comorbidity and discuss the potential strengths and limitations of the study.</p

Tailored Print Communication and Telephone Motivational Interviewing Are Equally Successful in Improving Multiple Lifestyle Behaviors in a Randomized Controlled Trial

Background: Computer tailoring and motivational interviewing show promise in promoting lifestyle change, despite few head-to-head comparative studies. Purpose: Vitalum is a randomized controlled trial in which the efficacy of these methods was compared in changing physical activity and fruit and vegetable consumption in middle-aged Dutch adults. Methods: Participants (n?=?1,629) were recruited via 23 general practices and randomly received either four tailored print letters, four motivational telephone calls, two of each type of intervention, or no information. The primary outcomes were absolute change in self-reported physical activity and fruit and vegetable consumption. Results: All three intervention groups (i.e., the tailored letters, the motivational calls, and the combined version) were equally and significantly more effective than the control group in increasing physical activity (hours/day), intake of fruit (servings/day), and consumption of vegetables (grams/day) from baseline to the intermediate measurement (week 25), follow-up 1 (week 47) and 2 (week 73). Effect sizes (Cohen's d) ranged from 0.15 to 0.18. Participants rated the interventions positively; interviews were more positively evaluated than letters. Conclusions: Tailored print communication and telephone motivational interviewing or their combination are equally successful in changing multiple behaviors. © 2010 The Author(s)