Weeks Of Active Treatment Research Articles

OP.LB03.09] THE ACUTE EFFECT OF THE SPECIFIC CREATINE KINASE INHIBITOR BETA- GPA IN HEALTHY MAN (ABC-TRIAL)

Objective: There is increasing evidence that the ATP generating enzyme creatine kinase (CK) is involved in hypertension. The enzyme is central to the regeneration of ATP by using creatine phosphate and ADP, thereby forming creatine and ATP. We recently showed that beta-guanidinopropionic acid (GPA), a creatine analogue and competitive CK inhibitor, effectively and safely reduced blood pressure in the spontaneously hypertensive rat. This renders GPA to be potentially beneficial for blood pressure lowering. However, no human data are available. Therefore, according to FDA and EMEA guidelines, we assessed the tolerability of a subtherapeutic GPA dose in man.Design and method: In this randomized, placebo and active controlled, triple blind, single center trial (randomization 1:1:1), we included healthy male volunteers, 18 to 50 years old, BMI 18.5–29.9 kg/m2, recruited in the Netherlands. The interventions consisted of one week daily oral administration of GPA in a subtherapeutic dose of 100 mg, creatine 5 gram, or placebo. The primary outcome was the tolerability of GPA as a descriptive measure, in an intent-to-treat analysis. Results: Twenty four randomized participants received the allocated intervention (8 in each treatment arm) and 23 completed the study. One participant in the placebo arm dropped out because of an external event in his family. He experienced no side effects, including not during a re-challenge with the assigned drug. GPA was well tolerated. There were no serious or severe adverse events with GPA, creatine and placebo after 1 week of active treatment, and no significant differences in safety measures including self-reported data obtained with structured and unstructured questionnaires. No abnormalities were reported from physical examination, laboratory determined toxicity including kidney and liver parameters, or cardiovascular safety including QT interval between treatment arms (Table 1). Conclusions: To our knowledge, these are the first human data of the specific CK inhibitor and potential new blood pressure lowering agent GPA. We found no evidence of toxicity with subtherapeutic doses, and will proceed to assess safety and tolerance in a dose-escalation trial in humans. Clinical trial registration number The Netherlands National Trial Register (NTR) number 4444, registered March 9, 2014.

Modulation of nociceptive threshold by combined hormonal contraceptives in women with oestrogen-withdrawal migraine attacks: a pilot study

BackgroundMenstrually-related headache and headaches associated with oestrogen withdrawal are common conditions, whose pathophysiology has not been completely elucidated. In this study we evaluated the influence of combined hormonal contraceptives (CHC) on pain threshold in women presenting migraine attacks during hormone-free interval.FindingsEleven women with migraine attacks recurring exclusively during the oestrogen-withdrawal period were studied with the nociceptive flexion reflex, a neurophysiological assessment of the pain control systems, during the third week of active treatment and during the hormone-free interval.During the hormone-free interval, nociceptive withdrawal reflex threshold was significantly lower (12.8 ± 8.0 mA) as compared to the third week of hormonal treatment (15.6 ± 6.6 mA) (p = 0.02). No change was observed in the pain perceived and in the temporal summation.ConclusionsOestrogen withdrawal may mediate an increased sensitivity to somatosensory stimuli in women with migraine attacks recurring during the hormone-free interval.

Bone Mineral Density Changes Among Young, Healthy African Women Receiving Oral Tenofovir for HIV Preexposure Prophylaxis.

Background:Limited data exist on effect of tenofovir disoproxil fumarate (TDF) when used for preexposure prophylaxis (PrEP) on bone mineral density (BMD) in HIV-negative women. We evaluated the effect of daily oral TDF and emtricitabine/TDF compared with placebo on BMD among women enrolled in an HIV-1 PrEP trial.Methods:HIV-uninfected women in Uganda and Zimbabwe had BMD measurements of lumbar spine (LS) and total hip (TH) by dual-energy x-ray absorptiometry at baseline and every 24 weeks for 48 weeks of active treatment and for 48 weeks after discontinuation of study medication. Plasma tenofovir levels were assessed every 12 weeks for the first 48 weeks.Results:Of 518 women enrolled, 432 had dual-energy x-ray absorptiometry results at baseline and week 48. In the primary analysis, no significant differences in percent BMD change in hip or spine between arms observed, likely because of low product adherence. Among the subset with tenofovir detection in 75%–100% of plasma samples, the mean percent BMD change from baseline to week 48 in the LS was 1.4% lower for TDF or emtricitabine/TDF recipients than for placebo (P = 0.002) and TH BMD was 0.9% lower (P = 0.018). BMD changes from end of active treatment to 48 weeks were significantly greater in the active arm participants compared with placebo participants with a net difference of approximately +0.9% at the LS (P = 0.007) and +0.7% (P = 0.003) at the TH.Conclusions:TDF-containing oral PrEP resulted in small but significant reversible decreases in hip and spine BMD among young African women.

Testofen, a specialised Trigonella foenum-graecum seed extract reduces age-related symptoms of androgen decrease, increases testosterone levels and improves sexual function in healthy aging males in a double-blind randomised clinical study

This study examined the effect of Testofen, a specialised Trigonella foenum-graecum seed extract on the symptoms of possible androgen deficiency, sexual function and serum androgen concentrations in healthy aging males. This was a double-blind, randomised, placebo-controlled trial involving 120 healthy men aged between 43 and 70 years of age. The active treatment was standardised Trigonella foenum-graecum seed extract at a dose of 600 mg/day for 12 weeks. The primary outcome measure was the change in the Aging Male Symptom questionnaire (AMS), a measure of possible androgen deficiency symptoms; secondary outcome measures were sexual function and serum testosterone. There was a significant decrease in AMS score over time and between the active and placebo groups. Sexual function improved, including number of morning erections and frequency of sexual activity. Both total serum testosterone and free testosterone increased compared to placebo after 12 weeks of active treatment. Trigonella foenum-graecum seed extract is a safe and effective treatment for reducing symptoms of possible androgen deficiency, improves sexual function and increases serum testosterone in healthy middle-aged and older men.

Effects of Green Tea and Coffee Polyphenols on Cardiometabolic Function in Women with Polycystic Ovary Syndrome

Green tea (catechins, GTC) and coffee polyphenols (chlorogenic acids, CGA) have been associated with reduced diabetes and cardiovascular risk. However, detailed investigations in at risk populations are needed to corroborate their efficacy and understand the underlying mechanisms. This study aimed to evaluate the effects of a combined supplementation of GTC and CGA on insulin sensitivity (SI), nitric oxide (NO) production and cardiometabolic risk factors in women with polycystic ovary syndrome (PCOS), a condition characterized by insulin resistance, endothelial dysfunction and increased cardiometabolic risk. In a 16‐week, single‐blind, unilateral crossover trial, 12 PCOS women (mean ± SD: age, 28 ± 10 y; BMI, 35 ± 7 kg/m2; fasting insulin, 97 ± 52 pmol/L) underwent 8 weeks of placebo treatment followed by 8 weeks of active treatment (tablets providing 2093 mg GTC and 220 mg CGA/day). At baseline, post‐placebo and post‐active treatments participants undertook glucose tolerance and oral nitrate tests for isotopic assessment of SI and NO production and additional cardiometabolic risk factors were measured. The polyphenol intervention did not improve SI and NO production, but it was associated with reduced waist circumference (MD: 2.4 cm; P = 0.02), altered eicosanoid profile and non‐significant trends for reductions in diastolic blood pressure, total and LDL cholesterol. Combined intake of GTC and CGA may modulate eicosanoid pathways, thereby reducing inflammation and abdominal adiposity. These changes may prove cardioprotective in at risk populations, in longer term intervention studies. 
 [MRC UK]

Cough reduction using capsaicin

Chronic unexplained cough triggered by environmental irritants is characterized by increased cough reflex sensitivity, which can be demonstrated by means of inhaled capsaicin. Topical capsaicin can be used to improve non-allergic rhinitis and intestinal hypersensitivity and to reduce neuropathic pain. We established whether an oral intake of natural capsaicin (chilli) could desensitize the cough reflex and improve unexplained coughing. Twenty-four patients with irritant-induced, unexplained chronic cough and 15 controls were included in the study. For 4 weeks, the participants took capsules with pure capsaicin, and for 4 weeks, they took placebo capsules. The protocol was crossover, randomized, and double blind. Cough sensitivity during the study was evaluated by a standardized capsaicin inhalation cough test that assessed the capsaicin concentration required to reach two coughs (C2) and five coughs (C5). Participants were also administered questionnaires on cough and cough-related symptoms. Three patients withdrew before the study end, one during the active treatment period and two during the placebo period. After treatment with capsaicin, the thresholds for C2 were higher (improved) both in patients (p<0.020) and in controls (p<0.0061) compared to after the placebo period. Among patients, the concentration needed to reach C2 (p<0.0004) and C5 (p<0.0009) increased after the period with the active substance compared to cough thresholds at baseline. The cough symptom scores improved after 4 weeks of active treatment (p<0.0030) compared to the baseline scores. Capsaicin powder taken orally decreased capsaicin cough sensitivity and cough symptoms. The findings suggest a desensitization of the cough-sensitive transient receptor potential vanilloid-1 (TRPV1).

EGCG slows post-traumatic OA Progression: in vivo evidence and a novel mechanism underlying the downregulation of ADAMTS5

s / Osteoarthritis and Cartilage 22 (2014) S57–S489 S322 Wilcoxon test was used within groups and the Man-Whitney test when comparing groups. Significance level was a p-value of <0.05. All data given are on the basis of the intention to treat (ITT). To test for a possible dose-dependency the bodyweight of each patient was plotted against the different symptom scores, and a correlation test was made on each of the two groups at the initial level and after 6 and 12 weeks of treatment. Results: The two groups were comparable at the initial level regarding age, sex, bodyweight, consumption of rescue medication and the severity of OA. Twelveweeks of active treatment resulted in a reduction inWOMAC pain from 17.79 þ/8.80 to 16.57þ/-9.88, p<0.14, whilst the placebo group showed a decline in pain score from 17.96þ/-7.08 to 14.41 þ/-7.60, p<0.001. Comparing groups yielded a Man-Whitney pvalue of 0.058. No correlation was present between weight and pain score in either of the two groups on the day of inclusion. After both 6 and 12 weeks of active treatment, there was a significant negative correlation between weight and pain score (p<0.021 and p<0.022, respectively). The lower the weight the more pronounced the reduction in pain. No correlation was observed at any time point during placebo. The ADL score declined from 60.59 þ/-31.33 to 53.91 þ/30.59 after 12 weeks of active treatment (p<0.016). Placebo resulted in a decline from 55.71 þ/-25.19 to 43.90 (p<0.001). Comparing groups yielded a ManWhitney p-value of 0.098. There was no correlation between weight and ADL score in either of the two groups on the day of inclusion. Six and 12 weeks of active treatment, however, resulted in a negative correlation between weight and ADL score (p<0.019 and p<0.009 respectively). To summarize, the less the weight of the patient the better the impact from treatment. In the placebo group there was no significant correlation betweenweight and ADL score at any time point. Similar results for active treatment and placebo were obtained when testing the secondary effect variable. CRP significantly declined as a result of active treatment. Man-Whitney p-value 0.042. Conclusions: The present data suggest that patients with osteoarthritis of the knee or hip can benefit from treatment with the present rose-hip powder, when given a booster of 5 grams daily for 3 weeks, followed by 2.5 g for the following 9 weeks, with the effect becoming statistically significant in the group of patients of lower weight than 84 kg. This lowdose also significantly reduces CRP. 561 EGCG SLOWS POST-TRAUMATIC OA PROGRESSION: IN VIVO EVIDENCE AND A NOVEL MECHANISM UNDERLYING THE DOWNREGULATION OF ADAMTS5 D.J. Leong y, Z. He y, D.M. Hirsh y, S.J. Kim y, K.E. Sperling y, R.J. Majeska z, M.B. Schaffler z, J.A. Hardin y, N.J. Cobelli y, H.B. Sun y. yAlbert Einstein Coll. of Med., Bronx, NY, USA; z The City Coll. of NY, New

Efficacy and tolerability of flexibly-dosed adjunct TC-5214 (dexmecamylamine) in patients with major depressive disorder and inadequate response to prior antidepressant

This paper reports the efficacy and tolerability of the nicotinic channel modulator TC-5214 (dexmecamylamine) as adjunct therapy for patients with major depressive disorder who have an inadequate response to initial antidepressant treatment in 2 Phase III studies. These double-blind, placebo-controlled studies (NCT01157078, D4130C00002 [Study 002] conducted in the US and India; NCT01180400, D4130C00003 [Study 003] conducted in Europe) comprised 8 weeks of open-label antidepressant treatment followed by 8 weeks of active treatment during which patients were randomized to flexibly-dosed TC-5214 1–4mg twice daily (BID) or placebo as an adjunct to ongoing therapy with SSRI/SNRI. The primary efficacy endpoint in both studies was change in Montgomery Åsberg Depression Rating Scale (MADRS) total score from randomization (week 8) to treatment end (week 16). Secondary endpoints included change in Sheehan Disability Scale and Hamilton Depression Rating Scale 17-item scores. Study 002 randomized 319 patients and Study 003 randomized 295 patients to TC-5214 or placebo. At treatment end, no significant differences were seen for change in MADRS total score with TC-5214 versus placebo. Furthermore, there were no significant differences in any of the secondary endpoints. The most commonly reported (≥10%) adverse events with TC-5214 in these studies were constipation and headache. In these 2 flexibly-dosed studies, no specific therapeutic effects were observed for TC-5214 (1–4mg BID) adjunct to antidepressant in the primary endpoint or any secondary endpoint; however, TC-5214 was generally well tolerated. In conclusion, no antidepressant effect of TC-5214 was observed in these studies.

Antidepressant Efficacy of High and Low Frequency rTMS at 110% of Motor Threshold versus Sham Stimulation over Left Prefrontal Cortex

BackgroundWhile the efficacy of repetitive transcranial magnetic stimulation (rTMS) at 10 Hz over the left prefrontal cortex has been repeatedly demonstrated, it is not clear that the optimal parameters for the treatment of depression have been adequately elucidated. ObjectivesWe sought to assess the antidepressant effectiveness of high and low frequency at a higher intensity rTMS compared to sham in patients with moderately treatment resistant depression. MethodThe authors conducted a three-week, double-blind, randomized, sham-controlled study of 24 acutely depressed patients given either active 20 Hz (n = 8) or 1 Hz (n = 8) rTMS (at 110% of motor threshold [MT]) or sham treatments (n = 8) over the left prefrontal cortex. Hamilton Depression ratings were analyzed by ANOVA. ResultsPatients on both frequencies showed greater improvement than on sham, which was associated with minor increases in depression. During open continuation to allow 7 weeks of active treatment in all individuals, additional improvement was observed. ConclusionsThe results seen here using 110% of MT for 3 weeks were more robust than those of previous studies of 1-Hz or 20-Hz rTMS for 2 weeks (at 80% and 100% of MT). The results also raise the possibility that both high and low frequency rTMS over left prefrontal cortex (and not just low frequency over the right prefrontal cortex) exert antidepressant effects, but further work is required to assess what parameters may be most effective in general and for a given individual.

Comparison of the efficacy between hydrochlorothiazide and chlorthalidone on central aortic pressure when added on to candesartan in treatment-naïve patients of hypertension

Thiazide-type diuretics are the most commonly used blood pressure (BP)-lowering drug for patients with uncomplicated hypertension. However, it has remained unclear whether hydrochlorothiazide (HCTZ) or chlorthalidone (CTD) shows better improvement in central aortic pressure. We conducted an open-label, randomized, prospective cross-over study with an 8-week active treatment (HCTZ of 25 mg with candesartan of 8 mg or CTD of 12.5 mg with candesartan of 8 mg) with a 4-week washout period (only candesartan during this period). Twenty-eight treatment-naïve patients of hypertension were enrolled (mean age: 50±9 years, male: 44.4%). Central aortic pressure, pulse wave velocity (PWV), augmentation index (AIx) and other BP-derived parameters were measured. After 8 weeks of active treatment, there was no significant difference in changes of central aortic pressure between HCTZ and CTD treatments (Δ=-14±8 vs. -16±7 mm Hg, P=0.645). However, CTD treatment showed a significant reduction in PWV compared with baseline (1321±194 vs. 1439±190 cm s(-1), P=0.007) and HCTZ treatment (Δ=-118±82 vs. Δ=5±72 cm s(-1), P=0.033), whereas HCTZ treatment showed a marginal, but not a significant reduction in AIx compared with baseline. In conclusion, CTD of 12.5 mg is as potent as HCTZ of 25 mg, when combined with candesartan of 8 mg, in lowering central aortic pressure. In addition, CTD treatment resulted in a significant reduction of PWV.

Low-level laser therapy for chemotherapy-induced peripheral neuropathy.

9019 Background: Chemotherapy induced peripheral neuropathy (CIPN) is a common and serious side effect from chemotherapy agents. Low-level laser light therapy (LLLT) devices were approved in 2002 for pain management. Studies suggest a local release of serotonin, increased mitochondrial ATP production, or anti-inflammatory effects as a mechanism of action. We then questioned whether LLLT would show efficacy in mitigating symptoms caused by CIPN. Methods: In a single center prospective randomized trial, participants were randomized to receive either treatment with LLLT twice a week for 8 weeks or placebo LLLT twice a week for 4 weeks followed by actual treatment twice a week for 4 weeks. FACT/GOG-NTX, Brief Pain Inventory (BPI -Severity and Interference), SF-36 Quality of Life (Physical and Mental Score), monofilament and function testing (buttoning, coin use and walking) were conducted prior to initiation of therapy, during, at completion, and 2 months after treatment. 20 participants, 16 women and 4 men (average age 58 and 63 respectively), were enrolled between October 2009 and June 2010. 10 patients were randomized to each group. Average time from end of chemotherapy to enrollment was 32.6 months (range 2 - 120 mo). All patients had neuropathic involvement of the feet. 14 patients had additional involvement of the hands. Results: Compared to baseline, patients receiving any amount of active treatment showed significant improvement at 8 weeks in NTX, BPI, function testing, and SF36 Mental score. Those receiving 4 weeks of placebo treatment showed improvement in only BPI, NTX and SF36 Mental score. At 2-month follow up, all 20 patients showed a significant improvement in walking and SF 36 mental score, suggesting 4 weeks of active treatment improved function. No significant difference in monofilament testing was observed throughout the study in either group. Direct comparison between 4 or 8 weeks of treatment vs. placebo showed a statistically significant difference in walking function at 2-months. All patients tolerated therapy well without side effects. Conclusions: Low-level laser light therapy improved functional test over placebo and may be a viable option for non-medical management of CIPN. Further study of LLLT in CIPN is warranted.

Omega-3 Fatty Acid Augmentation of Citalopram Treatment for Patients With Major Depressive Disorder

The objective of this study was to explore the efficacy of combination therapy with citalopram plus omega-3 fatty acids versus citalopram plus placebo (olive oil) in the initial treatment of individuals with major depressive disorder (MDD). We hypothesized that combination therapy would lead not only to greater efficacy but also to a more rapid onset of therapeutic response. Forty-two subjects participated in this 9-week randomized, masked, placebo-controlled study of combination therapy (two 1 g capsules containing a blend of 900 mg of eicosapentaenoic acid, 200 mg of and docosahexaenoic acid, and 100 mg of other omega-3 fatty acids twice daily plus citalopram) versus monotherapy (two 1 g capsules of olive oil per day plus citalopram) treatment of MDD. The combination therapy demonstrated significantly greater improvement in Hamilton Depression Rating scale scores over time (F = 7.32; df 1,177; P = 0.008) beginning at week 4 (t = -2.48; df 177; P = 0.014). Combination therapy was more effective than monotherapy in decreasing signs and symptoms of MDD during the 8 weeks of active treatment; however, combination therapy did not seem to enhance the speed of the initial antidepressant response. These findings suggest that there may be an advantage to combining omega-3 fatty acids with a selective serotonin uptake inhibitor in the initial treatment of individuals with MDD. A larger definitive study is warranted.

Accurate Position Monitoring and Improved Supine-Dependent Obstructive Sleep Apnea with a New Position Recording and Supine Avoidance Device

Approximately 30% of obstructive sleep apnea (OSA) patients have supine-predominant OSA, and simply avoiding supine sleep should normalise respiratory disturbance event rates. However, traditional supine-avoidance therapies are inherently uncomfortable, and treatment adherence is poor and difficult to monitor objectively. This study evaluated the efficacy of a novel, potentially more acceptable position monitor and supine-avoidance device for managing supine-predominant OSA and snoring. In-laboratory evaluation of position recording accuracy versus video recordings (validation study), and randomized controlled crossover trial of active versus inactive supine-avoidance therapy in the home setting (efficacy study). 17 patients undergoing in-laboratory sleep studies (validation) and 15 patients with supine-predominant OSA (efficacy). EFFICACY STUDY: 1 week of inactive and 1 week of active treatment in randomized order, separated by 1 week. Agreement between 30-sec epoch-based posture classifications from device versus video records was high (median κ 0.95, interquartile range: 0.88-1.00), and there was good supine time agreement (bias 0.3%, 95%CI: -4.0% to 4.6%). In the efficacy study, apnea-hypopnea index (AHI) and snoring frequency were measured in-home using a nasal pressure and microphone based system during inactive and active treatment weeks. The position monitoring and supine alarm device markedly inhibited supine time (mean ± SEM 19.3% ± 4.3% to 0.4% ± 0.3%, p < 0.001) and reduced AHI (25.0 ± 1.7 to 13.7 ± 1.1 events/h, p = 0.030) but not snoring frequency. This new position monitoring and supine alarm device records sleep position accurately and improves OSA but not snoring in patients with supine-predominant OSA.

A double-blind placebo-controlled randomized trial of adalimumab in the treatment of hidradenitis suppurativa

Hidradenitis suppurativa (HS) has an impact on patients' quality of life. Treatment of HS is generally unsatisfactory, thus new treatments are needed. To test the efficacy of adalimumab in HS. This was a prospective, randomized, double-blinded, placebo-controlled, two-centre clinical trial conducted in Denmark. Inclusion criteria were age above 18 years and a clinical diagnosis of moderate to severe HS defined as Hurley stage II or III for at least 6 months. The patients were randomized 1:2 (placebo/active). Actively treated patients received adalimumab 80 mg subcutaneously (s.c.) at baseline followed by 40 mg s.c. every other week for 12 weeks. Placebo-treated patients received identical-looking injections with no active ingredient. The medicine was dispensed in sequentially numbered computer-randomized containers. Participants, care givers and those assessing the outcomes were blinded to group assignment. The primary efficacy endpoints were changes in the HS scores (Sartorius and Hurley scoring systems). Secondary efficacy endpoints included changes in pain (visual analogue scale), days with lesions and Dermatology Life Quality Index, and evaluation of scarring. Recruitment was terminated early due to expiry date of trial medication. Twenty-one patients were included, of whom 15 received adalimumab and six received placebo. All participants were analysed according to the intention to treat principle. A significant reduction was seen in Sartorius score after 6 weeks and an almost significant reduction was seen after 12 weeks of active treatment (-10·7 vs. 7·5, P = 0·024 and -11·3 vs. 5·8, P = 0·07) when compared with the placebo group. A significant reduction in HS severity was gained after 6 weeks. No long-term curative effect was uniformly seen.

Management of Hypertension in Patients With Diabetes Using an Amlodipine-, Olmesartan Medoxomil-, and Hydrochlorothiazide-Based Titration Regimen

The safety and efficacy of an amlodipine/olmesartan medoxomil (OM)-based titration regimen was assessed in patients with type 2 diabetes mellitus and hypertension. After a 2- to 3-week placebo run-in period, 207 patients received amlodipine 5 mg and were uptitrated to amlodipine/OM 5/20, 5/40, and 10/40 mg and then amlodipine/OM 10/40 mg plus hydrochlorothiazide 12.5 and 25 mg in a step-wise manner at 3-week intervals if the seated blood pressure (BP) remained ≥120/70 mm Hg. The primary end point was the change from baseline in the mean 24-hour ambulatory systolic BP after 12 weeks of treatment. The baseline mean ± SD seated cuff systolic/diastolic BP was 158.8 ± 13.1/89.1 ± 10.1 mm Hg and the mean ± SD 24-hour ambulatory systolic/diastolic BP was 144.4 ± 11.7/81.6 ± 9.8 mm Hg. At week 12, the change from baseline in the mean ± SEM 24-hour ambulatory systolic/diastolic BP was -19.9 ± 0.8/-11.2 ± 0.5 mm Hg (p<0.0001 vs baseline), and 70% of patients had achieved a 24-hour ambulatory BP target of <130/80 mm Hg. At the end of 18 weeks of active treatment in patients uptitrated to amlodipine/OM 10/40 mg plus hydrochlorothiazide 25 mg, the change from baseline in the mean ± SEM seated BP was -28.0 ± 1.5/-13.7 ± 1.0 mm Hg (p<0.0001 vs baseline), with 62% of patients reaching the guideline-recommended seated BP goal of <130/80 mm Hg. Drug-related treatment-emergent adverse events occurred in 19.3% of patients. The most frequent events were peripheral edema (6%), dizziness (3%), and hypotension (2%). In conclusion, this amlodipine/OM-based titration regimen was well tolerated and effectively lowered BP throughout the 24-hour dosing interval in patients with hypertension and type 2 diabetes.

Aliskiren-based stepped-care treatment algorithm provides effective blood pressure control

Recent guidelines for the management of hypertension recommend an individualised stepped-care treatment approach in mild-to-moderate hypertensive patients, to achieve blood pressure (BP) goals. This study evaluated the probability of patients achieving BP targets with an aliskiren-based stepped-care treatment regimen. This was a 24-week, open-label, non-comparator study design that included six sequential 4-week treatment periods in patients with mild-to-moderate hypertension. Over the potential 24 weeks of active treatment, incremental therapy included the following add-on therapies at 4-week intervals: aliskiren 150-300 mg once daily, hydrochlorothiazide (HCTZ) 12.5-25 mg once daily, and finally amlodipine 5-10 mg once daily, as needed to achieve target BP. Subjects achieving BP targets following any given 4 weeks of therapy were considered study completers, while subjects not achieving their clinical BP target entered into the next step of incremental therapy. The primary efficacy end-point was the estimated cumulative probability of patients achieving BP target. Of 256 patients treated, 232 (90.6%) completed the study. Baseline mean sitting BP was 155.7/91.7 mmHg. At study end-point, the estimated cumulative probability of reaching BP target was 86.12%. The stepped-care treatment regimen was well tolerated at the maximal recommended doses of all the individual complimentary therapies. An aliskiren-based stepped-care treatment regimen that subsequently included both HCTZ and amlodipine is effective in achieving BP goals in approximately 90% of patients with mild-to-moderate hypertension.

Clinical Trial Experience with Cannabinoids

The identification of a peripheral cannabinoid receptor localized to the immune system around the gastrointestinal tract stimulated a clinical trial of oral cannabinoids in a patient with chronic pain and inflammation of gastrointestinal origin. The patient had the symptoms of familial Mediterranean fever and required oral opioids for pain control before the study. A long-term randomized double-blind placebo-controlled study with capsules containing oil of cannabis (active) and virgin olive oil (placebo) demonstrated significant opioid sparing, with morphine used as escape analgesia, during three weeks of active treatment while pain scores remained similar in the three placebo weeks. There were no changes in inflammatory markers measured. Compliance was demonstrated by urine analyses for cannabinoids. Difficulties during this prolonged study were encountered with a lack of effectiveness during the final two weeks, which may have been induced by tolerance, and with mood disorders during two consecutive placebo weeks, which suggested withdrawal symptoms. Central effects during the active weeks were avoided by choosing a suitable dosage of tetrahydrocannabinol and with the marked reduction in morphine requirements achieved with the cannabinoid preparation. In future studies it should be possible to define the active constituents of the natural preparation and their appropriate route, which can produce these desirable analgesic effects.

A preliminary investigation of varenicline for heavy drinking smokers.

Varenicline, an approved smoking cessation pharmacotherapy, also shows promise as a potential treatment for alcohol dependence. However, varenicline has not been tested in heavy drinkers, and it remains to be determined whether varenicline could reduce alcohol craving and consumption in smokers who are trying to quit smoking. We conducted a preliminary study to examine the effect of varenicline on drinking behavior and the effects of extended varenicline pretreatment on smoking. Thirty heavy drinking smokers received smoking cessation counseling and were randomly assigned to receive either an extended 4-week pretreatment with varenicline 2mg daily or the usual 1-week pretreatment. Those in the extended pretreatment group received active medication for 8weeks (i.e., 4weeks of active pre-treatment followed by 4weeks of active treatment), and participants in the usual pretreatment group received active medication after a placebo lead in (i.e., 3weeks of placebo followed by active medication for 5weeks). Participants who received varenicline during the first 3weeks reported significantly greater reductions in alcohol craving and numerically fewer heavy drinking days compared to those who received placebo, and these differences persisted during the open-label phase. Extended pretreatment was associated with numerically greater reductions in cigarette smoking over the entire study period. There were no differences, however, in smoking abstinence rates following the smoking quit date between the two groups. Findings from this preliminary study suggest that varenicline may be a promising strategy for concurrently reducing heavy drinking and promoting smoking changes in heavy drinkers.

Associations between parent behavior and adolescent weight control.

To evaluate associations between parent behaviors (i.e., parent weight change, self-monitoring of their behavior, and feeding practices and attitudes) and changes in adolescent BMI and weight following 16-weeks of behavioral weight control (BWC) intervention. Adolescents (N = 86) 13-16 years old and 30-90% overweight (M = 60.54%, SD = 15.10%) who completed BWC intervention and their parents. Adolescents were randomized to 1 of 2 interventions involving 16 consecutive weeks of active treatment with 4 biweekly maintenance sessions. Adolescent weight and BMI were measured at baseline and 16-weeks. Feeding practices were measured at baseline. Parent self-monitoring was measured during the intervention. The only independently significant predictor of adolescent BMI change (p < .01) was parent BMI change. Greater parent self-monitoring (p < .01) predicted greater adolescent weight loss. Greater parent pressure to eat predicted less adolescent weight loss (p < .01). Findings highlight the potential importance of parent weight-related behaviors and feeding practices in the context of adolescent BWC.

The costs and consequences of omalizumab in uncontrolled asthma from a USA payer perspective

Omalizumab, an anti-immunoglobulin E antibody, reduces exacerbations and symptoms in uncontrolled allergic asthma. The study objective was to estimate the costs and consequences of omalizumab compared to usual care from a US payer perspective. We estimated payer costs, quality-adjusted survival (QALYs), and the incremental cost-effectiveness ratio (ICER) of omalizumab compared to usual care using a state-transition simulation model that included sensitivity analyses. Every 2 weeks, patients could transition between chronic asthma and exacerbation health states. The best available evidence informed the clinical and cost input estimates. Five years of omalizumab treatment followed by usual care was assumed to estimate a lifetime horizon. Omalizumab responders (60.5% of treated) were modeled as a separate scenario where nonresponders reverted back to usual care after 16 weeks of active treatment. The mean lifetime discounted costs and QALYs were $83,400 and 13.87 for usual care and $174,500 and 14.19 for omalizumab plus usual care resulting in $287 200/QALY (95% interval: $219,300, $557, 900). The ICER was $172 300/QALY when comparing omalizumab to usual care in the responder scenario. One-way sensitivity analyses indicated that the results were sensitive to the difference in treatment-specific utilities for the chronic state, exacerbation-associated mortality, omalizumab price, exacerbation rates, and response definition. The results suggest that adding omalizumab to usual care improves QALYs at an increase in direct medical costs. The cost-effectiveness of omalizumab is similar to other chronic disease biologics. The value increases when omalizumab response is used to guide long-term treatment.