IPP-rich milk protein hydrolysate lowers blood pressure in subjects with stage 1 hypertension, a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Milk derived peptides have been identified as potential antihypertensive agents. The primary objective was to investigate the effectiveness of IPP-rich milk protein hydrolysates (MPH) on reducing blood pressure (BP) as well as to investigate safety parameters and tolerability. The secondary objective was to confirm or falsify ACE inhibition as the mechanism underlying BP reductions by measuring plasma renin activity and angiotensin I and II.</p> <p>Methods</p> <p>We conducted a randomized, placebo-controlled, double blind, crossover study including 70 Caucasian subjects with prehypertension or stage 1 hypertension. Study treatments consisted of daily consumption of two capsules MPH1 (each containing 7.5 mg Isoleucine-Proline-Proline; IPP), MPH2 (each containing 6.6 mg Methionine-Alanine-Proline, 2.3 mg Leucine-Proline-Proline, 1.8 mg IPP), or placebo (containing cellulose) for 4 weeks.</p> <p>Results</p> <p>In subjects with stage 1 hypertension, MPH1 lowered systolic BP by 3.8 mm Hg (P = 0.0080) and diastolic BP by 2.3 mm Hg (P = 0.0065) compared with placebo. In prehypertensive subjects, the differences in BP between MPH1 and placebo were not significant. MPH2 did not change BP significantly compared with placebo in stage I hypertensive or prehypertensive subjects. Intake of MPHs was well tolerated and safe. No treatment differences in hematology, clinical laboratory parameters or adverse effects were observed. No significant differences between MPHs and placebo were found in plasma renin activity, or angiotensin I and II.</p> <p>Conclusions</p> <p>MPH1, containing IPP and no minerals, exerts clinically relevant BP lowering effects in subjects with stage 1 hypertension. It may be included in lifestyle changes aiming to prevent or reduce high BP.</p> <p>Trial registration</p> <p>ClinicalTrials.gov NCT00471263</p

Apremilast for genital erosive lichen planus in women (the AP-GELP Study): study protocol for a randomised placebo-controlled clinical trial

Background Genital erosive lichen planus (GELP) is a genital subtype of lichen planus, a chronic autoimmune inflammatory disease of unknown aetiology. In women, GELP is characterised by painful vulvo-vaginal mucosal erosions and scarring, often resulting in poor sexual health and reduced quality of life. Treatment options are limited and often with little effect. Apremilast, a phosphodiesterase 4-inhibitor, has been shown to have a positive effect on psoriasis and other inflammatory skin diseases. We aim to investigate the effect and safety of peroral apremilast in women with GELP in a randomised placebo-controlled double-blinded clinical trial. Methods We will recruit 42 adult women with characteristic clinical and/or histological features of moderate-to-severe GELP from a specialised vulva clinic in Oslo, Norway. The patients will be randomised 1:1 to either apremilast 30 mg BID (with an initial dose titration on days 1–6) or a placebo for 24 weeks. The concomitant use of topical corticosteroids will be allowed. The primary end point will be the mean GELP score, a clinical scoring system, at week 24 in the apremilast-treated patients versus the placebo-treated patients. The secondary end points will include the mean GELP score improvement from weeks 0 to 24, patient-reported use of topical steroids, the pain score on a visual analogue scale and the number of patients with GELP score improvements at weeks 16 and 24. The Physician Global Assessment , Patient Global Assessment and selected quality of life and sexual function assessments will be recorded at weeks 0, 16 and 24. The exploratory endpoints include description of immunohistochemical changes before and after apremilast therapy, assessed in vulvar or vaginal biopsies at weeks 0 and 24. Regular follow-ups for possible adverse events will be conducted. Discussion The study design is based on experience from studies on apremilast in other inflammatory skin diseases using equivalent apremilast doses for approved indications. The trial may provide evidence for the use of apremilast in women with this burdensome genital dermatosis. Trial registration ClinicalTrials.gov NCT0365666. Registered on 4 September 2018

Less periprosthetic bone loss following the anterolateral approach to the hip compared with the direct lateral approach: A subgroup analysis from a randomized trial in patients with a femoral neck fracture

Background and purpose — The loss of bone mineral in the proximal femur following hip arthroplasty may increase the fracture risk around uncemented stems. We hypothesized that the surgical approach to the hip might influence bone mineral changes around the femoral stem in patients with a femoral neck fracture (FNF). Patients and methods — This was a pre-specified subgroup analysis (n = 51) of an ongoing randomized trial (n = 120) in patients with FNF. Participants were allocated to an uncemented hemiarthroplasty inserted through a direct lateral (Hardinge) approach or an anterolateral (modified Watson-Jones) approach. The 51 patients (mean age 83 (70–90) years, 33 women) were measured by dual-energy X-ray absorptiometry (DXA) to assess changes in periprosthetic bone mineral density (BMD). Results — The mean change in total BMD differed between groups at 12 months in favor of the anterolateral group (4.8%, 95% CI 0.0–9.6; p = 0.05). DXA at 3 months displayed BMD loss in the proximal Gruen zones in the lateral group compared with the anterolateral group. Zone 1 (–5.0% vs. 2.7%), zone 2 (–4.3% vs. 4.1%), zone 6 (–6.5% vs. 0.0%) and zone 7 (–11% vs. –2.4%, all p < 0.05). Interpretation — DXA measurements in this study indicate that surgical approach to the hip influences periprosthetic BMD. Clinical implications remain uncertain. Our conclusions should be interpreted with caution as we did not perform adjustments for multiple tests, possibly leading to inflation of false-positive findings

Heterotopic ossification and clinical outcome in nonconstrained cervical arthroplasty 2 years after surgery: the Norwegian Cervical Arthroplasty Trial (NORCAT)

Purpose Heterotopic ossification is a phenomenon in cervical arthroplasty. Previous reports have mainly focused on various semiconstrained devices and only a few publications have focused on ossification around devices that are nonconstrained. The purpose of this study was to assess the occurrence of heterotopic ossification around a nonconstrained cervical device and how it affects clinical outcome 2 years after surgery. Methods Thirty-seven patients were included from a larger cohort of a randomized controlled trial (NORCAT) which compared single-level cervical arthroplasty with fusion. The occurrence of heterotopic ossification was assessed with a CT scan and two neuroradiologists determined its degree. For grading, we used the Mehren/Suchomel classification system (grade 0–4). The patients were divided by level of ossification, low grade (0–2) or high grade (3–4), and clinical outcomes were compared. Self-rated disability for neck and arm pain (Neck Disability Index), health-related quality of life (the Short Form-36 and EuroQol-5D), and pain (the Numeric Rating Scale 11) were used as clinical outcome measures. Results Heterotopic ossification was encountered in all patients 2 years after surgery. Complete fusion (grade 4) was found in 16 % of participants, and high-grade ossification (grade 3–4) occurred in 62 %. The remaining patients were classified as having low-grade ossification (grade 2). There were no differences in the clinical outcomes of patients with low- and high-grade ossification. Conclusion High-grade heterotopic ossification and spontaneous fusion 2 years after surgery were seen in a significant number of patients. However, the degree of ossification did not influence the clinical outcome