Combination Therapy Is Superior to Sequential Monotherapy for the Initial Treatment of Hypertension:A Double-Blind Randomized Controlled Trial

Background: Guidelines for hypertension vary in their preference for initial combination therapy or initial monotherapy, stratified by patient profile; therefore, we compared the efficacy and tolerability of these approaches. Methods and Results: We performed a 1‐year, double‐blind, randomized controlled trial in 605 untreated patients aged 18 to 79 years with systolic blood pressure (BP) ≥150 mm Hg or diastolic BP ≥95 mm Hg. In phase 1 (weeks 0–16), patients were randomly assigned to initial monotherapy (losartan 50–100 mg or hydrochlorothiazide 12.5–25 mg crossing over at 8 weeks), or initial combination (losartan 50–100 mg plus hydrochlorothiazide 12.5–25 mg). In phase 2 (weeks 17–32), all patients received losartan 100 mg and hydrochlorothiazide 12.5 to 25 mg. In phase 3 (weeks 33–52), amlodipine with or without doxazosin could be added to achieve target BP. Hierarchical primary outcomes were the difference from baseline in home systolic BP, averaged over phases 1 and 2 and, if significant, at 32 weeks. Secondary outcomes included adverse events, and difference in home systolic BP responses between tertiles of plasma renin. Home systolic BP after initial monotherapy fell 4.9 mm Hg (range: 3.7–6.0 mm Hg) less over 32 weeks (P<0.001) than after initial combination but caught up at 32 weeks (difference 1.2 mm Hg [range: −0.4 to 2.8 mm Hg], P=0.13). In phase 1, home systolic BP response to each monotherapy differed substantially between renin tertiles, whereas response to combination therapy was uniform and at least 5 mm Hg more than to monotherapy. There were no differences in withdrawals due to adverse events. Conclusions: Initial combination therapy can be recommended for patients with BP >150/95 mm Hg. Clinical Trial Registration URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00994617

Imaging the electric field associated with mouse and human skin wounds

We have developed a noninvasive instrument called the bioelectric field imager (BFI) for mapping the electric field between the epidermis and the stratum corneum near wounds in both mouse and human skin. Rather than touching the skin, the BFI vibrates a small metal probe with a displacement of 180 ?m in air above the skin to detect the surface potential of the epidermis through capacitative coupling. Here we describe our first application of the BFI measuring the electric field between the stratum corneum and epidermis at the margin of skin wounds in mice. We measured an electric field of 177±14 (61) mV/mm immediately upon wounding and the field lines pointed away from the wound in all directions around it. Because the wound current flows immediately upon wounding, this is the first signal indicating skin damage. This electric field is generated at the outer surface of the epidermis by the outward flow of the current of injury. An equal and opposite current must flow within the multilayered epidermis to generate an intraepidermal field with the negative pole at the wound site. Because the current flowing within the multilayered epidermis is spread over a larger area, the current density and subsequent E field generated in that region is expected to be smaller than that measured by the BFI beneath the stratum corneum. The field beneath the stratum corneum typically remained in the 150–200 mV/mm range for 3 days and then began to decline over the next few days, falling to zero once wound healing was complete. The mean wound field strength decreased by 64±7% following the application of the sodium channel blocker, amiloride, to the skin near the wound and increased by 82±21% following the application of the Cl? channel activator, prostaglandin E2

Healing of ExcisionAl wounds on Lower legs by Secondary intention (HEALS) Cohort Study: A multi-centre prospective observational cohort study in patients without planned compression.

Background There is no agreed treatment pathway following excision of keratinocyte cancers. Compression therapy is considered beneficial for secondary intention healing on the lower limb, however there is a lack of supportive evidence. To plan a randomised controlled trial suitable data is needed. This paper reports a multi-centre prospective observational cohort study in this patient population, to inform a future trial design. Objectives 1. To estimate the time to healing in wounds healing by secondary intention without planned post-operative compression, following excision of keratinocyte cancers on the lower leg 2. To characterise the patient population including factors affecting healing 3. To assess the incidence of complications Methods INCLUSION CRITERIA: People over 18 years; planned excision of keratinocyte cancer on lower leg with healing by secondary intention; ankle-brachial pressure index (ABPI) greater than or equal to 0.8; written informed consent EXCLUSION CRITERIA: Planned: primary closure, skin graft or flap; compression therapy for another indication; unable to receive, comply or tolerate high compression; planned compression; suspected diagnosis other than keratinocyte cancer. Results This study recruited 58 patients from 9 secondary care dermatology clinics. In the analysis population (n=53): mean age was 81 (range 25-97) years; median time to healing was 81(95% Confidence Interval:73-92) days and at 6-month 45 patients (84.9%) had healed. Healing prognostic factors were wound parameters, and ABPI. Wound infections occurred in 16 participants(30.2%) and 4(7.5%) were admitted to hospital. Conclusions Data collected has informed the RCT preparation. A relatively high (7.5-15%) proportion of wounds not healed, incidence of infection and hospital admissions demonstrated the need for clearly establishing potentially effective treatments and improve outcomes for this population

Healing of ExcisionAl wounds on Lower legs by Secondary intention (HEALS) Cohort: Feasibility data from a multi-centre prospective observational cohort study to inform a future Randomised Controlled Trial (RCT)

Summary Background Compression therapy is considered beneficial for lower limb post-surgical wounds healing by secondary intention, however there is a lack of supportive evidence. To plan a randomised controlled trial suitable data is needed. Objectives: Determine feasibility of recruitment and estimate recruitment rate Understand the standard post-operative wound management pathway Determine uptake of optional additional clinic visit for healing confirmation Explore patient acceptability of compression bandaging and a future RCT Methods: Participant recruitment over 22 months from secondary care Dermatology clinics. Eligibility criteria: INCLUSION: over 18 years; planned excision of keratinocyte cancer on lower leg with healing by secondary intention; ankle-brachial pressure index ≥ 0.8 EXCLUSION: planned primary closure/graft or flap; unable to receive/comply/tolerate high compression; planned compression; suspected melanoma Followed up weekly (maximum 6 months) in secondary care clinics and/or by telephone. Information collected on healthcare resource use, unplanned compression, wound healing, optional clinic visit to confirm healing. Results: 58 patients recruited from 9 secondary care dermatology clinics in 22 months. Mean recruitment/centre/month was 0.8 (range 0.1-2.3). Four centres had dedicated Research Nurse support. The analysis population (n=53) attended weekly follow-up assessments. Standard care clinical contacts were: GP visits 7(1.2%), Community Nurse visits 169(28.5%), Practice nurse visits 189(31.8%), and Dermatology clinic visits 138(23.2%). Participants whose wounds healed, 34/45(75.6%) attended an optional clinic visit. Conclusions: Data were obtained to inform a future RCT. Recruitment rates are higher in centres with dedicated research support. People would be willing to take part in a trial and attend a confirmation of healing visit