Robinson-Cohen et al., Estimation of 24-hour urine phosphate excretion from spot urine collection: development of a predictive equation. Journal of Renal Nutrition, 2014; 24 (3): p. 194-9.
One thing that has always been tricky for doctors and scientists is how to analyze clinical tests. Most clinical tests come from either blood or urine samples, which are tested for the presence and levels of various compounds. First, scientists must demonstrate that these compounds are correlated (either in relatively high or low doses) to a pathology. One this has been determined, the normal/healthy level of the compound needs to be determined. However, just as your heart rate changes throughout the day as you wake up and perform various activities, so too do the levels of different compounds in your system. Thus you can say, most people tend to have a range of values over the course of a day.
Patients with severe chronic kidney disease often suffer from hypophosphatemia. In order to monitor the amount of phosphate intake of a patient, the gold-standard is considered to be a 24-hour urine collection test. However, as Robinson-Cohen et al. point out, doing this is very time consuming and also prone to error. They wanted to check whether spot urine phosphate measurements could be as effective as this “gold standard”.
Phosphatemia is treated through phosphate binders (which aid in phosphate retention). As this would naturally affect the phosphate levels in urine, Robinson-Cohen et al. piggy-backed their experiment onto the Phosphate Normalization Trial. Patients, all with hyperphosphatemia, were administered either a phosphate binder or a placebo. While the main purpose of the trial was to determine the efficacy of the phosphate binders, Robinson-Cohen et al. were mainly concerned with the accuracy of measurement methods used. 143 patients were measured both with spot checks as well as the traditional 24-hour method. Additionally, they used an external replication of the study to validate their results.
Robinson-Cohen et al. found that when certain parameters were applied to the spot checks, they could be indicative of the results shown in the 24-hour test. Notably, corrections had to be made for age, sex, and weight and the creatine concentration. The phosphate:creatine ratio in the spot checks related fairly accurately to the phosphate excretion in the 24-hour samples, once these other corrections were made. Thus, this newer simpler method seems to be an emerging option, although; judging by the tone of the paper, I’m not sure anyone will be calling it the “gold standard” just yet.
Pajoohesh-Ganji et al., Inhibition of amyloid precursor protein secretases reduces recovery after spinal cord injury. Brain Research, 2014; 1560: p. 73-82.
Say the words “amyloid precursor protein” (APP) to any student majoring in Biochemistry – and they’ll rattle off a bunch of facts for you – all centered around how, basically, APP cleavage leads to amyloid aggregation into “amyloid plaques” important for Alzheimer’s disease, but no one really knows how it works, or what purpose the protein serves when not running around ruining people’s lives. Well, no longer. Pajoohesh-Gangi et al. studied APP secretases; the enzymes that cleaves APP into Amyloid-β protein. The first reaction to this pathway would be the thought that preventing cleavage of APP would be an effective therapy for Alzheimer’s and other amyloid-implicated neurological disorders. However, it has always been postulated that Amyloid-β does actually serve a positive purpose most of the time.
Pajoohesh-Gangi et al. decided to study the effect that inhibiting amyloid secretases would have on the ability of mice to recover from spinal cord injury. The secretases were either inhibited using DAPT, an inhibitor drug, or through use of amyloid secretase knockout mice. When the recovery of mice after induced spinal cord injury was measured, both methods of inhibiting amyloid secretases were found to inhibit functional recovery, both in terms of the white matter spared as well as demonstrated through behavioral testing of the mice. Thus, although a specific method was not elucidated, a positive effect of amyloid-β protein has finally been shown in certain scenarios.
Baker et al., Efficacy of a single dose of a novel topical combination product containing eprinomectin to prevent heartworm infection in cats. Veterinary Parasitology; 202 (1-2): p. 49-53.
Unlike for dogs, there is no curative treatment for feline heartworm infection. Cats are infected through bites from infected mosquitos. The larvae grow into adults inside the cat and are able to move into the vasculature in the lungs as well as other tissues, causing significant health problems.
This study by Baker et al. comprised 3 controlled blinded laboratory studies to evaluate the efficacy of the preventative treatment of a product marketed as BROADLINE. The basic study set up was to inoculate cats with D. immitis larvae by injecting these under the skin. To control for geographic variation, larvae from naturally infected dogs from 3 distinct geographical areas were used (2 in the USA and one in Europe). For each independent group, the cats were randomly allocated to either an infected group or a control. 30 days after injection, Cats may be infected by heartworm, Dirofilaria immitis, through mosquito bites. They can develop severe heartworm disease when infective D. immitis larvae migrate and develop into adults in the pulmonary vasculature orc other tissues. As there is no curative treatment for feline heartworm infection, the monthly administration of preventative treatment is recommended in endemic areas. Three controlled, blinded laboratory studies were conducted to evaluate the preventative efficacy of BROADLINE(®), a novel combination of fipronil, (S)-methoprene, eprinomectin, and praziquantel against D. immitis in cats. In each study, 28 cats were inoculated with approximately 100 (studies 1 and 2) or 40 (study 3) infective third stage D. immitis larvae by subcutaneous injection, thirty days prior to treatment. The larvae were from recent field isolates from naturally infected dogs from three distinct geographic areas (two in the USA and one in Europe). In each study, the cats were allocated randomly to either receive BROADLINE at 30 days after larvae injection (0.5mg eprinomectin/kg of body weight), or a control group with no treatment. The control group remained untreated.
6 months after the larvae injection the cats were all euthanized and examined closely for heartworms. 68% of the untreated control cats had one or more heartworms, whereas 100% of the treated cats had no heartworms (not even one). No side-effects of treatment were observed. While the manufacturers of this product probably consider this a complete win, their study actually raised more questions in my mind than it actually solved. For instance, if there are mosquitos in the area carrying larvae, this might result in repeated larvae infection of the cats, not just a single instance. Additionally, the scientists fail to point out how the drug kills the heartworms – including information such as whether it targets adults or larvae. If the drug only targets the heartworm at a particular stage of the life-cycle – does the time after infection matter for when to apply the drug? If so, this would therefore be an incomplete test since it didn’t test different application timepoints and the cat owner stands no chance of knowing at which point her cat was bitten. In a related query – if BROADLINE is meant to be preventative, why is it not applied to the cat prior to larvae injection? Also, in terms of efficacy studies, Baker et al. fail to look at the effect if applied regularly every 4-6 weeks as they recommend, instead of once every 6 months. Nevertheless, it is promising to see real studies being conducted on products that we give our pets to validate their efficacy.
Chamberlain et al., the economic burden of post-transplant events in renal transplant recipients in Europe. Transplantation, 2014; 97 (8): p.854-61.
On September 15th, I wrote a post about how it matters whether a kidney transplant comes from a living or a deceased patient. However, regardless of the source of the transplant, and assuming that transplant was matched properly, the main factor determining the lifespan of the kidney transplant is how well the patient takes care of the transplant. In this study, Chamberlain et al. examined the costs of managing patients post-transplantation separated based on their glomerular filtration rate measured at 1 year post-transplant.
Chamberlain et al. looked at over three thousand patients spread over 9 countries in Europe. The 1 year glomerular filtration rate and also their average 3-year costs (not including any immunosuppression therapy or abnormal post-transplant event costs). As they expected, the glomerular filtration rate, a marker of the success of the transplant and functioning capability of the new kidney, was directly correlated with lower costs over the three year period post-transplantation. In order to overcome this, Chamberlain et al. stress the importance of reducing the cost burden of kidney transplants to European healthcare systems through methods to increase renal function over the first few years post-transplantation.