Comparison of drug administration logistics between prothrombin complex concentrates and plasma in the emergency department

Background

Prothrombin complex concentrate (PCC) is used as an alternative to fresh frozen plasma (FFP) for emergency bleeding. The primary objective of this study was to compare the time from order to start of administration between 3-factor PCC (PCC3), 4-factor (PCC4), and FFP in the emergency department (ED). The secondary objective was to evaluate the effect of an ED pharmacist on time to administration of PCCs.

Diabetic foot off loading and ulcer remission: Exploring surgical off-loading

IntroductionDiabetic peripheral neuropathy leads to foot deformity, soft tissues damage, and gait imbalance, all of which can increase the mechanical stress imposed on the foot and give rise to Charcot neuroarthropathy. The current International Working Group of the Diabetic Foot International Guidelines on offloading focus on managing neuropathic foot ulcers related to pressure: only 2 of their 9 recommendations deal with surgical interventions. We assess the role of surgical techniques in off-loading to heal and possibly prevent diabetic foot ulceration.MethodsWe systematically analysed published data from January 2000 to November 2020 to assess methods of surgical offloading and associated outcomes for the surgical reconstruction. We tried to identify healing, remission-rates, return to ambulation, complications and limitations.ResultsFive discrete categories of surgical offloading are used in recalcitrant ulcers: 1. Lesser toe tenotomies; 2. Metatarsal head resection ± Achilles tendon release; 3. Hallux procedures; 4. Bony off-loading procedures in the form of exostectomy; and 5. Complex surgical foot reconstruction. Adjuvant modalities including surgically placed antibiotic delivery systems show promise, but further studies are required to clarify their role and effect on systemic antibiotic requirements.Conclusions and implicationsSurgery is important to mechanically stabilise and harmonise the foot for long term off-loading and foot-protection. Surgery should not be reserved for recalcitrant cases only, but extended to ulcer prevention and remission. Further comparative studies will benefit surgical decision making to avoid recurrence and define time point when surgical off-loading could protect against irretrievable tissue loss/re-ulceration.     

Ultrasonographic findings in metatarsophalangeal and talocrural joints in healthy persons

The objective of this study was to establish whether healthy persons have effusions detectable by ultrasonography (US) in metatarsophalangeal (MTP) and talocrural (TC) joints. Fifty consecutive healthy persons without symptoms in ankles and feet were studied. Thirty-eight of them were women, and their mean age was 47.4 (range 23–62) years. Eighteen of the 500 MTP joints studied in nine persons and four of the 100 TC joints in three persons showed effusions upon investigation. One person had effusion in five MTP joints, one in four, two in two, and the remaining five in one MTP joint. None of the studied joints yielded pathological findings in Doppler US examination. These results indicate that the detection of effusion by grayscale US in the absence of Doppler US in MTP and TC joints can be found in healthy persons.     

The SLC40 basolateral iron transporter family (IREG1/ferroportin/MTP1)

The iron regulated-transporter-1 (Ireg1, also known as ferroportin or metal transporter protein-1, MTP1) appears to be the sole member of the SLC40 transporter family. It functions as a universal efflux pathway for iron in a number of cell types. The protein is most highly expressed in mature enterocytes of the duodenum, in syncytiotrophoblasts, which separate foetal and maternal circulations in the placenta, and in macrophages responsible for recycling iron from breakdown of aged red blood cells.     

Post-statin approaches to hyperlipidaemia

The advent of statins has virtually resolved the treatment of a majority of essential hypercholesterolaemic patients. Nevertheless, other abnormalities in lipoprotein metabolism, including such lipoprotein disturbances as hypertriglyceridaemia, mixed hyperlipidaemia, accumulation of small dense low density lipoprotein (LDL), high levels of lipoprotein (a) (Lp[a]) and hypo-HDL-cholesterolaemia, although also highly atherogenic, are not as efficiently treated as essential hypercholesterolaemia. Pharmaceutical companies are improving new molecules directed against old targets (PPARalpha: fibrates) or creating original molecules directed against new targets (acyl CoA:cholesterol acyltransferase (ACAT), microsomal triglyceride transfer protein (MTP), retinoid X receptor (RXR)). Of the multitude of ACAT inhibitors, only a few have reached preliminary clinical studies: e.g., F-1394, Sch48461 and CI-1011. They reduce LDL-cholesterol and atherosclerosis development in animals, partly by directly inhibiting cholesteryl ester formation in the artery wall. BW-USC-148 is a fibric acid derivative with ACAT-inhibiting activity. The hypocholesterolaemic activity for this novel ureido fibrate analogue was found to be over 100-fold greater than that of any ‘second generation' fibrate in cholesterol-fed rats, mainly through its fibrate activity (PPARalpha activation) but not its ACAT activity. Targretin (LGD1069), a member of the rexinoid family (RXR activator), was shown to decrease triglyceridaemia and to increase HDL levels in hypertriglyceridaemic rats. Microsomal triglyceride transfer protein inhibitors are potent inhibitors of the synthesis of all the atherogenic apolipoprotein B-containing particles and are under development, but in vivo data are not yet available in literature. Vitamin E, an old molecule, should be used in the near future as a potent anti-atherosclerotic treatment due to its anti-oxidant power. Results of preliminary gene therapy studies of homozygous familial hypercholesterolaemic patients and of hypo-HDL-cholesterolaemia in animals are promising but do not show hope for significant clinical use in the near future. The improvement in the understanding of the molecular mechanisms of dyslipoproteinaemia and atherosclerosis development, taken together with new strategies in drug design and drug synthesis, has led to the discovery of potent normolipidaemic drugs.     

Microsomal transfer protein (MTP) inhibition—a novel approach to the treatment of homozygous hypercholesterolemia

Abstract

Homozygous familial hypercholesterolemia (HoFH) represents the most severe lipoprotein disorder, generally attributable to mutation(s) of the low-density lipoprotein receptor (LDL-R), i.e. autosomal dominant hypercholesterolemia type 1 (ADH1). Much lower percentages are due to alterations of apolipoprotein B (ADH2), or gain-of-function mutations of proprotein convertase subtilisin/kexin type 9 (PCSK9) (ADH3). In certain geographical areas a significant number of patients may be affected by an autosomal recessive hypercholesterolemia (ARH). Mutations may be also combined (two mutations of the same gene, compound heterozygosity), or two in different genes (double heterozygosity). Among the most innovative therapeutic approaches made available recently, inhibitors of the microsomal transfer protein (MTP) system have shown a high clinical potential. MTP plays a critical role in the assembly/secretion of very-low-density lipoproteins (VLDL), and its absence leads to apo B deficiency. MTP antagonists dramatically lower LDL-cholesterol (LDL-C) in animals, although a reported increase of liver fat delayed their clinical development. Lomitapide, the best-studied MTP inhibitor, reduces LDL-C by 50% or more in HoFH patients, with modest, reversible, liver steatosis. Recent US approval has confirmed an acceptable tolerability, provided patients adhere to a strictly low-fat regimen. There are no clinical data on atherosclerosis reduction/regression, but animal models provide encouraging results.     

Misoprostol as aid in First Trimester MTP

Background

Medical Termination of Pregnancy (MTP) is a commonly performed during the first trimester. Dilatation and Evacuation (D & E) mandates rapid dilatation of cervix with metal dilators, which requires anaesthesia and may be associated with trauma to the uterus, cervix and later cervical incompetence. The problem of rapid cervical dilatation is obviated with intravaginal misoprostol.

Methods

Intravaginal misoprostol tablet 200 microgram was inserted, a night prior to MTP to ripen the cervix. Cervix was dilated with metal dilators only in cases where cervix did not loosen up sufficiently. Products of conception were removed by suction.

Results

Out of 108 cases cervical dilatation was not required in 96 cases (88.9%).

Conclusion

Intravaginal misoprostol 200 microgram proved effective as a priming agent prior to MTP in the first trimester.Key Words: Misoprostol, MTP