Leucocyte count as an alternative to ESR in general practice?

We investigated the ability of the leucocyte count to discriminate between "inflammatory diseases and malignancies" on the one hand and other, often harmless and self-limiting diseases on the other, and compared this ability with that of the erythrocyte sedimentation rate (ESR) in general practice. In cooperation with nine general practitioners (GP) we prospectively followed 151 patients who were seen by their GP because of a new complaint for which the GP wanted to know their ESR. ESR and one leucocyte count measurement (Technicon H6000) were performed at the local hospital laboratory. The patients were seen again after three months, to determine the follow-up diagnoses. By comparing the test results with the follow-up diagnoses, ESR was found to have a better discriminating ability than the leucocyte count test (ESR: sensitivity = 53%, specificity = 84%, positive predictive value = 29%, negative predictive value = 93%, Odds Ratio = 5.73). Using Receiver Operating Characteristic analysis, this conclusion could be shown to be independent of the chosen reference values. We conclude that the determination of the leucocyte count is not a clinically interesting alternative to ESR.     

Is it important to position foot in subtalar joint neutral position during non-weight-bearing molding for foot orthoses?

When taking molds for foot orthoses, it is accepted practice to position the subtalar joint in its neutral position. However, foot orthoses have no contact with the talus, and this leads to a hypothesis that as long as there is correction available to appropriately align the forefoot relative to the hindfoot when taking a mold, changes in subtalar joint angles do not lead to significant alterations in the plantar surface shapes of the molds taken. This study tested this presumption with 20 subjects between 22 and 46 years old. During non-weight-bearing casting, the subtalar joints were aligned at positions of 4° of eversion, 2° of eversion, 2° of inversion, and in neutral. At each orientation, forces were applied over the forefoot such that the metatarsal heads were aligned with the rearfoot. Digital scanning was used to analyze the shape of each negative mold. There were significant changes in projection volume in different subtalar joint orientations. However, the changes in arch heights, navicular height, and protrusion were insignificant and very small. It is therefore suggested that as long as the forefoot and hindfoot are appropriately aligned, variations in the orientation of the subtalar joint would be acceptable.     

Is there an advantage for preterm infants to feed orally in an upright or sidelying position?

Over the last decade, nursing staff and feeding therapists have promoted the upright and sidelying bottle feeding positions as ‘optimal’ for preterm infants. To verify such benefits, very low birth weight infants were randomized to being fed in the customary semi-reclined (control), upright, or sidelying position. The primary outcome was days from start to independent oral feeding. Secondary outcomes included infants' oral feeding skill levels monitored when taking 1,2, 3–5, and 6–8 oral feedings per day. Infants fed in the upright and sidelying groups attained independent oral feeding within the same number of days as control counterparts. There was no difference in the maturation of their oral feeding skills.     

Adacolumn for selective leukocytapheresis as a non‐pharmacological treatment for patients with disorders of the immune system: An adjunct or an alternative to drug therapy?

Inflammatory and/or autoimmune diseases like ulcerative colitis (UC) or Crohn's disease (CD) are debilitating chronic disorders that poorly respond to pharmacological interventions. Further, drug therapy has adverse effects that add to disease complications. The current thinking is that disorders like inflammatory bowel disease (IBD) reflect an over exuberant immune activation driven by cytokines including TNF-alpha. Major sources of cytokines include myeloid leukocytes (granulocytes, monocytes/macrophages), which in IBD are elevated with activation behavior and are found in vast numbers within the inflamed intestinal mucosa. Accordingly, myeloid cells should be the targets of therapy. Adacolumn is filled with cellulose acetate beads that selectively adsorb and deplete myeloid cells and a small fraction of lymphocytes (FcgammaR and complement receptors bearing cells). In one study, 20 steroid naive patients with moderate (n = 14) or severe (n = 6) UC according to Rachmilewitz despite 1.5-2.25 g/day of 5-aminosalicylic acid received 6 to 10 Adacolumn sessions at 2 sessions/week. Efficacy was assessed 1 week after the last session. The majority of patients responded to 6 sessions, 17 (85%) achieved remission. In 2 of the 3 non-responders, CAI was 8 and 12 in 1; all 3 had deep colonic ulcers at study initiation. Decreases were seen in total leukocytes (P = 0.003), % neutrophils (P = 0.003), % monocytes (P = 0.004), an increase in lymphocytes (P = 0.001), decreases in C-reactive protein (P = 0.0002), and rises in blood levels of soluble TNF-alpha receptors I (P = 0.0007), II (P = 0.0045). In a separate study, a case with very severe steroid refractory UC who received up to 11 sessions responded well and avoided colectomy. Further, myeloid cell purging with Adacolumn has been associated with the release of IL-1 receptor antagonist, suppression of TNF-alpha, IL-1beta, IL-6, IL-8, down-modulation of L-selectin and the chemokine receptor CXCR3. In conclusion, selective depletion of myeloid cells appears to induce anti-inflammatory effects and represents a non-pharmacological treatment for patients with active IBD. The treatment has a clear drug-sparing role. Changes in blood levels of inflammatory and anti-inflammatory factors are thought to contribute to the efficacy of this procedure.     

Landmark survival as an end-point for trials in critically ill patients – comparison of alternative durations of follow-up: an exploratory analysis

Introduction  

Interventional ICU trials have followed up patients for variable duration. However, the optimal duration of follow-up for the determination of mortality endpoint in such trials is uncertain. We aimed to determine the most logical and practical mortality end-point in clinical trials of critically ill patients.     

Thromboprophylaxis in patients with multiple organ injuries--is there an alternative to low-molecular-weight heparins (LMWH)?

The number of body injuries keeps growing and that is mostly due to increasing number of car accidents. How to prevent thrombosis in such cases is still under discussion with the biggest issue being the proper timing. Most of the input to such discussion usually comes from extrapolating data from other studies, which is hardly of help for treatment of such group of patients. The authors focus on collection and analysis of most recent data and recommendations that are available in literature. They show that low-molecular-weight heparins are by far the most common, if not sole pharmacologic means of thromboembolism prevention in patients with numerous body injuries.     

Milk thistle: is there a role for its use as an adjunct therapy in patients with cancer?

The use of complementary and alternative medicine (CAM) is common among patients with cancer. Many of these patients use CAM therapies to decrease the risk of late effects that are sometimes associated with cancer therapy. Certain classes of effective anticancer agents can induce short- and long-term toxicity to the liver. Currently, there are no safer alternatives to these medications. Milk thistle (Silybum marianum) is a botanical that may be useful in the prevention or treatment of liver dysfunction in patients undergoing anticancer therapy.     

Verisimilitude (or “truthlikeness”) as an alternative to pro and cons: migraine and cluster headache mechanisms

Calculating verisimilitude (or “truthlikeness”) ad modum Popper is a quantitative alternative to the usual pros and cons in migraine and cluster headache mechanisms. The following items were evaluated: dilation of large cranial arteries during migraine; CGRP increase during migraine; migraine as a brain disorder; aura and migraine headache; brain stem activation during migraine; rCBF in migraine without aura; NO and pathophysiology of migraine; neurogenic inflammation and migraine; aura in cluster headache; and hypothalamic activation in cluster headache. It is concluded that verisimilitude calculations can be helpful when judging pathophysiological problems in migraine and cluster headache.     

Cefoxitin as an alternative to carbapenems in a murine model of urinary tract infection due to Escherichia coli harboring CTX-M-15-type extended-spectrum β-lactamase

We investigated the efficiency of the cephamycin cefoxitin as an alternative to carbapenems for the treatment of urinary tract infections (UTIs) due to Escherichia coli producing CTX-M-type extended-spectrum β-lactamases. The susceptible, UTI-inducing E. coli CFT073-RR strain and its transconjugant CFT073-RR Tc (pbla(CTX-M-15)), harboring a bla(CTX-M-15) carrying-plasmid, were used for all experiments. MICs of cefoxitin (FOX), ceftriaxone (CRO), imipenem (IMP), and ertapenem (ETP) for CFT073-RR and CFT073-RR Tc (pbla(CTX-M-15)) were 4 and 4, 0.125 and 512, 0.5 and 0.5, and 0.016 and 0.032 μg/ml, respectively. Bactericidal activity was similarly achieved in vitro against the two strains after 3 h of exposure to concentrations of FOX, IMI, and ETP that were 2 times the MIC, whereas CRO was not bactericidal against CFT073-RR Tc (pbla(CTX-M-15)). The frequencies of spontaneous mutants of the 2 strains were not higher for FOX than for IMP or ETP. In the murine model of UTIs, mice infected for 5 days were treated over 24 h. Therapeutic regimens in mice (200 mg/kg of body weight every 3 h or 4 h for FOX, 70 mg/kg every 6 h for CRO, 100 mg/kg every 2 h for IMP, and 100 mg/kg every 4 h for ETP) were chosen in order to reproduce the percentage of time that free-drug concentrations above the MIC are obtained in humans with standard regimens. All antibiotic regimens produced a significant reduction in bacterial counts (greater than 2 log(10) CFU) in kidneys and bladders for both strains (P < 0.001) without selecting resistant mutants in vivo, but the reduction obtained with CRO against CFT073-RR Tc (pbla(CTX-M-15)) in kidneys was significantly lower than that obtained with FOX. In conclusion, FOX appears to be an effective therapeutic alternative to carbapenems for the treatment of UTIs due to CTX-M-producing E. coli.     

Double β-lactam regimen compared to an aminoglycoside/β-lactam regimen as empiric antibiotic therapy for febrile granulocytopenic cancer patients

In a prospective, randomized trial, 205 febrile episodes in granulocytopenic cancer patients were treated with ceftazidime with or without tobramycin (C±T), both agents being administered only if the initial granulocyte count was below 200/l, or ceftazidime plus piperacillin (C+P). The overall response rate was 71% (39 of 60 for C±T and 45 of 58 for C+P). Logistic regression analyses documented no evidence of a significant difference between the two regimens in overall treatment effect after accounting for the linear effects of potentially important variables, such as infection type and granulocyte count. Although the response rates for the subgroup of patients with bacteremias was better with the C+P regimen (P=0.06), there was no difference in response for patients with bacteremia and profound (<100/gml) sustained granulocytopenia. The double -lactam combination demonstrated in vitro synergism in 73%; antagonism was not seen. Both regimens produced execllent serum bactericidal levels (C±T geometric mean peak 1:170; C+P peak 1:137) against gram-negative but not gram-positive pathogens (1:4; 1:7 respectively) that had caused bacteremia. Emergence of resistance and significant coagulopathy and/or bleeding did not occur during therapy. Antibiotic-related nephrotoxicity was noted in 7 of 95 trials in the C+P and in 6 of 89 trials in the C±T group (P=0.19). The incidence of secondary infections in patients with profound (<100/l) sustained granulocytopenia was lower in the C±T group (P=0.04). Alimentary canal anaerobic flora preservation with C±T, and suppression with C+P, was demonstrated. These results suggest that these regimens are of similar effectiveness and neigher is associated with major toxicity.     

An Infant Screening Programme as an Attempt to Detect “at Risk” Factors for Language Acquisition in an Australian Population

During the years 1972 — 1974 some 2,829 infants between the ages of 8 and 11 months, born at Dandenong and District Hospital, were screened in an attempt to sift out those in the population who might be at risk for language acquisition.

Stimuli presented were noise-makers and soft voiced language and responses were recorded through behaviour observation techniques. Results showed that without establishing thresholds of hearing and despite subjective evaluation on the part of the examiner, such techniques are of use in finding children with impaired peripheral hearing and others at risk for language acquisition.