Considering formulation characteristics when prescribing and dispensing medicinal products for children: a qualitative study among GPs and pharmacists.

BACKGROUND: Finding appropriate medicinal product formulations and dosage forms for children can be challenging. Knowledge about considerations behind which medicinal product to prescribe or dispense for children is lacking. OBJECTIVE: To explore considerations of formulation characteristics of medicinal products made by GPs when prescribing and by pharmacists when dispensing medicines for children 0-6 years of age. METHOD: A qualitative study was performed by conducting three semi-structured focus groups with GPs and three with pharmacists, using nearly identical thematic interview guides. Analysis was performed using systematic text condensation. RESULTS: Both GPs and pharmacists considered whether children and parents were willing and able to use medicinal products such as tablets and poor-tasting liquids before prescribing and dispensing them. These considerations were commonly based on health care workers' prior experiences, although parents and sometimes children were asked about their experiences with solid formulations. For antibiotics, GPs primarily wanted to prescribe first-choice antibiotics according to guidelines. Parents' concerns about getting the child to take the medicinal product due to poor taste could lead to the prescription of second-choice antibiotics. The pharmacists sometimes changed the prescribed formulation at parents' request but never changed the type of antibiotic without contacting the prescriber. CONCLUSION: Formulation characteristics strongly influenced which medicinal product children were prescribed and dispensed. Individualizing formulation choices for children through an increased collaboration between physicians, pharmacists and parents is suggested.

Register-based study showed that the age when children were prescribed antibiotic tablets and capsules instead of liquids increased from 2004 to 2016.

AIM: We investigated the age when the prescriptions of oral antibiotic formulations for children from birth to 12 years of age changed from being mostly liquid to mostly solid and the associations between solid formulations and child, prescriber and medication characteristics. METHODS: This register-based study comprised data from the Norwegian Prescription Database on oral antibiotics dispensed between 2004 and 2016 when both solid and liquid dosage forms were available in appropriate doses. RESULTS: Just over 1.2 million prescriptions were studied, and the age when children were prescribed oral solid antibiotics gradually increased. The mean age of conversion from liquids to solid formulations was 6.9 years and ranged from 5.7 years in 2004/2005 to 7.9 years in 2015/2016. Patient factors associated with solid dosage forms were the children's increasing age and male gender. Practitioner factors were the prescribers' increasing age, male gender, being a general practitioner and issuing fewer than 23 paediatric antibiotic prescriptions per year. Medication factors were bad-tasting liquids and the size and shape of solid dosage forms. CONCLUSION: The age when children were prescribed antibiotic tablets and capsules increased from 2004 to 2016. The medicine characteristics were quite consistent, so this was probably caused by a shift in formulation preferences.

Requests for new oral antibiotic prescriptions in children within 2 days: a Norwegian population-based study.

Background: Children commonly refuse to take antibiotics, which may induce parents to request new antibiotic prescriptions with different pharmaceutical characteristics. Objectives: To investigate prescription changes for children 0-12 years receiving oral liquid or solid antibiotic formulations and to explore the relationships between prescription changes and characteristics related to the child, prescriber and antibiotic. Methods: A population-based registry study based on data from the Norwegian Prescription Database (NorPD) from 2004 to 2016. Antibiotic prescription changes were defined as the dispensing of subsequent antibiotics with different pharmaceutical characteristics to the same child within 2 days after initial prescriptions. Data were analysed using multivariable logistic regression and generalized estimating equations. Results: Requests for new prescriptions followed 3.0% of 2 691 483 initial antibiotic prescriptions for children. Young children who received solid formulations (10.9%) and certain poor-tasting antibiotics (8.6%) had the highest proportions of new prescriptions. Penicillin V was most commonly changed, while macrolides/lincosamides dominated subsequent prescriptions. In order of magnitude, the characteristics associated with requests for new prescriptions were the children's ages, poor taste and concentration of liquids, size and shape of solids, prescribers born in recent decades, and girl patients. Reimbursed prescriptions and scored solids were associated with fewer requests. Conclusions: While only 3% of the antibiotic prescriptions were changed, the preference of broad-spectrum over narrow-spectrum antibiotics for young children in this study mirrors international prescription patterns. Avoiding the costs of children's refusal and consequent changes may thus be a motivation for choosing more preferred antibiotics.

Reduced Th22 cell proportion and prevention of atopic dermatitis in infants following maternal probiotic supplementation.

BACKGROUND: In the randomized, controlled study Probiotics in the Prevention of Allergy among Children in Trondheim (ProPACT), maternal probiotic supplementation reduced the incidence of atopic dermatitis (AD) in the offspring. In the current study, we hypothesized that the effect was mediated by a shift in the T helper (Th) cells in the children. OBJECTIVE: To examine whether Th cell proportions were affected by maternal probiotic supplementation and thus could mediate the preventive effect of probiotics on AD. METHODS: A total of 415 pregnant women were randomized to ingest a combination of Lactobacillus rhamnosus GG (LGG), Bifidobacterium animalis subsp. lactis Bb-12 (Bb-12) and Lactobacillus acidophilus La-5 (La-5) or placebo, and their offspring were assessed for AD during the first 2 years of life. Peripheral blood collected at 3 months of age was analysed for regulatory T cells (n=140) and Th subsets (n=77) including Th1, Th2, Th9, Th17 and Th22. RESULTS: The proportion of Th22 cells was reduced in children in the probiotic group compared to the placebo group (median 0.038% vs 0.064%, P=.009). The difference between the probiotic and placebo groups was also observed in the children who did not develop AD during the 2-year follow-up. The proportion of Th22 cells was increased in children who developed AD compared to the children who did not develop AD (0.090% vs 0.044%, P<.001). Mediation analysis indicated that the preventive effect of probiotics was partially mediated through the reduction in Th22 cells. CONCLUSION: Perinatal maternal probiotic supplementation with a combination of LGG, Bb-12 and La-5 reduced the proportion of Th22 cells in 3-month-old children. This may partially explain the preventive effect of probiotics on AD.

Prostate cancer detection: the value of performing an MRI before a biopsy.

BACKGROUND: In recent years, prostate-specific antigen (PSA) screening has been widely performed. As a result, patients who need to undergo a complete physical examination for an elevated PSA level have been rapidly increasing. Magnetic resonance imaging (MRI) examination has previously been reported to be effective for the detection of prostate cancer. PURPOSE: To evaluate the detectability of prostate cancer by performing MRI before biopsy, and to evaluate the relationship between detectability with MRI and cancer location, Gleason score (GS), and tumor size. MATERIAL AND METHODS: MRI was performed at 1.5 Tesla in 122 consecutive patients before biopsy. The detectability of prostate cancer, including sensitivity and positive predictive value (PPV) of transrectal ultrasonography (TRUS), T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI) (b=2000 s/mm(2)), apparent diffusion coefficient (ADC) map, and biopsy, was calculated using whole-mount section histopathology as a gold standard. In addition, the relationship between the detectability on each MRI sequence and factors such as cancer location (peripheral zone vs. transition zone), GS 5-10, short-axis diameter (< or =4 mm, 5-9 mm, > or =10 mm), and long-axis diameter (< or =9 mm, 10-19 mm, > or =20 mm) were also evaluated. RESULTS: The sensitivities of TRUS, T2WI, DWI, ADC map, and biopsy were 26.9%, 41.2%, 56.7%, 57.7%, and 75.1%, respectively, and the PPVs of those modalities were 73.0%, 83.0%, 86.4%, 87.2%, and 91.5%, respectively. There was no correlation between the sensitivity of each MRI sequence and cancer location. The sensitivity of each MRI sequence increased as GS and short- and long-axis diameters of cancer lesions increased. CONCLUSION: MRI before a biopsy has a high detectability of prostate cancer, particularly with tumor size of more than 5 mm in short-axis diameter or 10 mm in long-axis diameter.

Fear of hypoglycaemia and its relation to hypoglycaemia awareness and symptom intensity in Type 1 diabetes.

AIMS: To investigate fear of hypoglycaemia (FoH) in relation to hypoglycaemia awareness, history of severe hypoglycaemia (SH) and hypoglycaemia symptoms in adults with Type 1 diabetes. METHODS: Questionnaire-based cross-sectional survey. We assessed FoH with the Hypoglycaemia Fear Survey-II Worry subscale, hypoglycaemia awareness status with the Gold score, and used the Edinburgh Hypoglycaemia Scale to grade the presence and intensity of hypoglycaemia symptoms. All these measures have previously been validated for research application. We used multivariable linear regression to examine associations between FoH and hypoglycaemia awareness status, history of SH and hypoglycaemia symptom score. RESULTS: Of 636 invitees, 445 (70%) responded, with 435 responses eligible for analyses. Seventy-four persons had IAH (17%). Among those, 47 (64%) reported ≥ 1 SH during the preceding year, in contrast to this being reported by 113 (31%) of persons with normal awareness. The mean (SD) FoH worry score was 1.33 (0.78). This score was 0.64 (95% CI, 0.45-0.83) higher among people with impaired vs. normal hypoglycaemia awareness and 0.53 (95% CI, 0.33-0.73) higher among people with ≥ 3 episodes of SH the preceding year vs. people with no such episode. A higher number and intensity of hypoglycaemia symptoms was associated with higher FoH, as demonstrated by an increase in mean FoH worry score of 0.30 (95% CI, 0.23-0.36) per point increase in mean Edinburgh hypoglycaemia score. CONCLUSIONS: Impaired awareness of hypoglycaemia, history of SH and higher Edinburgh hypoglycaemia scores were all associated with increased FoH in adults with Type 1 diabetes.

Perception of geometric illusions in hemispatial neglect.

A patient with left hemispatial neglect, while completely unaware of features on the left side of figures, nevertheless perceived geometric illusions dependent on these features. Bisection errors were amplified not only by increasing line length, but also by perceived line length induced by these illusions. Bisection of Judd illusion figures was as much influenced by neglected features on the left as by perceived features on the right. These observations demonstrate that geometric illusions are generated through preattentive processes. They also suggest that in visual neglect there may be preattentive processing of location as well as shape information.

Localization of the human frontal eye fields and motor hand area with transcranial magnetic stimulation and magnetic resonance imaging.

We localized the neuroanatomical correlates for control of saccadic eye movements and for finger movements using a combined transcranial magnetic stimulation (TMS) and magnetic resonance imaging (MRI) approach. Two participants underwent TMS while performing an endogenous saccade task. The motor hand area was localized by TMS and the region anterior to it was mapped to identify the borders of a region where TMS produced delays in generating contralateral saccades. MRI scans were then obtained with fiducial markers placed over the motor hand area and 2 cm anterior to it, the common cortical region that produced saccadic delays in these two subjects. It was also shown that the structural anatomy of the hand area, physiologically defined by visible contractions of the contralateral hand following TMS, corresponded to the knob-like structure recently reported [18, 19]. These results demonstrate that TMS can be a precise, non-invasive tool for neuroanatomical mapping of cortical structures when combined with structural images of the brain.

Response channel activation and the lateral prefrontal cortex.

The role of lateral prefrontal cortex in transducing perception into action was studied in 10 patients with chronic, unilateral lesions. They identified colors in the center of a visual display, while a flanking, distractor color was presented simultaneously in either the ipsilesional or contralesional field. The flanker could be either the same color as the target, or incompatible with the correct response. The effects of compatible and incompatible flankers on reaction time (RT) served as a measure of response channel activation by the flanker. Flankers in the contralesional field influenced RT less than did those in the ipsilesional field. These results suggest that the lateral prefrontal cortex is involved in maintaining stimulus-response channels.

Interactions between color and word processing in a flanker task.

To examine interactions between color and word attributes, participants responded, either manually or vocally, to a central target (color patch or word) flanked by a Stroop stimulus. Color and word attributes of the flanker affected both vocal and manual responding to color patches. Color and word flankers also affected manual responding to word targets, but only word flanker affected vocal responding to word targets. These results are not consistent with models (e.g., translational models) of Stroop tasks, which posit that interactions between colors and words occur only when vocal responding is required.

Object-based facilitation and inhibition from visual orienting in the human split-brain.

Object-based attention was examined in 2 split-brain patients. A precued object could move within a visual field or cross the midline to the opposite field. Normal individuals show an inhibition in detecting signals in the cued object whether it moves within or between fields. Both patients showed this effect when the cued object moved within a visual field. When it crossed the midline into the opposite visual field, however, detection was faster in the cued box. These results reveal both facilitatory and inhibitory effects on attention that are object based and may last for several hundred milliseconds. However, the inhibition requires an intact corpus callosum for interhemispheric transfer, whereas the facilitation is transferred subcortically.

Hepatocellular carcinoma with pyrexia: report of a case.

Reported here is a case of an unusual type of hepatocellular carcinoma (HCC). Since this patient with liver mass exhibited continuous pyrexia, an inflammatory pseudotumor or abscess was strongly suspected. Two-phased incremental CT, MR with and without Gd-DTPA administration, and angiography demonstrated peripheral enhancement of the hepatic mass. Histologically, the tumor proved to be HCC with sarcomatoid degeneration. When one encounters a patient with a mass clinically and radiologically mimicking an inflammatory pseudotumor or an abscess, poorly differentiated HCC with sarcomatoid degeneration should be suspected.

Bone morphogenetic protein-9 suppresses growth of myeloma cells by signaling through ALK2 but is inhibited by endoglin.

Multiple myeloma is a malignancy of plasma cells predominantly located in the bone marrow. A number of bone morphogenetic proteins (BMPs) induce apoptosis in myeloma cells in vitro, and with this study we add BMP-9 to the list. BMP-9 has been found in human serum at concentrations that inhibit cancer cell growth in vitro. We here show that the level of BMP-9 in serum was elevated in myeloma patients (median 176 pg/ml, range 8-809) compared with healthy controls (median 110 pg/ml, range 8-359). BMP-9 was also present in the bone marrow and was able to induce apoptosis in 4 out of 11 primary myeloma cell samples by signaling through ALK2. BMP-9-induced apoptosis in myeloma cells was associated with c-MYC downregulation. The effects of BMP-9 were counteracted by membrane-bound (CD105) or soluble endoglin present in the bone marrow microenvironment, suggesting a mechanism for how myeloma cells can evade the tumor suppressing activity of BMP-9 in multiple myeloma.

Increased sensitivity to ipsilateral cutaneous stimuli following transcranial magnetic stimulation of the parietal lobe.

Transcranial magnetic stimulation of the sensorimotor cortex results in decreased sensitivity of threshold electrical stimuli to fingers of the contralateral hand. It has been suggested that one factor contributing to neglect contralateral to a unilateral parietal lesion is a release of the normal hemisphere from reciprocal interhemispheric inhibition by the damaged hemisphere. Consistent with this account, the current study demonstrated that transcranial magnetic stimulation over the parietal cortex results in increased sensitivity to cutaneous stimulation ipsilateral to the stimulation. The likely mechanism is a transcranial magnetic stimulation-induced transient dysfunction of the ipsilateral parietal cortex that then results in disinhibition of the contralateral parietal cortex.

Changing faces: a detection advantage in the flicker paradigm.

Observers seem surprisingly poor at detecting changes in images following a large transient or flicker. In this study, we compared this change blindness phenomenon between human faces and other common objects (e.g., clothes). We found that changes were detected far more rapidly and accurately in faces than in other objects. This advantage for faces, however, was found only for upright faces in multiple-object arrays, and was completely eliminated when displays showed one photograph only or when the pictures were inverted. These results suggest a special role for faces in competition for visual attention, and provide support for previous claims that human faces are processed differently than stimuli that may be of less biological significance.

The dependence of two-dimensional shape perception on orientation.

While it is true that in daily life we generally recognize objects regardless of their orientation, previous experiments involving novel shapes indicate a decline in recognition when these are tested in altered orientation. Here the question is raised of whether there is a component of shape perception based purely on the geometry of an object, independent of orientation. By means of two tests designed to eliminate awareness of change of orientation, one more stringent than used heretofore, it was found that shape perception is dependent on orientation. The apparent contradiction between these findings and the apparent orientation-free character of recognition in daily life is discussed.

Components of reflexive visual orienting to moving objects.

Posner and Cohen (1984) and Maylor (1985) initially observed that a luminance change produces both facilitatory and inhibitory effects on subsequent detection. While Posner and Cohen claimed that the facilitatory effect was mapped in retinotopic coordinates, they showed that inhibition of return (IOR) was mapped in "environmental coordinates." Tipper and colleagues (Tipper, Driver, & Weaver, 1991; Tipper et al., 1997; Tipper, Weaver, Jerreat, & Burak, 1994) and Abrams and Dobkin (1994b) have recently reported that IOR can be object based, but contradictory results have also been reported (Müller & von Mühlenen, 1996). Here we report six experiments showing that an uninformative peripheral cue can generate either facilitatory or inhibitory object-based effects that can tag moving objects and that can persist for several hundred milliseconds. Although the boundary conditions determining which effect will be manifest remain to be defined, the present results suggest that facilitation and inhibition are generated independently, rather than being components of the same biphasic process.