Drug-related problems identified during medication review before and after the introduction of a clinical decision support system.

WHAT IS KNOWN AND OBJECTIVE: To facilitate the identification of drug-related problems (DRPs) during medication review, several tools have been developed. Explicit criteria, like Beers criteria or STOPP (Screening Tool of Older Peoples' Prescriptions) and START (Screening Tool to Alert doctors to Right Treatment) criteria, can easily be integrated into a clinical decision support system (CDSS). The aim of this study was to investigate the effect of adding a CDSS to medication review software on identifying and solving DRPs in daily pharmacy practice. METHODS: Pre- to post-analysis of clinical medication reviews (CMRs) performed by 121 pharmacies in 2012 and 2013, before and after the introduction of CDSS into medication review software. Mean number of DRPs per patient, type of DRPs and their resolution rates were compared in the pharmacies pre- and post-CDSS using paired t tests. RESULTS AND DISCUSSION: In total, 9151 DRPs were identified in 3100 patients pre-CDSS and 15 268 DRPs were identified in 4303 patients post-CDSS. The mean number of identified DRPs per patient (aggregated per pharmacy) was higher after the introduction of CDSS (3.2 vs 3.6 P < .01). The resolution rate was lower post-CDSS (50% vs 44%; P < .01), which overall resulted in 1.6 resolved DRPs per patient in both groups (P = .93). After the introduction of CDSS, 41% of DRPs were detected by the CDSS. The resolution rate of DRPs generated by CDSS was lower than of DRPs identified without the help of CDSS (29% vs 55%; P < .01). The two most prevalent DRP types were "Overtreatment" and "Suboptimal therapy" in both groups. The prevalence of "Overtreatment" was equal in both groups (mean DRPs per patient: 0.84 vs 0.77; P = .22), and "Suboptimal therapy" was more frequently identified post-CDSS (mean DRPs per patient: 0.54 vs 1.1; P < .01). WHAT IS NEW AND CONCLUSION: The introduction of CDSS to medication review software generated additional DRPs with a lower resolution rate. Structural assessment including a patient interview elicited the most relevant DRPs. Further development of CDSS with more specific alerts is needed to be clinical relevant.

[Clinical medication reviews in elderly patients with polypharmacy: a cross-sectional study in Dutch community pharmacies]. / Medicatiebeoordelingen bij ouderen met polyfarmacie.

OBJECTIVE: To investigate the nature and prevalence of drug related problems (DRPs) in older patients with polypharmacy identified by community pharmacists in daily practice through means of a clinical medication review (CMR) and assess the implementation rate of proposed interventions to solve DRPs. DESIGN: A cross-sectional study METHOD: We analysed the CMR data of 3,807 older patients (≥ 65 years) with polypharmacy (≥ 5 drugs) completed in January-August 2012. Using the "Service Apotheek Medicatie Review Tool" (SAMRT, Service Pharmacy Medication Review Tool), pharmacists in 258 community pharmacies registered the patients' year of birth, gender, dispensing data, DRPs, and proposed and implemented interventions. RESULTS: Pharmacists identified a median of two DRPs (interquartile range 1-4; mean 3.0) per patient. The DRP categories overtreatment (25.5 %) and undertreatment (15.9 %) were found to occur most frequently. On average, 46.2 % of the proposed interventions to address DRPs were implemented as proposed. In 22.4 % of cases the intervention differed from the proposal, whereas in 31.3 % of cases no intervention was implemented. CONCLUSION: In daily practice, community pharmacists identified a mean of three DRPs in older patients with polypharmacy, a number comparable to that found in controlled studies. Over- or undertreatment caused nearly half of the identified DRPs. The majority (69.9%) of the proposed interventions led to an intervention for the patient.

Anatomical evidence for an endocrine activity of the vomeronasal organ in humans.

The mammalian vomeronasal organ (VNO) is a well-adjusted chemosensory structure that facilitates social and reproductive behavior in mammals. The existence, locality, and function of this organ in human adults remain a matter of discussion. Most authors now agree that a neuroreceptive function of the adult human VNO can be excluded due to the absence of both neural receptive cells associated with the VNO in other mammals despite the enigmatic reports on the effects of pheromones on human behavior. Adult cadavers form European (Caucasoid) descent were used in this article and parasagittal dissection of the heads allowed access to the nasal septa, which were grossly examined for the VNO openings. Tissue samples were collected, embedded in gelatin and serially sectioned through cryomicrotomy. Nissl staining was performed as well as immunohistochemically stained with an antibody against calcium-binding protein. The findings presented here confirm the bilateral presence of the VNO in adult cadavers and demonstrate morphological connections of VNO receptor cells with the underlying capillaries. In addition, possible endocrine activity associated with the epithelium of this chemosensory structure has been demonstrated by the expression of calcium-binding protein in a part of these receptor cells.

The posterior intercostal vein: a thermoregulatory gateway to the internal vertebral venous plexus.

The internal vertebral venous plexus (IVVP) plays a putative role in thermoregulation of the spinal cord. Cold cutaneous venous blood may cool, while warm venous blood from muscles and brown fat areas may warm the spinal cord. The regulating mechanisms for both cooling and warming are still unknown. Warm venous blood mainly enters the IVVP via the intervertebral veins. In the thoracic area these veins are connected to the posterior intercostal veins. In this study, anatomical structures were investigated that might support the mechanisms by which warmed venous blood from the intercostal muscles and the recently described paravertebral patches of brown adipose tissue are able to drain into the vertebral venous plexus. Therefore, tissue samples from human cadavers (n = 21) containing the posterior intercostal vein and its connections to the IVVP and the azygos veins were removed and processed for histology. Serial sections revealed that the proximal parts of the posterior intercostal veins contained abundant smooth muscle fibers at their opening into the azygos vein. Furthermore, the walls of the proximal parts of the posterior intercostal veins contain plicae that allow the vessel to dilate, thereby allowing it to serve as a pressure chamber. It is suggested that a cold induced closure of the intercostal/azygos opening can result in retrograde blood flow from the proximal posterior intercostal vein towards the IVVP. This blood flow would be composed of warm blood from the paravertebral brown adipose tissue and blood containing metabolic heat from the muscles draining into the intercostal veins.

Possible thermoregulatory functions of the internal vertebral venous plexus in man and various other mammals: evidence from comparative anatomical studies.

Comparative anatomy was used to collect more evidence for a thermoregulatory function of the internal vertebral venous plexus (IVVP). The venous connections of the IVVP were studied and compared in various mammals in order to find evidence for the existence of climate related anatomical adaptations. Humans and vervet monkeys were chosen as representatives of mammals living in moderate climates, the IVVP of the dolphin was studied because this animal is always surrounded by cold water. The springbok was chosen as a representative of mammalian species living under very hot conditions. The present study was exclusively performed on post mortem material. After filling the venous system with latex the IVVP and its venous connections were dissected. It appeared that in the dolphin, veins from the trunk muscles were directly and exclusively connected to the IVVP in the absence of an azygos vein. In the vervet monkey and human specimens, veins originating in the muscles drained both into the caval veins and into the IVVP. In these mammals veins draining from brown fat areas were also connected to the IVVP. In the springbok, drainage of blood from the muscles was prevented to enter the IVVP by the presence of valves. In humans and vervet monkeys we found that the lumbar parts of the IVVP were connected to subcutaneous veins of the back. It was concluded that the anatomy of the IVVP and its connecting veins may serve to thermoregulate the spinal cord and that climate related anatomical adaptations were present in the species studied.

A morphological study of the vertebral venous plexus and its connections in the Cape dune mole-rat, Bathyergus suillus (Bathyergidae).

Bathyergus suillus are subterranean rodents found in the Western Cape of South Africa, where they inhabit sandy, humid burrows. Vertebral venous plexuses around the vertebral column have been implicated in aiding the maintenance of a constant central nervous system temperature via its connections with muscles and interscapular brown adipose tissue. The morphology of the vertebral venous plexuses and its connections in B.suillus were investigated. Frozen (n = 10) animals were defrosted; the venous system injected with latex and the vertebral venous plexuses, azygos- and intercostal veins dissected along the dorsal and ventral aspects of the vertebral column. Specimens (n = 4) were used for histological serial cross sections of the thoracic vertebrae. Veins drained from the interscapular brown adipose tissue to the external vertebral venous plexus, via a dorsal vein at the spinous process of T2 which might represent the "vein of Sulzer" described in rats. The intercostal veins cranial to the level of T8 drained directly into the ventral external vertebral venous plexus instead of into the azygos vein as seen in rats. The azygos vein was situated ventrally on the thoracic vertebral bodies in the median plane as opposed to most rodents that have a left sided azygos vein. The internal vertebral venous plexus consisted of two ventrolateraly placed longitudinal veins in the spinal epidural space. Veins from the forelimbs entered the internal vertebral venous plexus directly at the levels of C7 and T1 and have not been described in other rodents. Serial histological sections, revealed no regulatory valves in vessels leading toward the internal vertebral venous plexus, allowing blood to presumably move in both directions within the vertebral venous plexus. The vertebral venous plexus of B. suillus shows similarities to that of the rat but the vessels from the forelimbs draining directly into to the internal vertebral venous plexus and the position of the azygos vein and the intercostal veins draining into the external vertebral venous plexus are notable exceptions.

Lumbar extraforaminal ligaments act as a traction relief and prevent spinal nerve compression.

BACKGROUND: In a previous study, ligaments that connect the extraforaminal lumbar spinal nerves with the fibrous capsule of the facet joints and the dorsolateral side of the intervertebral disc were described. This anatomical configuration suggests a mechanical role in transferring extraforaminal spinal nerve traction. METHODS: One embalmed human lumbar spine was dissected from the twelfth thoracic vertebra to the first sacral vertebra to isolate the twelfth thoracic to the fourth lumbar spinal nerves. The spinal nerves from L1 to L4 were pulled at different angles with respect to the axis of the spine. Forces of 1-6N were applied. The displacements of reflective markers glued to the proximal and distal ends of the adjoining ligaments were recorded with a video system. FINDINGS: The spinal nerve proximal of the extraforaminal ligaments stays centred in the intervertebral foramen when pulling at an angle. At levels L1-L4 strain reduction by the extraforaminal ligaments was largest when pulling at a wider angle to the spinal axis in the sagittal plane. Proximal to the extraforaminal ligaments less displacement was seen compared to the displacement distal of the extraforaminal ligaments when pulling in longitudinal direction. A graded decrease in the displacement proximal to the extraforaminal ligaments was seen from the levels L1-L4. INTERPRETATION: Extraforaminal ligaments play an important role in the prevention of damage due to spinal nerve traction. The proximal attachments secure a spinal nerve position central in the intervertebral foramen and also reduce longitudinal tension.

Extraforaminal ligament attachments of the thoracic spinal nerves in humans.

An anatomical study of the extraforaminal attachments of the thoracic spinal nerves was performed using human spinal columns. The objectives of the study are to identify and describe the existence of ligamentous structures at each thoracic level that attach spinal nerves to structures at the extraforaminal region. During the last 120 years, several mechanisms have been described to protect the spinal nerve against traction. All the described structures were located inside the spinal canal proximal to the intervertebral foramen. Ligaments with a comparable function just outside the intervertebral foramen are mentioned ephemerally. No studies are available about ligamentous attachments of thoracic spinal nerves to the spine. Five embalmed human thoracic spines (Th2-Th11) were dissected. Bilaterally, the extraforaminal region was dissected to describe and measure anatomical structures and their relationships with the thoracic spinal nerves. Histology was done at the sites of attachment of the ligaments to the nerves and along the ligaments. The thoracic spinal nerves are attached to the transverse process of the vertebrae cranial and caudal to the intervertebral foramen. The ligaments consist mainly of collagenous fibers. In conclusion, at the thoracic level, direct ligamentous connections exist between extraforaminal thoracic spinal nerves and nearby structures. They may serve as a protective mechanism against traction and compression of the nerves by positioning the nerve in the intervertebral foramen.

Morphology of the human internal vertebral venous plexus: a cadaver study after latex injection in the 21-25-week fetus.

The morphology of the anterior and posterior internal vertebral venous plexus (IVVP) in human fetuses between 21-25 weeks of gestational age is described. The results are compared to the findings of a previous morphological study of the IVVP in the aged. The morphological pattern of the anterior IVVP in the fetus is very similar with the anterior IVVP in the aged human. In contrast, the posterior IVVP in the fetus lacks the prominent transverse bridging veins that are present in the aged lower thoracic and the lumbar posterior IVVP. The background of these morphological differences is unclear. Maybe the thoracolumbar part of the posterior IVVP is subject to "developmental delay," or the observed differences in the aged may result from functional and age-related factors that trigger this part of the vertebral venous system during (erect) life. The observed age related morphological differences of the posterior IVVP support the concept of the venous origin of the spontaneous spinal epidural hematoma (SSEH).

Extraforaminal ligament attachments of human lumbar nerves.

STUDY DESIGN: An anatomic study of the extraforaminal attachments of the lumbar spinal nerves was performed using human lumbar spinal columns. OBJECTIVES: To identify and describe the existence of ligamentous structures at each lumbar level that attach lumbar spinal nerves to structures at the level of the extraforaminal region. SUMMARY OF BACKGROUND DATA: During the last 120 years, several mechanisms to protect the spinal nerve against traction have been described. All these structures involved are located in the spinal canal, proximal to the intervertebral foramen. METHODS: Five embalmed human lumbar spines (T12-S1) were used. Bilaterally, the extraforaminal region was dissected to describe and measure anatomic structures and their relationships. Histology was performed with staining on the sites of attachment and along the ligament. RESULTS: The levels T12-L2 show bilaterally 2 ligaments, a superior extraforaminal ligament and an inferior extraforaminal ligament. The superior extraforaminal ligament emerges from the joint capsule of the facet joints and inserts in both, the intervertebral disc and the ventral crista of the intervertebral foramen, passing the spinal nerve laterally. In one specimen on level L2-L3, the superior extraforaminal ligament is not attached to the spinal nerve. The inferior extraforaminal ligament emerges from the intervertebral disc, passing the nerve medially and attaching the spinal nerve. At the levels L2-L5, the inferior extraforaminal ligaments are only attached to the intervertebral disc, not to the joint capsule. Histologically, the ligaments consisted of mainly collagenous structures. CONCLUSION: Ligamentous connections exist between lumbar extraforaminal spinal nerves and nearby structures.

Misrouted olfactory fibres and ectopic olfactory glomeruli in normal humans and in Parkinson and Alzheimer patients.

The presence and distribution of misrouted (MR) olfactory projection fibres were studied in the olfactory bulbs of control human brains and in the brains of people who had suffered from Parkinson's and Alzheimer's disease. It appeared that MR fibres, that is, fibres that terminate deep into the glomerular layer, are a common phenomenon in the bulbs of aged people. In all but one of the bulbs studied, MR fibres are present. The amount of MR fibres is not related to age. With a few exceptions, the MR fibres are restricted to the external plexiform layer (EPL). Only in Parkinson bulbs the MR fibres occasionally form glomerulus-like structures. These pseudo glomeruli are located in the EPL. It is concluded that MR olfactory projection fibres are a normal phenomenon in the human olfactory bulb. In nonhuman mammalians, MR fibres have only been observed in foetal and neonatal olfactory bulbs. Possibly, the age-related loss of mitral cells, which are the natural synaptic targets for the olfactory projection fibres, may play a role in the aberrant behaviour of the MR olfactory receptor cell axons. The ectopic glomerulus-like structures in Parkinson bulbs share some characteristics with normal rat glomeruli that are not observed in normal human olfactory glomeruli. This may refer to possible changes in the genetic content of olfactory structures in Parkinson patients.

A 43-year-old male with untreated panhypopituitarism due to absence of the pituitary stalk: from dwarf to giant.

A 43-yr-old male was referred because of an x-ray made after a fall, which showed open epiphysis of the arm. The man had always been short for his age; during childhood he once consulted a pediatrician because of short stature, but thereafter he never sought medical attention. At age 18 yr he was not allowed to join the army because of his height of 147 cm. He continued to grow steadily and finally reached 193 cm. He had no complaints and considered himself reasonably fit. Physical examination showed a disproportional man with a body mass index of 29.3 kg/m(2) and Tanner stage P1G1. Laboratory investigations showed hormone levels consistent with multiple pituitary deficiency, with dynamic tests consistent with hypothalamic or pituitary stalk disease. Magnetic resonance scanning of the brain showed a small anterior pituitary remnant, no pituitary stalk, and an ectopic neurohypophysis. This case of untreated panhypopituitarism shows a particular growth curve with an average growth velocity of 2 cm/yr, resembling patients with estrogen receptor mutation or aromatase deficiency. A literature study of other adult patients with untreated panhypopituitarism shows a variable growth pattern. Some speculations about possible reasons for this variability in clinical characteristics are presented.

Amaurosis fugax and stenosis of the ophthalmic artery--a case report.

Amaurosis fugax has many causes. Its most common cause is transient hypoperfusion of the eye, caused by thromboemboli from atherosclerotic carotid arteries. Thromboembolism from carotid arteries is a risk factor for cerebral infarction, and preventive endarterectomy could be performed. This report describes a patient with a rare ophthalmic artery stenosis, which was the probable origin of thromboemboli. This finding prevented surgical intervention.

Contrast enhanced color duplex for diagnosis of subtotal stenosis or occlusion of the internal carotid artery.

BACKGROUND AND PURPOSE: We initiated this prospective study to investigate the usefulness of contrast enhancement in combination with color Doppler-assisted duplex imaging (CDDI) for the distinction of subtotal internal carotid artery (ICA) stenosis and ICA occlusion. METHODS: During 1 year all patients with a previously unknown subtotal ICA stenosis (>90%) or ICA occlusion on routine CDDI were included in the study. These patients underwent a CDDI with and without intravenous contrast, Levovist 300 mg/ml. RESULTS: The study group consisted of 32 patients, 15 with subtotal stenosis and high velocity at the ICA stenosis, two with subtotal stenosis and minimal residual color flow and relative low velocity at the ICA stenosis and 15 with ICA occlusion. In all patients the diagnosis by CDDI without and with contrast were the same. Image quality was improved with contrast in 13 of the 17 patients at the subtotal ICA stenosis. There was no significant difference in mean velocities at the subtotal ICA stenoses without and with contrast. CONCLUSION: The usefulness of contrast enhancement with CDDI for differentiating subtotal ICA stenosis and ICA occlusion is limited. Possibly it is useful in patients with moderate image quality of the CCA and ICA and in patients with a subtotal stenosis with minimal residual color flow and relative low velocity at the ICA stenosis.

Tyrosine hydroxylase immunoreactive structures in the aged human olfactory bulb and olfactory peduncle.

We studied the anatomical distribution of dopaminergic structures in the normal, aged, human olfactory bulb and olfactory peduncle with a monoclonal antibody against tyrosine hydroxylase. Three different tyrosine hydroxylase containing cell groups are present in the olfactory bulbs: (1) a group of round, medium-sized cells within and around the glomeruli; (2) cells in the external plexiform layer; and (3) cells that are scattered in the stratum album. Occasionally, a few labeled neurons can be observed in the granule cell layer. In the olfactory peduncle a few labeled cells are present in the superficial layers just underneath the pia. Tyrosine hydroxylase containing terminal-like structures are present in the glomerular layer and the external plexiform layer. In a few cases dense terminal labeling is also observed in the cell groups that constitute the anterior olfactory nucleus. In the olfactory peduncle scattered labeled fibers are present. In addition, the present study makes clear that quantitative differences exist between the individual cases for which no explanation could be found.

Species-specific differences in the corticohypothalamic connections of lizards.

In lizards, information from the various senses is relayed to the hypothalamus via the cortico-septo-hypothalamic pathway. It appears that the anatomical organization of the incoming fibres in the medial cortex differs considerably between the various lizard species. In the present account it is shown that it is the location of the termination of the incoming fibres in the medial cortex that determines what kind of sensory information will reach the hypothalamic centres that are responsible for sexual and feeding behaviour.