Use of primary health care services and mortality in older patients with type 2 diabetes with or without comorbidities.

OBJECTIVE: This study aimed to examine primary health care (PHC) service utilization and mortality in older patients with type 2 diabetes (T2D) with or without comorbidities. DESIGN AND SETTING: A cohort study in PHC in the city of Vantaa, Finland. Follow-up period was set between the years 2011 and 2018. SUBJECTS: PHC patients aged 60 years or more with a T2D were included. MAIN OUTCOME MEASURES: Service utilization was defined as the number of face-to-face appointments and telephone contacts between a patient and general practitioner (GP) or nurse. The presence of comorbidities was defined using the Charlson Comorbidity Index (CCI). Mortality was assessed using hazard ratio (HR) and standardized mortality ratio (SMR). RESULTS: In total, 11,020 patients were included and followed for 71,596 person years. Mean age of the women and men in the beginning of follow-up were 71 and 69 years, respectively. The patients in the study cohort had a mean of eight appointments per person year to the GPs or nurses. Patients with T2D with comorbidities had more appointments than patients with T2D without comorbidities (incidence rate ratio (IRR) 1.44 [95% CI 1.39-1.49]). Increase in the number of all appointments reduced mortality in patients with T2D with and without comorbidities. Between patients with T2D with comorbidities and patients with T2D without comorbidities, the age and sex adjusted HR for death was 1.50 (95% CI 1.39-1.62). The SMR was higher in patients with T2D with comorbidities (1.83 [95% CI 1.74-1.92]) than in patients with T2D without comorbidities (0.91 [95% CI 0.86-0.96]). CONCLUSIONS: In older patients with T2D, the presence of comorbidities was associated with increased use of PHC services and increased mortality. Increase in the number of appointments was associated with reduced mortality in patients with T2D with or without comorbidities.Key PointsIn older patients with T2D, it has not been studied whether and to what extend multimorbidity affects use of PHC services and mortality.The presence of comorbidities according to the Charlson Comorbidity Index (CCI) was associated with increased use of PHC services.The number of appointments to GPs or nurses was associated with reduced mortality in patients with T2D with or without comorbidities according to the CCI.

Analysis of nitrogen-based explosives with desorption atmospheric pressure photoionization mass spectrometry.

RATIONALE: Fast methods that allow the in situ analysis of explosives from a variety of surfaces are needed in crime scene investigations and home-land security. Here, the feasibility of the ambient mass spectrometry technique desorption atmospheric pressure photoionization (DAPPI) in the analysis of the most common nitrogen-based explosives is studied. METHODS: DAPPI and desorption electrospray ionization (DESI) were compared in the direct analysis of trinitrotoluene (TNT), trinitrophenol (picric acid), octogen (HMX), cyclonite (RDX), pentaerythritol tetranitrate (PETN), and nitroglycerin (NG). The effect of different additives in DAPPI dopant and in DESI spray solvent on the ionization efficiency was tested, as well as the suitability of DAPPI to detect explosives from a variety of surfaces. RESULTS: The analytes showed ions only in negative ion mode. With negative DAPPI, TNT and picric acid formed deprotonated molecules with all dopant systems, while RDX, HMX, PETN and NG were ionized by adduct formation. The formation of adducts was enhanced by addition of chloroform, formic acid, acetic acid or nitric acid to the DAPPI dopant. DAPPI was more sensitive than DESI for TNT, while DESI was more sensitive for HMX and picric acid. CONCLUSIONS: DAPPI could become an important method for the direct analysis of nitroaromatics from a variety of surfaces. For compounds that are thermally labile, or that have very low vapor pressure, however, DESI is better suited.

Primary care-based facial pain unit in Vantaa: the first experiences 2003­2009.

As an attempt to tackle the challenge in serving facial pain patients, the first primary care-based facial pain unit was founded in 2003 as part of public dental primary care of Vantaa, Finland. Data were collected, consisting of sex, age, sources of referrals, reasons for seeking care, diagnoses made, therapeutic procedures, and numbers of visits to dentists and phone consultations. To describe the development of the present pain management system, we divided the observation periods into two parts: 2003-2006 and 2007-2009 and compared frequencies of the studied parameters between the two follow-up periods. During 2003-2006, 370 patients were examined and the number of visits was 659, corresponding patients' number was 437 and visits' number 960 during 2007-2009. Referrals to the primary care facial pain unit came from primary care dentists (80%), respective primary care pain unit GPs (6%), oral hygienists (3%) and ordinary GPs (2%). Four percentage of the patients' referrals came from secondary and tertiary care clinics of various types and 5% from private sector dentists and specialists. The average number of telephone consultations per year increased from 51 to 300 between study periods. During the follow-up period, the main reason for seeking care from our unit was temporomandibular disorders. Education in self-care, oral appliance therapy and physiotherapy were mostly used as management for these pain problems. The facial pain management unit in primary health care could be a useful model to serve increasing numbers of chronic facial pain patients.

Are biological communities in naturally unproductive streams resistant to additional anthropogenic stressors?

Studies on the interactive responses to multiple simultaneously acting stressors have focused on individual or population-level responses in laboratory microcosms, while field-based studies on community-level responses are rare. We examined the influence of a natural (non-anthropogenic acidity) vs. human-induced stress (land drainage) and their interaction on species richness and spatial turnover (ß diversity) of stream diatom, bryophyte, and benthic invertebrate communities. Our four stream categories were: circumneutral reference, circumneutral impacted, naturally acidic, and naturally acidic impacted streams. We expected the most sensitive species to be present only in the circumneutral reference streams. Therefore, species richness should be highest in these streams and lowest in the naturally acidic streams additionally stressed by forest drainage. Alternatively, communities in acidic streams may consist of the most tolerant taxa that are unaffected by further stressors, species richness in these streams remaining unaffected by drainage. We also expected spatial turnover to be highest in the circumneutral near-pristine streams and lowest in the drainage-impacted acidic streams. In all three taxonomic groups, α diversity was lower in the naturally acidic than in circumneutral streams. The additional impact of the anthropogenic stress on species richness varied between groups, having no effect on diatoms, antagonistic effect on bryophytes, and additive effect on invertebrates. We also found differences in how each stressor modified ß diversity of each taxonomic group. For diatoms, ß diversity showed an overall tendency to decrease with increasing stress level, while bryophyte ß diversity responded mainly to forest drainage. Benthic invertebrate ß diversity did not differ between treatments. Our results suggest that non-additive effects among stressors need special attention to improve the understanding and management of multifactor responses in streams. Our results also argue for the primacy of a multi-taxon approach to environmental impact detection, and for the inclusion of a wide array of ecological responses, particularly community turnover, in bioassessment programs to detect responses that may go unnoticed by conventional richness-based measures.

Desorption atmospheric pressure photoionization with polydimethylsiloxane as extraction phase and sample plate material.

Desorption atmospheric pressure photoionization (DAPPI) is an ambient ionization technique for mass spectrometry (MS) that can be used to ionize polar as well as neutral and completely non-polar analytes. In this study polydimethylsiloxane (PDMS) was used as a solid phase extraction sorbent for DAPPI-MS analysis. Pieces of PDMS polymer were soaked in an aqueous sample, where the analytes were sorbed from the sample solution to PDMS. After this, the extracted analytes were desorbed directly from the polymer by the hot DAPPI spray solvent plume, without an elution step. Swelling and extracting the PDMS with a cleaning solvent prior to extraction diminished the high background in the DAPPI mass spectrum caused by PDMS oligomers. Acetone, hexane, pentane, toluene, diisopropylamine and triethylamine were tested for this purpose. The amines were most efficient in reducing the PDMS background, but they also suppressed the signals of low proton affinity analytes. Toluene was chosen as the optimum cleaning solvent, since it reduced the PDMS background efficiently and gave intensive signals of most of the studied analytes. The effects of DAPPI spray solvents toluene, acetone and anisole on the PDMS background and the ionization of analytes were also compared and extraction conditions were optimized. Anisole gave a low background for native PDMS, but toluene ionized the widest range of analytes. Analysis of verapamil, testosterone and anthracene from purified, spiked wastewater was performed to demonstrate that the method is suited for in-situ analysis of water streams. In addition, urine spiked with several analytes was analyzed by the PDMS method and compared to the conventional DAPPI procedure, where sample droplets are applied on PMMA surface. With the PDMS method the background ion signals caused by the urine matrix were lower, the S/N ratios of analytes were 2-10 times higher, and testosterone, anthracene and benzo[a]pyrene that were not detected from PMMA in urine, were observed in the MS spectrum.

Evaluation of easily applicable pain measurement tools for the assessment of pain in demented patients.

BACKGROUND AND OBJECTIVES: Difficulties in communication and lack of suitable pain scales may lead to undertreatment of pain in cognitively impaired patients. We performed a study in this type of patients and evaluated the usefulness of four simple pain scales. PATIENTS AND METHODS: We studied 41 hospitalized elderly (76-95 years) who suffered from pain with an acute component. Cognitive function was assessed with the mini-mental state examination (MMSE) and the degree of depression was assessed on the geriatric depression scale (GDS). Pain intensity was assessed at rest and after a pain-provoking movement three times at 2-week intervals by repeating the test at a 10-min interval at each test session. The pain scales were the 50 cm red wedge scale (RWS), the seven-point faces pain scale (FPS), the 10 cm visual analogue scale (VAS) and the five-point verbal rating scale (VRS). RESULTS: In group MMSE> or =24, patients were able to use all four scales rather successfully. In the other groups (MMSE 17-23, 11-16 and < or =10), only the use of VRS was successful to a reasonable degree (64-85% on average). GDS scores did not correlate with the pain scores, with the exception of pain scores on FPS during movement (P<0.01). The estimations of intensity and frequency of pain performed by nurses failed to correlate with the patient's own pain intensity estimations. CONCLUSION: Scoring of pain with RWS, FPS and VAS seems to be feasible in elderly patients with a normal cognitive dysfunction. In our study VRS appeared to be applicable in the elderly with a clear cognitive dysfunction, i.e., with MMSE<17.

Atmospheric pressure photoionization-mass spectrometry and atmospheric pressure chemical ionization-mass spectrometry of neurotransmitters.

A group of five neurotransmitters with different properties was analyzed using atmospheric pressure photoionization (APPI) and atmospheric pressure chemical ionization-mass spectrometry (APCI-MS). The sensitivity of the techniques for the analytes was tested in six solvents and in positive and negative ion modes. APPI was found to be superior in sensitivity for all the compounds in both positive and negative ion modes. In positive ion mode, water/methanol/formic acid was found to be the best solvent, whereas in negative ion mode, water/methanol/ammonium hydroxide performed best. Detection limits using APPI were between 2.5-250 fmol, depending on the compound. The sensitivity was best for the neurosteroids dehydroepiandrosterone and beta-estradiol, and acetylcholine (LOD 2.5-10 fmol).

Particulate phosphorus and sediment in surface runoff and drainflow from clayey soils.

Recent work has shown that a significant portion of the total loss of phosphorus (P) from agricultural soils may occur via subsurface drainflow. The aim of this study was to compare the concentrations of different P forms in surface and subsurface runoff, and to assess the potential algal availability of particulate phosphorus (PP) in runoff waters. The material consisted of 91 water-sample pairs (surface runoff vs. subsurface drainage waters) from two artificially drained clayey soils (a Typic Cryaquept and an Aeric Cryaquept) and was analyzed for total suspended solids (TSS), total phosphorus (TP), dissolved molybdate-reactive phosphorus (DRP), and anion exchange resin-extractable phosphorus (AER-P). On the basis of these determinations, we calculated the concentrations of PP, desorbable particulate phosphorus (PPi), and particulate unavailable (nondesorbable) phosphorus (PUP). Some water samples and the soils were also analyzed for 137Cs activity and particle-size distribution. The major P fraction in the waters studied was PP and, on average, only 7% of it was desorbable by AER. However, a mean of 47% of potentially bioavailable P (AER-P) consisted of PPi. The suspended soil material carried by drainflow contained as much PPi (47-79 mg kg-1) as did the surface runoff sediment (45-82 mg kg-1). The runoff sediments were enriched in clay-sized particles and 137Cs by a factor of about two relative to the surface soils. Our results show that desorbable PP derived from topsoil may be as important a contributor to potentially algal-available P as DRP in both surface and subsurface runoff from clayey soils.

Cold exposure enhances tactile allodynia transiently in mononeuropathic rats.

A laser and erythrosin-B-induced sciatic nerve injury decreases thresholds of a mechanically induced paw withdrawal reflex and enhances cold-induced withdrawal behavior of the affected limb. Exposure of the affected paw to a normally innocuous cold stimulus results in a transient decrease in the threshold of the mechanically evoked paw withdrawal reflex in neuropathic but not in intact rats. The present data suggest that in an experimental neuropathic state a normally innocuous cold stimulus may further sensitize spinally mediated withdrawal reflexes to stimuli of another stimulus modality, in this case, to innocuous tactile stimuli. Therefore, testing mechanical allodynia in neuropathic rats immediately after testing cold allodynia may produce artifactual results.

Photochemically-induced ischemic injury of the rat sciatic nerve: a light- and electron microscopic study.

Lesion of presumably ischemic origin of the rat sciatic nerve was induced photochemically by laser irradiation combined with systemic administration of a photosensitizing organic dye, erythrosin B. We have studied the pathologic features of the nerve after the photochemical insult with light- and electronmicroscopy and related them to behavioral signs of neuropathic pain. At the irradiated nerve site, occlusion of blood vessels was seen and the vessels were packed with aggregated thrombocytes, fibrins and deformed erythrocytes, supporting the notion that photochemical reaction caused intraneural ischemia. The degree of the nerve injury at the center of irradiation was related to the duration of the laser exposure. Brief irradiation (30 seconds) only caused identifiable injury to myelinated fibers, whereas longer irradiation (2 minutes) caused greater injury to myelinated and unmyelinated fibers, characterized by extensive axonal degeneration and demyelination. The rats irradiated for 2 minutes, but not 30 seconds, exhibited neuropathic pain-like behaviors, expressed as mechanical and cold allodynia. The nerve injury was most severe 7 days after ischemia and regeneration of both myelinated and unmyelinated fibers was observed 3 months later. The nerve caudal to the irradiation exhibited Wallerian degeneration 7 days after the insult, whereas at 10 mm proximal to the irradiation the nerve was largely normal. It is thus concluded that photochemically induced intraneural ischemia caused injury to both myelinated and unmyelinated fibers, with myelinated fibers being more susceptible. However, the development of neuropathic pain-like behaviors may require injury to the unmyelinated fibers.

Behavioural measures of depression and anxiety in rats with spinal nerve ligation-induced neuropathy.

The behaviour of rats with spinal nerve ligation-induced neuropathic pain was studied using tests developed to measure depression and anxiety. Adult male Sprague-Dawley rats were tested with the open field test, elevated plus maze, two compartment test and forced swimming test. Spontaneous motility was measured in a photocell observation box. Mechanical sensitivity was tested with von Frey hairs and cold sensitivity with the acetone drop test. The L5-6 spinal nerves were ligated or a sham operation was performed and the rats were followed for 2 weeks before the same set of tests were repeated. Most of the neuropathy operated rats had mechanical and cold allodynia. With post-injury there was a significant decrease in the activity in the open field test and motility box tests, when compared with the pre-injury results. In the elevated plus maze test there was a significant reduction in the motility, but there was no change in the time spent in the closed wings. In the two compartment test there were no significant differences between the pre- and post-injury results. There were no differences between the rats with spinal nerve ligation injury and the sham operated rats in any of the tests. The results were also comparable when rats that developed a high degree of neuropathy were compared with the rats with low degree of neuropathy and the sham operated group. In conclusion, spinal nerve ligation injury of the spinal nerves L5-6 induces mechanical and cold allodynia, but it does not seem to produce general suffering or measurable anxiety to the animals. Furthermore, tests for anxiety and depression were not able to predict which animals were vulnerable to express symptoms of neuropathic pain after nerve injury.

Allodynia induced by regenerating axons is not positively correlated with degree of autotomy in the rat.

We studied in the rat whether the incidence of autotomy correlated positively with severity of tactile allodynia induced by regenerating axons. Before transection and surgical repair of the sciatic nerve, the status of sensory function was studied by stimulating mechanically the central part of the plantar paw with von Frey-hairs. Thereby we determined the threshold to evoke the hindpaw withdrawal reflex. One and 2 months after the nerve transection and repair, the thresholds of the traumatized paws were lower than the pre-trauma thresholds. The contralateral paw withdrawal thresholds did not change during the follow-up time. The results indicated that regenerating axons may cause tactile allodynia and that the severity of this allodynia does not correlate positively with the incidence of autotomy. We found no contralateral allodynia after nerve transection and repair.

Correlation between autotomy-behavior and current theories of neuropathic pain.

The past 10 years have brought several new experimental models with which to study chronic neuropathic pain in animals. Consequently, our knowledge about the mechanisms subserving neuropathic pain in humans has improved. However, the first animal model that was used for studying this type of chronic pain was the autotomy-model which can still be considered as a useful tool for pain studies. The present review assesses some of the similarities and differences between autotomy-model and more recent models of experimental traumatic mononeuropathy. In addition, it considers some of the similarities between the results obtained in clinical studies and in autotomy studies.

Influence of spinalization on spinal withdrawal reflex responses varies depending on the submodality of the test stimulus and the experimental pathophysiological condition in the rat.

The influence of midthoracic spinalization on thermally and mechanically induced spinal withdrawal reflex responses was studied in the rat. There were three experimental groups of rats: healthy controls, rats with a spinal nerve ligation-induced unilateral neuropathy, and rats with a carrageenan-induced inflammation of one hindpaw. Tail flick response was induced by radiant heat. Hindlimb withdrawal was induced by radiant heat, ice water, and innocuous or noxious mechanical stimulation of the paw. Prior to spinalization, spinal nerve ligated and carrageenan-treated animals had a marked unilateral allodynia and hyperalgesia. Spinalization tended to induce a facilitation of noxious heat-evoked reflexes. This spinalization-induced facilitation was stronger on tail than hindlimb withdrawal. Spinalization-induced skin temperature change did not explain the facilitation of noxious heat-evoked reflexes. In contrast, spinal withdrawal responses induced by noxious cold or mechanical stimulation were significantly suppressed following spinalization. The spinalization-induced facilitatory effects as well as inhibitory ones on spinal reflexes were enhanced in inflamed/neuropathic animals. The results indicate that the tonic descending control of spinal nocifensive responses varies depending on the submodality of the test stimulus, the segmental level of the reflex (tail vs. hindlimb), and on the pathophysiological condition.

Capsaicin-induced impairment of tactile spatial discrimination ability in man: indirect evidence for increased receptive fields in human nervous system.

The effects of capsaicin was investigated on vibration detection thresholds, touch detection thresholds, mechanically-evoked pain thresholds, two-point discrimination ability, and ability to detect roughness of different stimulation surfaces in the left hands of human volunteers in a double-blind controlled study. Capsaicin cream induced allodynia to mechanical stimulation in both primary and secondary area of hyperalgesia. Capsaicin impaired two-point discrimination ability, and reduced the ability to detect differences of the roughness of various stimulation surfaces only within the capsaicin treated area (area of primary hyperalgesia). These changes were not seen after placebo cream. We conclude that experimental inflammation and related pain impairs spatial discrimination ability which could be due to increases in the receptive fields of neurons in the peripheral and central nervous system (CNS).

Dextromethorphan potentiates the effect of morphine in rats with peripheral neuropathy.

Neuropathic pain responds poorly to opioids. We now report that combination of systemic morphine (2 mg/kg) and dextromethorphan (45 mg/kg), a clinically available antitussive with NMDA-antagonist properties, markedly alleviated mechanical and cold allodynia-like behavior in a rat model of peripheral mononeuropathy. Neither drug produced a significant effect on its own at these doses. The anti-allodynic effect of morphine plus dextromethorphan was reversed by naloxone. The present results suggest that a combination of NMDA-antagonist and opiates might be effective in treating neuropathic pain. Furthermore, the effect of this drug combination is mainly mediated via opioid receptors.

Carrageenan-induced changes in spinal nociception and its modulation by the brain stem.

Carrageenan was used to study inflammation-induced changes in spinal nociception and its brain stem modulation in the pentobarbitone-anesthetized rat. Carrageenan was administered intraplantarly into one hindpaw 2 h before the start of electrophysiological single unit recordings of wide-dynamic range (WDR) neurons of the spinal dorsal horn. Carrageenan produced a significant leftward shift in the stimulus-response function for mechanical stimuli, whereas that for noxious heat stimuli was short of statistical significance. Conditioning electrical stimulation in the rostroventromedial medulla (RVM) significantly attenuated noxious heat-evoked, but not mechanically evoked, responses to spinal dorsal horn WDR neurons in the control (contralateral) side. However, in the carrageenan-treated side RVM stimulation had no significant effect on mechanically or noxious heat-evoked responses. Following direct spinal administration of neuropeptide FF (NPFF), noxious heat-evoked responses, but not mechanically evoked responses, were attenuated by RVM-stimulation also in the carrageenan-treated side. This selective NPFF-induced enhancement of brain stem-spinal inhibition was not reversed by naloxone. The results indicate that carrageenan-induced inflammation significantly changes the response properties of spinal nociceptive neurons and their brain stem-spinal modulation. During inflammation, NPFF in the spinal cord produces a submodality-selective potentiation of the antinociceptive effect induced by brain stem-spinal pathways, independent of naloxone-sensitive opioid receptors.

The effect of a selective alpha2-adrenoceptor antagonist on pain behavior of the rat varies, depending on experimental parameters.

Effects of atipamezole, an alpha2-adrenoceptor antagonist, in various acute pain tests were studied in the rat. Atipamezole (at doses > or = 0.1 mg/kg I.P.) and idazoxan, another alpha2-adrenoceptor antagonist (2.5 mg/kg, I.P.), increased licking latency in the hot-plate test. Bilateral administration of atipamezole (10 microg) into the locus coeruleus did not increase licking latency in the hot-plate test. Medetomidine (an alpha2-adrenoceptor agonist; 1-3 mg/kg) or repeated pre-exposures to the testing apparatus reversed the effect of atipamezole (1.5 mg/kg) in the hot-plate test. Atipamezole also increased the latency to mechanically induced licking/biting response at a dose of 1.5 mg/kg, but not at lower doses. In the heat-induced tail-flick test, in contrast, atipamezole at doses of 0.1 and 1.5 mg/kg produced a medetomidine-reversible decrease of response latencies. This facilitation of the tail-flick response disappeared if the intensity of the heat stimulus was high. At a dose range from 0.03 to 1.5 mg/kg atipamezole did not significantly alter the paw withdrawal latency to noxious mechanical stimulation, nor pain behavior in the formalin test. Responses to nociceptive spinal dorsal horn neurons were not modulated by atipamezole (1 mg/kg) in anesthetized spinalized rats. The results indicate that an alpha2-adrenoceptor antagonist may have variable effects in behavioral pain tests, depending on habituation of the experimental animals to the testing conditions, the dose of the drug, the type of behavioral response and the submodality or the intensity of the noxious test stimulus. The atipamezole-induced changes in pain behavior observed in this study may rather be explained due to action on motor expression of pain than due to modulation of nociception.

Use of paper for treatment of a peripheral nerve trauma in the rat.

Reinnervation of the muscles and skin in the rat hindpaw was studied after transection and attempted repair of the sciatic nerve. Reconnecting the transected nerve with lens cleaning paper was at least as effective in rejoining the transected nerves as traditional microsurgical neurorraphy. Paper induced a slightly bigger fibrous scar around the site of transection than neurorraphy, but this scar did not cause impairment of functional recovery or excessive signs of neuropathic pain. We conclude that a paper graft can be used in restorative surgery of severed peripheral nerves.

Spinalization increases the mechanical stimulation-induced withdrawal reflex threshold after a sciatic cut in the rat.

The purpose of the present study was to establish whether supraspinal structures modulate mechanical 'adjacent hyperalgesia'. After a chronic sciatic cut, the paw withdrawal threshold to mechanical stimulation was lower, and the latency of noxious radiant heat-induced withdrawal reflex was shorter at the traumatized side than at the intact side. Then the rats were spinalized, and the withdrawal threshold to mechanical stimulus increased at the injured side, but the withdrawal latency induced by noxious heat decreased at the intact side. No side differences between the injured and the intact side could be detected after spinalization. Thus supraspinal structures may participate in maintenance of mechanically evoked paw withdrawal reflex after a sciatic injury.