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.

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.

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.

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).

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.

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.

Involvement of supraspinal and spinal segmental alpha-2-adrenergic mechanisms in the medetomidine-induced antinociception.

The effect of systemically administered medetomidine, a selective alpha-2-adrenoceptor agonist, was studied by electrophysiological recordings of the peripherally evoked responses of three different types of sensory neuronal populations in the rat: medial thalamic neurons exclusively responding to mechanical cutaneous stimuli at noxious intensities, spinothalamic tract neurons of the spinal cord responding exclusively or differentially to mechanical cutaneous stimuli at noxious intensities, and low-threshold mechanoreceptive spinal dorsal horn neurons with ascending projections. The neuronal effects were compared with the behavioral data obtained in mechanically and thermally induced nociceptive tail reflex tests in intact and spinal rats. A reversal of the antinociceptive effects was attempted by systemically (1.5 mg/kg, i.p.) or intrathecally (25 micrograms) administered atipamezole, a selective alpha-2-adrenoceptor antagonist. Systemically administered medetomidine produced an atipamezole-reversible, dose-dependent suppressive effect on the evoked responses of nociceptive medial thalamic and spinothalamic tract neurons. A lower dose of medetomidine was needed to suppress significantly (half-maximally) evoked responses of the nociceptive medial thalamic neurons (100 micrograms/kg) than those of the nociceptive spinothalamic tract neurons (300 micrograms/kg). The decrease of evoked responses of the nociceptive spinothalamic tract neurons was accompanied by a decrease in spontaneous activity. The responses of the low-threshold mechanoreceptive projection neurons of the spinal cord were not influenced by medetomidine (30-300 micrograms/kg). The reflex studies with a (anesthetic) medetomidine dose of 300 micrograms/kg indicated that in intact and otherwise drug-free rats, medetomidine produced a significant prolongation of the nociceptive reflex response latency to a tail-pinch and heat; these antinociceptive effects of systemic medetomidine were reversed by systemically and intrathecally applied atipamezole. In spinal rats systemically applied medetomidine (300 micrograms/kg) also produced a significant prolongation of the tail-flick latency, which was reversed by systemically applied atipamezole. The results suggest that a high anesthetic dose of systemically applied medetomidine (300 micrograms/kg) can suppress nociceptive sensory neuronal and reflex responses due to spinal segmental mechanisms through an action on alpha-2-adrenoceptors. This spinal effect is selective to responses of nociceptive neurons, and at least partly postsynaptic as indicated by the concomitant decrease in spontaneous activity. At a lower, subanesthetic (but sedative) dose (100 micrograms/kg) the antinociceptive effect of systemically applied medetomidine can be explained by supraspinal alpha-2-adrenergic mechanisms.

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.

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.

Polyamines enhance recovery after sciatic nerve trauma in the rat.

Spermine, a polyamine, is known to enhance motor functional recovery after a sciatic nerve lesion in the rat. The effect of spermine on the sensory axonal elongation after a sciatic crush was studied with the pinch-test from the sural nerve in the rat. The effect of spermidine, another polyamine, on the motor functional recovery after a trauma was studied by using the toe-spreading ability as an indicator of motor recovery after a sciatic crush in the rat. Spermine enhanced the rate of regeneration of the sensory axons by 16%. Spermidine enhanced the rate of the motor recovery by 30%. These results suggest that not only spermine but also spermidine enhance regeneration of peripheral somatic 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.

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).

The effect of medetomidine, an alpha 2-adrenoceptor agonist, in various pain tests.

Medetomidine, a new alpha 2-adrenoceptor agonist produced dose-dependent (30-100 micrograms/kg i.p.) analgesia in the formalin test in rats, and this effect was reversed by atipamezole (1 mg/kg), a new alpha 2-adrenoceptor antagonist. However, medetomidine at the dose of 100 micrograms/kg did not influence tail flick latencies or latencies of the biting response to mechanical pinch stimuli. Moreover, medetomidine produced sedation and a decrease in locomotor activity. In comparison, the non-sedative monoaminergic agent, cocaine (25 mg/kg), produced highly significant analgesic effects in the formalin and mechanical pain tests. The cocaine effect in the formalin test was not reversed by atipamezole (1 mg/kg). It is concluded that the analgesic effect of medetomidine in the formalin test is due to supraspinal mechanisms related to sedation and is mediated by alpha 2-adrenoceptors. The alpha 2-adrenoceptors are not involved in cocaine-induced anagesia.

Effects of atipamezole, a novel alpha 2-adrenoceptor antagonist, in open-field, plus-maze, two compartment exploratory, and forced swimming tests in the rat.

The behavioral effects of atipamezole (0.5-4.5 mg/kg), a new and highly selective alpha 2-adrenoceptor antagonist, were studied in four behavioral models: open-field, elevated plus-maze, two compartment exploratory test and forced swimming test. Atipamezole (1.5 and 4.5 mg/kg) produced a dose-dependent suppression of locomotor activity in the open field test. In the two compartment exploratory test, the same doses of atipamezole decreased locomotor activity in a 5 min test but not in a 10 min test. The numbers of transitions between the compartments were not significantly affected by atipamezole. Doses of 0.5-4.5 mg/kg did not significantly change the time spent in the open arms or the total number of arm entries in the plus-maze, and doses of 1.5 and 4.5 mg/kg decreased defecation marginally. Vocalization during the forced swimming test was increased by atipamezole (1.5 mg/kg) but the duration of immobility was not increased over the dose range (0.5-1.5 mg/kg) of atipamezole used. Our results suggest that, in the rat, atipamezole decreases motor activity in the early phase of the exploration of new surroundings. In the doses used, atipamezole may suppress defecation and increase vocalization in rats.

Effect of chronic sciatic nerve section on saphenous nerve input to midline bulboreticular formation in the rat.

The sciatic nerve was transected unilaterally 7-10 weeks before electrophysiological single unit recordings were made from somatically activated neurons in the midline bulboreticular formation of the rat. Their responses to high-intensity electrical stimulation of the saphenous nerve area were significantly stronger on the lesioned side. In control rats no such side difference was found. The result indicates that sciatic nerve transection unmasks polysynaptic somatic input to the midline bulboreticular formation.

alpha-Difluoromethylornithine (DFMO) disturbed the sensorimotor functional recovery from a sciatic lesion.

The effects of inhibition of polyamine synthesis on the motor and sensory functional neural recovery after a sciatic crush lesion was studied by measuring sensory and motor function of a crushed sciatic nerve after daily exposure to alpha-difluoromethylornithine (DFMO). DFMO increased the time needed for functional motor recovery by 13% in the toe-spread test when the lesion was about 20 mm proximal to the target muscle. DFMO reduced the rate of sensory axonal elongation by 24% in the pinch-test.