Persistent Orofacial Pain Attendances at General Medical Practitioners.

Patients with persistent orofacial pain (POFP) can go through complex care pathways to receive a diagnosis and management, which can negatively affect their pain. This study aimed to describe 44-y trends in attendances at Welsh medical practices for POFP and establish the number of attendances per patient and referrals associated with orofacial pain and factors that may predict whether a patient is referred. A retrospective observational study was completed using the nationwide Secure Anonymised Information Linkage Databank of visits to general medical practices in Wales (UK). Data were extracted using diagnostic codes ("Read codes"). Orofacial and migraine Read codes were extracted between 1974 and 2017. Data were analyzed using descriptive statistics and univariate and multivariable logistic regression. Over the 44-y period, there were 468,827 POFP and migraine diagnostic codes, accounting for 468,137 patient attendances, or 301,832 patients. The overall attendance rate was 4.22 attendances per 1,000 patient-years (95% confidence interval [CI], 4.21-4.23). The attendance rate increased over the study period. Almost one-third of patients (n = 92,192, 30.54%) attended more than once over the study period, and 15.83% attended more than once within a 12-mo period. There were 20,103 referral codes that were associated with 8,183 patients, with over half these patients being referred more than once. Odds of receiving a referral were highest in females (odds ratio [OR], 1.23; 95% CI, 1.17-1.29), in those living in rural locations (OR, 1.17; 95% CI, 1.12-1.22), and in the least deprived quintile (OR, 1.39; 95% CI, 1.29-1.48). Odds also increased with increasing age (OR, 1.03; 95% CI, 1.03-1.03). The increasing attendance may be explained by the increasing incidence of POFP within the population. These patients can attend on a repeated basis, and very few are referred, but when they are, this may occur multiple times; therefore, current care pathways could be improved.

Homoplasmy, heteroplasmy, and mitochondrial dystonia.

BACKGROUND: In clinical practice, mitochondrial disease is seldom considered until a variable combination of seizures, alteration in tone, muscle weakness, and developmental problems is evident. However, it is not uncommon for one symptom to occur in isolation and dominate the clinical phenotype. We report six patients from two families where dystonia was the principal clinical manifestation. A mitochondrial etiology was considered in each case because of the association of dystonia with other less prominent clinical features such as epilepsy. METHODS: Histochemical and biochemical analyses were undertaken in skeletal muscle biopsies from individuals in both families. Sequencing of skeletal muscle mtDNA was also performed and suspected mutations were quantified by hot last cycle PCR-RFLP or primer extension assay. Functional consequences of one of the mutations were investigated by measurement of steady state levels of mitochondrial tRNA. RESULTS: Two distinct mitochondrial pathologies were identified: a novel, homoplasmic mitochondrial tRNA(Cys) (MTTC) mutation and the primary, m.11778G>A Leber hereditary optic neuropathy (LHON) mutation. The mild nature of both mutations has permitted very high levels of mutated mtDNA to accumulate. Patients with the mutation in the MTTC gene have no wild type mtDNA detectable and although the LHON mutation is heteroplasmic in the patients we report, it is commonly observed to be homoplasmic. CONCLUSIONS: The mitochondrial etiology identified in these patients emphasizes the pathologic potential of homoplasmic mutations and has important implications for the investigation and genetic counseling of families where dystonia is the principal clinical feature. We advocate that mitochondrial disease should be given serious consideration in patients with familial, progressive dystonia, particularly when additional neurologic features such as epilepsy are present.

Can stroke physicians and neuroradiologists identify signs of early cerebral infarction on CT?

Doctors managing acute stroke are expected to recognise signs of early infarction on CT before choosing thrombolytic treatment, according to recent trials and guidelines. The ability of 13 physicians and two neuroradiologists to recognise early infarct signs and decide whether patients should be randomised in a hypothetical stroke treatment trial was tested. Only 65% of the CT scans from 14 stroke patients were correctly identified as normal or abnormal (95% CI 60-69%). Neither observer experience nor knowledge of symptoms significantly improved recognition of abnormality, although experience did significantly improve the observers' ability to reproduce their results. Parenchymal hypodensity was the least well recognised sign. Only 45% (95% CI 40%-50%) of patients were identified correctly for the hypothetical acute stroke treatment trial. Early infarction on CT is not well recognised even by experienced doctors. Part of the problem may be in understanding the definitions of the extent of infarction. These difficulties should be considered in the design of acute stroke treatment trials and in the introduction of any new acute stroke treatments.

Reports of randomized trials in acute stroke, 1955 to 1995. What proportions were commercially sponsored?

BACKGROUND AND PURPOSE: Research in acute stroke has expanded rapidly. Many potentially important interventions lack commercial potential (eg, admission to a stroke unit). We therefore wished to examine the frequency of reports of randomized trials of interventions for acute stroke over the past 40 years, the source of support for such trials, the reporting of the commercial involvement, and whether the proportion of commercially supported trials had changed. METHODS: Eligible trials were identified from the Cochrane Stroke Group's specialized register of controlled clinical trials. We included all randomized trials in patients with acute stroke which published a full text report, in English, between 1955 and 1995. Two reviewers independently extracted data on the involvement of the pharmaceutical industry in all eligible trials. RESULTS: There was a substantial increase in the number of acute stroke trials published per year between 1955 and 1995. The description of pharmaceutical industry involvement in each trial report was poor. Only a minority of supported trials made explicit statements about the role of the sponsoring company. The proportion of trials apparently supported by the pharmaceutical industry has increased substantially. CONCLUSIONS: The increasingly important role of the pharmaceutical industry in evaluating new treatments gives substantial scope for bias and may not be in the interests of public health. Poor reporting of the sponsor's involvement suggests that modifications to the guidelines for the reporting of randomized controlled trials to include more details of the sponsor's involvement in the design, conduct, management, analysis, and reporting of the trial are justified.

How do scores on the EuroQol relate to scores on the SF-36 after stroke?

BACKGROUND AND PURPOSE: The EuroQol and Medical Outcome Survey 36-item short-form health survey (SF-36) questionnaires have both been validated for the assessment of health-related quality of life after stroke. However, the relationship between these instruments has not been studied after stroke. We therefore sought to compare the responses of a group of stroke patients to both instruments. METHODS: A total of 2253 patients with stroke entered by United Kingdom hospitals in the International Stroke Trial were randomized to follow-up with either the EuroQol or SF-36 instruments. We randomly selected one third of patients who had responded to the EuroQol for follow-up, again using the SF-36, and two thirds of patients who had responded to the SF-36 for follow-up, again using the EuroQol. We assessed the patients' mean score for each domain of the SF-36 categorized by their response to the corresponding EuroQol domain and the correlation between the domains of the 2 instruments. RESULTS: The domains for both instruments, which assessed physical functioning, social functioning, bodily pain, and overall health-related quality of life, correlated closely. The mental health domain of the SF-36 correlated only poorly with the psychological functioning domain of the EuroQol. CONCLUSIONS: Both the EuroQol and SF-36 measure broadly similar domains of health. The weak relationship between the assessments of mental health may reflect a difference in content or more fundamental problems with the validity or reliability of the items in one of the instruments with respect to this domain. This study has provided the first empirical qualitative evidence by which the data on the SF-36 after stroke may be interpreted.

The influence of baseline prognostic variables on outcome after thrombolysis. MAST-Italy Collaborative Group.

Thrombolysis increases case fatality but reduces the proportion of disabled survivors in recent trials in acute ischaemic stroke, although some trials show much higher mortality rates than others. One possible explanation for the different outcomes between trials is that the treatment effect with thrombolysis varies with baseline prognostic factors such as stroke severity. We examined the interaction between baseline risk and thrombolysis on outcome using individual patient data from the Multicentre Acute Stroke Trial-Italy (MAST-I). A multiple logistic regression of the MAST-I data was performed to identify which factors, identifiable at randomisation, most strongly predict a poor functional outcome. We then stratified the patients into those with severe strokes and those with mild strokes and examined the effect of thrombolysis on (a) case fatality and (b) dependency at 6 months after the stroke in the 157 patients who received streptokinase alone and the 156 controls. Streptokinase was found to cause an absolute increase of about 3% in case fatality in both "severe" and "mild" strokes; however, there was a 12% reduction in the number of dead or dependent "mild" strokes but a 6% increase in "severe" strokes. The number of patients was small, and therefore neither finding was statistically significant. In this exploratory analysis, the hazard with streptokinase appears similar in "severe" and "mild" strokes, but the benefit may be greater in "mild" strokes. Thrombolysis may be more effective in patients with "mild" strokes, but more information is required to confirm this hypothesis.

Parkinsonism associated with obstructive hydrocephalus due to idiopathic aqueductal stenosis.

Two cases of parkinsonism after recurrent obstructive hydrocephalus due to idiopathic aqueductal stenosis are reported. In both patients an extrapyramidal syndrome was noted in the absence of contemporaneous evidence of hydrocephalus or shunt failure. One of the patients underwent a shunt operation, but showed no clinical improvement. However, both patients improved after the administration of dopaminergic therapy. The seven previously reported cases of this syndrome were reviewed and it is concluded that the prognosis of the parkinsonism is good, usually with total, or near total, resolution. It is recommended that if a patient with idiopathic aqueduct stenosis develops hydrocephalus or evidence of shunt malfunction in association with acute parkinsonism their shunt should be replaced. If there is no evidence of hydrocephalus or shunt malfunction they should initially be treated with domaminergic medication.

Is the EuroQol a valid measure of health-related quality of life after stroke?

BACKGROUND AND PURPOSE: The EuroQol measures aspects of quality of life that are highly relevant to stroke patients. It is short and simple and many stroke patients can complete the form without help. However, its validity has not been adequately assessed after stroke. We therefore assessed its concurrent and discriminant validity in a group of prospectively studied stroke survivors. METHODS: We assessed the validity of the EuroQol in a series of 152 patients with stroke who were all visited by a study nurse. The nurse gave the patients the EuroQol, the Frenchay Activities Index, a visual analogue pain scale, and the Hospital Anxiety and Depression Scale in the form of questionnaires to be self-completed where possible. The nurse interviewed the patient directly to assess disability using the Office of Population Censuses and Surveys Disability scale and Barthel Index. RESULTS: The nurse assessed 152 patients; of these 92 were able to complete the EuroQol without help, the remaining 60 could only be assessed by interview. The EuroQol had reasonable concurrent validity; median scores on the relevant standard instruments varied significantly (and in the appropriate direction) for groups defined by their response to the relevant EuroQol domain. The EuroQol had reasonable discriminant validity since the responses enabled separation between patients with differing stroke syndromes and stroke severities. Accuracy for predicting outcome after stroke was good for both self-completed and interview-completed questionnaires. CONCLUSIONS: The EuroQol appears to have acceptable concurrent and discriminant validity for the measurement of health-related quality of life after stroke. It may be administered by either a questionnaire for self-completion in patients with mild to moderate stroke or by interview in patients with significant motor deficits.

Are proxy assessments of health status after stroke with the EuroQol questionnaire feasible, accurate, and unbiased?

BACKGROUND AND PURPOSE: It is often difficult to determine the health-related quality of life (HRQoL) of stroke patients because physical and cognitive problems limit their ability to complete complex questionnaires. A proxy, such as a family member or caregiver, may be able to give an estimate of the patients' health status. We therefore examined the agreement between the HRQoL as assessed by a series of patients and that assessed by their proxies. METHODS: We studied the validity of the EuroQol in a series of 152 patients from our prospective registry of patients with first (or recurrent) stroke. We asked patients to ensure that a friend or relative (a proxy) who knew them well was available at the time of the interview. We asked each proxy to complete a EuroQol questionnaire independently on behalf of the patient. RESULTS: Proxies completed forms for 130 patients (86%). Agreement between responses from the patients and those from their proxies was better for patients who were able to self-complete the EuroQol than for patients who required the EuroQol to be administered by interview. For both groups, agreement was best for the self-care domain and worst for the domain that assessed psychological outcome. For the more severely affected patients, agreement was only fair for the pain and social functioning domains and no better than chance alone for the psychological functioning domain (kappa = 0.05, 95% confidence interval, 0 to 0.43). Patients tended to rate their own health status as better than their proxies did (P < .05). CONCLUSIONS: We found moderate agreement between responses from patients and those from their proxies for the more directly observable domains of the EuroQol. Proxy agreement was less good for the more subjective domains. In health surveys, allowing responses by a proxy increases response rate. However, the disadvantages inherent in the use of proxy responses must be considered carefully. In general, some domains of HRQoL information obtained from a proxy may be sufficiently valid and unbiased to be useable in most types of trials and surveys.

Doctors and patients don't agree: cross sectional study of patients' and doctors' perceptions and assessments of disability in multiple sclerosis.

OBJECTIVES: To compare the judgments of clinicians on which domains of health in the short form questionnaire (SF-36) would be most important to patients with multiple sclerosis with the opinions of patients themselves; to compare assessment of physical disability in multiple sclerosis by a clinician using Kurtzke's expanded disability status scale and a non-clinically qualified assistant using the Office of Population Census and Surveys' (OPCS) disability scale with self assessment of disability and other domains of health related quality of life by patients using the SF-36 and the EuroQol questionnaire; and to compare the scores of patients for each domain of the SF-36 with control data matched for age and sex. DESIGN: Cross sectional study. SETTING: Clinical department of neurology, Edinburgh. SUBJECTS: 42 consecutive patients with multiple sclerosis attending a neurology outpatient clinic for review or a neurology ward for rehabilitation. MAIN OUTCOME MEASURES: Scores on the SF-36; EuroQol; Kurtzke's expanded disability status scale; the OPCS disability scale. RESULTS: Patients and clinicians disagreed on which domains of health status were most important (chi 2 = 21, df = 7, P = 0.003). Patients' assessment of their physical disability using the physical functioning domain of the SF-36 was highly correlated with the clinicians' assessment (r = -0.87, P < 0.001) and the non-clinical assessment (r = -0.90, P < 0.001). However, none of the measures of physical disability correlated with overall health related quality of life measured with EuroQol, Quality of life correlated with vitality, general health, and mental health in the SF-36, each of which patients rated as more important than clinicians and for each of which patients scored lower than the controls. CONCLUSIONS: Patients with multiple sclerosis and possibly those with other chronic diseases are less concerned than their clinicians about physical disability in their illness. Clinical trials in multiple sclerosis should assess the effect of treatment on the other elements of health status that patients consider important, which are also affected by the disease process, are more closely related to overall health related quality of life, and may well be adversely affected by side effects of treatment.

Considerations in the design of clinical trials of neuroprotective therapy in acute stroke.

Any therapeutic trial of a new treatment for stroke must provide sufficient reliable evidence to convince clinicians and healthcare purchasers of its merits. Clinicians are most likely to be convinced by large independent studies that provide clear evidence of benefit. If the trial is really to alter healthcare delivery, it should also confirm that the treatment is cost-effective enough to satisfy the increasingly critical demands of the healthcare purchasers. Although some of the current trials will be able to detect large benefits, reliable detection of the moderate benefits that seem more plausible with neuroprotection will need to wait until completion of trials that are perhaps an order of magnitude larger. If tens of thousands of patients are to be recruited into trials of neuroprotective therapy, it is essential that the trials have simple practicable designs that allow participation not only by interested university hospitals but also busy general hospitals with few research resources.

Neuropathic urinary retention in the absence of neurological signs.

We present two cases of painless urinary retention secondary to central intervertebral disc prolapse. In neither case were there signs or symptoms suggesting an underlying neurological insult. Both patients voided spontaneously following neurosurgical intervention. The classical features of acute cauda equina compression may be absent in patients with central lumbar disc protrusion. Painless urinary retention may be the only physical sign.

Esophageal involvement in secondary amyloidosis mimicking achalasia.

Amyloidosis is usually considered as a cause of motor disorders of the esophagus, including achalasia. However, most patients with amyloid in the esophagus are AL-type amyloid. We report what we believe is the fourth case of secondary amyloidosis (AA-type) resulting from rheumatoid arthritis. Clinically and radiologically the picture was that of achalasia.

Alloantigen presenting capacity of human decidual tissue.

The capacity of first trimester human decidua-derived cells to serve as accessory cells for the presentation of alloantigens to unprimed T lymphocytes was assessed using a mixed lymphocyte culture (MLC) between accessory cell-depleted responder and stimulator peripheral blood lymphocytes (d PBL). In all of the seven experiments performed decidua-derived cells achieved significant reconstitution of the lymphoproliferative response between autologous responder and stimulator dPBL. Reconstitution indices (RIs) ranged between 3.1 and 22.2 and were significant in all cases. In six out of the seven experiments the level of lymphoproliferation exceeded that between untreated responder PBLs co-cultured with stimulator d PBL. Substitution of recombinant interleukin 1 (rIL-1) alpha or beta for the decidua-derived cells resulted in significantly lower RIs than those achieved by the decidua-derived cells. These findings suggest that decidua-derived cells can serve as antigen presenting cells for the presentation of membrane-bound alloantigens in a primary lymphoproliferative response. This may have implications for maternal recognition of fetal antigens during first pregnancy.

Hypophosphatemic osteomalacia and adult Fanconi syndrome due to light-chain nephropathy. Another form of oncogenous osteomalacia.

Two patients, one with myeloma (Patient 1) and the other with probable chronic lymphocytic leukemia (Patient 2), had reduced renal tubular phosphate reabsorption in the absence of hyperparathyroidism together with other features of the Fanconi syndrome, as consequences of the nephropathy associated with light-chain proteinuria. Both patients had hypophosphatemic osteomalacia, demonstrated for the first time in this condition by iliac bone histomorphometry after in vivo double tetracycline labeling, despite absence of bone pain or Looser zones. Neither patient was vitamin D-depleted, but plasma calcitriol level was normal in Patient 1 and low in Patient 2; only the latter patient had severe muscle weakness. Complete histologic correction of osteomalacia was achieved by treatment in accordance with the biochemical defects--oral phosphate therapy alone in Patient 1 and combined with calcitriol in Patient 2. Both patients are now symptom-free, five and three years after the initial diagnosis of bone disease and hematogenous malignancy. Thirteen previous instances of the same form of osteomalacia were reviewed; in most cases, the Fanconi syndrome developed before its probable cause became apparent. The Fanconi syndrome has also been reported in two cases of osteomalacia due to mesenchymal tumor, but not in osteomalacia associated with prostatic carcinoma. Light-chain nephropathy and consequent renal tubular dysfunction appears to be a third form of oncogenous osteomalacia.