Association of Health-Related Social Needs With Quality and Utilization Outcomes in a Medicare Advantage Population With Diabetes.

Importance: Recent research highlights the association of social determinants of health with health outcomes of patients with type 2 diabetes (T2D). Objective: To examine associations between health-related social needs (HRSNs) and health care quality and utilization outcomes in a Medicare Advantage population with T2D. Design, Setting, and Participants: This cross-sectional study used medical and pharmacy claims data from 2019. An HRSN survey was given between October 16, 2019, and February 29, 2020, to Medicare Advantage beneficiaries. Inclusion criteria were diagnosis of T2D, age of 20 to 89 years, continuous Medicare Advantage enrollment in 2019, and response to the HRSN survey. Data were analyzed between June 2021 and January 2022. Exposures: Enrollment in Medicare Advantage, diagnosis of T2D, and completion of a survey on HRSNs. Main Outcomes and Measures: Quality outcomes included diabetes medication adherence, statin adherence, completion of a glycated hemoglobin (HbA1c) laboratory test in the past 12 months, and controlled HbA1c. Utilization outcomes included all-cause hospitalization, potentially avoidable hospitalization, emergency department discharge, and readmission. Results: Of the 21 528 Medicare Advantage beneficiaries with T2D included in the study (mean [SD] age, 71.0 [8.3] years; 55.4% women), most (56.9%) had at least 1 HRSN. Among the population with T2D reporting HRSNs, the most prevalent were financial strain (73.6%), food insecurity (47.5%), and poor housing quality (39.1%). In adjusted models, loneliness (odds ratio [OR], 0.85; 95% CI, 0.73-0.99), lack of transportation (OR, 0.80; 95% CI, 0.69-0.92), utility insecurity (OR, 0.86; 95% CI, 0.76-0.98), and housing insecurity (OR, 0.78; 95% CI, 0.67-0.91) were each associated with lower diabetes medication adherence. Loneliness and lack of transportation were associated with increased emergency visits (marginal effects of 173.0 [95% CI, 74.2-271.9] and 244.6 [95% CI, 150.4-338.9] emergency visits per 1000 beneficiaries for loneliness and transportation, respectively). Food insecurity was the HRSN most consistently associated with higher acute care utilization (marginal effects of 84.6 [95% CI, 19.8-149.4] emergency visits, 30.4 [95% CI, 9.5-51.3] inpatient encounters, and 17.1 [95% CI, 4.7-29.5] avoidable hospitalizations per 1000 beneficiaries). Conclusions and Relevance: In this cross-sectional study of Medicare Advantage beneficiaries with T2D, some HRSNs were associated with care quality and utilization. The results of the study may be used to direct interventions to the social needs most associated with T2D health outcomes and inform policy decisions at the insurance plan and community level.

Association Between Self-reported Health-Related Social Needs and Acute Care Utilization Among Older Adults Enrolled in Medicare Advantage.

Importance: There is increased focus on identifying and addressing health-related social needs (HRSNs). Understanding how different HRSNs relate to different health outcomes can inform targeted, evidence-based policies, investments, and innovations to address HRSNs. Objective: To examine the association between self-reported HRSNs and acute care utilization among older adults enrolled in Medicare Advantage. Design Setting and Participants: This cross-sectional study used data from a large, national survey of Medicare Advantage beneficiaries to identify the presence of HRSNs. Survey data were linked to medical claims, and regression models were used to estimate the association between HRSNs and rates of acute care utilization from January 1, 2019, through December 31, 2019. Exposures: Self-reported HRSNs, including food insecurity, financial strain, loneliness, unreliable transportation, utility insecurity, housing insecurity, and poor housing quality. Main Outcomes and Measures: All-cause hospital stays (inpatient admissions and observation stays), avoidable hospital stays, all-cause emergency department (ED) visits, avoidable ED visits, and 30-day readmissions. Results: Among a final study population of 56 155 Medicare Advantage beneficiaries (mean [SD] age, 74.0 [5.8] years; 32 779 [58.4%] women; 44 278 [78.8%] White; and 7634 [13.6%] dual eligible for Medicaid), 27 676 (49.3%) reported 1 or more HRSNs. Health-related social needs were associated with statistically significantly higher rates of all utilization measures, with the largest association observed for avoidable hospital stays (incident rate ratio for any HRSN, 1.53; 95% CI, 1.35-1.74; P < .001). Compared with beneficiaries without HRSNs, beneficiaries with an HRSN had a 53.3% higher rate of avoidable hospitalization (incident rate ratio, 1.53; 95% CI, 1.35-1.74; P < .001). Financial strain and unreliable transportation were each independently associated with increased rates of hospital stays (marginal effects of 26.5 [95% CI, 14.2-38.9] and 51.2 [95% CI, 30.7-71.8] hospital stays per 1000 beneficiaries, respectively). All HRSNs, except for utility insecurity, were independently associated with increased rates of ED visits. Unreliable transportation had the largest association with increased hospital stays and ED visits, with marginal effects of 51.2 (95% CI, 30.7-71.8) and 95.5 (95% CI, 65.3-125.8) ED visits per 1000 beneficiaries, respectively. Only unreliable transportation and financial strain were associated with increased rates of 30-day readmissions, with marginal effects of 3.3% (95% CI, 2.0%-4.0%) and 0.4% (95% CI, 0.2%-0.6%), respectively. Conclusions and Relevance: In this cross-sectional study of older adults enrolled in Medicare Advantage, self-reported HRSNs were common and associated with statistically significantly increased rates of acute care utilization, with variation in which HRSNs were associated with different utilization measures. These findings provide evidence of the unique association between certain HRSNs and different types of acute care utilization, which could help refine the development and targeting of efforts to address HRSNs.

Health-Related Social Needs Among Older Adults Enrolled In Medicare Advantage.

Among older adults enrolled in Medicare Advantage, health-related social needs are highly prevalent, with financial strain, food insecurity, and poor housing quality the most commonly reported. The distribution of health-related social needs is uneven, with significant disparities according to race, socioeconomic status, and sex.

The impact of real-world cardiovascular-related pharmacogenetic testing in an insured population.

BACKGROUND: Pharmacogenomics is intended to help clinicians provide the right drug to the right patient at an appropriate dose. However, limited evidence of clinical utility has slowed uptake of pharmacogenomic testing (PGT). OBJECTIVE: To evaluate the impact of real-world cardiovascular (CV)-related PGT on clinical outcomes, healthcare resource utilisation (HCRU) and cost in a large, heterogeneous population. METHODS: Individuals with Medicare Advantage Prescription Drug, Medicaid, or commercial coverage between 1/1/2011 and 9/30/2015 and ≥1 atherosclerotic CV-related diagnosis were identified. Those with ≥1 claim for CV-related PGT were included in the test group (index date = 1st PGT claim) and matched 1:2 to controls without PGT. Individuals aged <22 or ≥90 years old on the index date, with <12 months continuous enrollment before and after the index date, or without an ASCVD-related diagnosis in the 12-month pre-index period were excluded. The primary outcome was occurrence of a major CV event during the 12-month post-index period. RESULTS: After adjustment, the PGT group was significantly more likely to experience ischaemic stroke, pulmonary embolism, deep vein thrombosis or a composite event compared with controls. Adjusting for baseline characteristics, HCRU was significantly higher for the test group across all measured outcomes except all-cause and ASCVD-related inpatient admissions. Median all-cause and ASCVD-related healthcare costs were significantly higher for the test group. CONCLUSIONS: Real world PGT in a large population did not improve outcomes. Tailoring medication therapy to each patient holds great promise for providing quality care but a deeper understanding of how widespread utilisation of PGT might impact objective health outcomes is needed.

Temporal patterns of digestive enzyme activities and feeding rate in gammarids (Gammarus fossarum) exposed to inland polluted waters.

The aim of this study was to use digestive enzyme activities in Gammarus fossarum as biomarkers during active biomonitoring. Standardised gammarids were transplanted for 7 days to five sites in the Riou Mort watershed contaminated by polymetallic pollution. This experiment was conducted on seven different dates from February 2009 to June 2010. Feeding rates were tracked, along with amylase, cellulase and trypsin activities. We found that feeding rate and digestive capacity were reduced in the most polluted site, "Joany," in comparison with the reference site "Up.Lot". The results suggested that trypsin was more sensitive than the other two carbohydrases. In the four other sites, seasonal differences were observed during the 2yr but no clear pattern can be established. This study highlights the ability of G. fossarum to demonstrate environmental disturbances and suggests the use of a caging process in certain seasons. Caging organisms and feeding ad libitum is advantageous, as it reduces inter-individual variability and removes dependence on the native food fluctuations. However, confounding factors other than temperature were present, and the interpretation of digestive enzyme activities is complex.

Effect of water quality and confounding factors on digestive enzyme activities in Gammarus fossarum.

The feeding activity and subsequent assimilation of the products resulting from food digestion allow organisms to obtain energy for growth, maintenance and reproduction. Among these biological parameters, we studied digestive enzymes (amylase, cellulase and trypsin) in Gammarus fossarum to assess the impact of contaminants on their access to energy resources. However, to enable objective assessment of a toxic effect of decreased water quality on an organisms' digestive capacity, it is necessary to establish reference values based on its natural variability as a function of changing biotic and abiotic factors. To limit the confounding influence of biotic factors, a caging approach with calibrated male organisms from the same population was used. This study applied an in situ deployment at 23 sites of the Rhone basin rivers, complemented by a laboratory experiment assessing the influence of two abiotic factors (temperature and conductivity). The results showed a small effect of conductivity on cellulase activity and a significant effect of temperature on digestive enzyme activity but only at the lowest temperature (7 °C). The experimental conditions allowed us to define an environmental reference value for digestive enzyme activities to select sites where the quality of the water impacted the digestive capacity of the organisms. In addition to the feeding rate, this study showed the relevance of digestive enzymes as biomarkers to be used as an early warning tool to reflect organisms' health and the chemical quality of aquatic ecosystems.

Improving laboratory monitoring at initiation of drug therapy in ambulatory care: a randomized trial.

BACKGROUND: The importance of laboratory monitoring for drugs is reflected in product labeling and published guidelines, but monitoring recommendations are followed inconsistently. Opportunity exists to improve monitoring, with the potential to decrease therapy complications. METHODS: The objective of this randomized trial was to determine whether computerized alerts were effective at increasing the percentage of ambulatory patients with laboratory monitoring at initiation of drug therapy. Physicians and pharmacists teamed up to develop organization-specific guidelines for monitoring selected drugs. In collaboration with physicians, pharmacists were alerted to missing laboratory test results, ordered missing tests, reminded patients to obtain tests, assessed test completion, reviewed test results, and managed abnormal results. Eligible individuals included patients with therapy initiated for any of 15 drugs among 400,000 health plan members. RESULTS: In the intervention group, 79.1% (n = 4076; 95% confidence interval [CI], 78.0%-80.2%) of dispensings were monitored compared with 70.2% (n = 3522; 95% CI, 68.9%-71.5%) in the usual-care group (P < .001). For example, 78.6% of amiodarone (95% CI, 73.1%-83.5%) dispensing was monitored in the intervention group vs 51.4% (95% CI, 44.4%-58.4%) in the group receiving usual care (P < .001). CONCLUSIONS: This study demonstrates the effectiveness of a computerized tool plus collaboration among health care professionals at increasing the percentage of patients receiving laboratory monitoring at initiation of therapy. Coupling data available from information systems with the knowledge and skills of physicians and pharmacists can result in improved patient monitoring.

Laboratory monitoring of drugs at initiation of therapy in ambulatory care.

BACKGROUND AND OBJECTIVES: Product labeling and published guidelines reflect the importance of monitoring laboratory parameters for drugs with a risk of organ system toxicity or electrolyte imbalance. Limited information exists about adherence to laboratory monitoring recommendations. The objective of this study was to describe laboratory monitoring among ambulatory patients dispensed medications for which laboratory testing is recommended at therapy initiation. DESIGN AND SUBJECTS: We conducted a retrospective cross-sectional analysis of patients in 10 geographically distributed health maintenance organizations who were newly prescribed medications with recommended laboratory test monitoring. The main outcome measure was the proportion of initial drug dispensing without recommended baseline laboratory monitoring for 35 newly initiated drugs or drug classes. RESULTS: One hundred seven thousand, seven hundred sixty-three of 279,354 (39%) initial drug dispensings occurred without recommended laboratory monitoring. Patients without monitoring were younger than patients who had monitoring (median 57 vs 61 years, P<.001). Thirty-two percent of dispensings where a serum creatinine was indicated did not have it evaluated (range across drugs, 12% to 61%); 39% did not have liver function testing (range 10% to 75%); 32% did not have hematologic monitoring (range 9% to 51%); and 34% did not have electrolyte monitoring (range 20% to 62%) (P<.001). CONCLUSIONS: Substantial opportunity exists to improve laboratory monitoring of drugs for which such monitoring is recommended. This study emphasizes the need for research to identify the clinical implications of not conducting recommended laboratory monitoring, existing barriers to monitoring, and methods to improve practice.

Compliance with dosing guidelines in patients with chronic kidney disease.

OBJECTIVE: To assess the level of reported compliance with renal dosing guidelines in inpatient, long-term care, and ambulatory settings. DATA SOURCES: Available databases (MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effectiveness, ACP Journal Club) were searched (1966-December 2002) to identify published literature pertaining to renal dosing guideline compliance in patients with chronic kidney disease. STUDY SELECTION AND DATA EXTRACTION: All articles addressing renal dosing guideline compliance in inpatient, long-term care or ambulatory settings were included. Six articles matching our inclusion criteria were reviewed. DATA SYNTHESIS: Patients with chronic kidney disease require appropriate medication dosing for disease severity and level of renal function for avoiding adverse drug events, preventing additional renal injury, and optimizing patient outcomes. Consensus-based medication dosing guidelines are readily available and provide initial dose estimations, which can be further individualized based on disease severity and therapeutic response. Studies conducted in hospitals found renal dosing guideline noncompliance rates ranged from 19% to 67%. Limited data in long-term care reported a noncompliance rate of 34%. While published studies concerning compliance to renal dosing recommendations in ambulatory settings are not available, an abstract indicated 69% noncompliance. CONCLUSIONS: Based on limited published data, improvements in renal dosing guideline compliance are needed in all settings where data are available. Research is needed to further assess the appropriateness of renal dosing in ambulatory settings and inform quality improvement efforts in all settings.

Clinical and methodological factors related to reliability of the best-estimate diagnostic procedure.

OBJECTIVE: The reliability and accuracy of the best-estimate diagnostic procedure were examined, and factors associated with reliability were determined. METHOD: The subjects were 134 members of large multigenerational pedigrees densely affected by bipolar disorders or schizophrenia. Three best-estimate diagnoses were derived: first, by a research psychiatrist and research assistant unblind to the relatives' diagnoses; second, by two blind independent psychiatrists; third, by a panel of four blind psychiatrists. The subjects were characterized on several clinical and methodological variables, which were used to compare the agreements of two types of best-estimate diagnoses with the disagreements. RESULTS: There was satisfactory agreement between the unblind and blind consensus best-estimate diagnoses and between the two blind independent psychiatrists. Latent class analyses revealed that limited sensitivity was the main source of imperfect reliability. Confusability analyses revealed that the most problematic diagnostic distinctions involved schizoaffective disorder, which was confused with schizophrenia, bipolar I disorder, and schizophreniform disorder. Blindness significantly affected diagnostic outcome in latent class analyses. Moreover, for diagnostic disagreements, unblind diagnoses had greater continuity with the most predominant diagnosis in the pedigree than did blind diagnoses. Diagnostic disagreements were associated with the presence of mixed affective and psychotic symptoms, less diagnostic certainty, and shorter duration of illness. CONCLUSIONS: These results suggest that it is possible to identify cases that are more likely to lead to diagnostic disagreements in family and epidemiological studies and that blind diagnoses may help to prevent false positive diagnoses, which may be particularly detrimental to genetic linkage analyses.

6p24-22 region and major psychoses in the Eastern Quebec population. Le Groupe IREP.

Recent reports of a linkage trend in 6p24-22 for schizophrenia (SZ), in different samples, were tempered by the concurrent evidence of negative reports in other samples. In the studies showing positive results, different definitions of affection and a wide spectrum of diagnoses were used. Our objectives were not only to test for linkage at 6p24-22 in the Eastern Quebec population, but also to test whether this putative vulnerability locus was either selectively linked to schizophrenia (SZ), or to bipolar disorder (BP), or to both major psychoses. Parametric and nonparametric linkage analyses with 12 microsatellite markers in 6p24-p22 were performed on a sample of 18 large multigenerational pedigrees (N = 354) either affected by SZ, or by BP, or equally affected by both major psychoses (i.e., mixed pedigrees). Three affection definitions were usually tested in our program: one on schizophrenia (SZ), one on bipolar disorder (BP), and one that comprised SZ and BP under the hypothesis of a susceptibility locus common to both in major psychoses (common locus, CL). The results of parametric analyses did not support a major gene hypothesis. However, in one large mixed pedigree (#151), we observed with the common locus phenotype (CL) lod scores of 2.49 and 2.15, respectively, at the D6S296 and D6S277 loci under a dominant model. Our data suggest the presence of a potential vulnerability locus at 6p24-22 that could be related to both schizophrenia and bipolar affective disorder. These results may be seen as congruent with former studies that used schizoaffective as well as schizophrenia diagnoses as entry criteria for the affected families, and used an affection definition that comprised affective psychoses as well as schizophrenia.

Long-term stability of diagnosis and symptom dimensions in a systematic sample of patients with onset of schizophrenia in childhood and early adolescence. II: Postnegative distinction and childhood predictors of adult outcome.

BACKGROUND: The aim of this study was to verify the presence and stability across life of the positive/negative distinction in early-onset schizophrenia (EO-SZ) through a longitudinal factor analysis of the schizophrenic dimensions, and to identify the factors predicting several indices of long-term outcome for EO-SZ. METHOD: Forty children consecutively referred for DSM-III-R schizophrenia (SZ) in a specific catchment area comprised the sample. RESULTS: Across a 14.8-year follow-up, longitudinal factor analysis identified two separate factors corresponding to the positive and negative symptom dimensions. We also observed that: the GAS rated over the last three years of adult illness and the severity of negative symptoms during the stabilised interepisode intervals in adulthood were the indices of adult outcome that were most easily predicted; and the best childhood predictors of adult outcome were premorbid functioning and severity of positive and negative symptoms during acute episodes. CONCLUSIONS: The presence of premorbid non-psychotic behaviour disturbances (NPBD) and premorbid developmental problems was not related to severity of outcome, in contrast to the former variables.

Three-dimensional computer-aided analysis of the intraganglionic topography of primary muscle afferent neurons in the rat.

A microcomputer system was used to reconstruct, in the L5 dorsal root ganglion (DRG) of the rat, the three-dimensional arrangement of primary neurons which had been labelled by application of horseradish peroxidase (HRP) and fluoro-gold (FG) to various muscle nerves of the leg. Analysis of the data and animation of the reconstructed images with commercially available software were instrumental in identifying the preferential intraganglionic locations of the neurons innervating muscles such as the soleus (SOL), the gastrocnemius lateralis (GL), and medialis (GM), or parts of the GM. These locations appeared to be somewhat related to the position of the muscles in the posterior compartment of the leg. Additionally, the study provided quantitative estimates of muscle afferent neuronal populations, allowed a comparison of the labelling performances of HRP and FG, and finally indicated that few DRG neurons project to two different muscles.

Changes in lectin binding of lumbar dorsal root ganglia neurons and peripheral axons after sciatic and spinal nerve injury in the rat.

The effects of chronic lesions of rat lumbar spinal or sciatic nerves on the binding of Glycine max (soybean) agglutinin to galacto-conjugates, in small- and medium-size primary sensory neurons of the L4 and L5 dorsal root ganglia, were examined over a 580-day period. Spinal nerve section resulted in a marked decrease in the population of stained neurons within 7 days. However, despite some retrograde morphological changes triggered by axonal injury, the proportion of stained nerve cells was normalized 180 days postoperatively. This temporary decrease in perikaryal lectin reactivity was initially associated with a marked accumulation of stained material in the nerve, proximal and distal to the site of section, with similar accumulations also being noticeable at each level of injury in sciatic nerves subjected to double ligature. This may reflect the presence of glycocompounds linked to the autolysis of nerve fibers during the phase of retrograde dying-back and Wallerian degeneration. At later stages, stained deposits could be seen scattered along central and peripheral axonal processes of the dorsal root ganglion neurons in the vicinity of the cell body. They may indicate a disturbance in the peripheral turnover of glycoproteins in chronically-transected nerves, with piling up of neuronal products. Sciatic nerve injury caused similar but less severe effects which, except for the L4 ganglion cells, were rapidly reversible.

A comparative study of the effects of chronic axotomy, crush lesion and re-anastomosis of the rat sural nerve on horseradish peroxidase labelling of primary sensory neurons.

Chronic axotomy is detrimental to the incorporation of horseradish peroxidase (HRP) by neurons of the central and peripheral nervous system. Using the rat sural nerve as a model, this study aimed to determine the effects of other types of nerve injury on the peroxidase labelling of dorsal root ganglion (DRG) cells. Compared to the decreased labelling occurring shortly after permanent transection of the sural axons at the ankle, crush injury of the nerve had no effect on the number and size distribution of peroxidase-stained cells. Re-anastomosing the sural nerve to its own distal segment or to the tibial nerve delayed the changes in HRP neuronal labelling, which subsequently were less severe in neurons allowed to reinnervate their own nerve. It also sustained the incorporation of HRP by many large DRG neurons, a function which is lost shortly after these cells are chronically axotomized. Nerve re-anastomosis also prevented the retrograde atrophy of myelinated and unmyelinated nerve fibers which is triggered by permanent transection. Based on the preservation of fiber counts in the sural nerves proximal to the site of surgery, with no evidence of degeneration, our observations possibly reflect alterations in the peroxidase metabolism of DRG neurons depending on the type of axonal injury they sustained and the possibility they had upon regeneration to contact endoneurial tubes and ultimately their original end-organs.

Histochemical localization of carbonic anhydrase in normal and diseased human muscle.

A method is described for histological localization of carbonic anhydrase (CA) in sections of frozen human muscle using the rapid and inexpensive histochemical technique of Hansson. Results obtained in normal subjects indicate clearly that CA reactive fibers are of type 1. Similarly, abnormalities seen with CA in the muscle biopsy of a patient presenting with type 1 fiber hypotrophy and preponderance duplicated almost exactly those observed with the actinomyosine adenosine triphosphatase and the reduced nicotinamide adenine dinucleotide dehydrogenase reactions. Observations of grouped CA-positive muscle fibers in a case of chronic neurogenic atrophy suggest that, like other enzymes, CA expression in muscle is under neurogenic control.

Carbonic anhydrase and horseradish peroxidase: double labelling of rat dorsal root ganglion neurons innervating motor and sensory peripheral nerves.

Dorsal root ganglion neurons supplying peroneus longus, soleus and gastrocnemius medius muscles and the sural nerve of the rat were labelled with horseradish peroxidase and analysed for their carbonic anhydrase content. Staining of the sections was done either on the same or on alternate slides. Both methods led to the same results, despite a slight fading of the carbonic anhydrase reaction in double-stained sections. The data indicated that the muscles under study were supplied by approximately the same number of horseradish peroxidase-labelled cells, irrespective of their differences in size. 74.9% of these labelled neurons had diameters exceeding 30 microns and 52.4% of them also stained for carbonic anhydrase. The double-labelled cells represented 66.9% of the population of large neurons (greater than 30 microns) and comprised most of those measuring over 47.5 microns. Richness in carbonic anhydrase of the large muscle afferent neurons may be linked to their innervation of the stretch receptors, as components of an active apparatus which includes the gamma motor axons which also stain positively for carbonic anhydrase. In contrast, the ganglion cells supplying the sural nerve were almost totally devoid of carbonic anhydrase, as only 6.4% showed double labelling. This contingent possibly represents the muscle afferents of the small motoneural population which supplies, through this nerve, part of the foot musculature of the rat.

Differential effects of distal and proximal nerve lesions on carbonic anhydrase activity in rat primary sensory neurons, ventral and dorsal root axons.

The effect of proximal and distal peripheral nerve injuries on the histochemistry of carbonic anhydrase (CA) in rat dorsal root ganglion (DRG) neurons, and myelinated (MyF) dorsal and ventral root fibers was studied. Sciatic neurectomy induced no change. Contrariwise, 7 days after lumbar spinal nerve section the numbers of CA-stained ventral root MyF and DRG cells at the L4 and L5 levels decreased to 73.2% and 51.9% of their original values respectively, although the numbers returned to normal by the 90th postoperative day. Dorsal root MyF followed a similar trend, albeit with some delay. Major morphological changes comprised atrophy of dorsal root sensory neurons and axons, particularly in long term experiments, as well as nuclear eccentricity in DRG neurons. These results suggest that, depending on the site of lesion, the rat peripheral nervous system (PNS) either maintains or quickly restores its capacity to synthesize CA. They stand in contrast to the long-lasting metabolic dysfunctions reported to occur when primary neurons are disconnected from the periphery. It is uncertain whether this difference is due to the critical role of CA in neuronal metabolism.