Substance use-related outpatient consultations in specialized health care: an underestimated entity

Background To study the occurrence and documentation of substance use related outpatient visits in specialized health care.
Methods The diagnosis recorded in retrospective discharge data in Tampere University Hospital for 6 years was compared with the prospective data gathered from separately completed forms added during an 8-week period to every outpatient's discharge data. In this form, the relation of substance use and the actual reason for the consultation were specifically elicited.
Results On the basis of diagnoses, retrospectively, 0.4% (6,666 of 1,555,898) of outpatient visits were caused by substance use. In the prospective part of the study, 5.6% of visits (1,401/25,014) were related to substance use. Retrospective study demonstrated 2% prevalence of substance use, whereas prospective study showed 36% substance use–related visits at the emergency room. According to the retrospective discharge data, alcohol-related organ damages were the major reason for substance use–related outpatient visits. In the prospective study, the proportion of acute traumas was most prevalent.
Conclusions Our study indicates that substance use–related visits often remain undetected in specialized health care. Substance use–related visits were underdocumented/undetected in the emergency room. Using a simple separate form could dramatically increase the detection of substance use–related visits.     

A‐Fibers Mediate Cold Hyperalgesia in Patients with Oxaliplatin‐Induced Neuropathy

Cold hyperalgesia is a common side effect of oxaliplatin treatment; still, the pathophysiological and molecular mechanisms as well as the contribution of different primary afferent fiber systems are unclear. Therefore, patients with oxaliplatin‐induced acute neuropathy with (n = 6) and without (n = 7) cold hyperalgesia were tested by applying a preferential blockade of peripheral myelinated A‐fiber afferents in combination with quantitative sensory testing. Additionally, an interview‐based questionnaire assessed the severity of symptoms and the impact on daily activities. Results indicate a deficit of cold perception in patients without cold hyperalgesia compared to patients with cold hyperalgesia prior to A‐fiber blockade. In patients with cold hyperalgesia, a preferential blockade of A‐fibers abolished cold hyperalgesia. This suggests that oxaliplatin‐induced cold hyperalgesia is mediated by A‐fibers and that a deficit in A‐fiber function might prevent the development of cold hyperalgesia. The work supports findings in rodents and in human sural nerve biopsies indicating that oxaliplatin interferes with axonal ion conductance in intact A‐fibers by sensitizing potassium and/or sodium channels. Drugs that act on these molecular targets might be of potential value to treat oxaliplatin‐induced cold hyperalgesia.     

Effect of carboxylesterase 1 c.428G?>?A single nucleotide variation on the pharmacokinetics of quinapril and enalapril

Aim

The aim of the present study was to investigate the effects of the carboxylesterase 1 (CES1) c.428G > A (p.G143E, rs71647871) single nucleotide variation (SNV) on the pharmacokinetics of quinapril and enalapril in a prospective genotype panel study in healthy volunteers.

Methods

In a fixed-order crossover study, 10 healthy volunteers with the CES1 c.428G/A genotype and 12 with the c.428G/G genotype ingested a single 10 mg dose of quinapril and enalapril with a washout period of at least 1 week. Plasma concentrations of quinapril and quinaprilat were measured for up to 24 h and those of enalapril and enalaprilat for up to 48 h. Their excretion into the urine was measured from 0 h to 12 h.

Results

The area under the plasma concentration–time curve from 0 h to infinity (AUC_0–∞) of active enalaprilat was 20% lower in subjects with the CES1 c.428G/A genotype than in those with the c.428G/G genotype (95% confidence interval of geometric mean ratio 0.64, 1.00; P = 0.049). The amount of enalaprilat excreted into the urine was 35% smaller in subjects with the CES1 c.428G/A genotype than in those with the c.428G/G genotype (P = 0.044). The CES1 genotype had no significant effect on the enalaprilat to enalapril AUC_0–∞ ratio or on any other pharmacokinetic or pharmacodynamic parameters of enalapril or enalaprilat. The CES1 genotype had no significant effect on the pharmacokinetic or pharmacodynamic parameters of quinapril.

Conclusions

The CES1 c.428G > A SNV decreased enalaprilat concentrations, probably by reducing the hydrolysis of enalapril, but had no observable effect on the pharmacokinetics of quinapril.     

The effect of atorvastatin treatment on serum oxysterol concentrations and cytochrome P450 3A4 activity

Aims

Atorvastatin is known to both inhibit and induce the cytochrome P450 3A4 (CYP3A4) enzyme in vitro. Some clinical studies indicate that atorvastatin inhibits CYP3A4 but there are no well-controlled longer term studies that could evaluate the inducing effect of atorvastatin. We aimed to determine if atorvastatin induces or inhibits CYP3A4 activity as measured by the 4β-hydroxycholesterol to cholesterol ratio (4βHC : C).

Methods

In this randomized, double-blind, placebo-controlled 6 month study we evaluated the effects of atorvastatin 20 mg day⁻¹ (n = 15) and placebo (n = 14) on oxysterol concentrations and determined if atorvastatin induces or inhibits CYP3A4 activity as assessed by the 4βHC : C index. The respective 25-hydroxycholesterol and 5α,6α-epoxycholesterol ratios were used as negative controls.

Results

Treatment with atorvastatin decreased 4βHC and 5α,6α-epoxycholesterol concentrations by 40% and 23%, respectively. The mean 4βHC : C ratio decreased by 13% (0.214 ± 0.04 to 0.182 ± 0.04, P = 0.024, 95% confidence interval (CI) of the difference –0.0595, –0.00483) in the atorvastatin group while no significant change occurred in the placebo group. The difference in change of 4βHC : C between study arms was statistically significant (atorvastatin –0.032, placebo 0.0055, P = 0.020, 95% CI of the difference –0.069, –0.0067). The ratios of 25-hydroxycholesterol and 5α,6α-epoxycholesterol to cholesterol did not change.

Conclusions

The results establish atorvastatin as an inhibitor of CYP3A4 activity. Furthermore, 4βHC : C is a useful index of CYP3A4 activity, including the conditions with altered cholesterol concentrations.     

Access to Social Protection by People Living with,at Risk of,or Affected by HIV in Eswatini,Malawi, Tanzania,and Zambia: Results from Population-Based HIV Impact Assessments

AIDS and Behavior - We aimed to measure social protection coverage among the general population, women and men living with HIV (WLHIV, MLHV), female and male sex workers (FSW, MSW), men who have...     

Exposure of chromatin and not high affinity for dsDNA determines the nephritogenic impact of anti-dsDNA antibodies in (NZB×NZW)F1 mice

Recent studies have demonstrated that the nephritogenicity of antibodies to dsDNA and nucleosomes confers to binding of glomerular membrane-associated nucleosomes, and not to cross-reacting glomerular antigens. There is no known parameter that determines antibody pathogenicity aside from specificity for dsDNA/nucleosomes, and systemic lupus erytheomatosus (SLE) patients may have high titer anti-dsDNA antibodies irrespective whether they have lupus nephritis or not. One parameter may be antibody affinity, as theoretically only high affinity antibodies may bind in vivo in a stable way. This was analyzed in (NZB × NZW)F1 mice with full-blown lupus nephritis. These mice had serum antibodies to dsDNA, and IgG autoantibodies bound in situ in glomerular membrane-associated electron dense structures as determined by immune electron microscopy (IEM). Intrinsic affinity of purified circulating and glomerular IgG anti-dsDNA antibodies was determined by surface plasmon resonance. The results demonstrate that affinity of glomerular-bound anti-dsDNA antibodies was higher than for those in circulation. However, affinity of glomerular in situ-bound antibodies from different mice varied considerably, from K_D in the range from 10^{? 8} to 10^{? 13}. These results indicate that antibody affinity is not a decisive pathogenic factor, but rather that availability of chromatin fragments may be the factor that determines whether an anti-dsDNA antibody binds in glomeruli or not.     

Results at 10 to 14 years after osteochondral autografting (mosaicplasty) in articular cartilage defects in the knee

PurposeThe aim of this study was to evaluate the medium-term (5–9 years) and long-term (10–14 years) outcomes of mosaicplasty in the knee and identify possible risk factors for poor outcome.MethodsWe included patients 60 years or younger with symptomatic focal full-thickness chondral lesions. Seventy-three patients (87%) with median age of 34 years were available for analyses. Clinical outcome was evaluated by Lysholm score and VAS of pain.ResultsBoth the mean Lysholm score and mean VAS pain score improved significantly from baseline, 49 (SD 17) and 58 (SD 23), respectively, to both the mid-term follow-up, 72 (SD18, p < 0.001) and 27 (SD 20, p < 0.001), respectively, and the long-term follow-up, 72 (SD 21, p < 0.001) and 33 (SD 23, p < 0.001), respectively. A poor outcome at the long-term follow-up – defined as a Lysholm score of 64 or less or having had a knee replacement – was found in 40%. A poor outcome was more frequent in patients 40 years or older (59%), in women (61%) and in defects with an area of 3 cm² or more (57%). Conversely, in a subgroup of male individuals younger than 40 years with defect size less than 3 cm² the failure rate was 12.5% and the mean Lysholm score was 82 (SD 16).ConclusionWe conclude that the long-term clinical outcome after mosaicplasty varies greatly depending on age, gender and the size of the lesion.Level of evidenceIV-Retrospective Case Series.