Incidence of acute complications of herpes zoster among immunocompetent adults in England: a matched cohort study using routine health data.

BACKGROUND: Herpes zoster can cause rare but serious complications; the frequency of these complications has not been well described. OBJECTIVES: To quantify the risks of acute non-postherpetic neuralgia (PHN) zoster complications, to inform vaccination policy. METHODS: We conducted a cohort study among unvaccinated immunocompetent adults with incident zoster, and age-, sex- and practice-matched control adults without zoster, using routinely collected health data from the UK Clinical Practice Research Datalink (years 2001 to 2018). Crude attributable risks of complications were estimated as the difference between Kaplan-Meier-estimated 3-month cumulative incidences in patients with zoster vs. controls. We used Cox models to obtain hazard ratios for our primary outcomes in patients with and without zoster. Primary outcomes were ocular, neurological, cutaneous, visceral and zoster-specific complications. We also assessed whether antivirals during acute zoster protected against the complications. RESULTS: In total 178 964 incident cases of zoster and 1 799 380 controls were included. The absolute risks of zoster-specific complications within 3 months of zoster diagnosis were 0·37% [95% confidence interval (CI) 0·34-0·39] for Ramsay Hunt syndrome, 0·01% (95% CI 0·0-0·01) for disseminated zoster, 0·04% (95% CI 0·03-0·05) for zoster death and 0·97% (95% CI 0·92-1·00) for zoster hospitalization. For other complications, attributable risks were 0·48% (95% CI 0·44-0·51) for neurological complications, 1·33% (95% CI 1·28-1·39) for ocular complications, 0·29% (95% CI 0·26-0·32) for cutaneous complications and 0·78% (95% CI 0·73-0·84) for visceral complications. Attributable risks were higher among patients > 50 years old. Patients with zoster had raised risks of all primary outcomes relative to controls. Antiviral prescription was associated with reduced risk of neurological complications (hazard ratio 0·61, 95% CI 0·53-0·70). CONCLUSIONS: Non-PHN complications of zoster were relatively common, which may affect cost-effectiveness calculations for zoster vaccination. Clinicians should be aware that zoster can lead to various complications, besides PHN.

Partner bereavement and risk of psoriasis and atopic eczema: cohort studies in the U.K. and Denmark.

BACKGROUND: Stress is commonly cited as a risk factor for psoriasis and atopic eczema, but such evidence is limited. OBJECTIVES: To investigate the association between partner bereavement (an extreme life stressor) and psoriasis or atopic eczema. METHODS: We conducted cohort studies using data from the U.K. Clinical Practice Research Datalink (1997-2017) and Danish nationwide registries (1997-2016). The exposed cohort was partners who experienced partner bereavement. The comparison cohort was up to 10 nonbereaved partners, matched to each bereaved partner by age, sex, county of residence (Denmark) and general practice (U.K.). Outcomes were the first recorded diagnosis of psoriasis or atopic eczema. We estimated hazard ratios (HRs) and confidence intervals (CIs) using a stratified Cox proportional hazards model in both settings, which were then pooled in a meta-analysis. RESULTS: The pooled adjusted HR for the association between bereavement and psoriasis was 1·01 (95% CI 0·98-1·04) across the entire follow-up. Similar results were found in other shorter follow-up periods. Pooled adjusted HRs for the association between bereavement and atopic eczema were 0·97 (95% CI 0·84-1·12) across the entire follow-up, 1·09 (95% CI 0·86-1·38) within 0-30 days, 1·18 (95% CI 1·04-1·35) within 0-90 days, 1·14 (95% CI 1·06-1·22) within 0-365 days and 1·07 (95% CI 1·02-1·12) within 0-1095 days. CONCLUSIONS: We found a modest increase in the risk of atopic eczema within 3 years following bereavement, which peaked in the first 3 months. Acute stress may play a role in triggering onset of new atopic eczema or relapse of atopic eczema previously in remission. We observed no evidence for increased long-term risk of psoriasis and atopic eczema following bereavement.

The association between partner bereavement and melanoma: cohort studies in the U.K. and Denmark.

BACKGROUND: Psychological stress is commonly cited as a risk factor for melanoma, but clinical evidence is limited. OBJECTIVES: This study aimed to evaluate the association between partner bereavement and (i) first-time melanoma diagnosis and (ii) mortality in patients with melanoma. METHODS: We conducted two cohort studies using data from the U.K. Clinical Practice Research Datalink (1997-2017) and Danish nationwide registries (1997-2016). In study 1, we compared the risk of first melanoma diagnosis in bereaved vs. matched nonbereaved people using stratified Cox regression. In study 2 we estimated hazard ratios (HRs) for death from melanoma in bereaved compared with nonbereaved individuals with melanoma using Cox regression. We estimated HRs separately for the U.K. and for Denmark, and then pooled the data to perform a random-effects meta-analysis. RESULTS: In study 1, the pooled adjusted HR for the association between partner bereavement and melanoma diagnosis was 0·88 [95% confidence interval (CI) 0·84-0·92] across the entire follow-up period. In study 2, we observed increased melanoma-specific mortality in people experiencing partner bereavement across the entire follow-up period (HR 1·17, 95% CI 1·06-1·30), with the peak occurring during the first year of follow-up (HR 1·31, 95% CI 1·07-1·60). CONCLUSIONS: We found decreased risk of melanoma diagnosis, but increased mortality associated with partner bereavement. These findings may be partly explained by delayed detection resulting from the loss of a partner who could notice skin changes. Stress may play a role in melanoma progression. Our findings indicate the need for a low threshold for skin examination in individuals whose partners have died. What is already known about this topic? Psychological stress has been proposed as a risk factor for the development and progression of cancer, including melanoma, but evidence is conflicting. Clinical evidence is limited by small sample sizes, potential recall bias associated with self-report, and heterogeneous stress definitions. What does this study add? We found a decreased risk of melanoma diagnosis, but increased mortality associated with partner bereavement. While stress might play a role in the progression of melanoma, an alternative explanation is that bereaved people no longer have a close person to help notice skin changes, leading to delayed melanoma detection. Linked Comment: Talaganis et al. Br J Dermatol 2020; 183:607-608.

Inequalities in zoster disease burden: a population-based cohort study to identify social determinants using linked data from the U.K. Clinical Practice Research Datalink.

BACKGROUND: Zoster vaccination was introduced in England in 2013, where tackling health inequalities is a statutory requirement. However, specific population groups with higher zoster burden remain largely unidentified. OBJECTIVES: To evaluate health inequalities in zoster disease burden prior to zoster vaccine introduction in England. METHODS: This population-based cohort study used anonymized U.K. primary care data linked to hospitalization and deprivation data. Individuals aged ≥ 65 years without prior zoster history (N = 862 470) were followed from 1 September 2003 to 31 August 2013. Poisson regression was used to obtain adjusted rate ratios (ARRs) for the association of sociodemographic factors (ethnicity, immigration status, individuals' area-level deprivation, care home residence, living arrangements) with first zoster episode. Possible mediation by comorbidities and immunosuppressive medications was also assessed. RESULTS: There were 37 014 first zoster episodes, with an incidence of 8·79 [95% confidence interval (CI) 8·70-8·88] per 1000 person-years at risk. In multivariable analyses, factors associated with higher zoster rates included care home residence (10% higher vs. those not in care homes), being a woman (16% higher vs. men), nonimmigrants (~30% higher than immigrants) and white ethnicity (for example, twice the rate compared with those of black ethnicity). Zoster incidence decreased slightly with increasing deprivation (ARR most vs. least deprived 0·96 (95% CI 0·92-0·99) and among those living alone (ARR 0·96, 95% CI 0·94-0·98). Mediating variables made little difference to the ARR of social factors but were themselves associated with increased zoster burden (ARR varied from 1·11 to 3·84). CONCLUSIONS: The burden of zoster was higher in specific sociodemographic groups. Further study is needed to ascertain whether these individuals are attending for zoster vaccination.

Pineal gland N-acetyltransferase and hydroxyindole-O-methyltransferase activity in the rainbow trout (Salmo gairdneri): seasonal variation linked to photoperiod.

The activities of rainbow trout pineal gland N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) were determined at various times during a 24 h period in mid-winter and mid-summer. The results indicate a small diurnal fluctuation in HIOMT and a marked diurnal fluctuation in NAT activity with peak enzyme activities occurring during the dark phase. NAT can be assumed to be the rate limiting enzyme for the production of melatonin and, as NAT activity increases were associated with the dark phase, it can also be assumed that melatonin production would be greater in winter than in summer.

Spinal cord monitoring in scoliosis surgery. Experience with 1168 cases.

Since 1981, during operations for spinal deformity, we have routinely used electrophysiological monitoring of the spinal cord by the epidural measurement of somatosensory evoked potentials (SEPs) in response to stimulation of the posterior tibial nerve. We present the results in 1168 consecutive cases. Decreases in SEP amplitude of more than 50% occurred in 119 patients, of whom 32 had clinically detectable neurological changes postoperatively. In 35 cases the SEP amplitude was rapidly restored, either spontaneously or by repositioning of the recording electrode; they had no postoperative neurological changes. One patient had delayed onset of postoperative symptoms referrable to nerve root lesions without evidence of spinal cord involvement, but there were no false negative cases of intra-operative spinal cord damage. In 52 patients persistent, significant, SEP changes were noted without clinically detectable neurological sequelae. None of the many cases which showed falls in SEP amplitude of less than 50% experienced neurological problems. Neuromuscular scoliosis, the use of sublaminar wires, the magnitude of SEP decrement, and a limited or absent intra-operative recovery of SEP amplitude were identified as factors which increased the risk of postoperative neurological deficit.

Probable mechanism of catalysis of pineal gland hydroxyindole-O-methyltransferase (HIOMT) from rainbow trout (Salmo gairdneri).

Activity of trout pineal HIOMT was found to increase with increase in incubation temperature from 5 to 40 degrees C although the activation energy remained constant over this range. From examination of the effects of the products of HIOMT catalysis on the enzyme it was apparent that the catalytic mechanism was ordered Bi-Bi with S-adenosylmethionine as the obligatory first substrate. Trout HIOMT was found to methylate all the common pineal hydroxyindoles with hydroxytryptophol having the greatest affinity for the enzyme. The pH optimum for trout HIOMT was found to be about pH 9.0 although routine use of a pH of 7.9 is recommended to limit potentially deliterious effects caused by degradation of S-adenosylmethionine at elevated pHs.

Inhibition of the catalytic activity of bovine pineal gland hydroxyindole-O-methyltransferase (EC 2.1.1.4) by estrone, estradiol, progesterone, and testosterone but not pteridines.

The effect of pteridines and sex hormones on hydroxyindole-O-methyltransferase (HIOMT) catalysis was examined. Equivalent quantities of partially purified bovine HIOMT was incubated in the presence and absence of the various test substances and the results fitted to the Michaelis-Menten equation. The pteridines (triampterene and xanthopterin) had no noticeable effect on HIOMT catalysis, while all the sex hormones examined were found to be competitive inhibitors of the enzyme with respect to the hydroxy-substrate. Testosterone concentrations causing noticeable inhibition were above physiological while estrone, estradiol, and progesterone all caused inhibition within the physiological range; estrone was the most potent and progesterone the least potent inhibitor. The possible significance of these findings are discussed.

Pineal gland hydroxyindole-O-methyl transferase (HIOMT) from rainbow trout (Salmo gairdneri) subject to temperature-dependent substrate inhibition by N-acetylserotonin.

The effect of different incubation temperatures on the activity of trout hydroxyindole-O-methyltransferase (HIOMT) was determined in order to study the potential effects of changes in environmental temperature on production of melatonin. In the study, N-acetylserotonin (NAS) was found to inhibit trout pineal HIOMT, inhibitory concentration decreasing with a decrease in incubation temperature. An increase in incubation temperature was accompanied by an increase in maximal velocity (Vm) and a decrease in affinity of the substrate NAS for the enzyme, while the affinity of the inhibitor NAS remained more or less constant with increase in temperature up to 30 degrees C. It was interesting to note that at subinhibitory concentrations of NAS, possibly concentrations within the normal physiological range, there was a balance between increased velocity and decreased affinity for substrate, with increase in temperature resulting in a constant rate of melatonin production. On the basis of these results it is suggested that substrate inhibition might be involved in modulation of melatonin production and that trout pineal HIOMT can maintain a constant rate of melatonin production over a wide range of temperatures by a combination of compensatory changes in enzyme kinetic parameters.

Dietary supplements used in the treatment of depression, anxiety, and sleep disorders.

Dietary supplement use has increased during the past decade. Epidemiologic studies suggest that patients turn to dietary supplements because of a reluctance to take prescription medications or a lack of satisfaction with the results. They often perceive dietary supplements to be a safer or more natural alternative. Patients with mental health conditions, including depression, anxiety, and sleep disorders, are among those who use dietary supplements. St. John's Wort is used to treat depression. Clinical studies comparing dietary supplements with low-dose antidepressants (maprotiline, amitriptyline, or imipramine at 75 mg/day) or high-dose antidepressants (imipramine at 150 mg/day) find no significant difference between treatments. Kava kava is used to treat anxiety. Clinical trials demonstrate it to be superior to placebo, and roughly equivalent to oxazepam 15 mg/day or bromazepam 9 mg/day. Agents discussed for use in sleep disorders include melatonin, valerian, 5-hydroxytryptamine, catnip, chamomile, gotu kola, hops, L-tryptophan, lavender, passionflower, skullcap, and valerian. Familiarity with the evidence for use and the possible resulting risks can help health professionals to guide patient decisions regarding use of dietary supplements.