Impact of the COVID-19 pandemic on Bordetella pertussis infections in England.

BACKGROUND: In March 2020, England went into its first lockdown in response to the COVID-19 pandemic. Restrictions eased temporarily, followed by second and third waves in October 2020 and January 2021. Recent data showed that the COVID-19 pandemic resulted in reduced transmission of some invasive diseases. We assess the impact of the COVID-19 pandemic on pertussis incidence and on the immunisation programme in England. METHODS: We assessed trends in pertussis cases from 2012 to 2020 by age group and month. Incidence from the time that England eased its initial lockdown measures in July 2020 through to summer 2021 was calculated and the incidence rate ratios of pertussis cases from five years prior to the pandemic (July 2014 - June 2019) compared to the same time period during the pandemic (July 2020 - June 2021). Vaccine coverage estimates for pertussis containing vaccines were reviewed for the maternal and childhood programmes. RESULTS: A substantial decline in pertussis cases was observed from April 2020 onwards, marking the lowest number of cases in the last decade. Pertussis incidence dropped in all age groups, particularly among infants less than one year old (0.50 / 100,000 during July 2020 to June 2021 compared to 24.49/ 100,000 from July 2014 to June 2019). The incidence rate ratio was 0.02 (95% CI 0.01 to 0.02) for July 2014 to June 2019 (pre-pandemic) compared to the pandemic period of July 2020 to June 2021. None of the cases had a co-infection with SARS-CoV-2. Vaccine coverage for infants born between January to March 2020 with three doses of pertussis vaccine by 12 months of age decreased by 1.1% points compared to infants born between January to March 2019 (91.6% and 92.7%, respectively). Prenatal pertussis coverage for the 2020 to 2021 financial year was 2.7% points lower than the year prior to the pandemic (70.5% and 76.8%, respectively). CONCLUSIONS: Lockdown measures due to the COVID-19 pandemic have had a significant impact on pertussis transmission. With the easing of restrictions it is important to continue monitoring pertussis cases in England alongside coverage of the maternal and childhood immunisation programmes.

Symptom domains of schizophrenia: the role of atypical antipsychotic agents.

Given their more obvious presentation, the reduction of positive symptoms and their associated behavioural problems have been considered the most important treatment outcome parameter in patients with schizophrenia. However, the development of the atypical antipsychotic agents in the early 1990s resulted in the adoption of more wide-reaching measures of therapeutic outcome. The aim of this review was to evaluate the efficacy of currently available atypical agents across multiple symptom domains of schizophrenia with a specific focus on negative symptoms, neurocognition, social functioning, quality of life and insight. As such, studies published between January 1990 and December 2005 that evaluated the clinical efficacy and tolerability of atypical antipsychotics in different symptom domains of schizophrenia were reviewed as identified from literature researches using MEDLINE and Embase. Abstracts and posters presented at key psychiatry and schizophrenia congresses during this period were also reviewed where available in the public domain. Results from the studies identified have consistently demonstrated that atypical antipsychotics have substantial advantages over conventional antipsychotics with a broader spectrum of efficacy across symptomatic domains of schizophrenia as proven by greater improvements in negative symptoms and cognitive function and a beneficial effect on affective symptoms and quality of life. However, their clinical advantages have often been limited by patients' partial compliance with therapy. As such, the development of a long-acting atypical antipsychotic agent may provide a new and valuable treatment option for patients with schizophrenia.

The C/C genotype of the C957T polymorphism of the dopamine D2 receptor is associated with schizophrenia.

The T allele of the human dopamine D2 receptor (DRD2) gene C957T polymorphism is associated with reduced mRNA translation and stability. This results in decreased dopamine induced DRD2 upregulation and decreased in vivo D2 dopamine binding. Conversely, the C allele of the C957T polymorphism is not associated with such changes in mRNA leading to increased DRD2 expression. PET and postmortem binding studies show that schizophrenia is often associated with increased DRD2 availability. We report that on the basis of comparing the frequencies of the C/C and T/T genotypes of 153 patients with schizophrenia and 148 controls that schizophrenia is associated with the C/C genotype. The C957T shows a population attributable risk for schizophrenia of 24% and an attributable risk in those with schizophrenia of 42%. Increased expression of D2 receptors associated with the C allele is likely to be important in the underlying pathophysiology of at least some forms of schizophrenia. Enhanced understanding of schizophrenia afforded by this finding may lead to advances in treatment and prevention.

Strategies for improving adherence to second-generation antipsychotics in patients with schizophrenia by increasing ease of use.

Despite the advances in the treatment of patients with schizophrenia that have occurred since the introduction of the second-generation (atypical) antipsychotic agents, a leading cause of suboptimal outcome is poor patient adherence to oral medication. Partial adherence can be attributed to a number of factors, including lack of insight, cognitive dysfunction, a complicated treatment regimen, drug-related side effects, patient attitude, lack of patient education, and cultural factors. A number of strategies, including psychosocial interventions, cognitive-behavioral techniques, strategies that minimize side effects, and pharmacological approaches that increase ease of medication use, can be employed to support adherence and improve long-term outcomes. This article focuses on strategies for increasing ease of use of antipsychotics in the treatment of patients with schizophrenia. These strategies include using monotherapy rather than polypharmacy, simplifying the medication regimen, and using a long-acting antipsychotic formulation. The goal of these strategies is to improve adherence and help prevent relapse by ensuring continuous antipsychotic coverage. Strategies that optimize ease of use of medication treatment for schizophrenia and thus improve adherence to treatment are likely to promote the attainment of new treatment goals and improved patient outcomes.

Impact of the physical and topographical characteristics of adsorbent solid-phases upon the fluidised bed recovery of plasmid DNA from Escherichia coli lysates.

A comparison is made of the performance of two types of adsorbent solid phases (commercially sourced Streamline composites and custom-assembled Zirblast pelliculates), derivatised with similar anion exchange chemistries and applied to the recovery of plasmid DNA from Escherichia coli extracts prepared by chemical lysis and coarse filtration. Streamline and Zirblast adsorbents were characterised by average particle diameters of 200 and 95 microm, densities of 1.16 and 3.85 g/m2, and small ion capacities of 170 and 8 micromol/ml settled adsorbent, respectively. Detailed analysis of products and impurities in a full operational cycle of adsorption, washing, pre-elution, elution and regeneration processes was enabled by the harnessing of a battery of analyses for nucleic acid and organic solute content of feedstocks and bed effluents exploiting ultra-violet spectrophotometry, agarose gel electrophoresis and specific reactions with the fluorescent probe PicoGreen. In comparative tests operated under near identical conditions, Streamline and Zirblast adsorbents exhibited plasmid recoveries of 76 and 90% of bound product characterised by purity ratios (relative PicoGreen and A254 estimates of mass) of 9 and 32, respectively. Conclusions are drawn regarding the specific impact of the physical and topographical characteristics of solid-phase geometry upon product throughput, achievable product purity, process time-scales and operational economics for the manufacture of plasmid DNA.

Smoking and schizophrenia: is symptom profile related to smoking and which antipsychotic medication is of benefit in reducing cigarette use?

OBJECTIVE: Smoking rate is disproportionately high among patients with schizophrenia, resulting in significant morbidity and mortality. However, cigarette smoking has been reported to have beneficial effects on negative symptoms, extrapyramidal symptoms, cognitive functioning and mood symptoms. Therefore, smoking cessation may worsen disability in schizophrenia. The association between smoking and these key clinical parameters was examined. Additionally, severity of smoking across four different antipsychotic treatment groups was explored. METHOD: One hundred and forty-six patients with schizophrenia were assessed for smoking using expired carbon monoxide and smoking history. They were administered the Positive and Negative Symptom Scale, The Extrapyramidal Symptom Rating Scale, the Barnes Akathisia Rating Scale, Reitans Trail-making Test (A and B) and General Health Questionnaire-28. RESULTS: There was no difference in the chlorpromazine equivalent dose of any of the medications studied. Atypical agents were associated with significantly lower levels of smoking when compared with typical medications. There was no difference in smoking severity between the individual atypical medications examined. Similarly, there were no significant differences between smoking and non-smoking groups with regard to Positive and Negative Symptom Scale, Extrapyramidal Symptom Rating Scale, Trail-making Test and General Health Questionnaire-28. However, there was a significant difference between these groups with the smoking group demonstrating less akathisia. CONCLUSIONS: Smoking is not associated with positive, negative cognitive and mood symptoms in schizophrenia. Smoking is associated with lower levels of antipsychotic induced akathisia. Clinicians should not be discouraged from helping patients stop smoking for fear of worsening symptoms. However, akathisia may emerge upon cessation of smoking. Switching patients from typical to atypical antipsychotics may assist patients with schizophrenia to give up smoking.

Prolactin levels in antipsychotic treatment of patients with schizophrenia carrying the DRD2*A1 allele.

BACKGROUND: Hyperprolactinaemia induced by D(2) dopamine receptor antagonist antipsychotic medication can result in significant health problems. AIMS: To examine the role of DRD2 polymorphism on prolactin levels in patients treated with antipsychotic medication. METHOD: Antipsychotic drugs with different degrees of D(2) receptor binding were given to 144 patients with schizophrenia. Serum prolactin levels were obtained and Taq1A DRD2 alleles were determined. RESULTS: Prolactin levels increased across medication groups reflecting increasingly tight D(2) receptor binding (clozapine, olanzapine, typical antipsychotics and risperidone). In the combined medication group, patients with the DRD2(*)A1allele had 40% higher prolactin levels than patients without this allele. In patients treated with clozapine (the loosest D(2) receptor binding agent), patients with the DRD2(*)A1allele had prolactin levels twice those of patients without this allele. CONCLUSIONS: Patients with the DRD2A1 allele receiving antipsychotic medications had higher prolactin levels and were overrepresented among those with hyperprolactinaemia, suggesting greater functional D(2) receptor binding in this group.