Thyroid abnormalities following the use of cytotoxic T-lymphocyte antigen-4 and programmed death receptor protein-1 inhibitors in the treatment of melanoma.

CONTEXT: Checkpoint inhibitors are emerging as important cancer therapies but are associated with a high rate of immune side effects, including endocrinopathy. OBJECTIVE: To determine the burden of thyroid dysfunction in patients with melanoma treated with immune checkpoint inhibitors and describe the clinical course. DESIGN AND PATIENTS: Consecutive patients with melanoma treated with either ipilimumab, nivolumab, pembrolizumab or the combination of ipilimumab and nivolumab were identified. Baseline thyroid function tests were used to exclude those with pre-existing thyroid abnormalities, and thyroid function tests during treatment used to identify those with thyroid dysfunction. RESULTS: Rates of overt thyroid dysfunction were in keeping with the published phase 3 trials. Hypothyroidism occurred in 13·0% treated with a programmed death receptor-1 (PD-1) inhibitor and 22·2% with a combination of PD-1 inhibitor and ipilimumab. Transient subclinical hyperthyroidism was observed in 13·0% treated with a PD-1 inhibitor, 15·9% following a PD-1 inhibitor, and 22·2% following combination treatment with investigations suggesting a thyroiditic mechanism rather than Graves' disease, and a high frequency of subsequent hypothyroidism. Any thyroid abnormality occurred in 23·0% following ipilimumab, 39·1% following a PD-1 inhibitor and 50% following combination treatment. Abnormal thyroid function was more common in female patients. CONCLUSION: Thyroid dysfunction occurs commonly in patients with melanoma treated with immune checkpoint inhibitors, with rates, including subclinical dysfunction, occurring in up to 50%.

Improving access to affordable quality-assured inhaled medicines in low- and middle-income countries.

BACKGROUND: Access to affordable inhaled medicines for chronic respiratory diseases (CRDs) is severely limited in low- and middle-income countries (LMICs), causing avoidable morbidity and mortality. The International Union Against Tuberculosis and Lung Disease convened a stakeholder meeting on this topic in February 2022.METHODS: Focused group discussions were informed by literature and presentations summarising experiences of obtaining inhaled medicines in LMICs. The virtual meeting was moderated using a topic guide around barriers and solutions to improve access. The thematic framework approach was used for analysis.RESULTS: A total of 58 key stakeholders, including patients, healthcare practitioners, members of national and international organisations, industry and WHO representatives attended the meeting. There were 20 pre-meeting material submissions. The main barriers identified were 1) low awareness of CRDs; 2) limited data on CRD burden and treatments in LMICs; 3) ineffective procurement and distribution networks; and 4) poor communication of the needs of people with CRDs. Solutions discussed were 1) generation of data to inform policy and practice; 2) capacity building; 3) improved procurement mechanisms; 4) strengthened advocacy practices; and 5) a World Health Assembly Resolution.CONCLUSION: There are opportunities to achieve improved access to affordable, quality-assured inhaled medicines in LMICs through coordinated, multi-stakeholder, collaborative efforts.

Substandard medicines in resource-poor settings: a problem that can no longer be ignored.

The circulation of substandard medicines in the developing world is a serious clinical and public health concern. Problems include under or over concentration of ingredients, contamination, poor quality ingredients, poor stability and inadequate packaging. There are multiple causes. Drugs manufactured for export are not regulated to the same standard as those for domestic use, while regulatory agencies in the less-developed world are poorly equipped to assess and address the problem. A number of recent initiatives have been established to address the problem, most notably the WHO pre-qualification programme. However, much more action is required. Donors should encourage their partners to include more explicit quality requirements in their tender mechanisms, while purchasers should insist that producers and distributors supply drugs that comply with international quality standards. Governments in rich countries should not tolerate the export of substandard pharmaceutical products to poor countries, while developing country governments should improve their ability to detect substandard medicines.

The contribution of the French Muskoka Fund to improving access to essential medicines and priority health products for mothers and children.

One objective of the French Muskoka Fund since 2011 has been to improve the availability of quality healthcare services for mothers and children and thus to contribute to the continued presence of essential drugs and affordable quality health products and to their rational use by healthcare personnel. This project thus contributed to reinforcing the work of the national regulatory authorities, guarantor of the quality of the products supplied to the populations, but also to strengthening the coordination of supplies at the country level. It also enabled the provision of support for the implementation of drug price controls and helped to strengthen the ability of healthcare staff to optimize their use of the products available to them. This work should be continued in these countries as they meet the agenda of the Sustainable Development Goals, which require the establishment of universal healthcare coverage.

Access of over-the-counter nicotine replacement therapy products to minors.

BACKGROUND: Public health policy guidelines recommend that health care providers (eg, physicians, nurses, others) counsel adolescent smokers to quit and that nicotine replacement therapy (NRT) may be considered to aid in smoking cessation for nicotine-dependent youth. This recommendation is discrepant with Food and Drug Administration-approved labeling of NRT products, stating that they not be sold to persons younger than 18 years. It is not clear how easily minors are able to purchase NRT products in retail markets. OBJECTIVE: To explore youth access to NRT by conducting the first study, to our knowledge, to determine the ability of minors to purchase over-the-counter NRT products. DESIGN: Observational case series of NRT purchase attempts and survey description of store characteristics. SETTING: Retail businesses in Memphis, Tenn. PARTICIPANTS: Population-based sample of 165 stores that sold over-the-counter medications. MAIN OUTCOME MEASURE: Successfully completed purchase attempts of NRT by the minor buyer. RESULTS: In most stores that stocked NRT products, the age of the minor was not queried at any time during the purchase attempt (79%) and the minor was able to successfully purchase the product (81%). If the minor was asked her age, the store was much less likely to sell the NRT product. Stores in which a cash register gave an age query prompt or in which alcohol was sold were more likely to inquire about the minor's age and less likely to sell NRT products. CONCLUSIONS: Nicotine replacement therapy products were successfully obtained in most purchases by a minor buyer without proof of age. While ease of purchasing NRT products is potentially beneficial to young smokers attempting to quit, these purchases are discrepant with Food and Drug Administration labeling regarding the sale of NRT products to minors.

'Hysteria', 'functional' or 'psychogenic'? A survey of British neurologists' preferences.

The diagnostic preferences of British neurologists for patients who lack a physical explanation for their symptoms were assessed by means of a postal questionnaire. Analysis of 168 completed replies showed 'functional', 'psychogenic' and 'hysteria' to be the most popular terms in use. The number of different terms a clinician would use rose in line with the volume of such patients they encountered, but was unrelated to clinician factors such as the extent of their clinical experience in psychiatry. A specific enquiry into these respondents' interpretation of the term 'functional' revealed a clear consensus as to which syndromes it should apply to, although this consensus was not shared by a comparison group of psychiatrists.

Adoption of revised dosage recommendations for childhood tuberculosis in countries with different childhood tuberculosis burdens.

BACKGROUND AND OBJECTIVE: In 2010, the World Health Organization (WHO) published revised dosage recommendations for the treatment of tuberculosis (TB) in children. The aim of the survey was to assess whether countries adopt these new dosage recommendations, as well as to identify challenges in the management and treatment of childhood TB. In addition, countries were asked to provide 2010 surveillance data on childhood TB. DESIGN: A survey questionnaire was developed and broadly disseminated to National Tuberculosis Programmes or people with close links to them. RESULTS: Among the 34 countries that responded to the survey, the proportion of total national TB caseload reported in children in 2010 ranged from 0.67% to 23.6%. The data on new cases reported to this survey varied from data provided to the WHO global TB database. Most countries had childhood TB guidelines in place, and half had adopted the new dosage recommendations. Countries reported a number of challenges related to the implementation of the new recommendations and general management of childhood TB. CONCLUSIONS: Despite the adoption of the new dosage recommendations, their implementation is complicated by the lack of appropriate fixed-dose combinations. In addition, accurate and consistent estimates of the global burden of childhood TB remained a major challenge. Technical assistance and support to countries is needed to improve childhood TB activities.

Associations of openness and conscientiousness with walking speed decline: findings from the Health, Aging, and Body Composition Study.

OBJECTIVES: The objective of this study was to explore the associations between openness to experience and conscientiousness, two dimensions of the five-factor model of personality, and usual gait speed and gait speed decline. METHOD: Baseline analyses were conducted on 907 men and women aged 71-82 years participating in the Cognitive Vitality substudy of the Health, Aging, and Body Composition study. The longitudinal analytic sample consisted of 740 participants who had walking speed assessed 3 years later. RESULTS: At baseline, gait speed averaged 1.2 m/s, and an average decline of 5% over the 3-year follow-up period was observed. Higher conscientiousness was associated with faster initial walking speed and less decline in walking speed over the study period, independent of sociodemographic characteristics. Lifestyle factors and disease status appear to play a role in the baseline but not the longitudinal association between conscientiousness and gait speed. Openness was not associated with either initial or decline in gait speed. DISCUSSION: These findings extend the body of evidence suggesting a protective association between conscientiousness and physical function to performance-based assessment of gait speed. Future studies are needed to confirm these associations and to explore mechanisms that underlie the conscientiousness mobility connection in aging adults.

On facing facts: what kinds of information do pre-assessment psychotherapy questionnaires provide?

More than two-thirds of NHS psychotherapy departments now use questionnaires in assessment of new patients. Their content is described for the first time. Most are primarily designed to gather biographical information but salient questions are frequently omitted. These questionnaires have suffered from being designed and used in isolation. Psychotherapy service providers need to consider how collaboration will enable questionnaires to be more effective during their assessments and to assist research into which historical factors are of greatest prognostic significance among newly referred patients.

Epilepsy and schizophrenia.

Slater's work on the schizophrenia-like psychoses of epilepsy is re-examined in the light of subsequent developments in psychiatry and neurology. Simple causal links of the sort he postulated between epilepsies and psychoses appear increasingly tenuous, despite indications that some psychotic symptoms and some localised structural changes are linked. A resumption of the study of electrophysiological similarities between schizophrenia and limbic epilepsy may offer a useful alternative programme for research.

Hysterical conversion. I: A history.

'Hysterical conversion' dates from a century before Freud, from an important attempt to rationalise the nosological status of hysteria. Freud's own concept of 'conversion' followed as a quite independent synthesis of 19th-century medical thinking on the subject. Subsequent analytical usage of 'conversion' which has influenced the description of hysterical syndromes within mainstream psychiatry, has not been consistent with Freud's own.

Hysterical conversion. II: A critique.

The career of the diagnosis of conversion hysteria is reviewed at a time when it is threatened with expulsion from classifications of psychiatric disorder. Criticism of its face validity has not led to adequate diagnostic alternatives, and has been insensitive to its unusual form as a category as well as the contribution it has made to the stability of the classificatory system around it.

Attachment and psychotherapy: an overview.

Attachment theory has an important role in clarifying personality development, and attachment style is increasingly recognised as a key intervening variable between personality and the response to psychotherapeutic interventions. Recent developments in attachment theory and its relationship to practice are reviewed as an introduction to a series of papers on Attachment and Psychotherapy.

Psychosis following temporal lobe surgery: a report of six cases.

Six consecutive patients who had had temporal lobe surgery for epilepsy, and been referred for psychiatric assessment of psychotic symptoms, are reported. Their symptoms (a delusional depression, four schizophrenia-like illnesses, and a case of Capgras' syndrome) are discussed in relation to the possible role of their operations, all of which were on the right hemisphere.

Ten-year prognosis of conversion disorder.

BACKGROUND: Previous work suggests neurological disease commonly supervenes in cases of conversion disorder but has not identified clear predisposing factors. Patients' subsequent use of services has been neglected. METHOD: Clinical outcomes for 73 patients investigated for pseudoneurological symptoms at a neurological hospital 10 years earlier were compared with findings on presentation. Fifty-six patients complied with a structured interview concerning use of services. RESULTS: Thirty patients had no relief from their original symptom at follow-up. They had been older, with more chronic symptoms, and different auxiliary psychiatric diagnoses. In 11 patients a clear neurological diagnosis was subsequently made for the original symptom. Provisional neurological diagnoses at presentation had been disproportionately common among these 11. Small numbers of patients with poor outcomes made most use of hospital and community services. High attenders met screening criteria for somatisation disorder at follow-up. CONCLUSIONS: The prognosis for chronic symptoms remains poor, but subsequent rediagnosis of neurological disease is less frequent than commonly supposed. Somatisation disorder may develop if hospital contact does not lead to diagnosis of another disease.

Constant chemical potential titration. Application to determination of nonionic surfactant concentrations.

Titration is most often associated with the idea of a stoichiometric reaction. Generally, it is not considered possible to titrate a compound against a reagent unless the titration reaction is near total and if the result is not a product of well-defined stoichiometry. In this work, we illustrate that accurate titration is possible with compounds and reagents that interact to form an association of undefined stoichiometry. Our model is the potentiometric titration of nonionic surfactant with cationic surfactant using a cationic surfactant-selective electrode. The result of this reaction is mixed micelles, the composition of which depends on the concentrations of the two surfactants in solution.