N-Mannich-Base Prodrugs of 5-Iodo-2′-deoxycytidine as Topical Delivery Enhancers

Two Mannich-base prodrugs of 5-iodo-2-deoxycytidine (5-IDC) have been synthesized. The prodrugs exhibit increased lipid solubility compared to 5-IDC and rapidly revert to 5-IDC in buffer. One of the prodrugs delivered about twice as much 5-IDC from isopropyl myristate (IPM) through hairless mouse skin in diffusion-cell experiments as did 5-IDC from IPM. Subsequent applications of theophylline/ propylene glycol onto the diffusion cells to determine the effect of prodrug/IPM, 5-IDC/IPM, or IPM on the resistance of the skins to subsequent applications showed that the prodrug/IPM had no more effect than IPM itself.     

Problems in establishing accurate family history in patients with ovarian cancer of epithelial origin

A detailed family history was obtained from 90 ovarian cancer patients and 90 age-matched controls. Relatives who died in Alberta had their death year and cancer history verified. Year of death was accurate in 12/20 and negative history of cancer in 30/30. Cancer was reported in 229/2,544 relatives. Of these, 104 were or had been residents of Western Canada, but only 69 malignancies were confirmed through population-based cancer registries. This resulted in an error rate of 10/39 (26%) for parents, 7/31 (23%) for siblings, and 18/34 (53%) for uncles and aunts; error rate is similar for patients and controls. A "positive" history of cancer was reported by 53/90 (59%) of patients and 68/90 (76%) of the controls (chi 2 = 5.7); this difference disappears when the total number of relatives is considered: 92/1,179 (7.8%) in patients and 134/1,366 (9.8%) in controls (chi 2 = 3.3). The age of relatives should also be considered for age/sex-specific years at risk comparison. In summary, the validity of studies showing family history of cancer is questionable owing to the multiple sources of error and the lack of specificity of the methods of analysis.     

Significance of preoperative prognosis

The granulocyte phagocytosis test, Karnofsky index, and ASA standard were used in the context of 287 patients for general surgery, for the purpose of retrospective elucidation of the relationship between presurgical prognostication and postsurgical complications. Sensitivity, specificity, and "predictive values" were calculated. The highest information potential in terms of prognostication was recorded from objectively measurable granulocyte phagocytosis. Presurgical prognostication was found to be of clinical relevance only to surgical problem patients.     

Absorption of oral aminoglycosides following bone marrow transplantation

Four patients with severe gastrointestinal reactions receiving oral "nonabsorbable" antibiotics for gut sterilization following bone marrow transplantation absorbed clinically significant amounts of aminoglycoside (gentamicin and/or tobramycin). Serum concentrations of 2.2, 2.6, 5.8, and 12.0 micrograms/ml were measured. Two of these patients had acute graft versus host reactions and two had severe mucositis following cytoreduction with intensive chemotherapy and irradiation. Nephrotoxicity occurred in the latter patients. One patient was studied in detail. Her hospital course and investigative results are presented. Four additional patients with mild gastrointestinal reactions following cytoreduction did not absorb gentamicin when their toxicity was maximal. Serum aminoglycoside determinations are necessary in patients receiving oral aminoglycosides for gut sterilization following bone marrow transplantation if moderate to severe gastrointestinal reactions occur.     

Difficulties in navigating the intersection of generalist and specialist palliative care services: A cross-sectional study of bereaved family's experiences of care at home in New Zealand

A generalist–specialist model of palliative care is well established as a framework for the provision of community care in resource-rich countries. However, evidence is lacking regarding how the model is experienced by family carers and the extent to which access to both generalist and specialist palliative care is equitable. A cross-sectional postal survey was undertaken to explore bereaved family's experiences of generalist palliative care and its intersection with hospice services in the last 3 months of life. A modified version of the Views of Informal Carers—Evaluation of Services survey was sent to 4,778 bereaved family. Data were collected between February 2017 and October 2018. Chi-square was utilised to identify factors that impacted on experiences of generalist palliative care; analysis of free text data comprising 45,823 words was undertaken using a directed content analysis approach. Eight hundred and twenty-six questionnaires were returned (response rate = 21%). Seventy per cent of people (n = 579) spent some time at home in the last 3 months prior to death. People who received support from hospice were more likely to receive support from multiple other services. Those who received no community services were less likely to feel supported by their general practitioner, less likely to spend the last 2 days of life or die at home. Feeling supported had a strong association with services working well together, being involved in decision-making and being aware of the poor prognosis. The provision of palliative care is complicated by a lack of integration with specialist palliative care and may be the basis of continuing inequities in the provision of community care at the end of life. The assumption at a policy level that “generalists” are willing and able to play a key role in palliative care provision needs to be further challenged.     

Understanding the Enablers and Barriers to Appropriate Infants and Young Child Feeding Practices in India: A Systematic Review

Despite efforts to promote infant and young child feeding (IYCF) practices, there is no collective review of evidence on IYCF enablers and barriers in India. This review was conducted using 2015 Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines. Six computerized bibliographic databases, Scopus, PubMed, PsycINFO, CINAHL, Embase, and Ovid MEDLINE, were searched for published studies on factors associated with IYCF practices in India from 1 January 1993, to 30 April 2020. IYCF practices examined were early initiation of breastfeeding, exclusive breastfeeding, continued breastfeeding at one year, introduction to solid semi-solid or soft foods, minimum dietary diversity, minimum meal frequency, minimum acceptable diet, continued breastfeeding at two years, predominant breastfeeding, and bottle feeding. In total, 6968 articles were retrieved, and 46 studies met the inclusion criteria. The common enablers of IYCF were higher maternal socioeconomic status (SES) and more frequent antenatal care visits (ANC) (≥3). Common barriers to IYCF practices were low SES and less frequent ANC. The review showed that the factors associated with IYCF practices in India are largely modifiable and multi-factorial. Improving IYCF practices would require the adoption of both facilities- and community-based policy interventions at the subnational and national levels in India.     

Investigating the relationship between social care supply and healthcare utilization by older people in England

Since 2010, adult social care spending in England has fallen significantly in real terms whilst demand has risen. Reductions in social care supply may also have impacted demand for NHS services, particularly for those whose care is provided at the interface of the health and care systems. We analyzed a panel dataset of 150 local authorities (councils) to test potential impacts on hospital utilization by people aged 65 and over: emergency admission rates for falls and hip fractures (“front‐door” measures); and extended stays of 7 days or longer; and 21 days or longer (“back‐door” measures). Changes in social care supply were assessed in two ways: gross current expenditure (per capita 65 and over) adjusted by local labor costs and social care workforce (per capita 18 and over). We ran negative binomial models, controlling for deprivation, ethnicity, age, unpaid care, council class, and year effects. To account for potential endogeneity, we ran instrumental variable regressions and dynamic panel models. Sensitivity analysis explored potential effects of funding for integrated care (the Better Care Fund). There was no consistent evidence that councils with higher per capita spend or higher social care staffing rates had lower hospital admission rates or shorter hospital stays.     

Spinal metastases treated with bipolar radiofrequency ablation with increased (> 70 °C) target temperature: Pain management and local tumor control

PurposeTo investigate the safety and clinical efficacy of bipolar radiofrequency ablation (b-RFA) with increased (> 70 °C) target temperature for the treatment of spine metastases with the intent of achieving pain relief or local tumor control.Materials and methodsThirty-one patients with a total of 37 metastases who were treated with b-RFA with increased temperature and vertebroplasty from January 2016 to May 2019 were retrospectively included. There were 20 women and 11 men with a mean age of 62.4 ± 10.5 (SD) years (range: 40–78 years). Patients and metastases characteristics, procedure details and clinical outcomes were analyzed.ResultsMetastases were predominantly located in lumbar (22/37; 59.5%) or thoracic spine (13/37; 35.1%). Mean target temperature was 88.4 ± 3.5 (SD) °C (range: 70–90 °C). Technical success was 100% (37/37 metastases). One (1/37; 2.7%) major complication unrelated to b-RFA was reported. One (1/37; 2.7%) metastasis was lost to follow-up. Favorable outcome was noted in patients receiving b-RFA for pain management (16/20 metastases; 80%; mean follow-up, 3.4 ± 2.9 [SD] months) or with oligometastatic/oligoprogressive disease (6/6 metastases; 100%; mean follow-up, 5.0 ± 4.6 [SD] months). In patients receiving b-RFA to prevent complications, favorable outcome was noted in 6/10 metastases (60%; mean follow-up, 3.8 ± 4.8 [SD] months).ConclusionsB-RFA with increased target temperature has an excellent safety profile and results in high rates of pain relief and local metastasis control in patients with oligometastatic/oligoprogressive disease. Suboptimal results are achieved in patients receiving b-RFA to prevent complications related to the growth of the index tumor.