Cause specific mortality and morbidity outcomes in the syste

Cause-specific mortality and morbidity outcomes in the systematic review and meta-analysis are reported using the International Classification of Disease (ICD 10) nomenclature and hierarchy (Supplementary File S5). A total of 13 publications were suitable for only the systematic review, including study IDs 56–61, which present risk estimates comparing two temperatures (Supplementary Table 2). The risk of cardiovascular and cerebrovascular outcomes, including cerebral infarction, cerebral haemorrhage and ischemic heart disease increased with heat [study IDs 56–61] and cold exposure in most studies [study IDs 56–61]. Only Pan, et al. report a 0.73 lower odds of cerebral haemorrhage at 32 versus 28°C. Respiratory deaths decreased by 2.5% with heat exposure in Chicago, USA at 29 versus 18°C [study ID 59]. Cold exposure increased the risk of allergy [study ID 61] and respiratory mortality and morbidity [study IDs 58,59,61]. A non-linear relative risk of mental health emergency department visits ranging from 1.05 to 1.09 at 25°C was observed across three regions of Quebec, Canada [study ID 36]. Studies applying DTR [study IDs 4,11,23,27,29,34], an exposure metric not comparable to temperature or apparent temperature was included only in the systematic review. Cardiovascular mortality and morbidity relative risk increased in all but the 75+; 0.95 (95% CI 0.06–1.84) [study ID 4], and 65–74 group; 0.99 (0.99–1.0) [study ID 27] per 1°C increase in DTR. Heart failure morbidity increased dramatically in Hong Kong, China [study ID 29]. Interestingly, the risk of respiratory morbidity (all respiratory, respiratory tract infection) increased with a 1°C increase in DTR [study IDs 23,27,34], whereas mortality decreased (Basu et al., 2005). In Taiwan [study ID 27], the 75+ group exhibited slightly elevated risks per 1°C increase in DTR for renal; 1.02 (1.0–1.04) and digestive; 1.04 (1.02–1.05) morbidity compared with the 65+ age group. We report mortality meta-estimates (where k>2) for ischemic heart disease (ICD-10 codes I20–25), all cardiovascular (I00–99), all cerebrovascular (I60–69), and all respiratory outcomes (J00–99). Morbidity meta-estimates (k>2) are presented for ischemic stroke (I63), intracerebral haemorrhage (I61), myocardial infarction (I21–23), dna alkylation pectoris (I20), heart failure (I50), asthma (J45–46), pneumonia (J09–18), diabetes mellitus (E10–14), acute renal failure (N17), intestinal infectious (A00–99), heat-related outcomes (E70–90, T66–78 and R00–99), all cardiovascular (I00–99), all cerebrovascular (I60–69), and all respiratory outcomes (J00–99). In addition, we present an ‘overall’ estimate for both mortality and morbidity outcomes, an amalgamation of the subgroups presented by individual studies including the ‘all’ category. The frequency count of each disease subgroup in the meta-analysis is given in Fig. 3. All cardiovascular disease (CVD) and all respiratory disease (RD) outweighed other mortality subgroups. A greater range of disease groups were represented by morbidity outcomes, including all RD and all CVD, followed by cerebral infarction, myocardial infarction, heart failure, all genitourinary disease, intestinal infection and diabetes mellitus. Threshold temperatures were selected by individual studies based on study location. Lag times, presented as cumulative or single day lags describing the delay between exposure and outcome, varied with high and low temperature. Heat lags were shorter than cold lags, generally between lag 0–1 to 0–3days prior to the event. Cold lags ranged between to 30days. We observed a striking increase in the risk of all mortality outcomes, including cerebrovascular, cardiovascular and respiratory outcomes (Table 2 and forest plots in Supplementary File 6). The greatest risks were for heat-induced CVD and RD, and cold-induced RD mortality. Cerebrovascular (CBD) risks also increased with cold exposure. No protective effect (risk reduction) was found for any mortality outcome; only ischemic heart disease risk was statistically insignificant; 0.45% (95% CI −0.01–0.91) per 1°C decrease in temperature. Compared to the universally elevated mortality risks, temperature-related morbidity risks were mixed for CBD and CVD outcomes (Table 3 and forest plots in Supplementary File 6). In warm periods, the risk of intracerebral haemorrhage, myocardial infarction and all CBD morbidity reduced per 1°C increase in temperature. In winter, the risk of morbidity from angina, heart failure, all CVD, and all CBD reduced per 1°C decrease in temperature. Heat exposure led to an increase in RD morbidity by 2.76% (1.51–4.03). A statistically significant increase was noted for heat-induced diabetes mellitus 1.02% (0.43–1.62) and an even greater risk for heat-related overall genitourinary morbidity 2.12% (1.65–2.59). A 1°C increase in temperature resulted in elevated risks for overall infectious and heat-related morbidity. The greatest statistically significant risk was associated with pneumonia; 1°C reduction in temperature caused a 6.89% (1.20–12.99) increase in morbidity in cold periods.